Tog Thrombocytopenia in Pregnancy
Tog Thrombocytopenia in Pregnancy
Tog Thrombocytopenia in Pregnancy
Review Thrombocytopenia
in pregnancy
Author Bethan Myers
Key content:
• Thrombocytopenia occurs in 8–10% of all pregnancies.
• In pregnancy it is usually mild and benign.
• Rare causes can be associated with severe complications for mother and baby.
• Cases thought to be due to immune thrombocytopenic purpura or
microangiopathic processes should be managed in a specialist centre.
Learning objectives:
• To learn about the underlying causes.
• To be aware of the management of the more severe cases.
• To ensure appropriate referral of high-risk cases.
Ethical issues:
• Clear prepregnancy counselling is important to enable women to make informed
decisions regarding future pregnancies.
• Women need to understand the percentage risk of recurrence of certain conditions
and the risks to fetal wellbeing.
Keywords HELLP syndrome / immune (idiopathic) thrombocytopenic purpura /
pre-eclampsia / thrombotic thrombocytopenic purpura
Please cite this article as: Myers B. Thrombocytopenia in pregnancy. The Obstetrician & Gynaecologist 2009;11:177–183.
Author details
Bethan Myers MA FRCP FRCPath
Consultant Haematologist
Department of Haematology, Nottingham
University Hospitals NHS Trust, QMC Campus,
Derby Road, Nottingham NG7 2UH, UK
Email: [email protected]
(corresponding author)
is also defective. Common signs of thrombocytopenia disorder, which is the most common cause of
include petechiae, nose bleeding and, more rarely, thrombocytopenia in pregnancy, occurring in
haematuria and gastrointestinal bleeding. approximately 75% of cases of thrombocytopenia
and 8% of all pregnancies. It is a benign condition
During pregnancy there is a general downward usually found incidentally later in pregnancy and
drift in platelet count, particularly during the last there is no bleeding risk to mother or fetus.
trimester.1,2 This results at term in a level that is Counts are typically 70 and usually 100.4
approximately 10% less than the prepregnancy Many of the features are similar to mild immune
level. The mechanisms for this are thought to be a thrombocytopenia and it can be difficult to
combination of dilutional effects and acceleration of distinguish between the two disorders. There are
platelet destruction across the placenta. Most women no specific diagnostic tests for either and both
still have platelet counts within the normal range; conditions are diagnoses of exclusion. Rarely,
however, if the starting count is at the lower end of cases of gestational thrombocytopenia with
the normal range, or there is a more severe drop, platelet counts as low as 50 have been described.5
thrombocytopenia occurs. Hence thrombocytopenia Again, the outcome appears good.
is a common finding in pregnancy.2 Most cases are
mild and have no significance for mother or fetus but, The pathophysiological process is not known but
in some instances, where thrombocytopenia is part is thought to represent an acceleration of platelet
of a complex clinical disorder, there can be profound consumption via an exaggeration of the
and even life-threatening results for both mother and physiological process across the placenta, or
baby. The effect of pregnancy on the disorder and, possibly via a mild immune process.
conversely, of the disorder on the pregnancy, must be
taken into account. In some instances, the aetiology Gestational thrombocytopenia resolves quickly
is unique to pregnancy and the puerperium. after delivery, but it can recur in subsequent
pregnancies. A count should be performed 6 weeks
postnatally and the result documented.
Aetiology and prevalence
A platelet count below the normal range is found Management
in 8–10% of pregnancies.2 Approximately 75% of For the vast majority of cases the pregnancy and
these cases are due to a benign process of gestational delivery should be treated as normal. In cases of
thrombocytopenia; 15–20% can be attributed to moderate or severe thrombocytopenia an anaesthetic
Box 1
Causative diagnosis Mechanism Diagnostic features
Causes of thrombocytopenia in
pregnancy Gestational thrombocytopenia Physiological dilution, accelerated Third trimester, platelets 70 109/l;
destruction incidental finding
Immune thrombocytopenic purpura Immune destruction, suppressed Diagnosis of exclusion
production
Thrombotic thrombocytopenic purpura, Peripheral consumption, microthrombi Unwell, fever, neurological and renal
haemolytic uraemic syndrome dysfunction
Haemolysis, elevated liver enzymes Peripheral consumption, microthrombi Raised LDH, ALT and bilirubin,
and low platelet count syndrome haemolytic anaemia /
(HELLP syndrome) pre-eclampsia, DIC
Hereditary thrombocytopenia Bone marrow underproduction Family history, abnormal platelets
Pseudothrombocytopenia Laboratory artefact Platelet clumps on blood film
Viral infection/drugs Multifactorial Viral illness, drugs taken, risk factors
Leukaemia/lymphoma Bone marrow infiltration Abnormal blood film; enlarged
liver/spleen/nodes
ALT alanine aminotransferase; DIC disseminated intravascular coagulation; LDH lactate dehydrogenase
consultation is useful to discuss analgesic options, 1. Diagnosis of exclusion; no tests are available to distinguish
Box 2
Features of gestational
since most units will not consider epidural anaesthesia from immune thrombocytopenic purpura
thrombocytopenia
with platelet counts of 80. A trial of steroids 2. Mild thrombocytopenia, platelet count usually 70 10 /l 9
haemorrhage in this area could lead to spinal cord by capillary sample. If the count is mildly reduced,
compression. There is controversy over the safe further samples on days 1 and 4 should be
threshold for epidural anaesthesia: in most collected, but if the initial result is normal, no
institutions a threshold of 80 is typical (based on further sampling is required.
British Committee for Standards in Haematology
and anaesthetic guidelines)8. An anaesthetic Intramuscular vitamin K should be avoided
consultation in the latter part of pregnancy to until the count is known. Babies with severe
discuss alternative analgesia for delivery is helpful. thrombocytopenia should be treated with
intravenous immunoglobulin; cranial Doppler
Management of delivery: neonatal considerations ultrasound can be helpful. Platelets should be
Since antibodies are of the IgG subtype, they can administered in addition to intravenous
cross the placenta and cause thrombocytopenia in immunoglobulin if there is life-threatening
the fetus and neonate. The main worry is possible haemorrhage.
intracranial haemorrhage in the neonate. This is
an extremely rare but devastating complication. Prepregnancy counselling
The effect of the antibodies on fetal counts is Where possible it is useful to discuss the
unpredictable, maternal treatments near term management issues that can arise during the
with steroids or intravenous immunoglobulin do pregnancy. These are listed in Box 3.
not have any effect on the fetal count and there is
no correlation between the severity of maternal
thrombocytopenia and the fetal count. The Hypertensive disorders
incidence of thrombocytopenia among neonates of pregnancy
is reported as between 14–37%. Approximately See Table 2. These comprise pre-eclampsia and
5% of babies will have counts 20 and a further eclampsia; the combined haemolysis, elevated
10% will have counts of 20–50.9,12 Although there liver enzymes and low platelet count (HELLP)
are no reliable predictors, fetal or neonatal syndrome; thrombotic thrombocytopenic
thrombocytopenia is more likely if there has been a purpura (TTP); and haemolytic uraemic
sibling with thrombocytopenia or the mother has syndrome.
had a splenectomy or her platelet count has been
50 during the pregnancy.11,12 Fetal scalp samples Pre-eclampsia
do not produce reliable counts and should not be Diagnostic criteria for pre-eclampsia include new
taken. Nor is there a role for percutaneous umbilical onset, hypertension and proteinuria (300 mg/
blood sampling, since the procedure carries a risk 24 hours) at 20 weeks of gestation. The estimated
of fetal haemorrhage and possibly death of incidence is 5–10% of all pregnancies worldwide
approximately 2%; this is higher than the risk of with increased incidence among primigravidae or
intracranial haemorrhage, at 1%. multigravidae with new partners. The aetiology is
not fully understood, but there is an association
Mode of delivery with the presence of laboratory thrombophilia
Caesarean section is not routinely reccommended, and a known genetic predisposition.
as there is no evidence that this will reduce the
incidence of intracranial haemorrhage among There is increased endothelial cell activation
susceptible babies. Measures should be in place to leading to the activation of platelets and the
avoid trauma to the baby’s head during delivery, as coagulation cascade. In general, women with pre-
stated previously—there should be avoidance, eclampsia have lower platelet counts than normal:
where possible, of fetal scalp electrodes or sampling approximately 15% within the thrombocytopenic
and of high- or mid-cavity operative delivery. The range. The condition resolves quickly after
neonatal team should be alerted to the possibility of delivery, therefore conservative management is
a thrombocytopenic baby before the birth. A cord appropriate for mild or moderate pre-eclampsia.13
sample should be taken to assess the neonatal Severe thrombocytopenia occurs among 5% of
platelet count and if low this should be confirmed women with pre-eclampsia, but it can be associated
Box 3
1. ITP may relapse or worsen during pregnancy.
Prepregnancy counselling for
women with immune (idiopathic) 2. If treatment of ITP is required it will carry both maternal and fetal risks.
thrombocytopenia
3. Around one-third of women will require treatment at some stage of pregnancy, most commonly around the time of delivery.
4. There is an increased risk of haemorrhage at delivery but the risk is small even if the platelet count is low.
5. Epidural anaesthesia may not be possible.
6. Although it is not possible to predict accurately whether a neonate will be affected, the risk is high if a sibling has had
thrombocytopenia, or the mother has undergone splenectomy.
7. Maternal death or serious adverse outcomes for mothers with ITP are rare.
8. The risk of intracranial haemorrhage for the fetus/neonate is very low.
As delivery is the mainstay of treatment for the There can be major difficulties in the
mother, steroids should be given (to help mature differential diagnosis of TTP, haemolytic
the baby’s lungs) and supportive care with fresh uraemic syndrome, HELLP and severe
frozen plasma with or without cryoprecipitate if pre-eclampsia. The typical features of each
disseminated intravascular coagulation is present. disorder are listed in Table 2.
The platelet count should be maintained at 50.
The condition usually improves quite quickly Management
after delivery, although it may worsen during the Despite the difficulties of diagnostic certainty,
first 24–48 hours postpartum. Depending on the plasma exchange needs to be commenced
clinical scenario, e.g. worsening maternal condition urgently and good clinical judgement is required.
or severe fetal growth restriction, delivery may be By using this procedure antibodies are removed
indicated at any time from 20 weeks of gestation. and 1–1.5 l fresh frozen plasma containing the
Conservative management for very early HELLP is absent enzyme is infused daily until the platelet
controversial and a difficult decision sometimes count is normal and the lactate dehydrogenase
has to be made between gaining extra time for the level is reduced. The number of treatments
baby and the maternal risks. required is extremely variable and high doses of
steroids may be indicated. Rituximab, a mono-
Microangiopathies clonal antibody against CD20, has been used
Thrombotic thrombocytopenic purpura successfully when improvement has been slow.
This is a rare, life-threatening disorder with a About 25% of women affected experience
characteristic pentad of signs and symptoms, recurrent episodes. In the rare congenital cases,
CNS central nervous system; DIC disseminated intravascular coagulation; HELLP haemolysis, elevated liver enzymes and low platelet count syndrome;
HUS haemolytic uraemic syndrome; MAHA microangiopathic haemolytic anaemia; TTP thrombotic thrombocytopenic purpura
a
Including postpartum
infusion of fresh frozen plasma rather than plasma thrombocytopenia and should be sought when
exchange is carried out, since these women do appropriate.
not have antibodies. Platelet transfusions are
contraindicated because they are known to pre- Medication
cipitate or exacerbate central nervous symptoms. Medication is an important cause of
A central line should be placed without platelet thrombocytopenia: it is a frequent adverse
support, as the risk of bleeding is low in this effect of commonly used drugs. Heparin-induced
condition. Predictors of relapse include previous thrombocytopenia can, rarely, occur with the
clinical presentation and low levels of ADAMTS administration of unfractionated heparin in
13 while in remission. pregnancy, but has not been described with the
use of low molecular weight heparin in pregnancy.
Haemolytic uraemic syndrome
This is a similar syndrome, with microangiopath- Other causes of thrombocytopenia
ic haemolytic anaemia and thrombocytopenia These are rare and include constitutional
but with predominant renal involvement. In thrombocytopenias and those due to
childhood the disorder is usually associated with haematological malignancy.
Escherichia coli infection and a good outcome. In
adulthood and in pregnancy there is a poor
response to plasma exchange.
Fetal and neonatal
thrombocytopenia
Microangiopathies and neonatal issues This topic deserves a separate review; however, it
The prognosis for the baby in all the microan- needs to be emphasised that thrombocytopenia in
giopathies described is poor because of extensive pregnancy affects the fetus.
placental ischaemia. Disseminated intravascular
coagulation can complicate the picture or exist The reduction in neonatal platelet count that can
secondary to another cause and is usually occur in maternal ITP has already been described.
associated with bleeding. Infections of the fetus can also lead to a reduced
platelet count. A serious cause of fetal and
neonatal thrombocytopenia is fetal and neonatal
Other causes of maternal alloimmune thrombocytopenia (FNAIT). In this
thrombocytopenia condition the maternal platelet count is usually
Antiphospholipid syndrome normal, but antigens on the fetal platelets that are
Thrombocytopenia can be associated with not present on the maternal platelets cause the
antiphospholipid syndrome but this is rarely development in the mother of antibodies that
severe. In primary antiphospholipid syndrome cross the placenta to destroy fetal platelets. This is
and systemic lupus erythematosus with the platelet equivalent of rhesus haemolytic
antiphospholipid antibodies, women need disease of the newborn. Intracranial haemorrhage
aspirin and Clexane® (enoxaparin sodium) is a devastating consequence of the condition; a
(Rhone-Poulenc Rorer, Guildford, UK) large literature review identified its occurrence in
during pregnancy, as this has been shown 26% of cases. Approximately 80% of the
to give a better outcome. Occasionally, haemorrhages occur before birth, 14% before
thrombocytopenia can make this treatment 20 weeks of gestation. Prompt recognition of
more difficult to achieve. FNAIT in the neonate and treatment with
appropriate matched platelets improve outcome.
Counselling of parents regarding recurrence
Viral infection
should be undertaken. Various antenatal
Almost any virus can cause a reduction in
management regimens are in use, none of which
platelet count. This is usually very transient, but
are ideal. These include high doses of intravenous
there may be a more prolonged reduction for a
immunoglobulin with or without prednisolone
number of weeks. HIV and cytomegalovirus
(0.5 g/kg), or serial fetal platelet transfusions.
infections are particularly associated with