Immune Thrombocytopenia and Pregnancy

Updated: Aug 19, 2019
  • Author: Muhammad A Mir, MD, FACP; Chief Editor: Srikanth Nagalla, MBBS, MS, FACP  more...
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Overview

Practice Essentials

Thrombocytopenia is common in mothers and newborns and usually is caused by an increased rate of platelet destruction. The reference range of a normal platelet count in nonpregnant women and newborns is 150,000-400,000/µL; however, mean platelet counts in pregnant women generally are lower.

Thrombocytopenia in pregnancy has many common causes, including gestational thrombocytopenia, viral and bacterial infections, and preeclampsia complicated by hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome. [1]  This article focuses on the immune thrombocytopenias, immune thrombocytopenic purpura (ITP) and neonatal alloimmune thrombocytopenia (NAIT). These relatively rare causes of thrombocytopenia are important, as neonatal outcomes can be significantly impaired and subsequent pregnancies can be affected. (See images below.)

Immune thrombocytopenia. An infant born with neona Immune thrombocytopenia. An infant born with neonatal lupus syndrome and severe thrombocytopenia. Note extensive bruising and petechiae.
Immune thrombocytopenia. An infant born with a cep Immune thrombocytopenia. An infant born with a cephalohematoma.
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Pathophysiology

Immune thrombocytopenia is a rare autoimmune disease due to an abnormal T cell response, notably supported by splenic T follicular helper cells, that stimulates the proliferation and differentiation of autoreactive B cells. The antiplatelet autoantibodies they produce facilitate platelet phagocytosis by macrophages, essentially in the spleen. Macrophages contribute to the perpetuation of the auto-immune response as the main antigen-presenting cell during ITP. CD8+ T cells also participate to thrombocytopenia by increasing platelet apoptosis. Besides this peripheral platelet destruction, inappropriate bone marrow production also exacerbates thrombocytopenia, due to an immune response against megakaryocytes. Moreover, the level of circulating thrombopoietin, the main growth factor of megakaryocytes, is low. These autoantibodies can cross the placenta; thus, both mother and newborn can be affected. [2]  

NAIT is caused by maternal immunization against fetal paternally derived platelet-specific antigens (similar to rhesus [Rh] disease). The mother has a normal platelet count, while the fetus can be severely thrombocytopenic. NAIT occurs when the mother is exposed to fetal platelets with incompatible paternally derived cell surface antigens. The mother's response to the foreign antigens is to produce immunoglobulin. This is initially immunoglobulin M, and the large size of this molecule prevents transplacental passage. Subsequently, the mother produces immunoglobulin G. The smaller size of this molecule permits passage across the placenta, resulting in the destruction of fetal platelets and neonatal thrombocytopenia.

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Epidemiology

ITP occurs in 1 to 2 of every 1000 pregnancies, which in the United States represents about 3000 to 6000 cases of ITP in pregnancy per year. [3]  Although ITP accounts for less than 3% of all cases of thrombocytopenia during pregnancy, it is the most common cause of a platelet count below 50 × 109/L detected in the first and second trimesters. [4]  The frequency of NAIT is estimated at 1-2 cases per thousand deliveries.

The frequency of ITP is 1.8 cases per 1000 deliveries in Helsinki, Finland. [5]  The frequency of NAIT was reported as 0.5 cases per 1000 and 1.5 cases per 1000 liveborn neonates in England [6] and France, [7] respectively. In Japan, the frequency of NAIT was 0.3 cases per 1000 liveborn neonates, and incompatibility for human platelet antigen (HPA)-4 was the cause of 80% of these cases. [8] The recurrence risk for NAIT is extremely high (nearly 100% of subsequent pregnancies are affected if the sibling carries the significant paternally derived antigen). [9] In general, siblings with the platelet antigen will be as severely affected or more severely affected than the preceding affected child. [9]

ITP occurs in all races. However, more than 50% of all cases of NAIT have been reported in whites. Most cases of alloimmune thrombocytopenia (and the most severe cases) occur in white mothers homozygous for the P1A2 allele (HPA-1b). [10]  The prevalence of homozygous HPA-1b in whites is estimated at 2.5%. [11]  Multiple other platelet-specific antigens exist that can cause alloimmune thrombocytopenia; the prevalence of these varies in different ethnic groups.

ITP is diagnosed more commonly in females than males (ratio 3:1). [12]  NAIT occurs in newborns of both sexes.  ITP commonly is diagnosed in the second or third decade of life. NAIT develops in fetal life, with 25-50% of fetal intracranial hemorrhages detectable on prenatal ultrasound prior to the onset of labor. [13]

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Prognosis

Women with ITP generally do well in pregnancy. ITP is an autoimmune disease and exacerbations, and remissions are common. Pregnancy does not appear to affect the course of the disease. ITP is not an absolute contraindication to pregnancy but in unusually severe or refractory cases or for women taking potentially teratogenic medications, deferring pregnancy may be indicated. [4]   Duration of maternal ITP is a risk factor for preterm birth and women with chronic ITP experience more adverse outcomes than those with a pregnancy-related diagnosis of ITP. [3]  

Fetuses and newborns with NAIT can experience permanent neurologic sequelae, organ damage, and death from intracranial and intra-abdominal bleeds due to severe thrombocytopenia. However, after birth, maternal antibodies are fairly rapidly degraded and the thrombocytopenia resolves.

Women and newborns with severe thrombocytopenia can experience intracranial and intra-abdominal bleeding. This can result in significant morbidity, including neurologic damage and/or death. Women requiring long-term steroid therapy can develop complications from the medication exposure.

Transfusion of blood products can result in transfusion reactions in the recipient. With current blood bank crossmatching, significant transfusion reactions are rare. Additionally, a risk of transmission of viral infections, especially hepatitis and human immunodeficiency virus, exists. [14]

Maternal hemorrhage at time of birth is a risk in women with ITP, particularly if the platelet count decreases to less than 20,000/µL. However, no maternal deaths have been reported in the last 20 years, [9]  and maternal morbidity is minimal if appropriate therapy is administered during pregnancy and childbirth.

Neonatal thrombocytopenia due to the active transport of antiplatelet antibodies through the placenta is a clinically more significant problem, and it occurred in 9 of 66 (13.6%) pregnancies complicated by ITP in one review. [15]  Of these infants, 5 of 66 (7.5%) had severe thrombocytopenia, with platelet counts less than 50,000/µL. Splenectomy prior to pregnancy was the only risk factor associated with the development of neonatal thrombocytopenia by logistic regression analysis.

Severe neonatal thrombocytopenia places the infant at risk for intracranial or visceral hemorrhage. None of the 9 thrombocytopenic infants in the Yamada trial had intracranial hemorrhage documented on clinical neurological examination or ultrasound. Neonatal intracranial hemorrhage previously has been reported to have a very low incidence (0-2.3%) in newborns of mothers with ITP. [16]

Neonatal morbidity is far more common in NAIT, with 10% of affected newborns dying and 20% experiencing neurological sequelae secondary to intracranial hemorrhage. [11]  Affected infants can have generalized petechiae, hemorrhage into abdominal viscera, and excessive bleeding after venipuncture or circumcision.

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