Causes of Thrombocytopenia in Pregnancy
Pregnancy related Non related to Pregnancy
Gestational thrombocytopenia
Pre-eclampsia/Eclampsia
HELLP syndrome
Acute fatty liver of pregnancy
Pseudothrombocytopenia
Immune thrombocytopenic purpura
Thrombotic thrombocytopenic purpura/ hemolytic-
uremic syndrome
Autoimmune diseases: lupus, antiphospholipid
syndrome
Infections –HIV, HBV, HCV etc.
Disseminated intravascular coagulation
Drug-related causes: Heparin,statins
Von willebranddisease type IIB
Bone marrow dysfunction
Hypersplenism
Nutritional deficiencies: vitamin B12 ,folate
5-10 % of women during pregnancy or immediate postpartum
may be affected by thrombocytopenia.
Incidence
75% -Gestational thrombocytopenia.
15-20% -Hypertensive disorders.
3-4% -Immune disorders.
1-2% -Infections, malignancy, drugs
•Diagnosis of exclusion –No tests are available to distinguish from
immune thrombocytopenic purpura.
•Mild thrombocytopenia –Platelet count > 70X10
9
and usually
<100 per liter.
•No history of thrombocytopenia preceding pregnancy.
•Usually occurs in third trimester.
Gestational Thrombocytopenia
Thrombocytopeniaassociatedwithhypertensivedisorders(PET,
eclampsia,HELLPsyndrome,acutefattyliverofpregnancy)isthe
secondleadingcauseofthrombocytopeniainpregnancy.
Thrombocytopenia associated with Hypertensive disorders
PETcauses20%casesofthrombocytopenia.
•HELLP syndrome complicates 20% cases of PET. It consists of –
–Hemolysis
–Elevated liver enzymes
–Low platelet
•The syndrome can occur without proteinuria(25%) or hypertension (40%)
and diagnosis may be missed
•70% of cases develop in antenatal period and 30% in postpartum period.
•Platelet count <100,000 /micro liter is one of the diagnostic criteria
Thrombocytopenia associated with Hypertensive disorders
•Acutefattyliverofpregnancy–1in7,000to1-20,000.
•Occursin3
rd
trimesterofpregnancy.
•Presentswithabdominalpain,nausea,vomitingandanorexia.
Thrombocytopenia associated with Hypertensive disorders
Labfindings–
–Hypoglycaemia, hyperuricemia, markedly elevated
transaminases, elevated creatinine, platelets in the order of
20,000 per micro liter.
•Thrombotic microangiopathies are characterized by –
Pathophysiology
Shistocytes in peripheral blood smear, increased bilirubin >1.2
mg/dl, decreased haptoglobin <25 mg/dl and increased LDH.
Endothelial
injury
Platelet
aggregesion
Thrombus formation
in small vessels
•Aim is to maintain platelet count above 50,000 per liter.
•Dexamethasone 10 mg every 12 hours 2-4 doses ante-partum and
2 doses post-partum is recommended.
•If hemolysis, thrombocytopenia or renal dysfunction continues-
plasmapheresis can be done.
Management
•It is autoimmune disorder characterized by anti-platelet
glycoprotein antibodies that stimulate platelet destruction in
spleen.
•Two types of ITP –
Immune Thrombocytopenic Purpura.
ACUTE
Occurs in children,
associated with
viral infection and is
self-limiting.
CHRONIC
Affects women,
incidence with 0.1
to 1/1000 pregnancy.
•In 2/3
rd
cases diagnosis is established before pregnancy.
•Pre-pregnancy counseling can be done.
•Platelet transfusion is not indicated for ITP due to consumptive
mechanism of this condition.
•Steroids or IVG are recommended before 36 weeks if –
–Platelet count is under 30,000 per liter
–The patient is symptomatic.
–Invasive procedure is considered.
•IVG -1gm/kg has a rapid response in 1-3 days.
•Prednisolone–1gm/kg has a therapeutic response within 2-14 days.
Management
Prednisolone can exacerbate –
Management
Gestational diabetes Maternal hypertension
Psychosis
↑in incidence of cleft lip and
cleft palate in fetus.
Weight gain
Fetal adrenal suppression
•Immune thrombocytopenia is not an indications for caesarean
section.
•If emergency caesarean section is required with a platelet count
<50,000 per liter –Platelet transfusion in association with IVIG is
recommended.
•The anti-glycoprotein antibodies cross placenta and can induce fetal
thrombocytopenia.
•Neonatal platelet level are monitored at birth and then daily.
Management
If thrombocytopenia is unresponsive
Splenectomy can be performed in second trimester.
Management
•Incidence -1 in 25,000 pregnancies.
•Pentad of microangiopathic hemolytic anaemia,
thrombocytopenia, fever, neurological manifestation and renal
impairment.
•TTP has been shown to be due to a severe deficiency of von
Willebrand’s factor cleaving protein. ADAMTS 13.
•This is most commonly an acquired deficiency caused by an
autoantibody or rarely a congenital deficiency caused by a genetic
defect.
Thrombotic Thrombocytopenic Purpura.
•ADAMTS 13 is a metalloprotease acting to cleave the von
Willebrand factor multimers and thus it prevents thrombus
formation by the impaired platelet aggregation.
•Severely reduced ADAMTS 13 activity or the presence of an
inhibitor or IgG antibodies confirm the diagnosis of TTP.
Thrombotic Thrombocytopenic Purpura.
•It may cause spontaneous abortion, pre-maturity and IUFD.
•Major pathophysiological mechanism for IUGR and IUFD may be
placental ischemia.
•Fetal monitoring should be done by colour doppler.
Thrombotic Thrombocytopenic Purpura.
•Plasma exchange should be done to remove antibodies in acquired type.
•FFPdaily–1-1.5litertilltheplateletcountisnormalandLDHlevelis
reduced.
•Highdosesofsteroid
•Rituximabamonoclonalantibodyhasbeentried.
•Platelettransfusionsarecontraindicatedbecausetheyareknownto
precipitateCNSsymptoms.
•Recurrence–
–20%inacquiredtype
–100%incongenitaltype
Management
•Presents with microangiopathic hemolytic anaemia and thrombocytopenia.
•Predominant renal involvement.
•In childhood this disorder is associated with E Coli infections and has a good
outcome.
•Atypical form is associated with pregnancy and is related to congenital
defect of the alternative pathway of the compliment system.
•It occurs mostly in postpartum period.
•Prognosis for the babies in all microangiopathies is poor because of
extensive placental ischaemia and DIC.
Hemolytic Uraemic Syndrome.
•Plasmapheresis and administration of FFP till the levels of
platelets and LDH are normal.
•For renal impairment –Dialysis is offered
•For atypical HUS, Eculizumab, a monoclonal anti-C5 inhibitor
appears a promising agent.
Management
•DIC mostly occurs in placental abruption, amniotic fluid embolism,
rupture uterus -
–Activation of coagulation system.
–Microvascular thrombus formation in different organs and multi-
organ failure.
–Increase of PT, APTT.
–Thrombocytopenia
–Decreased fibrinogen.
–Increased FDP and D dimer.
DIC
•Von Willebrand disease type II b is a rare cause of
thrombocytopenia in pregnancy.
•There is a qualitative defect of the von Willebrand factor inducing
high affinity to the platelet receptor of glycoprotein 1 b.
•It can present for the first time in pregnancy.
•Platelet can drop below 20,000-30,000/il.
•Platelet transfusion and factor VIII replacement should be done if
the platelet count is less than 20,000/microl antenatally, prior to
invasive procedures, if bleeding occurs or if platelet count is
<50,000/l around delivery.
Von Willebrand disease
•APLA –It is treated with aspirin and heparin.
•Infections such as HIV, Cytomegalovirus, Dengue, Malaria.
•Medication –Heparin, Aspirin, Statins.
•Hematological malignancy
•Pseudo thrombocytopenia –when anti coagulant such as
EDTA is used. It can cause platelet aggregation and therefore
false low platelet count.
•Bone marrow dysfunction, Hypersplenism, Nutritional
deficiencies, vitamin B2 and folate.
Other cause of maternal thrombocytopenia
•ITP,infections,fetalandneonatalalloimmunethrombocytopenia
(FNAIT)ofthefetusmaycausefetalthrombocytopenia.
•Inthisconditionmaternalplateletcountisnormalbutantigenson
thefetalplateletsthatarenotpresentonthematernalplatelets
causedevelopmentofantibodiesinthemotherthatcrossthe
placentatodestroythefetalplatelets.
Fetal and neonatal thrombocytopenia
•Intracranial haemorrhage is a devastating consequence of this
condition.
•CT Scan of neonatal head should be done.
•Prompt recognition of FNAIT and treatment with appropriate
matched platelets improve outcome.
•High doses of IVIG with or without steroid or serial fetal platelet
transfusions should be given
Fetal and neonatal thrombocytopenia
Key Points
•5-10% of women during pregnancy have thrombocytopenia
•Gestational hypertension (75%), hypertensive disorders (15-20%),
immune disorders (3-4%), infections, malignancy, drugs (1-2%) are
important causes of thrombocytopenia
•Gestational thrombocytopenia is mild and reverts back to normal
after delivery
•In ITP -Prednisolone, IVIG is recommended if counts are below
30000, patient is symptomatic or invasive procedure is considered
•Splenctomy can be done in unresponsive thrombocytopenia.
Key Points
•Platelet transfusion should be given if CS has to be done and
platelet is below 50000 µl.
•TTP is associated with abortion, IUGR and IUFD. FFP, steroids are
the cornerstone of treatment. Platelet should not be given as they
exacerbate CNS symptoms.
•Other important causes of thrombocytopenia are DIC, Von
Willibrands disease, APLA, Infections, medications , bone marrow
dysfunction etc. Treatment is according to cause.
•ITP, infections, FNAIT may cause fetal thrombocytopenia –
intracranial haemorrhage is a devastating consequence. IVIG steroid
and platelets should be given to correct it .