Mædica - a Journal of Clinical Medicine

MAEDICA – a Journal of Clinical Medicine

2016; 11(5): 55-60

S TATE OF THE ART

Thrombocytopenia in Pregnancy
Anca Marina CIOBANUa; Simona COLIBABAa; Brandusa CIMPOCAa;
Gheorghe PELTECUa,b; Anca Maria PANAITESCUa,b
a
Filantropia Clinical Hospital, Bucharest, Romania
b
“Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

ABSTRACT
Thrombocytopenia, defined as blood platelet count below 150,000/μL is the second leading cause of
blood disorders in pregnancy after anemia. Gestational thrombocytopenia explains 70-80% of all cases
of thrombocytopenia in pregnancy. Hypertensive disorders account for approximately 20% and immune
thrombocytopenic purpura for about 3-4%. Other etiologies are considered rare in pregnancy.
The aim of this study is to review the specific causes of thrombocytopenia in pregnancy, their obstetri-
cal implications and management.

Keywords: thrombocytopenia, pregnancy, gestational thrombocytopenia

T
hrombocytopenia, defined as blood when platelet count is higher then 30.000/μL.
platelet count below 150.000/μL is For operative vaginal or cesarean deliveries the
the second leading cause of blood safe platelet count should be at least 50.000
disorders in pregnancy after anemia. platelets/μL. The exact platelet number needed
It complicates 7 to 10% of all preg- to achieve a safe epidural anesthesia is de-
nancies (1). bated, but in most guidelines, the reference
This review aims to present the specific value is around 75.000-80.000/μL (2). There is
causes of thrombocytopenia in pregnancy and a theoretical concern over the risk of epidural
discuss their obstetrical implications. hematoma with lower platelet values. Sponta-
There is a physiological decrease in platelet neous bleeding may occur with less than
count during normal pregnancy due to haemo- 20.000 platelets/μL and the risk of internal
dilution, increased consumption in peripheral bleeding is increased if the platelet count falls
tissue and increased aggregation (higher levels below 10.000/μL (3).
of thromboxane A2). The physiological throm- Commune causes of thrombocytopenia in
bocytopenia of pregnancy is mild and has no pregnancy are presented in Table 1.
adverse effects for the mother and fetus. By Gestational thrombocytopenia explains 70-
contrast, a significant thrombocytopenia asso- 80% of all cases of thrombocytopenia in preg-
ciated with medical conditions can have seri- nancy. Hypertensive disorders account for ap-
ous maternal-fetal consequences and requires proximately 20% and immune thrombocy-
specific monitoring and appropriate manage- topenic purpura for about 3-4%. Other etiolo-
ment. gies are considered rare in pregnancy. 
From a practical standpoint, the current
guidelines consider that vaginal delivery is safe

Address for correspondence:

Anca Panaitescu, Department of Obstetrics and Gynecology, Filantropia Clinical Hospital, 11th Ion Mihalache Boulevard, 1st District,
Bucharest, Romania.
E-mail: panaitescu.anca@yahoo.com

Article received on the 16th of January 2016. Article accepted on the 23rd of March 2016.

Maedica A Journal of Clinical Medicine, Volume 11 No.1 2016 55

THROMBOCYTOPENIA IN PREGNANCY

Pregnancy related Not related to pregnancy

Gestational thrombocytopenia Pseudothrombocytopenia
Preeclampsia/eclampsia Immune thrombocytopenic purpura
HELLP syndrome Thrombotic thrombocytopenic purpura/hemolytic
Acute fatty liver of pregnancy uremic syndrome
Autoimmune diseases: lupus, antiphospholipid
syndrome
Infections: HIV, HBV, HCV, sepsis
Disseminated intravascular coagulation
Drug related causes: heparin
von Willebrand Disease Type IIb
Bone marrow dysfunction
Hypersplenism
Nutritional deficiencies: vitamin B12, folate
TABLE 1. Causes of thrombocytopenia in pregnant women.

GESTATIONAL THROMBOCYTOPENIA is associated with viral infections and is self-

limiting and the chronic form which predomi-

G estational thrombocytopenia (GT) is a be-

nign condition with moderate thrombocy-
topenia (platelet count of 130-150.000/μL) in
nantly affects women. The diagnosis is clinical.
Thrombocytopenia in ITP is generally moder-
ate but with platelet count usually below
most of the cases (4). Platelet values below 100.000/μL and the symptoms are in direct re-
50.000/μL in a pregnant woman exclude GT lation to the platelet levels. Patients could be
and require the search of another etiology. completely asymptomatic or present ecchymo-
Gestational thrombocytopenia is a diagnosis of sis, petechiae, purpura, gums bleeding or men-
exclusion. The condition is asymptomatic, usu- orrhagia (1). Unlike gestational thrombocyto-
ally occurs in the second half of pregnancy, in penia, ITP can occur anytime during pregnancy.
the absence of a history of thrombocytopenia Moreover, most pregnant women with ITP may
outside the pregnancy and the platelet count have a history of thrombocytopenia prior to
spontaneously returns to normal levels within pregnancy or may present with other immune-
the first two months postpartum (1). Gestation- mediated diseases. The platelet count does not
al thrombocytopenia is not associated with ma- spontaneously improve postpartum and the
ternal or fetal risks and does not require further therapeutic response to steroids or IVIG (intra-
investigation, except for a periodical monitor- venous immunoglobulins) contributes to the
ing of the blood count. In these cases, a platelet diagnosis of ITP.
count should be obtained before epidural an- Pregnancy does not worsen the outcome of
esthesia (5). When GT is suspected but platelet ITP, but there may be adverse fetal and mater-
count falls between 50.000-80.000/μL, a diag- nal consequences in some cases. Although
nosis of immune thrombocytopenic purpura rare, spontaneous bleeding is the main mater-
cannot be excluded. Prednisone in a daily nal risk especially when the platelet count falls
dose for 10 days before birth should be admin- below 20.000/μL. Steroids or IVIG are recom-
istered in such cases in order to increase plate- mended before 36 weeks if platelet count is
let count and avoid possible anesthetic and under 30.000/μL, the patient is symptomatic or
obstetrical risks (3). In GT there is no therapeu- an invasive procedure is considered (7). Around
tic answer to steroids and the lack of response delivery, the aim is to maintain platelet count
is an additional argument for the diagnosis.  above 50.000/μL, the level considered safe for
both vaginal and cesarean delivery. Intravenous
IMMUNE THROMBOCYTOPENIC PURPURA immunoglobulin at a dose of 1 g/kg have a rela-
tively rapid therapeutic response (within 1-3
A more rare cause of thrombocytopenia in
pregnancy is the immune thrombocytope-
nic purpura (ITP), an autoimmune disorder
days) or prednisone 1 mg/kg with a therapeutic
response within 2-14 days could be used for
characterized by the anti-platelet glycoprotein treatment during pregnancy. The first-line ther-
antibodies that stimulate the platelet destruc- apy drug, prednisone, is considered safe, but
tion in the spleen (6). There are two types of can induce or exacerbate gestational diabetes,
ITP: the acute form that is common in children, maternal hypertension, osteoporosis, weight

56 Maedica A Journal of Clinical Medicine, Volume 11 No.1 2016

 THROMBOCYTOPENIA IN PREGNANCY

gain and psychosis. Prednisone is metabolized vated liver function tests, low platelets) is an-
by placenta but high doses have been linked to other pregnancy specific disorder and it com-
fetal adrenal suppression and a small increase plicates 10-20% of cases of severe preeclampsia
in incidence of cleft lip and palate if used in the (12). The syndrome can occur without protein-
first trimester (8). uria (25% of cases) or hypertension (40% of
In severe cases of thrombocytopenia, unre- cases) and the diagnosis may then be missed
sponsive to alternative therapies, splenectomy (11). About 70% of the cases develop before
can safely be performed, especially in second delivery, the majority between the 27th and 37th
trimester of pregnancy. Pre-splenectomy im- gestational week, but in some women the signs
munizations are safe in pregnancy, as all the suggestive of HELLP syndrome may occur post-
vaccines required are inactivated. Platelet partum (30% of cases) (12). A platelet count of
transfusion is not indicated for ITP treatment <100.000/μL is one of the diagnostic criteria of
due to the consumptive mechanism of this HELLP syndrome.
condition. When emergency cesarean delivery The pathophysiology is similar to that of
is required with a platelet count under 50.000/ pre-eclampsia, with endothelial damage and
μL, platelet transfusions in association with release of tissue factors and coagulation activa-
IVIG is recommended (7). tion.
Immune thrombocytopenic purpura is not Acute fatty liver of pregnancy (AFLP) is a
an indication for caesarean delivery (3,9). rare (1:7000 - 1:20000 pregnancies), but se-
The IgG anti-glycoprotein platelet antibod- vere condition of the third trimester of preg-
ies can cross the placenta and could induce nancy. Clinical manifestations such as abdomi-
neonatal thrombocytopenia (with an estimated nal pain, nausea, vomiting, anorexia, in
risk of 5-10%) (4). There is no correlation be- conjunction with several specific laboratory
tween maternal and fetal platelet levels and changes such as severe hypoglycemia, hyper-
maternal response to treatment does not pro- uricemia, markedly elevated transaminases, re-
tect the fetus from a possible neonatal throm- nal impairment with elevated creatinine, blood
bocytopenia (3). Neonatal platelet levels should pressures in the normal range, may lead to the
be determined at birth and further daily moni- diagnosis of acute fatty liver of pregnancy (13).
tored. The lowest levels are recorded during Thrombocytopenia associated with this pathol-
days 2 to 5 postnatally (10). When platelet ogy is sometimes severe, with a platelet count
count in the newborn is below 50.000/μL, under 20.000/μL (3).
there is a risk of 0.5-1.5%, of intracranial hem- The only effective treatment of preeclamp-
orrhage and a head ultrasound is recommend- sia/eclampsia, HELLP Syndrome and acute fat-
ed even in the absence of symptoms. When ty liver of pregnancy is delivery.
the platelet count is between 30.000 to 50.000/ The aim is to maintain platelet count around
μL, IVIG treatment should be started. With the safety limit of above 50.000/μL. Dexameth-
platelet count under 30.000/μL platelet transfu- asone 10 mg every 12 hours, 2 to 4 doses ante-
sion along with IVIG is recommended (11).  partum and two doses postpartum is usually
recommended. If hemolysis, thrombocytope-
THROMBOCYTOPENIA ASSOCIATED WITH nia and renal dysfunction worsen plasmapher-
HYPERTENSIVE DISORDERS esis could be used. In the absence of other
complications such as disseminated intravascu-
T hrombocytopenia associated with hyper-
tensive disorders (preeclampsia, eclampsia,
HELLP syndrome, acute fatty liver of pregnan-
lar coagulation (DIC) or renal dysfunction, the
platelet count usually returns to normal values
cy) is the second leading cause of thrombocy- by day 4 postpartum and reach 100.000/μL by
topenia in pregnancy. Thrombocytopenia oc- day 6 (3).
curring in this context is a sign of hypertensive The pathophysiologic mechanism of throm-
disorder severity. Levels rarely fall below bocytopenia in hypertensive disorders is the
20.000/μL. thrombotic microangiopathy characterized by
Preeclampsia causes about 20% of cases of endothelial injury, followed by platelet aggre-
thrombocytopenia in pregnancy. Thrombocy- gation and thrombus formation in small vessels.
topenia is sometimes the only initial sign of this The mark of thrombotic microangiopathy are
condition, predating all the other laboratory the presence of schistocytes on peripheral
changes (3). HELLP syndrome (hemolysis, ele- blood smear and increased bilirubin >1.2 mg/

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THROMBOCYTOPENIA IN PREGNANCY

dL, decreased haptoglobin <25 mg/dl and in- Globally, the stillbirth rate in pregnancy - as-
creased LDH biochemically. sociated TTP is reported to be about 40%,
Thrombotic microangiopathy is the patho- mainly due to intrauterine fetal death (IUFD),
physiological mechanism for thrombotic spontaneous abortions and prematurity. The
thrombocytopenic purpura (TTP) and the he- major pathophysiological mechanism for intra-
molytic uremic syndrome (HUS), two patho- uterine fetal growth restriction and death may
logic conditions difficult to distinguish one from be placental ischemia (19). No cases of fetal
another and from preeclampsia/HELLP syn- thrombocytopenia or hemolytic anemia have
drome and AFLP. been described in maternal TTP, although the
Both TPT and HUS are not pregnancy spe- anti ADAMTS 13 IgG cross the placental barrier
cific pathologic conditions, occurring with (20). Because of the risk of IUFD caused by the
higher incidence (1: 25000) especially towards thrombosis of the decidua arterioles and pla-
the end of the pregnancy (14). cental hypoperfusion, it is recommended to
TTP is defined by a pentad of microangio- perform a careful fetal monitoring by Doppler
pathic hemolytic anemia, thrombocytopenia, ultrasound of the uterine arteries and fetal ar-
fever, neurological manifestations, renal im- teries to detect signs of fetal distress or intra-
pairment. Creatinine levels in TTP are not in- uterine growth restriction. Delivery may be re-
creased and the median platelet count is typi- quired earlier and fetal prognosis is dependent
cally 10-30000/μL. on the gestational age at birth (3).
However, TTP can present without the full HUS has a common mechanism with TTP,
pentad, up to 35% of patients not having neu- but the distinctive feature is the more severe
rological signs at presentation and renal abnor- kidney impairment with HUS. There are two
malities and fever are not prominent features. types of HUS: the typical form, represents 90%
Neurological presentation could include a myr- of cases of HUS, is common in children and is
iad of signs as headache, altered personality, caused by E. coli O157:H7 which produces the
reduced cognition, transient ischemic attacks, Shiga-toxin and the atypical form which is usu-
different levels of consciousness alteration in- ally associated with pregnancy and is related to
cluding coma (15). a congenital defect of the alternative pathway
Pregnancy can be the trigger event for ap- of the complement system. It occurs in most
proximately 5-25% of TTP cases (16). TTP oc- cases postpartum.
curs in the second part of pregnancy and some- Both TTP and HUS can have immediate fe-
times in postpartum, while it remains unusual tal and maternal consequences in the absence
during the first trimester of gestation. If TTP of treatment, so establishing an early diagnosis
develops in the first trimester, regular plasma is very important. Therefore, every pregnant
exchange may allow continuation of pregnancy woman with thrombocytopenia and microan-
(15). giopathic hemolytic anemia should be consid-
There are two types of TTP: a familial type ered suspicious for TTP or HUS until proven
characterized by a constitutional deficiency of otherwise (3). The laboratory investigations are
ADAMTS 13 (the Upshaw-Schulman Syn- useful in establishing the diagnosis are micro-
drome USS) and a non-familial type character- angiopathic hemolytic anemia, presence of
ized by the production of anti- ADAMTS 13 schistocytes in blood smear, normal coagula-
antibodies (aquired). ADAMTS 13 is a metallo- tion tests and increased creatinine as a marker
protease acting to cleave the von Willebrand of renal injury.
factor multimers and thus it prevents thrombus Unlike preeclampsia/HELLP syndrome, de-
formation by the impaired platelet aggregation. livery does not influence the outcome of the
A deficiency in ADAMTS 13 activity can be disease; the first-line treatment in cases of TTP/
seen also in DIC, HUS, preeclampsia and the HUS is plasmapheresis and administration of
HELLP syndrome (<40% but >10%), but the fresh frozen plasma as soon as possible. Plas-
severe deficiency <5% of the normal activity, is mapheresis is repeated until the normal levels
specific for TTP (17). Severely reduced AD- of platelets and LDH are reached. For kidney
AMTS 13 activity or the presence of an inhibi- impairment temporary dialysis could be re-
tor or IgG antibodies confirm the diagnosis of quired.
TTP. Blood must be taken prior to treatment to For atypical HUS, eculizumab, a monoclo-
asses baseline ADAMTS 13 activity (18). nal anti-C5 inhibitor appears a promising agent.

58 Maedica A Journal of Clinical Medicine, Volume 11 No.1 2016

 THROMBOCYTOPENIA IN PREGNANCY

Eculizumab was approved for treatment of coagulation system, microvascular thrombus

complement mediated HUS by Food and Drug formation in different organs and multiple or-
Administration and the European Medicine gan failure. Biochemically is defined by an in-
Agency. Eculizumab has been proven efficient crease of the PT, aPTT, thrombocytopenia, de-
in paroxysmal nocturnal hemoglobinuria dur- creased fibrinogen, fibrin degradation product
ing pregnancy and treatment with eculizumab accumulation and the presence of D-dimers. In
is generally safe. The main concerns are the pregnancy, DIC is caused by a number of
high costs and a small risk of Neisseria infec- causes, the most important being placental ab-
tion, requiring vaccination prior to treatment ruption, amniotic embolus and uterine rupture.
(21). Von Willebrand disease type IIb is a rare
The risk of recurrence in subsequent preg- cause of thrombocytopenia in pregnancy.
nancies in women with acquired TTP is about There is a qualitative defect of the von Wille-
20% (16). Regular plasma exchange and serial brand factor inducing high affinity to the plate-
monitoring of ADAMTS 13 activity have a ben- let receptor of glycoprotein 1b. Thrombocyto-
efit for both the maternal and the baby out- penia is explained by increased aggregation.
come (15). Women with this condition may present with
In congenital TTP the risk for relapse in the thrombocytopenia for the first time in pregnan-
subsequent pregnancies is 100% in the ab- cy and platelets can drop to values below
sence of prophylaxis. Plasma exchange should 20.000-30.000/μL. Levels of von Willebrand
be initiated at the end of first trimester and re- factor and factor VIII should be increased to
peated throughout the pregnancy and post- >50 IU/dL to cover any surgical procedures.
partum if necessary (20). Platelet transfusions may be required together
Pseudothrombocytopenia is often seen with the factor VIII replacement if the platelet
when anticoagulants such as EDTA are used count is <20.000/μL antenatally, prior to any
when collecting blood. They induce platelet invasive procedures, if bleeding occurs or if
aggregation and therefore false low platelet platelet count is <50.000/μL around delivery
count. A peripheral blood smear is important (11).
for establishing the diagnosis (the platelets are
seen arranged in stacks). Conflict of interests: none declared.
Disseminated intravascular coagulation Financial support: none declared.
(DIC) is characterized by the activation of the

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