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Immune Thrombocytopenia and Pregnancy

  • Author: Muhammad A Mir, MD, FACP; Chief Editor: Srikanth Nagalla, MBBS, MS, FACP  more...
 
Updated: Oct 09, 2015
 

Background

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. 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

Thrombocytopenia in ITP occurs because of platelet destruction mediated by platelet autoantibodies directed against cell surface antigens. The reticuloendothelial system destroys platelet/antibody complexes. These autoantibodies can cross the placenta; thus, both mother and newborn can be affected.

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.

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Epidemiology

Frequency

United States

The frequency of ITP has been reported to be 1-2 cases per 1000 deliveries in the United States.[1] ITP can be diagnosed during pregnancy, though, most often, women present for prenatal care with a history of the disorder.

The frequency of NAIT is estimated at 1-2 cases per thousand deliveries

International

The frequency of ITP is 1.8 cases per 1000 deliveries in Helsinki, Finland.[2]

The frequency of NAIT was reported as 0.5 cases per 1000 and 1.5 cases per 1000 liveborn neonates in England[3] and France,[4] 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.[5] The recurrence risk for NAIT is extremely high (nearly 100% of subsequent pregnancies are affected if the sibling carries the significant paternally derived antigen).[6] In general, siblings with the platelet antigen will be as severely affected or more severely affected than the preceding affected child.[6]

Mortality/Morbidity

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,[6] 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.[7] 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.[8]

Neonatal morbidity is far more common in NAIT, with 10% of affected newborns dying and 20% experiencing neurological sequelae secondary to intracranial hemorrhage.[9] Affected infants can have generalized petechiae, hemorrhage into abdominal viscera, and excessive bleeding after venipuncture or circumcision.

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Race-, Sex-, and Age-related Demographics

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%.[9] 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).[11] 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.[12]

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Contributor Information and Disclosures
Author

Muhammad A Mir, MD, FACP Assistant Professor of Medicine (Hematology, Blood/Marrow Transplant) Milton S Hershey Medical Center, Pennsylvania State University College of Medicine

Muhammad A Mir, MD, FACP is a member of the following medical societies: American College of Physicians, American Society of Hematology, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Ronald A Sacher, MB, BCh, FRCPC, DTM&H Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MB, BCh, FRCPC, DTM&H is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society on Thrombosis and Haemostasis, Royal College of Physicians and Surgeons of Canada, American Clinical and Climatological Association, International Society of Blood Transfusion

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: GSK Pharmaceuticals,Alexion,Johnson & Johnson Talecris,,Grifols<br/>Received honoraria from all the above companies for speaking and teaching.

Chief Editor

Srikanth Nagalla, MBBS, MS, FACP Director, Clinical Hematology, Cardeza Foundation for Hematologic Research; Assistant Professor of Medicine, Division of Hematology, Associate Program Director, Hematology/Medical Oncology Fellowship, Assistant Program Director, Internal Medicine Residency, Jefferson Medical College of Thomas Jefferson University

Srikanth Nagalla, MBBS, MS, FACP is a member of the following medical societies: American Society of Hematology, Association of Specialty Professors

Disclosure: Nothing to disclose.

Acknowledgements

Wadie F Bahou, MD Chief, Division of Hematology, Hematology/Oncology Fellowship Director, Professor, Department of Internal Medicine, State University of New York at Stony Brook

Wadie F Bahou, MD is a member of the following medical societies: American Society of Hematology

Disclosure: Nothing to disclose.

Lynnae Millar, MD Professor, Chair, Department of Obstetrics and Gynecology, University of Hawaii, John A Burns School of Medicine

Lynnae Millar, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Obstetricians and Gynecologists, American Medical Association, and Society for Maternal-Fetal Medicine

Disclosure: Nothing to disclose.

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Immune thrombocytopenia. Nonstress test 1 week before delivery showing a normal reactive fetal heart rate pattern.
Immune thrombocytopenia. Nonstress test 4 days before delivery showing a reactive fetal heart rate with an unusual pseudosinusoidal pattern that lasted 9 minutes.
Immune thrombocytopenia. Neonatal brain at autopsy showing extensive subdural hemorrhage.
Immune thrombocytopenia. Neonatal spine at autopsy showing extensive hemorrhage at base of spine.
Immune thrombocytopenia. An infant born with neonatal lupus syndrome and severe thrombocytopenia. Note extensive bruising and petechiae.
Immune thrombocytopenia. An infant born with a cephalohematoma.
 
 
 
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