eMedicine Specialties > Hematology > Coagulation, Hemostasis, and Disorders
Immune Thrombocytopenia and Pregnancy
Updated: Nov 2, 2009
Introduction
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 and Images 5-6.)
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.
Recent research
In a retrospective study, Giers et al concluded that in the treatment of fetal alloimmune thrombocytopenia, there was equal clinical effectiveness in the intrauterine transfusion of either maternal platelets or human platelet antigen (HPA)–matched donor platelets.1 No procedure-related fetal or neonatal loss resulted from the use of either maternal (15 fetuses) or donor (42 fetuses) platelets, and both types of treatment reliably increased fetal platelet counts.
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.
Frequency
United States
The frequency of ITP has been reported to be 1-2 cases per 1000 deliveries in the United States.2 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.3
The frequency of NAIT was reported as 0.5 cases per 1000 and 1.5 cases per 1000 liveborn neonates in England4 and France,5 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.6 The recurrence risk for NAIT is extremely high (nearly 100% of subsequent pregnancies are affected if the sibling carries the significant paternally derived antigen).7 In general, siblings with the platelet antigen will be as severely affected or more severely affected than the preceding affected child.7
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,7 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.8 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.9
- Neonatal morbidity is far more common in NAIT, with 10% of affected newborns dying and 20% experiencing neurological sequelae secondary to intracranial hemorrhage.10 Affected infants can have generalized petechiae, hemorrhage into abdominal viscera, and excessive bleeding after venipuncture or circumcision.
Race
- ITP occurs in all races.
- 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).11 The prevalence of homozygous HPA-1b in whites is estimated at 2.5%.10 Multiple other platelet-specific antigens exist that can cause alloimmune thrombocytopenia; the prevalence of these varies in different ethnic groups.
Sex
- ITP is diagnosed more commonly in females than males (ratio 3:1).12
- NAIT occurs in newborns of both sexes.
Age
- 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
Clinical
History
Pregnant women with ITP can be asymptomatic or can present with a history of easy bruisability, bleeding into the mucous membranes (epistaxis or gingival bleeding), or petechiae. They may have a history of menorrhagia or menometrorrhagia prior to pregnancy.
A maternal history of delivering a term newborn with thrombocytopenia, visceral or intracranial hemorrhage, or spontaneous or prolonged bleeding after venipuncture or circumcision raises suspicion for NAIT. However, about 50% of neonates with NAIT are first-born children and thus are delivered to women whose risk for the disorder is previously unrecognized and unknown.
Case history
A woman is 24 years old. She has been pregnant 4 times and given birth once (G4 P1). She has had zero spontaneous abortions (SAB0) and 2 elective abortions (EAB2). She is part Hawaiian and part Samoan and was referred for twice weekly antepartum testing due to a prior stillbirth at 31 weeks' estimated gestational age. A specific cause of her fetal demise was never determined. Chromosome analysis revealed a normal male (46, XY) pattern. Placental pathology was normal, and an autopsy was not performed.
Her pregnancy and antepartum testing results are normal until 35 and 5/7 weeks' estimated gestational age (see images below and Images 1-2). This woman is admitted for prolonged fetal monitoring, the findings of which are completely normal. She is discharged home later that day.
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.
She presents 4 days later with 2 days of decreased fetal movement. Fetal heart tones cannot be auscultated, and an ultrasound confirms an intrauterine fetal demise. Labor is induced, and she delivers a 2729-g male fetus. Autopsy demonstrates a large subdural hemorrhage surrounding the brain and spinal cord (54 g) (see images below and Images 3-4).
Immune thrombocytopenia. Neonatal brain at autopsy showing extensive subdural hemorrhage.
Immune thrombocytopenia. Neonatal spine at autopsy showing extensive hemorrhage at base of spine.
The woman's blood is sent for platelet antigen typing. Her platelet-associated immunoglobulins are high, at 7.5 (reference range 0-4.3). She tests positive for HPA-1a, the platelet-specific antigen implicated in most cases of neonatal alloimmune thrombocytopenia (amongst whites). The father of the baby declines to have his blood drawn; therefore, platelets from the father cannot be tested with the mother's serum. Thus, these studies do not support a diagnosis for NAIT, but they do not exclude it either because many different platelet antigens exist. This mother is of Hawaiian, Samoan heritage, and different platelet antigens (not HPA-1a) probably are significant in nonwhite ethnic groups. HPA-4 has been shown to be important in NAIT in Japanese women.
Therefore, when the woman presents 2 years later pregnant with a new partner, the new father's platelets are tested against the mother's serum to verify that no antibodies in the maternal serum will react to paternal platelets. No antiplatelet antibodies are present, and she has an uncomplicated pregnancy delivering a full-term healthy infant.
Physical
Most women with ITP have normal findings on physical examination (splenomegaly is absent). Petechiae can be identified in the presence of severe thrombocytopenia.
Newborns with NAIT may have normal findings on physical examinations, or they may have a cephalohematoma, ecchymoses over the presenting part, and generalized petechiae (see images below and Images 5-6).
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.
Causes
- Women with ITP have an autoimmune disease and produce immunoglobulin to their own cell surface platelet antigens. Platelets coated with IgG autoantibodies undergo accelerated destruction, predominately in the spleen and liver, resulting in thrombocytopenia.
- 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.
More on Immune Thrombocytopenia and Pregnancy |
 Overview: Immune Thrombocytopenia and Pregnancy |
| Differential Diagnoses & Workup: Immune Thrombocytopenia and Pregnancy |
| Treatment & Medication: Immune Thrombocytopenia and Pregnancy |
| Follow-up: Immune Thrombocytopenia and Pregnancy |
| Multimedia: Immune Thrombocytopenia and Pregnancy |
| References |
| Further Reading |
| Next Page » |
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Further Reading
Clinical guidelines
Thrombocytopenia.
Finnish Medical Society Duodecim - Professional Association. 2001 Apr 30 (revised 2007 Apr 27). Various pagings. NGC:005827
Clinical trials
A Randomized Study of IVIG vs. IVIG With High Dose Methylprednisolone in Childhood ITP.
Open Label Extension Study of AMG 531 in Japanese Subjects With ITP
Efficacy and Safety Study of Eltrombopag in Pediatric Patients With Thrombocytopenia From Chronic ITP
Keywords
immune thrombocytopenia, immune thrombocytopenic purpura, thrombocytopenia, low blood platelets, thrombocytopenic purpura, ITP blood disorder, ITP treatment, autoimmune thrombocytopenia, neonatal thrombocytopenia, neonatal alloimmune thrombocytopenia, fetomaternal alloimmune thrombocytopenia, low platelet count
