case studies by : Catherine Nelson-Piercy

by **mandible** Sat Aug 28, 2010 3:36 pm

[size=18][]SICKLE CELL DISEASE
Ms A was a 28 year old woman in her second pregnancy (she had one
previous termination of pregnancy) who booked-in at 19 weeks’ gestation.
She was known to have sickle cell disease (specifically sickle cell
anaemia [HbSS]), and her last crisis had occurred 3 years before this
pregnancy.
Her booking bloods were unremarkable. Her blood pressure and
haemoglobin (Hb) concentration were recorded as 90/60 mmHg and
8.1 g/dl, respectively, with an mean cell volume (MCV) of 87 fL.
At this visit, she was commenced on penicillin (250 mg/day), folate
(5 mg/day) and 4-weekly growth scans were organized.
Her first admission to hospital was a month later (at 23 weeks’ gestation),
when she was admitted for 6 days with a crisis (pain in her
back), which was possibly precipitated by a urinary tract infection.
She was initially treated with intravenous cefuroxime and thereafter
with oral clarithromycin. She received a 3-unit blood transfusion,
which co-incided with a symptomatic improvement.
Her second admission (for 12 days) occurred 2 weeks later (at
25 weeks’ gestation); again, she was treated for a crisis. She required
another 3-unit blood transfusion because her Hb concentration had
fallen to 6.8 g/dl. She required an opiate patient-controlled analgesia
(PCA) and was treated with intravenous fluids, cefuroxime, metronidazole
and flucloxacillin.
During her third admission (at 30 weeks’ gestation for 7 days),
when she had chest pain and blood-stained sputum, she was treated
with intravenous antibiotics and a therapeutic dose (1 mg/kg body
weight/twice daily) of enoxaparin (until a ventilation/perfusion [V/Q]
lung scan was negative). Her blood cultures and sputum were negative
and a further 2-unit transfusion was required.
Her fourth admission occurred within days of discharge from the
hospital. Her symptoms included worsening chest pain and shortness
of breath. On examination, there were crepitations and dullness
in the base of the right lung. She was treated with further intravenous
antibiotics for presumptive community-acquired pneumonia, but she
also had another inconclusive V/Q lung scan and was thus recommenced
on a therapeutic dose of enoxaparin. She was discharged at
33 weeks’ gestation with oral antibiotics (clarithromycin, flucloxacillin,
cephadroxil and nystatin) and enoxaparin.
In total, she had seven ultrasound scans, which showed a small
baby (growth on the third centile), with normal liquor volume and
umbilical Doppler scan.
At 38 weeks’ gestation, she underwent induction of labour and
received two doses of vaginal prostaglandin. However, fetal distress
necessitated a Caesarean section under general anaesthetic. She delivered
a 2.72 kg baby, with a pH of 7.22 and Apgar score of 5 and 9 at
1 minute and 5 minutes, respectively.
Discussion
Sickle cell disease results when there is a variant of the beta-globin
chain (a one amino-acid substitution of valine with glutamine). In
times of crises, which can be precipitated by a number of factors (e.g.
hypoxia, infection, cold, acidosis and dehydration), the red cell takes
on a characteristic, distorted shape. Because of this rigidity, it tends
to block small vessels, producing vaso-occlusive symptoms (pain) and
even infarction.
This patient last had a crisis 3 years before this pregnancy, but
during this pregnancy she developed three crises. This reflects the
increased complication rate and increased tendency to crises in
women with sickle cell disease who fall pregnant. They suffer from
chronic anaemia (Ms A’s booking Hb concentration was 8.1 g/dl),
because of chronic haemolysis, which is often asymptomatic. This is
because of the low affinity of sickle Hb (HbS) for oxygen, which
facilitates oxygen delivery to the tissues.
The possible effects of sickle cell disease on the pregnancy were
also reflected by the small, growth-restricted baby who could not
tolerate the stress of labour. This necessitated a Caesarean section.
Unexplained stillbirth is not uncommon in these patients because of
both impaired oxygen supply and sickling infarcts in the placental
circulation. Therefore, it is the unit policy to offer induction to all
women with sickle cell disease at 38 weeks’ gestation.
This pregnancy was complicated by frequent admissions with
crises and chest infections. It is often difficult to distinguish between
pneumonia, sickle chest syndrome and pulmonary embolism because
these conditions share similar signs and symptoms (tachypnoea,
pleuritic chest pain and leucocytosis) [1]. Early recourse to antibiotics
and rehydration is important to prevent further morbidity and mortality
because most deaths are due to massive sickling following an
infection, which leads to a pulmonary embolism [2].
Ms A received three blood transfusions during this pregnancy.
Letsky [2] reported that the only consistently successful way to
reduce the incidence of complications from sickling is regular blood
transfusion at approximately 6-weekly intervals. This aims to dilute the
existing HbS, and by raising the Hb concentration, thus reduce the
stimulus to the bone marrow to produce more defective cells. This
policy does, however, expose the patient to the risks of multiple transfusions
(i.e. alloimmunization and infection) and it does not have universal
acceptance.
At present, there is no effective long-term method of reducing the
lability of red cells in vivo. There is no evidence to support the use of
alkalis, hyperbaric oxygen, vasodilators, plasma expanders or anticoagulation
once the crisis is established. The best approach is meticulous
care and supportive therapy with adequate fluids, analgesia and
treatment of possible infection. Prophylactic antibiotics (e.g. penicillin)
are used because patients with sickle cell disease often have a
nonfunctioning spleen and penicillin affords protection against pneumococcal
septicaemia.[/size]

[/size]

by **mandible** Sat Aug 28, 2010 3:45 pm

Ms B was a 29 year old primigravid who booked-in at 16 weeks’ gestation.
Her booking bloods were unremarkable. Her blood pressure
and Hb concentration were recorded as 100/60 mmHg and 11.2 g/dl,
respectively.
She had seven uneventful antenatal visits throughout which she had
a normal blood pressure and no abnormalities were found in her urine.
She self-presented at term in spontaneous labour, and in the ensuing
48 hours, despite a prolonged latent phase, she delivered a 3.54 kg
infant with Apgar scores of 8 and 9 at 1 and 5 mins respectively. This
was facilitated by an instrumental delivery in theatre. She required an
epidural and Syntocinon for the last 12 hours of her labour. The
Syntocinon was infused (as per protocol) at an increasing rate of
1 mu/min and titrated to her contractions.
It was noted that she had only passed 70 ml of urine 5 hours after
the insertion of the epidural and urinary catheter, despite receiving
1500 ml of intravenous and oral fluids. The catheter was flushed and
a 500 ml fluid challenge was given. Her vital signs were stable. After
2 hours (at 7.30 a.m.), a baseline renal function test was performed
(Table 5.1).
TABLE 5.1. Serial urea and electrolytes
Time 7.30 a.m. 12.30 p.m. 8.10 p.m. 5.30 a.m.
Sodium, mmol/l 124 121 131 140
Creatinine, mol/l 96 131 110 81
Urea, mmol/l 4.7 5.4 5.7 4.6
Serum osmolality 262
Bicarbonate, mmol/l 19 17 19 22
Because of continuing oliguria, a further fluid challenge was administered
at 10.30 a.m. Her serum osmolality was 262 mOsm/kg (normal
range, 275–285 mOsm/kg) and her urine osmolality was 338 mOsm/kg.
Further blood testing performed before ventouse delivery (at 12.30
p.m.) showed worsening renal function and hyponatraemia (Table 5.1).
With a presumptive diagnosis of “water intoxication” secondary to
Syntocinon administration, Ms B received treatment postoperatively
with fluid restriction (500 ml/12 hours). In the following 8 hours, a
massive diuresis occurred (6.5 l). By 17 hours postdelivery, her renal
function had significantly improved (Table 1) and she was discharged
home a day later.
Discussion
Hyponatraemia is the commonest electrolyte disturbance seen in a
general hospital population, occurring in 1% of all patients. It
is defined as a decrease in serum sodium concentration below the normal
range (136–145 mmol/l), usually indicative of hypo-osmolality of
body fluid due to an excess of water relative to solute.
It has two principle causes, as follows:
1. Sodium depletion in excess of water or replacement of sodium
losses with water alone, for example in gastrointestinal and thirdspace
losses, sweating and dialysis/renal failure.
2. Dilutional hyponatraemia occurs if the water intake is in excess of
its output and usually implies impaired excretion. This occurs in
cases ranging from inappropriate secretion of antidiuretic hormone
(ADH) to those resulting from neuroendocrine, adrenal or
pituitary insufficiency.
The causes of the syndrome of inappropriate secretion of ADH
(SIADH) can broadly be divided into those secondary to malignancy
(tumours of the lung, pancreas or duodenum), central nervous system
disorders (meningitis, head injury or haemorrhage), chest disease
(tuberculosis or pneumonia) or metabolic disease (porphyria).
Well-known complications of oxytocin include overstimulation of
the myometrium, resulting in tetanic contractions, fetal hypoxia or
occasionally uterine rupture. A lesser-known side effect is that it has
an ADH-like effect, leading to suppression of diuresis and features
including concentrated urine, hyponatraemia and low plasma osmolality
with no apparent dehydration or oedema. “Water intoxication”,
as it was called, was first reported in 1962 by Liggins [3]. This complication
occurred in women receiving large doses of oxytocin, most
commonly in those having midtrimester termination of pregnancy or
the induction of premature labour associated with fetal death in
utero. It usually involved large amounts of oxytocin in electrolytefree
solutions administered over an extended time period, which
resulted in severe electrolyte derangements, convulsions, coma and
even death [4].
The pathogenesis involves progressive hyponatraemia and fluid
shifts from the extravascular to the intravascular compartment, with
resultant cerebral oedema. Transplacental passage can occur with
similar derangements in neonatal biochemistry [5]. Convulsions are
unlikely unless the fluid input exceeds output by 3 l in 24 hours,
and are, therefore, uncommon following oxytocin-induced labour
at term.
This patient, however, was given low doses of Syntocinon
(1 mu/min and then 2 mu/min) over a moderate time period (7 hours).
Even allowing for the small incremental dosage increases that
occurred with the step-up Syntocinon regimen, a low total dose of
oxytocin was infused. In retrospect, the two fluid challenges she
received probably exacerbated hyponatraemia.
Current labour ward protocols limit the use of oxytocin in terms
of concentration, duration of administration and type of additional
fluids. Stratton et al. [6] showed that patients who received co-infusions
of dextrose solution had significantly lower sodium levels compared
with patients who received electrolyte infusions (normal saline).
Most units use Hartmann’s solution or normal saline for oxytocin
administration.
Correct use of the partogram limits the duration of the active
phase of labour; thus, rarely do patients “labour” for 24 hours in
hospital, minimizing oxytocin infusion times and risks.
A literature review using Medline revealed a predominance of
cases in the early 1970s and 1980s, with a paucity of new reports, suggesting
that water intoxication secondary to oxytocin administration
rarely occurs nowadays. However, clinicians should remain vigilant
to the possibility.
The primary treatment is recognition of the underlying cause (stopping
oxytocin) and thereafter restricting intake to 1000–1500 ml/ 24 hours
This might seem an illogical step because of oliguria, but if the
diagnosis is correct, it will result in rapid improvement. Similar to
pre-eclampsia, the use of repeated blind fluid challenges should be
avoided in the labouring or postpartum patient unless volume depletion
or blood loss is suspected.

by **mandible** Sat Aug 28, 2010 3:48 pm

Ms C was a 32 year old caucasian woman. She was para 0 1, having
had a fetal loss at 23 weeks’ gestation 1 year previously. She attended
the obstetric medicine clinic at 7 weeks’ gestation, having been referred
by her general practitioner (GP).
In her past medical history, she had had a myocardial infarction
with coronary artery stenting aged 27, with ongoing angina, hypercholesterolaemia,
hypertension, asthma, oesophageal reflux and chronic
back pain.
She had conceived while taking aspirin, isosorbide mononitrate,
glyceryl trinitrate (GTN) spray, ramipril, simvastatin, montelukast,
omeprazole, codeine phosphate, diazepam, and beclomethasone and
salbutamol inhalers.
She was a current smoker of 40 cigarettes/day and was homeless
and living in a hostel. During investigation of the previous intrauterine
death, raised anticardiolipin antibodies were detected on two
occasions 8 weeks apart. She had an initial booking ultrasound that
showed a twin pregnancy.
There was a long discussion regarding her medication, and after
appropriate counselling, she was advised to stop simvastatin,
ramipril and omeprazole and to reduce codeine phosphate and
diazepam as much as possible. She was also referred to a smoking
cessation clinic. Her angiotensin-converting enzyme (ACE)
inhibitor was changed to methyldopa and omeprazole was changed
to ranitidine. She was commenced on enoxaparin (40 mg once
daily) and folic acid (5 mg/day), which was to be continued
throughout the pregnancy. She was understandably very anxious
regarding the pregnancy.
She returned for her booking appointment at 10 weeks’ gestation.
A repeat scan showed no fetal heart in one twin. Booking bloods were
taken, plus urea, electrolytes and urate measurements, which were
normal. Repeat anticardiolipin antibodies remained elevated.
A management plan was made for the pregnancy. She was to be
seen in the obstetric medicine clinic once per fortnight for blood
pressure measurement and urinalysis, and monitoring of her angina
symptoms, which she was at times reluctant to admit to. She was
offered serum screening at 16 weeks’ gestation.

At her request she was commenced on high-dose vitamin C
(1 g/day) and vitamin E (400 iu/day) [7]. A fetal anomaly scan was
organized at 18 weeks’ gestation, with maternal uterine artery
Doppler estimation. Growth scans were planned from 24 weeks’ gestation
and delivery was planned by elective Caesarean section at
38–39 weeks’ gestation.
The pregnancy progressed uneventfully until 20 weeks’ gestation.
The fetal anomaly scan showed no anomalies in the fetus but there
was bilateral notching on the uterine artery Doppler scan. She managed
to cut down smoking to two to three cigarettes/day and the
social work department was involved regarding her housing situation.
She became increasingly stressed and complained of increasing
angina. Her isosorbide mononitrate was increased. Her anxiety grew
further around the time of her previous loss.
Growth scans estimated that the baby was growing between the
5th and the 50th centiles.
The woman complained of further episodes of angina, even on
minimal exertion and despite using her GTN spray. Her isosorbide
mononitrate was further increased. An echocardiogram was performed
at 36 weeks’ gestation. This showed a normal ejection fraction, with
good systolic function. An electrocardiogram (ECG) was normal. She
was reviewed by the obstetric anaesthetic team.
The planned elective Caesarean section was carried out at 38 weeks’
gestation.
Her low-molecular-weight heparin (LMWH) was stopped on the
day before the planned surgery. A combined spinal epidural was used
for analgesia and the Caesarean section was uncomplicated, with
400 ml blood loss. She delivered a live male infant, with a birth
weight of 2.95 kg.
Ms C recovered well from the Caesarean section and wished to
breastfeed. Unfortunately, varying advice was given over the safety of
her medication in breastfeeding. Breastfeeding did not establish easily
and she bottle fed her son from 6 days of age. She continued on
enoxaparin (40 mg once daily) for 6 weeks postpartum. Her ACE
inhibitor and statin were restarted. At 6 weeks postpartum, both
mother and baby were well. She was considering a Mirena intrauterine
system (IUS) for future contraception, although she was not
currently with her partner. She was counselled regarding the risks of
a further pregnancy.
Discussion
This was a high-risk pregnancy in a woman with extensive medical
and social problems. She had significant risk factors and ischaemic

heart disease, with ongoing symptoms, despite her young age. It was
felt that her previous myocardial infarction was due to ischaemic
heart disease in the presence of underlying risk factors of hypercholesterolaemia,
hypertension and smoking rather than because of arterial
thrombosis from her antiphospholipid antibody syndrome
(APS). APS (late fetal loss in the presence of raised anticardiolipin
antibodies) also posed risks to the pregnancy, which could be reduced
by LMWH and low-dose aspirin. She conceived while receiving a
large number of drugs, for which there are minimal data on use in
pregnancy and breastfeeding.
There is very little literature on women with ischaemic heart
disease in pregnancy because until recently this was rare in women of
childbearing age [8,9].
The continued use of ACE inhibitors in pregnancy has been associated
with foetotoxicity (fetal renal failure and renal dysgenesis,
hypotension, oligohydramnios, pulmonary hypoplasia and hypocalvaria).
The risks are greatest during the second and third trimester
[10]. Women should change to an alternative antihypertensive pre
pregnancy. ACE inhibitors are safe to use while breastfeeding, but as
this case illustrates, this is not widely appreciated.
A recent multicentre study showed no increase in anomalies in the
fetus exposed to omeprazole in the first trimester [11]. Montelukast has
little safety data in human pregnancy; however, animal studies have
been reassuring (it has been categorized as US Food and Drug
Administration [FDA] pregnancy category B). In cases of severe asthma
requiring the use of montelukast during pregnancy, many clinicians continue
this drug because the risks to the fetus of poorly controlled asthma
in the mother outweigh any potential risks of the drug.
APS has been extensively studied in pregnancy and there is good
evidence for the benefit of the use of both low-dose aspirin and
LMWH in these women, both to prevent early miscarriage and to
prevent thrombosis [12]. There is less evidence that it reduces the
risk of intrauterine growth restriction (IUGR) or late still birth.

by **mandible** Sat Aug 28, 2010 3:51 pm

CARDIAC TRANSPLANT

Mrs D was a 33 year old para 0 1 who attended for prepregnancy
counselling with her husband and mother. She had received a cardiac
transplant 10 years previously at the age of 24 following multiple
myocardial infarcts caused by thromboemboli. Postmyocardial
infarction, her left ventricular ejection fraction was 13% on an
echocardiogram. She was, therefore, placed on the cardiac transplant
waiting list and received a transplant 5 months after her initial
myocardial infarction. She had three episodes of rejection in the

early period following her transplant, but these were all mild. She
had not had any other episodes of rejection.
She had been followed-up regularly at the transplant centre and
remained very well.
Her most recent coronary angiogram, performed a year earlier,
was normal with no evidence of allograft coronary artery disease. She
had also had an echocardiogram showing mild left-ventricular hypertrophy,
but with good function. The right ventricle was normal. She
had a thickened aortic valve with mild aortic regurgitation and a
mildly thickened mitral valve with mild mitral regurgitation. An
ECG showed right bundle branch block.
Her current medication was as follows:
Ciclosporin A, 125 mg twice daily.
Azathioprine, 75 mg once daily.
Prednisolone, 5 mg once daily.
Atorvastatin, 10 mg at night had been stopped in preparation for
pregnancy.
A thrombophilia screen was negative and prepregnancy serum
creatinine was 116 mol/l.
A review of the literature was performed in order to advise her and
she was given a follow-up appointment for further discussion.
At her follow-up appointment, Mrs D reported a positive pregnancy
test. Her booking blood pressure was 140/84 mmHg at
8 weeks’ gestation. Urinalysis showed 4 blood, 1 protein (she
reported some PV bleeding.) Baseline electrolytes, urate level and
ciclosporin A levels were performed. A 24-hour urine collection for
creatinine clearance and total protein estimation and an MSU were
also performed. Mrs D was commenced on aspirin (75 mg/day)
and folate (5 mg/day) to be continued throughout the pregnancy.
She had a normal nuchal translucency and first trimester scan.
Maternal uterine artery Doppler studies were arranged for 24
weeks’ gestation and showed a prediastolic “notch” and persistent
high-resistance waveform predictive of subsequent pre-eclampsia,
IUGR or placental abruption.
Mrs D had an uneventful antenatal course but delivered by
emergency Caesarean section at 36 weeks’ gestation in another unit
following an abruption. Mother and baby are well.
Discussion
The literature describes 57 pregnancies in 41 women postcardiac
transplantation. The overall reported incidence of miscarriage is
14%, with a preterm delivery rate at 37 weeks’ gestation of 30% and
an incidence of pre-eclampsia of 17.5% [13,14,15].

The main clinical issues for Mrs D were as follows:
Medication – there is evidence that ciclosporin A causes IUGR in
women who become pregnant while taking this drug. Therefore, the
lowest dose possible should be the aim. However, the maternal risks of
voluntarily ceasing the medication are very high and in the literature
three reported maternal deaths followed voluntary cessation of
immunosuppressants.
Renal impairment – baseline bloods were normal, with the exception
of serum creatinine, which was raised (105 mol/l), although
this represented an appropriate pregnancy-related fall compared with
the preconception level (116 mol/l). Raised serum creatinine might
have been due, in part, to her excess muscle mass (she was an avid
weight-training enthusiast), in which case it should fall following cessation
of excessive exercise as she was advised, or it could have been
due to a degree of nephrotoxicity from ciclosporin A. If it was due to
nephrotoxicity, the development of pre-eclampsia was more likely.
This was the rationale behind starting aspirin therapy.
Measurement of resting pulse rate was important because
transplanted hearts are denervated and thus there is always a resting
tachycardia. It is important to document the patient’s normal heart rate.
She should also have an ECG because there might be minor abnormalities,
which are normal for her, and it is important to record this.
In the largest series of heart-transplant recipients with subsequent
pregnancy, maternal survival was 71% at 7.5 years [15]. In all other
case series, the mothers were described as healthy in the immediate
postpartum period. Reduced maternal survival while the child is still
young was also discussed with the couple.
This largest series reported 47 pregnancies in 35 women: 6 pregnancies
ended in miscarriage and 6 ended in therapeutic abortion.
The incidence of preterm delivery at 37 weeks’ gestation was
43% and the mean birth weight was 2543 g 696 g. There were no
structural abnormalities reported in the infants. The incidence of
pre-eclampsia was 20% and allograft vasculopathy was 24%, which is
not higher than would be expected in any 1 year in a heart-transplant
patient who was not pregnant.
Nine women in this series died and, importantly, three of these
women had ceased taking their immunosuppressant therapy because
of concerns regarding the fetus.

by **mandible** Sat Aug 28, 2010 4:12 pm

POSTPARTUM ECLAMPSIA

Ms E was a 22 year old primigravid woman. She attended for routine
booking at 12 weeks’ gestation, at which time all investigations were
normal. Shewas fit andwell, with no significant past medical or family
history. Her booking blood pressure was 96/50 mmHg, and urinalysis
was negative. She received routine antenatal care and remained well
throughout her pregnancy; she was normotensive with no proteinuria
throughout.
At 413 weeks’ gestation she was admitted in spontaneous labour.
On admission, her blood pressure was recorded as 150/87 mmHg.
Labour progressed well, but at full dilation, following active pushing
for 1 hour, the head was in a deflexed occipito-posterior position
with the vertex above the ischial spines, and a decision for emergency
Caesarean section was made. This was carried out uneventfully and a
live male infant weighing 3.3 kg was delivered in good condition.
Blood loss at the time of operation was estimated at 700 ml, with subsequent
blood loss of approximately 500 ml.
On day 1 post Caesarean section, she developed abdominal distension.
Her blood pressure was recorded as 121/54 mmHg. An abdominal
X-ray was performed and this showed dilated loops of bowel
consistent with a paralytic ileus. She was thus transferred to the highdependency
unit, where a nasogastric tube was inserted and intravenous
fluids were commenced. Routine bloods were taken
(Table 5.2). She was found to be anaemic, with a Hb concentration of
8.4 g/dl and was transfused with two units of red blood cells. The following
day, her abdominal distension was less. Her bowels opened
following an enema and there were some bowel sounds present.
On day 3 postnatally, she complained of a severe headache at
midnight; her blood pressure was recorded as 185/87 mmHg and she
was given 50 mg of pethidine intramuscularly because simple analgesia
was inadequate. After 1 hour (on day 4 at 1 a.m.), the on-call registrar
was called to see her urgently because she was having a
tonic–clonic convulsion. She was given facial oxygen and a magnesium
sulphate (MgSO4) bolus, followed by an infusion. The convulsion
terminated after 10 minutes. In retrospect, on her chart her
blood pressure had been recorded as 178/81–185/90 mmHg since
5 p.m. that day. Urinalysis showed 2 proteinuria. Electrolytes,
urate, a full blood count, coagulation screen and liver function tests
were checked (Table 5.2).
Her blood pressure remained stable at about 126/78 mmHg.
Further bloods tests were repeated. A computed tomography (CT)
brain scan was performed the following day and reported as normal.
By day 5, she was feeling better and her ileus was improving. MgSO4
infusion was stopped after 24 hours.
At 6 a.m. on day 6 post Caesarean section, the registrar was called
urgently to see her because she was having a further tonic–clonic
convulsion. She had not complained of any prodromal symptoms.

TABLE 5.2. Flow chart of Ms E’s blood test results
convulsion convulsion
Result ↓ ↓
Post-C/S Day 2 Day 4 Day 6 Day 7 Day 8 Day 10 Day 12
Na, mmol/l 141 144 141 143 140 142 135
K, mmol/l 4.0 3.6 3.5 3.7 3.3 4.7 4.3
Urea mmol/l 2.9 4.6 7.4 10.6 12.4 9.9 5.7
Creatinine, 60 87 176 225 264 202 117
mol/l
Urate, mmol/l 0.40 0.69 0.71 0.58 0.42
Albumin, g/l 18 19 20 22 21 25
ALT, iu/l 7 11 8 8 7 19
Alkaline 188 179 149 159 142 143
phosphatase,
iu/l
ALT - alanine transaminase; C/S - Caesarean section; K - potassium; Na - sodium.

This convulsion terminated after 3 minutes. In retrospect, her blood
pressure had been recorded as 146/99 mmHg at 3 a.m. Repeat blood
tests were performed. She was commenced on atenolol, 50 mg once
daily. Her blood pressure was subsequently well controlled and she
had no further convulsions. However her renal function continued to
deteriorate (Table 5.2).
Her abdominal distension gradually reduced and she began eating
and drinking normally again. There were issues regarding bonding
with the baby: Ms E showed no interest in her son and wanted her
family to look after him at home. She was encouraged to have him
beside her as much as possible. She had regular reviews by obstetric
medicine and renal physicians. Her urine output remained excellent
despite deteriorating renal function. A renal scan was performed on
day 11. This was reported as showing normal kidneys of equal size,
slight pelvicaliceal system dilatation, probably because of incomplete
bladder emptying, and a postmicturition residual volume of 450 ml.
This scan result was discussed with the urologists and she was
allowed home with an in-dwelling catheter and plans for out-patient
review.
Her renal function improved (Table 5.2). She was well enough to
be discharged home on day 13, with the following discharge medication:
ferrous sulphate (FeSO4) 200 mg twice per day and atenolol
(50 mg once per day).

When reviewed in the obstetric medicine clinic at 5 weeks postpartum,
she was well and normotensive (110/70 mmHg), and urinalysis
was clear. Her serum creatinine was 87 mol/l. Atenolol was discontinued
and GP follow-up was arranged. Urodynamic follow-up was
organized by the urology department.
Discussion
With improvements in antenatal care and both improved recognition
and earlier diagnosis of pre-eclampsia, in addition to earlier delivery
for those with severe pre-eclampsia, there seems to have been a shift
in the timing of eclampsia towards the postpartum period, perhaps
increasingly 48 hours post-delivery. Of eclamptic convulsions, 44%
occur postpartum.
More than one-third of women experience their first convulsion
before the development of hypertension and proteinuria. In the vast
majority of patients, at least one prodromal symptom is experienced.
In a recent study, 87% had headache, 44% had visual symptoms, 22%
had nausea or vomiting and 9% had epigastric pain [16].
Fortuitously, this woman remained an in-patient because she developed
a paralytic ileus; she would otherwise have been discharged and
had the convulsion at home.
Her blood pressure was elevated both in the immediate postpartum
period and between her convulsions, but it remained untreated;
this was probably owing, in part, to the focus on her paralytic ileus
and, in part, because of being falsely reassured by the normal blood
profile on day 2 [17].
Her headache, severe enough to require opiate analgesia, should
have prompted further examination and investigation because it
heralded her first convulsion.
Her blood pressure was markedly elevated before her second
convulsion, although there were no prodromal symptoms.
MgSO4 had been discontinued after 24 hours (as per protocol),
and it is difficult to predict which patients will develop recurrent convulsions
and require additional therapy [18].
Beware of the routine use of nonsteroidal anti-inflammatory
drugs (NSAIDs) following Caesarean section. This patient received
two doses of voltarol despite deteriorating renal function.

by **mandible** Sat Aug 28, 2010 4:16 pm

HYPEREMESIS GRAVIDARUM
Ms F was a 35 year old woman in her third pregnancy. In her first pregnancy,
she had been admitted on four occasions with severe hyperemesis
and needed prolonged periods of hospitalization, in addition to regular
antiemetics until 33 weeks’ gestation. She terminated her second pregnancy
because she could not face such severe hyperemesis again.
She was previously fit and well, but in the index pregnancy, she
experienced nausea and vomiting from her first missed period and presented
to the hospital at 8 weeks’ gestation. On examination, she was
tachycardiac and had postural hypotension and ketonuria. Ms F was
admitted and treated with intravenous fluids and metoclopramide,
10 mg intramuscularly three times daily. A viable intrauterine pregnancy
was confirmed on ultrasound scan; she improved on the above
therapy and was discharged 2 days later. In the subsequent 2 weeks, she
had three further admissions with hyperemesis gravidarum (HG). On
the third occasion, she was severely dehydrated, had lost 7 kg in weight
and was ketotic. She was admitted, rehydrated and given regular
cyclizine, 50 mg intravenously three times daily. Over the following
week, she improved and was sent home with oral antiemetics, folic acid
(5 mg) and thiamine hydrochloride (25 mg three times daily).
Her next admission was at 12 weeks’ gestation despite regular use
of oral cyclizine. She had lost a further 3 kg in weight and, again, had
4 ketones in her urine. Investigations revealed a raised free thyroxine
(fT4) level, undetectable thyroid-stimulating hormone (TSH),
abnormal liver function with an alanine aminotransferase (ALT)
level of 70 iu/l and hypokalaemia (serum potassium, 3.1 mmol/l).
She was once again rehydrated with normal saline and potassium
chloride (40 mmol/l in each 1 l bag) and given domperidone, 60 mg
per rectum three times daily, cyclizine, 50 mg intravenously three
times daily and oral metoclopramide. Enoxaparin (40 mg) was given
daily for thromboprophylaxis. This time she was maintained on
intravenous fluids and parenteral anitemetics for 1 week. After 1 week,
she was still vomiting up to three times daily and was unable to drink
enough to avoid intravenous fluids. She was noted to be very
depressed by her husband and the nurses caring for her and was
requesting a termination of pregnancy.
The decision was made to undertake a trial of corticosteroid therapy.
This was begun as hydrocortisone, 100 mg intravenously twice
daily. After the first two doses, Ms F was able to tolerate oral fluids
and the intravenous fluids and antiemetics were discontinued.
Therapy was changed to prednisolone, 20 mg oral twice daily and she
was discharged. On review in clinic 1 week later, she had had no further
vomiting or nausea but still complained of “spitting”. Serum
electrolytes were normal, repeat liver function tests showed a normal
ALT level and a repeat thyroid function test showed resolving biochemical
thyrotoxicosis, with a free T4 level just above the normal
range. The prednisolone dose was decreased to 15 mg twice daily
The dose was gradually weaned over the next month to 10 mg
twice daily. Ptyalism had resolved by 19 weeks’ gestation. An anomaly
scan of the baby was normal. Several times over the next 2 months
she attempted decreasing the steroid dose but would not tolerate
doses below 20 mg/day. If she reduced the dose to 15 mg/day, the
vomiting returned. She was thus maintained on a dose of 20 mg/day.
A glucose tolerance test at 28 weeks’ gestation was normal. At 30 weeks’
gestation, the prednisolone dose was successfully reduced to
15 mg/day and thereafter reduced by 5 mg every 2 weeks, such that
she was weaned off steroids by 36 weeks’ gestation.
At 39 weeks’ gestation, she presented in spontaneous labour
having ruptures her membranes. She vaginally delivered a healthy
female infant weighing 6 lbs 3 ozs. Postnatally, she was counselled
regarding the likely recurrence of hyperemesis in future pregnancies
and a plan was made to use corticosteroids at the first admission for
HG.
Discussion
This was a case of severe HG causing associated abnormal liver and
thyroid function. In her first pregnancy, symptoms had lasted until
the third trimester and, therefore, it was likely that this would happen
in any future pregnancy.
Nausea and vomiting occur commonly in pregnancy, usually
between the 6th and 16th week. In 20% of cases, it persists into the
second and third trimesters. Management involves reassurance, small,
frequent high-carbohydrate food and avoidance of large-volume drinks.
Acupunture, ginger and vitamin B6 might relieve symptoms. Other
causes of vomiting in pregnancy include the following:
Ear, nose and throat diseases, for example, labyrinthitis or Meniere’s
disease.
Acute fatty liver of pregnancy (AFLP; in the third trimester).
HELLP syndrome.
Gastrointestinal causes, for example, cholecystitis, pancreatitis, peptic
ulceration and, rarely, gastric cancer.
Metabolic/endocrine, for example, hypercalcaemia, Addison’s disease
and hyperparathyroidism.
Drugs, for example, opioids, iron therapy and antibiotics.
Psychological, for example, eating disorders.
If abdominal pain and tenderness is a marked feature, consideration
should be given to further investigation with endoscopy.
HG is defined as vomiting occurring before the 20th week of
pregnancy that is sufficient to cause dehydration, acidosis and a
minimum weight loss of 5%. Some definitions include the inability
to maintain the fluid and electrolyte balance without hospital admission.
It occurs in about 0.5–1.5% of pregnancies and remains the
third most common cause for admission to hospital during pregnancy.
Before the introduction of intravenous fluids, mortality from
HG was 159 deaths/1 million pregnancies. Complications of HG
include Wernicke’s encephalopathy, central pontine myelinosis
and peripheral neuropathy. Pneumomediastinum and oesophageal
rupture secondary to the mechanical forces of vomiting have been
described.
Meta-analysis of the available data showed a small reduction in the
risk of spontaneous miscarriage, stillbirth and preterm delivery in
women who experience HG. However, when HG is severe and associated
with maternal weight loss and repeated hospital admissions,
there is a slight increase in the incidence of IUGR. There is no
known increase in rate of congenital defects in vomiting pregnancies
compared with nonvomiting pregnancies.
The aetiology of HG remains elusive. It is believed that the
genetic variation in incidence is related to the presence of specific isoforms
of human chorionic gonadotrophin (HCG) that cause HG
[19]. Elevated levels of oestrogen and progesterone have also been
implicated. Although high levels of oestrogen do cause slower intestinal
transit times, there are no studies showing a relationship
between severity of HG and oestrogen levels. Prospective cohort
studies have not shown any consistent relationship between progesterone
levels and HG.
Thyroid hormone values deviate from the normal range in early
pregnancy, leading to gestational transient thyrotoxicosis [20].
Although evidence supports a relationship between HCG and gestational
transient thyrotoxicosis, the exact role of this in HG is obscure.
Overactivity of the adrenal cortex is also associated with HG, but it
is uncertain whether it has a role in its pathogenesis. Helicobacter
pylori infection was found in a significant number of patients with
HG in 11 prospective, case-controlled studies [21]. Liver function
abnormalities have been reported in about 67% of women with HG.
Elevations of aspartate aminotransferase (AST) or ALT levels can be
very dramatic, but return to normal with the cessation of vomiting
and the end of starvation.
Clinical assessment should include measurement of the pulse, lying
and standing blood pressures, urinalysis and weight, in addition to a
complete examination to exclude other causes of vomiting,
particularly infection. Further investigations should include urea and
electrolytes, liver function tests, thyroid function tests, and serum
phosphate, magnesium and calcium levels. A full blood count,
midstream urine sample and blood glucose level should also be
determined.
Management of HG involves rehydration with intravenous fluids,
replacement of electrolytes, vitamins, antiemetics and cessation of oral
nutrition and fluids. Fluid replacement can be with either sodium
chloride (plus potassium, 20 mmol or 40 mmol) or Hartmann’s solution.
Protracted vomiting is associated with Mallory-Weiss oesophageal
tears, Mendelson’s syndrome and jaundice. The neurological disturbances
are a result of vitamin B1 deficiency. It is imperative that
thiamine hydrochloride (25–50 mg orally three times daily or as Pabrinex
intravenous weekly supplements) is prescribed in these cases, to avoid
Wernicke’s encephalopathy and Korsakov’s psychosis.
Antiemetic therapy is a mainstay of treatment, although no antiemetic
treatment is specifically licensed for use in pregnancy. Pyridoxine
hydrochloride (vitamin B6) and ginger have been shown to relieve
symptoms in severe HG.
Dopamine receptor antagonists can be used, including the
following: metoclopramide, domperidone, and phenothiazines.
These drugs are safe but can cause extrapyramidal side effects. Other
antiemetics that can be used include the following: cyclizine,
prochlorperazine, and chlorpromazine.
Ondansetron, a potent and highly selective type 3 serotonin
(5-hydroxytryptamine; 5-HT)receptor (5-HT3) antagonist can be
used if all other antiemetics have failed. The safety of this drug has
not been sufficiently evaluated in large-scale trials. If management
has been optimal and there is no improvement, consideration might
be given to starting steroids (prednisolone, 20 mg twice daily or
hydrocortisone, 100 mg intravenously twice daily) [22,23]. The
response is usually dramatic, but if there is no response, steroids
should be discontinued after 2–3 days. For those who respond to
steroids, it is important to continue the therapy after discharge and
wean the dose slowly. Usually, steroids will need to be continued in
reduced doses until such time as nausea and vomiting have abated.
With prolonged use of steroids in pregnancy, it is important to
monitor blood glucose levels.
Parenteral nutrition is only recommended if there is maternal
protein-calorie malnutrition and all other therapy has failed. Total
parenteral nutrition (TPN) is safe, with expert advice and monitoring
of maternal levels of nutrition. The fetus must be monitored with
serial growth scans, and there must be facilities to accommodate
preterm delivery available.
HG can be mild or severe, but most cases improve with optimal
management and termination is rarely required for medical reasons.
Early treatment of a recurrence is advised.

by **mandible** Sat Aug 28, 2010 4:19 pm

POSTPARTUM CEREBRAL HAEMORRHAGE

Ms G was a 34 year old para 2 5 with pre-existing renal disease and
hypertension who presented 7 days after a normal vaginal delivery with
sudden onset of right-sided weakness and loss of speech.
Her obstetric history was that of five miscarriages at 12 weeks’
gestation. Her sixth pregnancy was complicated by severe preeclampsia,
requiring induction at 29 weeks’ gestation. She had a
normal delivery of a live infant weighing 1.1 kg. Following this pregnancy,
she was diagnosed with essential hypertension requiring
medication. She had a renal biopsy 3 years later to investigate renal
impairment and was diagnosed with Alport syndrome.
In the index pregnancy, her hypertension was controlled with
methyldopa, 750 mg three times daily. Aspirin was commenced to
reduce her significant risk of recurrent pre-eclampsia because of her
pre-existing renal disease and hypertension, and history of previous
early onset pre-eclampsia. A thrombophilia screen was negative.
Renal function remained stable with serum creatinine ranging
between 107–132 mol/l. She had pre-existing significant proteinuria
of 2.08 g/24 hours at the beginning of pregnancy, which
dropped to 1.24 g/24 hours towards the end of the pregnancy. Serial
scans confirmed normal fetal growth. There was no evidence,
clinically or from blood parameters, of superimposed pre-eclampsia.
She went into premature labour at 35 weeks’ gestation, with a vaginal
delivery of a live infant who had a birth weight of 2.2 kg. After delivery,
methyldopa was converted to atenolol, 50 mg/day and her blood
pressure remained stable. She was discharged home 2 days postpartum.
The last blood pressure recording before discharge was
138/86 mmHg.
She was re-admitted on day 7 postpartum, having had sudden
onset of headache, vomiting, one witnessed seizure, right-sided weakness
and loss of speech. She had been taking atenolol, 50 mg/day for
hypertension. Findings on examination were as follows: blood pressure,
182/91 mmHg; heart rate, 60 bpm; sinus rhythm; and urinalysis
showed 4 proteinuria. Neurological assessment revealed a dense
right-sided hemiplegia with receptive and expressive dysphasia and a
Glasgow coma scale of 11/15. Abnormal parameters on her blood results
were as follows: ALT, 70 iu/l; and serum creatinine, 145 mol/l.
An urgent CT scan of the brain, with contrast, showed features
suggestive of intracerebral haemorrhage in the left frontal lobe, with
evidence of cerebral oedema.
She was transferred to a neurosurgical unit, where the haematoma
was evacuated. This was followed by a multidisciplinary package of care
on the stroke unit, involving the stroke physician, physiotherapist,

speech and language therapist and clinical psychologist. She made
steady progress and was able to verbalize, saying a few words and
responding appropriately to commands, within 5 days of the event. Her
right leg regained power, but the right arm remained flaccid. Initially,
with some assistance, she was able to sit out of bed, started mobilizing
by day 10 and was able to walk without supervision by day 15. During
her admission, her baby was cared for at home by her mother.
She was discharged home 1 month after the event and was able to
communicate well, although slowly. She had residual right-hand
weakness. Power scores were 2–3 out of 5 in her right arm and 4 out
of 5 in her right leg. Her hypertension was well controlled with indapamide
and nifedipine. Follow-up arrangements were made with the
community physiotherapist, speech and language therapist and the
stroke clinic.
At her 1-year follow-up review in the stroke clinic, she had
regained normal power in her right upper and lower limbs and her
speech was back to normal. She had one episode of seizures and was
commenced on cabamazepine. Her hypertension was well controlled
with lisinopril, and simvastatin was added. She had an intrauterine
contraceptive device for contraception.
Discussion
Cerebrovascular disorders are uncommon and feared complications
of pregnancy. Collectively, they contributed to 15% of indirect maternal
deaths in the latest confidential enquiry into maternal deaths
survey. Most cases occur in the first week after delivery [24]. As highlighted
in this case, there could be diagnostic confusion with eclampsia,
because of the common presentation of seizures, hypertension and
visual disturbance. Although Ms G had significant proteinuria at
presentation, this was because of previously diagnosed underlying renal
disease. Her mildly raised liver enzymes were probably a normal
physiological change in the puerperium. The seizure in this case was
secondary to the intracerebral bleed.
The association of pregnancy-related hypertension with stroke
during pregnancy and the puerperium is consistent in many studies
and with the known pathophysiology of cerebrovascular complications
of hypertension.
Blood pressure at discharge after delivery is not expected to be
predictive of the development of postpartum stroke. Therefore, a
longer period of closer monitoring of blood pressure as an in-patient
after delivery is unlikely to reduce the risk of postpartum stroke. The
finding of raised blood pressure after an intracerebral bleed is related

to the phenomenon of hypertension in response to seizures and
central neurological insult with resulting failure of cerebral autoregulation.
Hypertension is thus a result and not a cause of most
cerebrovascular events.
Prompt neuroimaging studies, in addition to an elevated level of
suspicion and neurological consultation, as clearly demonstrated in
this case, are the key to diagnosis and an optimal prognosis. CT is usually
the first imaging study performed because of its ready availability.
However, an initial negative result of the CT study and the presence of
a highly suggestive clinical history and physical findings suggest the
need for additional studies, such as magnetic resonance imaging (MRI)
and cerebral angiography, to confirm the appropriate diagnosis.
The morbidity and mortality associated with intracranial haemorrhage
is high, with a risk of neurological or cardiovascular sequelae in
survivors and a need for close medical surveillance. Ms G made a
complete recovery from her hemiplegia but was left with seizures.
Patients who have had stroke in the past can be reassured that they
are unlikely to have a recurrence in pregnancy, unless they have an
obvious risk factor, such as APS or hypertension. The combined oral
contraceptive pill should be avoided because it carries a significant
risk of recurrence of stroke. Ms G was advised to seek prepregnancy
counselling before embarking on another pregnancy.
5.8

by **mandible** Sat Aug 28, 2010 4:23 pm

HYPOKALAEMIA

Mrs H was a 31 year old primigravida who presented at 26 weeks’
gestation with extreme lethargy such that she was virtually bed
bound. She had a diagnosis of Sjogren’s syndrome and was anti-Ro
and anti-La positive. Her pregnancy had been complicated by recurrent
admissions for HG, and on each occasion she was noted to be
hypokalaemic (serum potassium, 2.4–3.1 mmol/l), which improved
with appropriate rehydration with normal saline and potassium chloride.
However, at this admission she denied nausea or vomiting,
which had improved markedly since 20 weeks’ gestation.
Investigations revealed a serum potassium level of 2.9 mmol/l and
serum bicarbonate of 14 mmol/l. Retrospective review of biochemistry
results during the previous admissions showed that on each admission
she had been acidotic, with serum bicarbonate levels as low as 10 mmol/l.
Because persistent vomiting in HG usually causes a hypochloraemic
alkalosis (related to the loss of hydrochloric acid from the stomach),
alternative causes for the hypokalaemia were considered. Because of the
association of Sjogren’s syndrome with distal type 1 renal tubular
acidosis (RTA), this was felt to be the most likely diagnosis. Urinary pH
was 9 when serum bicarbonate was 15 mmol/l. This was highly suggestive
of RTA.
Treatment was commenced with oral sodium bicarbonate, 1.8 g
three times daily and oral potassium citrate, 10 ml (28 mmol/l/10 ml)
three times daily. Within 1 week, she had normal energy levels and
felt enormously better. Within 2 weeks, her serum bicarbonate and
potassium levels were normal and potassium supplementation was
discontinued.
Mrs H was delivered by emergency Caesarean section for fetal distress
at 38 weeks’ gestation; the birth weight of her infant was 3.1 kg.
Postpartum, the dose of bicarbonate was reduced to 1.2 g three times
daily. She was referred to a nephrologist for further management
postpartum.
Discussion
Hypokalaemia occurs in up to 20% of hospitalized patients but is only
clinically apparent in 5%. No pregnancy-specific incidence has been
reported. Hypokalaemia is a biochemical finding and is not a diagnosis
in itself. It is almost always secondary to an underlying problem.
Hypokalaemia is frequently asymptomatic. Severe hypokalaemia
(serum potassium, 2.5 mmol/l) can cause muscle weakness and
fatigue. It rarely causes arrhythmia in patients without cardiac disease.
Despite the 50% increase in plasma volume and associated haemodilution
of pregnancy, the concentration of plasma electrolytes
remains unchanged compared with the nonpregnant state. The range
of normal serum potassium is 3.5–5.5 mmol/l. This phenomenon is
probably because of decreased excretion in pregnancy and net gain
from gastric absorption. In rat studies, fluctuations in maternal serum
potassium levels did not seem to have a deleterious effect on fetal
potassium levels.
Hypokalaemia has many causes. Acute hypokalaemia is most
commonly due to severe vomiting and/or diarrhoea. Chronic
hypokalaemia is most commonly due to diuretic use and hyperaldosteronism.
A logical review of possible causes of potassium loss
should facilitate the correct diagnosis:
Renal losses:
● RTA
● Hyperaldosteronism
● Hypomagnesaemia
● Leukaemia
Gastrointestinal losses:
● Vomiting or nasogastric suctioning
● Diarrhoea
● Enemas/laxatives
● Ileal loop
Drugs:
● Diuretics (except potassium-sparing diuretics)
● Beta-adrenoceptor agonists
● Steroids
● Aminophyllins
● Aminoglycosides
Transcellular shifts:
● Insulin
● Alkalosis
Reduced intake:
● Dietary deficiency, including malnutrition
● Parenteral nutrition
● Intravenous fluids lacking potassium
The following are pregnancy-specific/related causes:
HG
Tocolysis with intravenous sympathomimetics, such as salbutamol [25].
Oral glucose load screening for gestational diabetes [26].
Abnormal cravings in pregnancy (pica), such as cravings for cola or
clay, and caffeine abuse in pregnancy [27,28,29].
A thorough search for the aetiology of hypokalaemia is required. It
will generally resolve with the treatment of its primary cause.
Supportive replacement therapy is, however, indicated in 5% of
patients, where the potassium level is 3 mmol/l. Oral therapy is usually
sufficient. However, intravenous therapy might be indicated if
symptoms are severe, cardiac arrhythmias are present and oral intake
is not possible (vomiting or diarrhoea). Potassium supplementation is
safe in pregnancy. When hypokalaemia is refractory to treatment,
hypomagnesaemia should be suspected and corrected concurrently.
RTA is systemic acidosis due to the inability of the renal tubules to
maintain the acid–base balance. Type 4 RTA is the commonest form,
but it is associated with hyperkalaemia. RTA types 1 and 2 are associated
with hypokalaemia. Type 2 (proximal) RTA is very rare. Type 1
(distal) RTA is usually secondary to systemic conditions such as diabetic
ketoacidosis, liver disease, sickle cell anaemia and autoimmune
conditions, including Sjogren’s syndrome (as present in Mrs H),
thyrotoxicosis and systemic lupus erythematosus (SLE). It can be
sporadic, in which case it is usually an autosomal dominant familial
condition. Characteristically, there is failure to acidify the urine despite
systemic acidosis. It is characterized by episodes of weakness and
paralysis and is accompanied by hypokalaemia, acidosis and hypocalcaemia.
Diagnosis is usually made following an acid-load test, during
which the patient takes an oral solution of ammonium chloride; if the
urine fails to acidify but the bicarbonate level falls, this is diagnostic of
RTA. Treatment is usually supportive with potassium, bicarbonate
and calcium supplementation during episodes.
During pregnancy, symptoms such as fatigue and lethargy can
mimic muscular weakness and make the diagnosis even harder to
reach. The ammonium load test is contraindicated in pregnancy
because acidosis can cause fetal distress. Untreated RTA can cause
severe weakness affecting labour and maternal well-being. Chronic
acidosis affects fetal bone growth, causing IUGR, and can cause cardiotocographic
changes. Potassium, bicarbonate and calcium supplementation
is safe in pregnancy. The potassium and bicarbonate
requirements are sevenfold and fourfold higher, respectively, in pregnancy
than outside pregnancy.
In a review by Hardadottir et al. [30], RTA cases were associated
with IUGR, preterm labour and Caesarean section. Most cases of
RTA were secondary. It seems prudent to follow RTA pregnancies
with serial fetal growth scans and institute intrapartum cardiotocographic
monitoring. Neonatal admissions were common in the above
mentioned series, and therefore paediatric colleagues should be
involved before delivery. If tocolysis is required, it is best to avoid
beta-sympathomimetics because they induce hyperglycaemia and
hypokalaemia.
In labour, attention should be paid to avoid potential precipitating
factors, including mental and physical stress, cold and carbohydrate
loads. Adequate analgesia should be administered, and an early
epidural might be ideal. Serum potassium should be monitored and
replaced as necessary, usually intravenously. The second stage of
labour can be shortened with assisted delivery if maternal exhaustion
or fetal distress supervenes. Glucose infusions should be avoided
because they can precipitate further hypokalaemia.
In the first 2 weeks of the puerperium, potassium, bicarbonate
and calcium supplementation usually decreases rapidly towards
prepregnancy doses. If the diagnosis has not been confirmed, the
ammonium load test can be completed postnatally.

by **mandible** Sat Aug 28, 2010 4:27 pm

HEPATITIS A

Mrs J, a 28 year old nulliparous woman at 34 weeks’ gestation, was
admitted with a history of worsening malaise, diarrhoea, nausea
and vomiting, and generalized itching. There was associated dark
urine, but no paleness of stools. Her pregnancy had being uneventful
apart from intermittent diarrhoea, presumed to be secondary to
her history of irritable bowel syndrome and managed with loperamide.
Her booking bloods at the beginning of the pregnancy,
were negative for human immunodeficiency virus (HIV) and
hepatitis B. She was from South Africa and had been a resident in
the UK for 3 years. She worked as a secondary school teacher.
There was no history of recent travel, or use of herbal remedies or
hepatotoxic drugs.
On examination, she was afebrile and jaundiced, with normal blood
pressure and without proteinuria on urine dipstick assessment and
signs of chronic liver disease apart from telangectasia over the upper
chest and abdomen, which was associated with pregnancy. Abdominal
examination revealed no organomegaly and her fundal heightwas consistent
with gestational age. Fetal movementswere normal and the cardiotocograph
(CTG) was reactive. Blood tests revealed a normal full
blood count, with Hb concentration of 12.5 g/dl, white blood cell
count of 9.6 109 cells/l and platelet count of 198 109 platelets/l.
Her renal function and random blood glucose were normal, but her
liver function was de-ranged (bilirubin, 98 mol/l; ALT, 769 iu/l;
alkaline phosphatase (AlkP), 185 iu/l; gamma-GT, 47 iu/l; and serum
albumin, 24 g/l). Her coagulation was normal.
She was transferred into a side room and barrier-nursed, with
institution of mainly supportive management, in addition to antihistamines
and vitamin K. Upper abdominal ultrasound revealed a
normal liver, gallbladder and spleen. Cultures of blood, urine and
sputum were negative.
Over the next 2 days, she gradually improved clinically, in addition
to biochemically (Table 3). Serum titres for hepatitis A revealed a
raised immunoglobulin (Ig) M consistent with acute hepatitis A
infection. Titres for hepatitis B and C were negative. Antimitochondrial
and anti-smooth muscle antibodies were negative. She was discharged
home after 1 week because she continued to improve.
She went into premature labour at 36 weeks’ gestation and had a
normal vaginal delivery of a male infant, weighing 2.8 kg. By 2 weeks
post delivery, her liver function had normalized.
Discussion
Liver disease in pregnancy can be subdivided into three types:
1. Liver disease peculiar to pregnancy, such as AFLP, obstetric
cholestasis, HG and pre-eclampsia
2. Intercurrent liver disease affecting pregnant women, such as viral
hepatitis and gall bladder disease.
3. The effect of pregnancy on underlying liver disease, such as
chronic hepatitis or cirrhosis.
Clearly, the last category was not considered as a differential diagnosis
in this case because there was no previous history of liver disease.
As a symptom of liver disease, jaundice occurs in 1:1500 pregnancies:
40% of cases result from viral hepatitis, 20% of cases are
secondary to intrahepatic cholestasis, and 6% of cases result from
common biliary duct obstruction and gallstones. A normal gall bladder
scan excluded the latter in this patient.
Pruritus can occur in a broad spectrum of liver disease and its presence
does not necessarily help in reaching the correct diagnosis.
Although pruritus classically occurs in conditions associated with
intrahepatic cholestasis, such as primary biliary cirrhosis and obstetric
cholestasis, drug hepatotoxicity, viral hepatitis, AFLP and even preeclampsia
are sometimes associated with itching. The absence of
antimitochondrial antibodies and lack of a positive history of drug
ingestion excluded primary biliary cirrhosis (PBC) and drug-induced
causes in Mrs J.
The length of gestation at presentation is important in considering
possible diagnoses because, unlike viral hepatitis, which can occur
at anytime, liver disease specifically associated with pregnancy occurs
at characteristic times. In the third trimester, HELLP syndrome,
AFLP, obstetric cholestasis and pre-eclampsia (PET) should be
considered.
The pattern of serum liver enzyme abnormalities cannot be relied
on to make a diagnosis. Classically, in intrahepatic liver disease,
transaminases tend to be high, with only a small increase in alkaline
phosphatase; in extrahepatic obstruction, alkaline phosphatase is
high and transaminases are relatively lower. In Mrs J, the pattern was
consistent with the picture in viral hepatitis, drug-induced hepatotoxicity,
obstetric cholestasis, AFLP, HELLP syndrome and PET.
The absence of thrombocytopenia, which is one of the hallmarks of
HELLP syndrome, and impaired liver function (coagulation and glucose
were both normal), which is a prominent feature of AFLP, made
these two conditions unlikely. There is a tendency in pregnancy to
assume that pruritus is always due to obstetric cholestasis: it was vital
in this case that the viral titres were obtained quickly, because this
enabled the correct diagnosis to be made.
Viral hepatitis is mostly due to hepatitis A, B, C, D or E, Epstein-
Barr virus, or cytomegalovirus. Pregnant women are not more
susceptible to hepatitis, and the incidence in epidemics is usually
the same in pregnant and nonpregnant women. However, hepatitis
E is more aggressive in pregnancy, with a maternal mortality rate of
up to 50% [31].
Acute hepatitis A in pregnancy is a systemic, short-term viral
illness, with general symptoms of malaise and jaundice. It is the most
common cause of jaundice in pregnancy [32]. The virus belongs to
the picornaviridae RNA family. Transmission is through the faecooral
route, and it is endemic in countries with poor sanitation. The
incubation period is generally 15–50 days. It multiplies in the intestine
and invades the blood, liver and saliva before any clinical manifestation
of the disease appears. It is highly contagious, with maximal
viral shedding occurring in the 1–2 week period before the onset of
symptoms and lasting 3 weeks. The virus disappears soon after the
peak of serum transaminases is reached, at which time the immune
response and hepatocellular repair start. The risk of transmission
diminishes following the onset of symptoms and is minimal in the
week after the onset of jaundice.
Hepatitis A is not debilitating, even in the presence of jaundice.
Jaundice lasts 7–10 days and the whole illness lasts about 4 weeks.
Typically, all clinical forms, with the exception of the rare, lethal,
fulminant type, resolve with complete liver regeneration, and without
chronicity or long-term carrier state. Serum IgM antibodies
are present during the acute phase and disappear within 3 months.
Serum IgG antibodies develop after the acute illness and persist
for life, representing immunity. Serum transaminases rise with
acute illness and return to normal with recovery; they seldom are
higher than 1000 iu/l. There is no correlation between their level
and prognosis.
Maternal–fetal transmission is rare but could result if the mother
has hepatitis at or around the time of delivery. In such cases, the baby
should be given Ig at birth. It is recommended that pregnant women
who are exposed to hepatitis A are given Ig prophylaxis, because it
reduces the risk of infection. Ig must be given within 2 weeks of
exposure but should be given as soon as possible.
Hepatitis A vaccination (inactivated noninfectious hepatitis A
virus) is not contraindicated in pregnancy. It is recommended for
some individuals working in high-risk professions, people travelling
to at-risk countries and individuals with medical conditions that
place them at a high risk of complications from hepatitis A. It offers
good protection and is thought to be effective for 20 years.
Breastfeeding can continue without interruption if a mother
has hepatitis A. If the mother becomes acutely ill or jaundiced
breastfeeding might be interrupted. The mother should practise
good handwashing and other appropriate hygiene.
Acute hepatitis A is the commonest cause of viral hepatitis in pregnancy;
it is usually self-limiting and nondebilitating and is associated
with transient abnormal liver function, mostly with no significant
implications to the pregnancy. It is vital that abnormal liver function in
pregnancy is investigated fully so that the correct diagnosis is reached.

by **mandible** Sat Aug 28, 2010 4:30 pm

RENAL ARTERY STENOSIS
Mrs K was a 25 year old Asian woman who presented in her third
pregnancy at 22 weeks’ gestation with severe secondary hypertension.
She was diagnosed with bilateral renal artery stenosis following
a limited angiogram during her second pregnancy, when she was
found to be severely hypertensive. She unfortunately miscarried her
second pregnancy at 20 weeks’ gestation. Her first pregnancy was a
termination at 9 weeks’ gestation. Following her miscarriage, she
had a left renal artery angioplasty, and the right angioplasty was
planned as an interval procedure. Before having the right renal
artery angioplasty, she was found to be pregnant. It was felt that
angioplasty during pregnancy would, on one hand, be an unwarranted
radiation dose but, in contrast, would reduce the risk of
severe hypertension.
She booked-in late in her third pregnancy at 22 weeks’ gestation
with a blood pressure of 199/125 mmHg, despite therapy with two
agents, atenolol (50 mg once daily) and doxazosin (4 mg twice daily).
Methyldopa (500 mg three times daily) and aspirin (75 mg once
daily) were added. Booking bloods were normal, in addition to baseline
renal function: urea, 3.5 mmol/l; creatinine, 65 mol/l; uric
acid, 0.31 mmol/l. Urinalysis was normal and 24-hour urine protein
leak was 0.24 g/save. An obstetric scan at 22 weeks’ gestation
revealed bilateral uterine artery Doppler notching, with a raised
resistance index.
Mrs K was closely monitored and her blood pressure remained
well controlled on the above three antihypertensive agents. At 26
weeks’ gestation, a growth scan revealed evidence of IUGR with
reduced liquor volume and AC below the fifth centile. An umbilical
artery Doppler scan showed absent end diastolic flow. Estimated fetal
weight (EFW) was 669 g. She was admitted because of the scan finding
and also to exclude a possible diagnosis of pre-eclampsia.
Investigations for pre-eclampsia were normal and the protein leak
remained nonsignificant. The risk of a poor outcome, including a
high risk of intrauterine death, reduced chance of neonatal survival
and significant risk of neurological impairment, was discussed. It was
decided to avoid delivery at this gestation and wait for the fetus to
gain more maturity. Mrs K was discharged home with a plan for
weekly umbilical Doppler scans and 2-weekly growth scans.
Her blood pressure remained stable and well controlled, with no
signs of superimposed pre-eclampsia. At 30 weeks’ gestation, her scan
revealed no fetal growth in 4 weeks, brain sparing and anhydramnios.
It was felt that delivery was now necessary because the additional
weeks gained had improved the fetal prognosis. She had a course of
steroids and was delivered 24 hours later, at 30 weeks 6 days, by
Caesarean section with an inverted T-incision on the uterus; Apgar
scores at delivery were 9 and 10 at 1 minute and 5 minutes, respectively,
and the infant had a birth weight of 815 g. Postoperatively, she
was converted to her prepregnancy antihypertensive medication, with
good blood pressure control. The neonatal course was complicated by
necrotizing enterocolitis, which required surgical intervention, with
subsequent full recovery. She was referred to the renal physician for
renal angioplasty.
Discussion
Renovascular hypertension is one of the potentially curable secondary
causes of hypertension. It is the cause of hypertension in 5% of
all patients. In women of child-bearing age, fibromuscular hyperplasia
is more often the aetiology. Patients with renal artery stenosis usually
present with hypertension and varying degrees of renal impairment.
Narrowing of the renal artery, because of fibromuscular dysplasia,
leads to reduced renal perfusion. The consequent activation of
renin–angiotensin system causes hypertension (mediated by
angiotensin II), hypokalaemia and hypernatraemia (which are features
of secondary hyperaldosteronism). Correcting the stenosis
might reverse these features and improve hypertension control.
Before her first angioplasty, Mrs K required three antihypertensive
agents, which was reduced to two agents after the angioplasty. It
would be expected that following angioplasty of the other renal
artery a cure might be achieved, without the need for medication.
Secondary, potentially curable causes of hypertension should be
sought whenever hypertension is present in young women, whether
pregnant or not.This is especially true for pre-existing hypertension in
pregnancy that has not been previously diagnosed. Clinical features
and pointers to a diagnosis of renal artery stenosis are as follows: young
hypertensive patients with no family history, resistant hypertension,
1.5 cm difference in kidney size on ultrasonography, and secondary
hyperaldosteronism (low plasma potassium concentration). Clinical
examination might reveal bruits over major vessels, including the
abdominal aorta.
Angiography remains the standard test for diagnosis, but it is not
without risks and could worsen renal function. Noninvasive techniques
are beginning to replace conventional angiography. These
include Doppler ultrasonography, captopril renography, spiral CT
scanning and magnetic resonance angiography. The significance of
lesions found by renal arteriography should be confirmed by differential
renal function studies and renal venous renin activity before
surgical management is undertaken. The severity of stenosis determines
treatment. Hypertension caused by slight or moderate stenosis
commonly responds favourably to medical management.
The concern in pregnancy, and especially in the case discussed,
was the risk of the radiation dose involved with angiography. Mrs K
had had a renal angiogram in her second pregnancy, which resulted
in the diagnosis of renal artery stenosis, but subsequently miscarried.
Although one can argue that the radiation dose involved with an
angiogram would not be greater than the maximum allowed in pregnancy
(˜5 rad), it was felt wise to avoid angioplasty in the subsequent
pregnancy because the patient perceived the angiogram as a possible
causal factor for the miscarriage. It is more likely that this late miscarriage
related to severe hypertension rather than radiation. By contrast,
performing the second angioplasty in the third pregnancy
might have led to a better outcome for the patient and her fetus.
Although Mrs K’s blood pressure was well controlled by antihypertensive
therapy, poor fetal growth resulted from the effects of hypertension
on placental perfusion, which might have been avoided if an
angioplasty had been carried out in the pregnancy.
Angioplasty is the traditional revascularization procedure, and this
often leads to cure in patients with fibromuscular dysplasia. Resistant
hypertension secondary to fibromuscular dysplasia has been the
primary indication cited for dilatation of the renal artery. Although a
modest improvement in blood pressure or reduction in antihypertensive
drug requirement might be the goal of revascularization, renal
protection could emerge as the more important factor.
Drugs alone can control hypertension in almost 90% of patients
with renal artery stenosis. Antihypertensive therapy during pregnancy
might need to be adjusted. Methyldopa, labetalol, hydralazine and nifedipine
are safe. Angiotensin receptor blockers and ACE inhibitors are
contraindicated in pregnant women and in renal artery stenosis. It is
important to note that lowering blood pressure might decrease uteroplacental
perfusion and impair fetal growth.
Renal artery stenosis is an uncommon secondary cause of hypertension
in pregnancy, which can be associated with poorly controlled
hypertension and poor fetal outcome. It can usually be managed with
antihypertensive medication, but definitive treatment is revascularization
with angioplasty, which should be considered in pregnancy, in
the face of resistant hypertension

by **mandible** Sat Aug 28, 2010 4:32 pm

THYROID CANCER

Ms L was a 34 year old nulliparous caucasian woman who presented
to her GP at 11 weeks’ gestation complaining of a thyroid lump,
which she had noticed during the preceeding year. On examination,
she was clinically euthyroid. An irregular mass was palpable in the
right lobe of the thyroid, measuring 5 cm 3 cm. There was no
bruit or palpable lymphadenopathy. An ultrasound scan confirmed a
solid thyroid mass, with a 9 mm lymph node at its inferio-lateral
aspect. Fine-needle aspiration (FNA) of the thyroid mass was suggestive
of papillary thyroid carcinoma. Biochemically she was euthyroid.
She was commenced on a suppressive dose of thyroxine, 300 g/day.
Mrs L was reviewed at a tertiary oncology centre at 12 weeks’
gestation. A repeat FNA confirmed the diagnosis of papillary thyroid
carcinoma, and an MRI confirmed nodal involvement. She had a
total thyroidectomy with selective right-neck dissection and conservation
of two parathyroid glands at 16 weeks’ gestation. Histology
reported complete excision of a 4 cm papillary carcinoma with follicular
pattern, with extranodal extension but no extension to the capsule.
Because of the constellation of adverse pathological features (i.e. the
site, nodal involvement and extranodal spread), radio- iodine ablation
was planned after delivery. Her pregnancy progressed well, with a
satisfactory growth scan at 32 weeks’ gestation. Her thyroid function
was regularly monitored, with TSH level moderately suppressed to a
low-to-middle range of normal (0.5–2.8 mu/1). Her free T4 level was
14 pmol/l on a dose of 200 g of thyroxine. Her corrected calcium
level was initially low and required calcium supplementation, which
was discontinued after the calcium level normalized.
Mrs L went into spontaneous labour at 39 weeks’ gestation and
was delivered by vacuum extraction of a live infant in good condition
and with birth weight of 3.41 kg. At 6 weeks postpartum, her TSH
level was significantly suppressed, at 0.1 mu/1, with a free T4 level
of 21.5 pmol/l on a dose of 200 g of thyroxine. This dose was
reduced to 150 g. She was clinically euthyroid and was supplementing
breastfeeding with bottle feeding. At 3 months postdelivery, when
her T4 had been suspended for several weeks, she had radio-iodine
ablation treatment. She was advised not to conceive within the next
6–12 months and to avoid close contact with her baby for 3–4 weeks.
Discussion
Half of all thyroid cancers occur in women of child-bearing age, but
presentation in pregnancy is rare, occurring in approximately 1 in
10,000 pregnancies. The most common complaint is that of a thyroid
nodule, but these occur in up to 5% of women of child-bearing age,
and only a small proportion are malignant. Overall, most authorities
believe that pregnancy neither stimulates the growth of thyroid
cancer nor worsens the prognosis [33].
If thyroid cancer is diagnosed before the mid-trimester, surgical
intervention can be performed with normal surgical management, as
in the case described above. Recent data suggest that the risk of fetal
loss related to surgery is minimal. When the diagnosis is reached during
late pregnancy, resection after delivery is the option of choice,
with surgery being performed once the pregnancy-associated vascularity
is judged to have resolved. In women whose FNA suggests a
well-differentiated tumour, some studies have shown no difference in
the outcome between those patients that had early surgery and those
patients who had surgery delayed. There is no indication for termination
of pregnancy, although if the tumour is felt to be aggressive or
disseminated, early delivery might be appropriate, in which case the
balance of risks of fetal and maternal well-being must be carefully
assessed [34].
In this case, radio-iodine ablation was indicated postdelivery. T4
must be stopped 4 weeks before treatment to enable the TSH level
to rise, which facilitates uptake of iodine into the residual thyroid
tissue. Pregnancy should be delayed usually for at least 12 months
after radio-iodine treatment, because it has a long half-life and is
associated with an increased risk of miscarriage and congenital
abnormality if conception occurs sooner. In addition, this time period
enables appropriate suppression of TSH to be achieved; if there is
an early recurrence, management is easier. Clearly, radio-iodine
should not be given in pregnancy: inadvertent use in the early
second trimester causes fetal thyroid destruction and subsequent
hypothyroidism [35].
The mammary gland binds iodide avidly, especially during lactation,
so if radio-iodine treatment is required, breastfeeding should
be stopped and contact with the baby reduced to limit the radiation
to the child to the lowest levels: the length of time is determined
by the dose of radioactive iodine required, but is often around
3 weeks [36].
The prognosis of most thyroid cancers is excellent. Many women
are maintained on a suppressive dose of thyroxine, aiming for an
undetectable TSH level, and so minimizing the risk of stimulation of
any residual thyroid tumour. Subsequent pregnancies do not alter the
risk of disease recurrence, but for women on a suppressive dose of
T4, thyroid function should be monitored and the dose adjusted as
indicated.

by **mandible** Sun Aug 29, 2010 3:47 pm

ABDOMINAL PAIN
Ms M was a 24 year old para 1 1 who presented to the antenatal
day unit at 30 2 weeks’ gestation with a history of a fall on a wet
surface that caused some bruising on the left leg and left side of the
abdomen. Her examination was normal and no uterine contractions,
vaginal discharge or bleeding were noted. A CTG was normal, and
after being given anti-D for a rhesus-negative blood type, she was
discharged.
Her past obstetric history was of one miscarriage at 9 weeks’ gestation
and one Caesarean section at 41 weeks’ gestation (delivering a
2.5 kg baby) because of suspected fetal distress after prostaglandin
administration for induction of labour. Her past medical history
included mild asthma, for which she was using regular salbutamol
and beclomethasone inhalers.
At 31 1 weeks’ gestation, Ms M was admitted with continuing
abdominal pain and decreased fetal movements. The abdominal pain
was in the left iliac fossa, constant in nature and made worse by movement.
No cause for the abdominal pain could be found and fetal
assessment, with both CTG and umbilical artery Doppler scanning,
was normal. Fetal movements returned to normal the day after admission.
Ms M was reviewed at 31 6 weeks’ gestation and had continuing
left iliac fossa pain, which radiated to her back and was constant
in nature, but worse on movement. While in the day unit waiting for
the results of repeat blood tests, she noticed sudden-onset epigastric
pain, which was associated with shortness of breath, a
nonproductive cough and inspiratory chest pain. On examination, her
heart rate was 100 bpm, her respiratory rate was 28 per minute, her
temperature was normal and her blood pressure was 117/65 mmHg.
The jugular venous pressure (JVP) was not raised, the chest was clear
on auscultation and heart sounds were normal. Neither calf was tender.
Her oxygen saturation on air was 94%. After 1 hour, she started
complaining of dizziness at rest.
Further urgent investigations included a 12-lead ECG, which
showed a sinus tachycardia, a full blood count, which showed polymorphonuclear
leukocytosis, liver function tests, which were normal,
and measurement of serum amylase and C-reactive protein. Arterial
blood gases showed a pH of 7.431, pCO2 of 3.59 kPa and a pO2 of
9.1 kPa (hypoxaemia). A chest X-ray was normal.
Pulmonary thromboembolism was felt to be the most likely diagnosis
and therapy was commenced with a therapeutic dose of enoxaparin
(1 mg/kg body weight/twice daily). The following day, a (V/Q)
lung scan confirmed bilateral ventilation perfusion mismatches consistent
with pulmonary emboli. Her leg vein Doppler scans showed
extensive thrombus in the left iliac vein.
Anticoagulation was continued until 39 2 weeks’ gestation,
when Ms M went into spontaneous labour. Because a dose of 80 mg
of enoxaparin had been given 6 hours before the request for epidural
analgesia, this was declined. Pain relief was achieved with patientcontrolled
intravenous opiate analgesia and Ms M had a spontaneous
vaginal delivery of a 2.9 kg baby boy. The estimated blood loss was
300 ml. Following delivery and 26 hours after her last dose of enoxaparin,
anticoagulation was restarted with enoxaparin, 120 mg once
daily (1.5 mg/kg body weight once daily). Warfarin was commenced at a
dose of 7 mg on day 3, and by day 6, the international normalized
ration (INR) was 2.3 and the enoxaparin was discontinued. Warfarin
was continued for a further 3 months postpartum. A thrombophilia
screen after the discontinuation of warfarin showed that Ms M was
heterozygous for factor V Leiden.
Discussion
Ms M had several risk factors for venous thromboembolism. She was
pregnant and had recently sustained a minor injury that had left her
relatively immobile. Her mother had suffered a deep vein thrombosis
(DVT) aged 42 years.
Included in the differential diagnosis of the epigastric and pleuritic
pain should be an atypical acute asthmatic episode, pneumonia,
pneumothorax, ischaemic/cardiac causes, aortic dissection, cholecystitis,
pancreatitis and gastro-oesophageal reflux. The presence of
hypoxia made pulmonary embolism a likely diagnosis.
Arterial blood gases in pulmonary embolism might show hypoxaemia,
as in Ms M, with or without hypocapnia caused by hyperventilation
to compensate for the loss of pulmonary function. In a small
pulmonary embolism hyperventilation causing respiratory alkalosis
might be the first change in arterial blood gases. Using pulse oximetry,
a drop in oxygen saturation after exercise (such as walking up
and down a flight of stairs) is a useful screening test if the oxygen
saturation at rest is normal. In normal pregnancy, there is relative
hypocapnia because of the increased respiratory work of pregnancy,
such that the normal pCO2 is 3.5–4.5 kPa, approximately 1 kPa lower
than outside pregnancy.
D-dimer measurement in pregnancy is not useful. In nonpregnant
women they are thought to be fairly sensitive, but nonspecific, for
thrombosis and therefore are helpful, if negative, to exclude diagnosis
of thrombosis. In the pregnant woman, there is a physiological
rise in D-dimers, but normal ranges for pregnancy have not been
fully established, such that the false-positive rate is high [37].
In retrospect, it is likely that the left iliac fossa pain was due to iliac
vein thrombosis, which then dislodged to cause the pulmonary
embolism. Iliac vein thrombosis is more common on the left-hand
side in pregnancy because the inferior vena cava runs on the righthand
side of the aorta and therefore the left iliac vein is more likely
to be compressed by the right iliac artery. DVT in pregnancy is eight
to nine times more common on the left than the right [38,39].
Alternative to awaiting spontaneous labour would have been
induction of labour or elective repeat Caesarean section. Both these
strategies would have allowed planned temporary interruption of
LMWH to permit regional analgesia or anaesthesia, but the latter
would have increased the risk of thrombosis compared with vaginal
delivery. However, Ms M was keen for a vaginal birth after
Caesarean section (VBAC) and induction of labour was not felt to
be desirable because of the previous Caesarean section, and because
it might have introduced extended bed rest and dehydration. It is
important that women receiving therapeutic LMWH are seen and
counselled by an obstetric anaesthetist before delivery so that the
issues surrounding options for analgesia and anaesthesia can be
discussed before delivery.

by **mandible** Sun Aug 29, 2010 3:49 pm

MITRAL STENOSIS
Ms N was a 26 year old primiparous woman from East Africa who
booked-in at her local hospital in the sixth week of her pregnancy.
She was known to have “mild mitral stenosis” from an echocardiogram
she had following an earlier miscarriage. She had previously
been investigated, but the results of those investigations were not
known. She had mild asthma and used a salbutamol inhaler for this
on an “as required” basis. She was also a smoker.
MsNpresented locally at 24 weeks’ gestation with possible haemoptysis.
The differential diagnosis was haematemesis and gastroscopy was
carried out, in addition to a V/Q scan and sputum microscopy and culture,
to exclude tuberculosis. The gastroscopy, under antibiotic cover
revealed a Mallory-Weiss tear and she was therefore prescribed ranitidine.
An echocardiogram repeated at this time confirmed “mild mitral
stenosis” and at this time Ms N was asymptomatic. At 26 weeks’gestation,
shewas becoming breathless on climbing stairs, but could stillwalk
well on the flat. There was no orthopnoea. An anaesthetic opinion was
arranged.
At 35 weeks’ gestation, Ms N was admitted through the accident
and emergency department to a tertiary obstetric unit. She gave a
history of 4 hours of cough, pink frothy sputum and no response to
her inhaler. There was also associated pleuritic chest pain. A malar
flush, typical of mitral stenosis, was also evident [40].
On examination, she had a pulse rate of 130 bpm, her blood pressure
was 84/51 mmHg, her respiratory rate was 18 breaths per
minute and she had a PEFR of 300 l/min. The JVP was elevated, and
she had a mid-diastolic murmur and bibasal lung crepitations.
Oxygen saturation was 97% in room air. An ECG revealed a sinus
tachycardia and the chest X-ray showed consolidation at the right
base. Obstetrically, all was well. She was given frusemide, 40 mg
intravenously and diamorphine, 5 mg intravenously, with oxygen, by
mask, at 5 l/min. The transthoracic echocardiogram showed rheumatic
mitral stenosis of moderate severity, with a dilated left atrium
(5.6 cm), mitral valve area of 1.1 cm2 and mean gradient of
8.5 mmHg (normal, 0–2), and good biventricular function. The diagnosis
was pulmonary oedema, related to mitral stenosis.
A history of 7 years of dyspnoea was then obtained through the
husband; dyspnoea was worse in pregnancy, with orthopnoea and
paroxysmal nocturnal dyspnoea. He also reported recent onset of
haemoptysis and a much reduced exercise tolerance, i.e. five steps up
a flight of stairs.
Treatment commenced with regular frusemide and diltiazem.
Diltiazem was used to control the heart rate instead of a beta-blocker,
because of the history of asthma. She was also commenced on
LMWH prophylaxis and required potassium supplementation.
Amiloride was added to frusemide for potassium conservation.
Despite this therapy, she remained tachycardic. Diltiazem was, therefore,
increased and the option of balloon valvotomy was discussed,
should medical therapy fail to prevent further episodes of pulmonary
oedema. Ms N was placed on a 1500 ml/24 hours fluid restriction
regimen as an adjunct to drug therapy.
By day 3 after admission, her heart rate had dropped below
100 bpm and she was less dyspnoeic. By day 4, there was still significant
difficulty maintaining the serum potassium; therefore, the
amiloride dose was doubled. She was also given an infusion of 8 mM
of magnesium in 100 ml of physiological saline, to help maintain her
potassium level and prevent atrial fibrillation. After a few more days
of diuretics in combination with fluid restriction (1500 ml/24 hours),
she became asymptomatic. Induction of labour was scheduled for
38 weeks’ gestation. An obstetric anaesthetic opinion was obtained
and a plan was made for an elective epidural.
At 38 weeks’ gestation, Ms N went into spontaneous labour.
During labour, fluids were restricted to 85 ml/hour. Antibiotics were
given for endocarditis prophylaxis and care was taken to avoid the
lithotomy and supine positions. Labour progressed well until augmentation
was necessary, with a low-volume Syntocinon infusion,
at 9 cm. The morning diuretic dose was administered as usual. After
pushing for 35 minutes she was delivered, with the ventouse and a
right medio-lateral episiotomy. The estimated blood loss was 200 ml.
Ms N had routine postnatal care, with an appointment scheduled
for valvotomy. She was advised not to conceive again before treatment
of the valve. Warfarin was commenced on the third postnatal day and
Ms N was discharged with sustained-release diltiazem and
co-amilofruse. She was also given contraceptive advice, choosing
Depo-Provera as her preferred method. She underwent balloon
mitral valvuloplasty 2 months later; her postprocedure echocardiogram
showed a mitral valve area of 2.2 cm2.
Discussion
Globally, rheumatic heart disease is the most common cardiac disease
presenting in pregnancy, with mitral stenosis the commonest lesion
[41]. The most likely time for complications to present is during the
late second and third trimesters, as occurred in this case and can be
expected in up to 60% of all cases. Complications are usually pulmonary
oedema, arrhythmias or deterioration in New York Heart
Association (NYHA) functional class [41].
Ms N presented during the third trimester with pulmonary
oedema, which took a long time to bring under control. The deterioration
seemed to be associated with pneumonia (basal consolidation
on chest X-ray) [42] and a tachycardia of 130 bpm, which
resulted in elevation of left atrial pressure (as evidenced by a dilated
left atrium on echocardiography) and pulmonary oedema. If the
medical measures had been unsuccessful in treating her pulmonary
oedema, a mitral valvotomy would have been undertaken, which
would have improved cardiac function significantly for labour and
delivery [41].
Therapeutic strategies include off-loading the heart by reducing
both preload (volume) and afterload (peripheral resistance). Ms N
immediately received emergency treatment for pulmonary oedema
with diamorphine, frusemide and oxygen. With the history of
haemoptysis, one of the most obvious diagnoses to exclude would be
pulmonary embolus, which might have explained the tachycardia and
basal consolidation. However, an urgent echocardiogram showed no
evidence of acute pulmonary embolus and suggested mitral stenosis
as the cause of the pulmonary oedema.
Diagnosis and management were further complicated in this case by
the history of asthma. The PEFR, carried out at the bedside, did not
suggest significant reversible airway obstruction as a cause for the
breathlessness. Before the cardiac diagnosis is made, many pregnant
women with heart disease causing pulmonary oedema are initially
labelled as having asthma. It is possible that this was also the case with
Ms N. The possibility of asthma also dictated the medication used to
slow her heart rate and therefore improve left-ventricular filling time
(thus reducing left atrial pressure). Beta-blockers were avoided, but
would have been more effective than diltiazem, a calcium-channel
antagonist. Other possibilities would have been cardioselective betablockers,
such as bisoprolol or carvedilol.
LMWH was given as recommended by Lupton et al. [43], because
there was a risk of atrial fibrillation and mural thrombus.
Vaginal delivery in controlled circumstances is advocated in mitral
stenosis, with careful attention to the length and normal progress of
labour. A very careful epidural was given by a senior anaesthetist.
Regional analgesia given slowly minimizes the risk of abrupt vasodilation
that would be poorly tolerated in mitral stenosis. Adequate
analagesia is important to limit the increased cardiac output from
pain and thus reduce the risk of pulmonary oedema during the intrapartum
period. LMWH administration was withheld once labour
had started to ensure time for safe epidural administration. The strategy
of fluid restriction was continued. The second stage of labour
was curtailed, as recommended, by ventouse.
A further pregnancy without mitral valvotomy or valve replacement
in this woman would be high risk, and for that reason, a plan
for contraception was made, in addition to a plan for definitive
treatment of the underlying cardiac disease.

by **mandible** Sun Aug 29, 2010 3:54 pm

SPONTANEOUS PNEUMOTHORAX
Ms P was a 29 year old nonsmoker in the 33rd week of her first pregnancy.
She attended the accident and emergency department with a
2-day history of breathlessness and chest pain. On examination,
there was reduced air entry on the right and reduced chest expansion.
At the time, she looked well and could talk in sentences
A chest X-ray with abdominal shielding confirmed a large rightsided
pneumothorax, with no mediastinal shift. Air (100 ml) was
aspirated and she was transferred to the delivery suite. A repeat X-ray
confirmed 70% expansion; a further 60 ml of air was aspirated and a
chest drain was inserted. She continued to be well overnight, with
oxygen saturation 97% and a respiratory rate of 31 breaths/min.
She was given inspired oxygen by mask. The drain fell out, with consequent
recurrence of the pneumothorax; a second drain was placed
and had an underwater seal.
After 4 days, because there was a persistent air leak, pleurodesis
was discussed due to the high possibility of a recurrent pneumothorax
at delivery. High-volume, low-pressure suction was set up and she was
transferred to the cardiothoracic ward 1 week after admission.
On day 10 after her original admission, she was taken to theatre for
video-assisted thoracoscopic surgery (VATS). She was anaesthetized
with a left lateral tilt. A pulmonary bleb was excised and abrasion
pleurodesis was carried out. The following chest X-ray showed a small
apical pneumothorax, but the drain still “bubbled” on coughing. This
continued and she was transferred to the maternity unit with a
Heimlich (flutter) valve rather than an underwater seal. By this time,
she was at 35 weeks’ gestation and all investigations on the fetus
remained normal.
However, 10 days after VATS, the persistent air leak continued
and a plan was made to remove the drain if the bubbling ceased for
24 hours. Furthermore, 3 weeks after the original admission, the possibility
of performing talc pleurodesis was discussed because of the
persistent air leak. The chest drain was, therefore, clamped and
adjusted, with a reduction in the volume of the pneumothorax to
5%. Because this manoeuvre had been successful, the decision was
then made to leave the chest drain in until delivery, with a plan for a
further surgical procedure postpartum.
At 39 weeks’ gestation, Ms P spontaneously ruptured her membranes,
draining meconium-stained liquor. Following a failed stimulation
of labour, she was delivered of a live male infant by emergency
Caesarean section under epidural anaesthesia. The chest drain was
clamped for some hours on the day after delivery, with no deterioration
in symptoms. The following day, the drain was clamped for 24
hours. The drain was finally removed on day 11 postcaesarean
section. A further 4 days later, she remained asymptomatic and
there was no radiological evidence of pneumothorax, only pleural
thickening at the apex of the right lung where the original pleurodesis
was attempted.
Follow-up was planned with the chest physicians 2 weeks after
discharge.
5. CASE STUDIES 135
Primary spontaneous pneumothorax is a rare complication of pregnancy,
mostly occurring in the late third trimester, although sometimes
at other times in pregnancy or the early postpartum period.
There is a high risk of recurrence following initial resolution.
In this case, there were no obvious predisposing factors, such as
smoking, either before or during pregnancy, or asthma. Ms P was of
slim build, but not particularly tall. Management was in keeping with
the recommendations made by the British Thoracic Society’s
(BTS’s) latest guideline for management of primary spontaneous
pneumothorax [44].
Ms P presented 2 days after onset of her symptoms, which seems
to be the median time for presentation. The significance of the time
lag between lung collapse and re-expansion is the risk of pulmonary
oedema that can occur with re-expansion and when early suction is
applied to a chest drain [44]. Here, the BTS recommendations differ
from the consensus statement of the American College of Chest
Physicians [45].
Because the pneumothorax was large and the patient was clinically
stable, the first management measure was aspiration, followed by a
repeat chest X-ray. This should be standard practice, as discussed in
the BTS guideline. The pneumothorax was too large for observation
alone. Again, when the lung was found not to have fully re-expanded,
aspiration without recourse to a chest drain with an underwater seal
was in keeping with the BTS guideline. During this time, oxygen was
given by mask because this has been found to increase the
reabsorption rate and improve hypoxaemia resulting from the
pneumothorax [46].
Ms P needed a drain with an underwater seal once the small-bore
drain had fallen out. She could equally have had a small-bore drain
with a Heimlich valve inserted, giving the opportunity for outpatient
management or mobilization, which was important in the
prevention of thromboembolic disease, because she was in the third
trimester of her pregnancy. A high-resolution CT scan could have
been used at this point to image the chest and establish an underlying
cause for spontaneous pneumothorax, but this would have
exposed the fetus to more radiation than a plain X-ray, and several
chest X-rays are likely to be requested for someone with a pneumothorax
checking for resolution. The CT scan might have demonstrated
underlying abnormalities and suggested the need for early
surgical intervention. However, there is currently insufficient evidence
to support routine use of CT, except in very specific situations
Because of the continued air leak despite the use of an effective
chest drain, the BTS guideline was followed, with two considerations
in mind:
1. Definitive treatment for a protracted air leak, which was not
responding to drainage with the chest drain.
2. Prevention of recurrence at the time of labour and delivery, when
she was most at risk of recurrent spontaneous pneumothorax.
VATS was the treatment of choice because it enabled a good view of
the lung surface, with the facility to carry out bullectomy or bleb
resection, in addition to mechanical pleurodesis, an additional measure
to prevent recurrence. VATS was chosen instead of talc pleurodesis
because the evidence shows that VATS has a greater efficacy in preventing
recurrence than talc or other forms of chemical pleurodesis
because the primary cause can be located and removed [48].
Unfortunately, the VATS procedure was unsuccessful, possibly
because they were unable to gain full lung re-expansion postoperatively,
despite applying suction, and possibly because there was an inadequate
inflammatory response to the pleurodesis procedure, perhaps due to the
pregnancy. It has been suggested that VATS procedures have a higher
failure rate because of a less intense pleural reaction compared with thoracotomy
procedures. It is also possible that the anatomical defect
responsible for the pneumothorax was not identified and removed. At
this point, the small-bore chest drain with the Heimlich valve was used.
Unfortunately, despite the possibility of being treated as an out-patient,
Ms P no longer had the confidence to go home with the chest drain in
situ, having been in hospital for 2 weeks by this time.
The decision was finally made to allow her to labour with the chest
drain in situ because this was the safest option and the concern about
curtailing the second stage of labour due to the risk of recurrence
would be avoided. This was followed by spontaneous resolution in
the immediate postpartum period.
By its very nature, management of this condition requires that
several chest X-rays be carried out to demonstrate resolution. In this
woman, some of these X-rays were performed in the delivery suite
using portable equipment that produced antero posterior (AP) films.
Because of the potential risks to the fetus of ionizing radiation (i.e.
an increased risk of malignancy in later life) [47], it might have been
wiser to try as far as possible to have all films taken in the X-ray
department because this ensures that the lowest dose of radiation
possible is given to the mother and fetus. By definition, the portable
film increases exposure because of the position of the patient, the
equipment itself, the difficulty in the patient holding her breath in
expiration and the need for extended exposure time [47]. This
should encourage departmental X-rays, where possible. However,
the risk from chest X-rays is very low, whether portable or within the
department, because the radiation dose is small, being equivalent to
only a few days of background irradiation. Chest X-rays that are
clinically indicated should never be withheld because of pregnancy.
Although CT has been suggested to have a limited role in the management
of pneumothorax, the type of CT has not been elucidated.
Spiral CT, as used in the diagnosis of pulmonary embolus, will afford
reduced radiation doses, but it could be that high-resolution CT is
more appropriate for the investigation of pneumothorax, particularly
secondary pneumothorax.
It is difficult to know whether chemical pleurodesis would have
given success in this case, when mechanical pleurodesis did not. The
only other procedure that could have been considered to prevent a
recurrence of pneumothorax is pleurectomy, either at the time of the
VATS procedure or through open thoracotomy. Chemical
pleurodesis is known to have reduced efficacy, compared with VATS,
for prevention of recurrence and is also associated with particular
dangers. Doxycycline, a tetracycline, could not have been used in this
patient because she was pregnant and there is a potential risk of discolouration
of fetal teeth and bones. With talc pleurodesis, there is a
potential risk of empyema and acute adult respiratory distress syndrome
(ARDS), especially with doses above 5 g [44].
Finally, the question of whether an adequate sterile inflammation
would develop in a pregnant patient remains unaddressed in
the literature.

by **mandible** Sun Aug 29, 2010 3:57 pm

SEVERE PRE-ECLAMPSIA AND HAEMOLYTIC
URAEMIC SYNDROME
Mrs Q was a 26 year old, black African nurse booked-in during her
first ongoing pregnancy. She had a normal booking blood pressure of
100/60 mmHg and normal booking investigations, including a full
infection screen that was negative. She remained well until 25 weeks’
gestation, when she was admitted from the antenatal clinic with a blood
pressure of 190/108 mmHg, 4 proteinuria and 2 blood in her urine.
She also said she had passed less urine during the preceding 3 days and
was complaining of headache, nausea and vomiting.
Mrs Q was admitted and therapy with methyldopa, 500 mg three
times daily was commenced. A 24-hour urinary protein collection of
528 ml was analysed and found to have a protein excretion rate of
15.75 g/24 hours. Her MSU, which was sent that day, was negative.
Other results of note were as follows: platelet count, 275 109
platelets/l; creatinine, 63 mol/l; albumin, 27 g/l; and urate, 0.32 mmol/l.
With the diagnosis of pre-eclampsia confirmed, the plan was for continued
in-patient management and delivery for the usual fetal or
maternal indications.
After 5 days, Mrs Q awoke with a severe frontal headache and
blood pressure of 198/110 mmHg; she was also complaining of
severe blurring of vision and epigastric pain. There was no vaginal
bleeding. The CTG trace at this point was also suspicious, with
recurrent, unprovoked, shallow decelerations. She was transferred to
the obstetric high-dependency unit, for stabilization before delivery,
and the pre-eclampsia protocol was commenced. She was given a preload
of 500 ml of colloid and then bolus doses of hydralazine and
MgSO4 (4 g), followed by a MgSO4 infusion of 1 g/hour. Within 30
minutes, she was found to be coughing up pink frothy sputum. On
examination, she had a raised JVP and bilateral basal inspiratory
crepitations, suggesting pulmonary oedema. She was treated with a
40 mg intravenous bolus of frusemide. Blood results, from serum
taken that morning, were then obtained. These showed creatinine of
126 m/l, albumin of 18 g/l (the previous day’s result was 24 g/l),
bilirubin of 30 m/l and urate of 0.4 mmol/l. Her platelet count had
dropped to 108 109 platelets/l. The serum potassium value was
unavailable because the sample was thought to be haemolysed. The
MgSO4 infusion was stopped because of anuria. Fetal demise was
also confirmed at this time by ultrasound scan, once the heart trace
was lost on the CTG.
An urgent ultrasound of the renal tract excluded renal vein
thrombosis and showed normal-size kidneys, but suggested diffuse
parenchymal renal disease. She was given misoprostol per
vagina, followed by oral misoprostol 3 hours later. By this time,
her serum urea level was 7.5 mmol/l and her creatinine level was
189 mol/l.
By the following morning, her creatinine level had risen to
273 mol/l and her urea level had risen to 10.3 mmol/l. The Hb
concentration was 8.5 g/dl and the platelet count was 40 109
platelets/l. A blood film showed burr cells, fragmented red cells,
spherocytes and normal platelets, suggesting a microangiopathic
coagulopathy. At that point, a reticulocyte count, direct Coombs’
antibody test (DAT) and serum antibodies were requested.
Despite the rising creatinine level and oliguria, her serum potassium
level was not raised. Her liver function remained normal, but
her serum albumin level dropped to 16 g/l. The expectation was that
once the fetus was delivered, which occurred 3 hours later, renal
function would improve. This was also the opinion of the renal
physician that morning.
Unfortunately, despite vaginal delivery of a 960 g male fetus, her
renal function continued to deteriorate over the next 36 hours:
her creatinine level was 791 m/l, her urea level was 23.5 mmol/l
and her serum potassium level was 6.0 mmol/l. The anaemia and
thrombocytopenia had also worsened: her Hb concentration was
6.7 g/dl, her haematocrit was 0.197 and her platelet count was
34 109 platelets/l. Treatment for hyperkalaemia was instituted with
actrapid insulin, glucose and calcium resonium (15 g orally). Once
the serum potassium level had fallen to 5.1 mmol/l, 2 days after delivery,
Mrs Q was transferred to the renal unit.
On the renal unit, she was treated with plasmapheresis on five
occasions and had two episodes of dialysis. With the last four treatments
of plasmapheresis, she was given chlorpheniramine and hydrocortisone
because she had a severe allergic reaction to the first treatment.
She was discharged 10 days later with a creatinine level of
191 mmol/l and on the following medication:
Doxazocin, 8 mg twice daily
Nifedipine modified release, 20 mg twice daily
Bisoprolol, 10 mg once daily
Sandocal, 1 tablet twice daily
Her blood pressure was well controlled on these drugs and she
remained under the care of the renal physicians for follow-up.
Discussion
Haemolytic uraemic syndrome (HUS) is a constellation of three clinical
features, as follows:
Microangiopathic haemolytic anaemia ( DAT negative)
Thrombocytopenia
Renal failure [49]
HUS can be further divided into diarrhoeal and nondiarrhoeal subtypes;
the diarrhoeal form is seen most commonly in children and
adults in association with bacterial gastrointestinal infection, notably
with Escherichia coli 0157. HUS is thought to develop because of
the verocytotoxin produced by the interaction of E. coli with a
lipopolysaccharide co-factor [49]. It is a very rare condition, related
to thrombotic thrombocytopenic purpura (TTP), with an incidence
of 3.7 cases per million (in adults) [50]. In pregnancy, it is thought to
occur 3–10 weeks postpartum [51].
Nondiarrhoeal HUS can be familial or sporadic. In the familial
form, there are autosomal dominant and autosomal recessive patterns
of inheritance [49].
Sporadic HUS can be associated with a number of factors, such as
the following:
Pregnancy
SLE
Antiphospholipid syndrome
HIV
The combined oral contraceptive pill (COCP)
Ciclosporin
In Mrs Q, pregnancy was obviously an issue, but SLE or other
autoantibody condition could have been contributory [52].
Interestingly, Mrs Q subsequently tested positive for both anticardiolipin
antibodies and lupus anticoagulant and had a high (1/1280)
antinuclear antibody (ANA) titre.
HUS in this case declared itself at the time of delivery but it has also
been described in the first trimester. If, as in this case,HUSoccurs immediately
postpartum or in the third trimester of pregnancy, the following
differential diagnoses, or associated conditions,must be excluded:
HELLP syndrome
AFLP
TTP
In both AFLP and HELLP syndrome, liver function tests are abnormal;
however, abnormal liver function tests are unusual in HUS and
TTP. TTP can be more difficult to differentiate clinically, although
it causes a more widespread thrombotic angiopathy, often with
neurological symptoms.
Nondiarrhoeal HUS is thought to be due to a deficiency or mutation
in the gene coding for factor H, a complement regulator. As a
result, low complement C3 levels might be a feature, although they are
not always. Because of the absence or deficiency of this factor, it could
be that the alternative complement pathway cannot be activated to
interrupt the clotting cascade once endothelial damage has occurred.
The following treatments have been described as effective in the
literature:
Plasmapheresis
Antithrombin infusions
Prostacyclin infusions
Immunoglobulin (Ig) after failed plasmapheresis and plasma replacement
[51].
The mainstay of therapy is now plasmapheresis, and platelet transfusion
is contraindicated, because it can exacerbate rather than ameliorate
the condition. Currently, it is unclear why plasmapheresis
works in HUS. It might help to remove large platelet aggregates
and might, in some way, help to control or reduce further platelet
agglutination.
Although the differential diagnosis, especially between HELLP
syndrome and HUS, is often difficult, this case was relatively clear-cut
because there was little liver dysfunction, thereby excluding AFLP
and HELLP syndrome. There were no focal neurological symptoms,
making TTP unlikely, and renal dysfunction seemed to be out of proportion
to the pre-eclampsia. Until relatively recently, HUS had a
high mortality rate (of 60%). Thankfully, the advent of plasmapheresis
has reduced this considerably. However, for Mrs Q, careful
counselling is required concerning the next pregnancy.

by **mandible** Sun Aug 29, 2010 4:00 pm

HYPERSPLENISM
Mrs R was a 28 year old black, African woman, who booked in her first
pregnancy at 9 weeks’ gestation. She was fit and well, apart from
splenomegaly, for which she had undergone extensive investigation during
the previous year. She was known to have sickle cell trait and
received appropriate counselling from the haemaglobinopathy specialist
nurse counsellor. Her partner was sickle cell negative. Her other booking
results confirmed that she was negative for HIV 1 and 2, and that
she was a low infectivity carrier of hepatitis B. After a consultation with
the consultant virologist, her partner was vaccinated and arrangements
were set in place for the baby to be treated after birth. Results of the
booking full blood count showed a platelet count of 38 109 platelets/l,
a Hb concentration of 11.9 g/dl and that there was relative leucopenia.
Splenomegaly was first detected by her GP, before this pregnancy,
when she attended the surgery complaining of constipation. During
the examination, the spleen was palpable five fingerbreadths below
the left costal margin. She was referred to a gastroenterologist and
investigated over a 12-month period (Table 5.4).
It was felt that splenomegaly was secondary to a previous malarial
infection and no further action was taken, apart from regular follow-up.
After the finding of thrombocytopenia in pregnancy, a trial of prednisolone
(20 mgfor 2weeks)was given in the hope that the platelet count
might rise. However, the platelet count remained between 31 109
platelets/l and 53 109 platelets/l, and thus prednisolone was stopped.
The clinical haematologists became involved in her care and suggested
that splenectomy should be considered following delivery, to allow the
platelet level to rise. The pregnancy continued uneventfully, with Hb
levels within the normal range for pregnancy and no evidence of
haemolysis. There were no episodes of bruising, vaginal bleeding or
epistaxis during the pregnancy.
TABLE 5.4. Results of investigations for splenomegaly
Upper abdominal Normal liver, no ascites. Spleen 19 cm
ultrasound with normal uniform texture
Brucella serology Negative
Malaria Negative
Abdominal CT scan Confirmed normal liver, with normal portal
circulation, and normal kidneys. Massively
enlarged spleen with no focal abnormality
G6PD assay Negative
Reticulocyte count Normal, with normal ferritin levels
FBC Hb, 13.2 g/dl; WBC, 7.6 109/l; platelet count,
44 109 platelets/l
Clotting INR, 1.18; APTT, 1.07 (both with 50/50
correction)
Fibrinogen, 1.48 g/l
Bone marrow Normal
APTT - activated partial thromboplastin time; CT - computed tomography; FBC - full
blood count; G6PD - glucose 6 phosphate dehydrogenase; Hb - haemoglobin; INR -
international normalized ratio; WBC - white blood cells
The plan for labour included taking samples for a full blood count
and crossmatching two units of blood on admission, and establishing
intravenous access. A consultant obstetric anaesthetist counselled
that regional anaesthesia was contraindicated if the platelet count was
below 80 109 platelets/l and suggested that Entonox and intravenous
opioids could be used for analgesia in labour. General anaesthesia
was recommended in the event of an emergency Caesarean
section. It was also noted that NSAIDs should not be used for analgesia
and that intramuscular injections should be avoided.
At 41 weeks’ gestation, a membrane sweep was carried out. She
was admitted at 41 3 weeks’ gestation for induction of labour. The
Hb concentration was 11.9 g/dl and the platelet count was 54 109
platelets/l when induction was commenced. She laboured after
receiving 5 mg of intravaginal prostin in divided doses. Unfortunately,
an emergency Caesarean section was necessary at 8 cm dilatation, for
suspected fetal distress. Free fluid was noted at the time of the
Caesarean. A live female infant was delivered, weighing 3.13 kg. The
estimated blood loss was 750 ml and an infusion of Syntocinon
(40 iu) was commenced at a rate of 10 iu/hour. A negative pressure
drain was placed at the time of surgery, which drained 370 ml in the
first 24 hours and, subsequently, a further 870 ml of serosanguinous
fluid. Postpartum ultrasound confirmed the presence of ascites and
revealed that the splenic size had reduced from a maximum of 21 cm
to 12 cm. On the first day postcaesarean section, she was found to
be anaemic with a Hb concentration of 8.8 g/dl and a platelet count
of 38 109 platelets/l; iron was prescribed. The drain was removed
and she was discharged on the fifth postoperative day, with arrangements
for haematology and gastroenterology follow-up appointments.
Discussion
“Hypersplenism” is a term used to describe splenomegaly, from any
cause, and its consequences.
The causes of splenomegaly include the following:
Infection
Inflammation
Haematological
Miscellaneous
A greatly enlarged spleen is more common in the presence of myelofibrosis,
chronic leukaemia, chronic malaria, kala-azar or Gaucher’s disease
(lysosomal storage disease). Chronic malaria was felt to be the
cause of splenomegaly in this case, although no evidence of malarial
parasites had ever been found. Other infectious causes had been
excluded, including hepatitis. Although Mrs R was known to be hepatitis
B positive, she was shown to be of low infectivity and did not
have evidence of chronic hepatitis [53]. There was no evidence of
investigation for sarcoidosis, another recognised cause for hypersplenism
[54].
Hypersplenism can result in pancytopenia, haemolysis and an
increased plasma volume, but the only features present during pregnancy
in Mrs R were thrombocytopenia and intermittent leucopenia,
which had been evident before pregnancy.
When she was first seen by the obstetrician, her previous medical
notes were unavailable. The first thought was that the thrombocytopenia
was caused by immune thrombocytopenic pupura (ITP),
because the count was lower than expected for gestational thrombocytopenia
at 20 weeks’ gestation. It was known that Mrs R was HIV 1
and 2 negative and that she did not have lupus anticoagulant or anticardiolipin
anibodies. Antiplatelet antibodies were not assayed,
because they were considered unlikely to change management. There
was no evidence of SLE. The platelet count was checked using a citrate
sample, which confirmed that it was a true thrombocytopenia,
rather than a spurious result due to in-vitro platelet clumping.
A trial of prednisolone was given to promote a rise in the platelet
count, assuming the low count was related to an immunological cause.
The platelet count did not rise and prednisolone was stopped. It could
be argued that immune thrombocytopenia was not adequately excluded
because the steroid trial was not at a dose high enough to bring about a
response. The usual treatment for suspected refractory ITP is prednisolone
at a dose of 1 mg/kg body weight, but this is often associated
with relapse. A dose equivalent to 250 mg of prednisolone over 4 days
has been recommended [55] and found to produce a sustained rise in the
platelet count; however, this runs the significant risk of side effects, such
as mood swings, steroid psychosis, hypertension and deranged glucose
metabolism, all of which would be best avoided in pregnancy.
It was appropriate to make appointments for a predelivery anaesthetic
opinion, both to give the obstetric anaesthetic staff warning of
this high-risk patient and to allow the patient to be fully informed of
her choices and the potential difficulties surrounding delivery and
analgesia. It meant that when an emergency caesarean was carried out,
she was emotionally and mentally prepared, and the unit was prepared
with crossmatched blood and intravenous access. The haematologists
should have been informed when she went into labour, because of the
possibility of needing platelet cover during delivery, if her platelets
had dropped low enough (20 109 platelets/l) [56]. In fact, at the
time of induction (which was carried out because she was approaching
42 weeks of completed gestation), her platelet level was 50 109
platelets/l, a level at which she was not expected to be at higher risk of
bleeding, although it still precluded regional anaesthesia.
Fetal blood sampling was avoided because Mrs R was known to be
hepatitis B positive and fetal thrombocytopenia remained a possibility.
Her blood pressure during labour was around 140/80 mmHg,
compared with a booking blood pressure of 94/60 mmHg, and it is
noteworthy that there was a degree of renal impairment, with the creatinine
level rising from 71 mol/l in the mid-trimester to
138 mol/l peripartum. This was associated with a rise in bilirubin
26 mol/l and ALT 180 iu/l, which together with an additional fall in
the platelet count and a drop in the Hb concentration greater than
expected for the estimated blood loss, suggested HELLP syndrome;
there was no record of proteinuria or urinalysis during labour, but
this does not preclude the diagnosis. Alternatively, the rise in creatinine
might have been related to postpartum haemorrhage and the rise
in ALT might have been related to the usual physiological postpartum
effect, although both changes were more marked than is usually
seen in those circumstances.
The cause of the splenomegaly remains unresolved in this case,
although the new finding of ascites might help future investigations.
The platelet count is one of the factors that will determine management,
including the need for splenectomy.

case studies by : Catherine Nelson-Piercy

case studies by : Catherine Nelson-Piercy

HYPONATRAEMIA

ISCHAEMIC HEART DISEASE

CARDIAC TRANSPLANT

POSTPARTUM ECLAMPSIA

HYPEREMESIS GRAVIDARUM

POSTPARTUM CEREBRAL HAEMORRHAGE

HYPOKALAEMIA

HEPATITIS A

RENAL ARTERY STENOSIS

THYROID CANCER

ABDOMINAL PAIN

MITRAL STENOSIS

SPONTANEOUS PNEUMOTHORAX

SEVERE PRE-ECLAMPSIA AND HAEMOLYTIC

HYPERSPLENISM