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Case Studies for Fellows

Prenatal Management of 21-Year-Old Woman to Reduce Risk of Severe Thrombocytopenia and Intracranial Hemorrhage 

A 21-year-old woman G2P1 (two pregnancies, one birth) is referred by her obstetrician at 16 weeks gestation. Her first-born son, who is now two years old, was born via vaginal delivery at 38 weeks with generalized petechiae and bruising and was found to have a platelet count of 8 × 109/L. Maternal platelet count at the time was 144 × 109/L. Her son received random-donor platelets and intravenous immune globulin (IVIG) with minimal response, but responded well to human platelet antigen (HPA) –1a Ag-negative platelet transfusion. There was no evidence of intracerebral hemorrhage. Further workup showed positive HPA-1a in maternal serum, and the father was found to be homozygous for HPA-1a/1a. Maternal platelet antigen typing: HPA-1b/1b; paternal platelet antigen typing: HPA-1a/1a.

What is the recommended prenatal management to reduce the risk of severe thrombocytopenia and intracranial hemorrhage in her second child?

  1. Observation
  2. Steroids
  3. IVIG with or without steroids
  4. Intrauterine platelet transfusions


Answer: C

Neonatal alloimmune thrombocytopenia (NAIT) should be suspected in any newborn with severe unexpected thrombocytopenia, especially if maternal history is negative and maternal platelet count is normal. NAIT results from the transplacental passage of maternal antibodies that are reactive against paternal-derived HPAs expressed on the infant’s platelets. This condition is analogous to Rhesus (Rh) disease in that the mother lacks the antigen and the infant inherits the antigen from the father. Unlike Rh disease, however, first pregnancies may be affected by NAIT. The majority of NAIT cases (80%) arise because of a maternal antibody against HPA-1a. Other antigens, including HPA-5b and HPA-3b, are less common.

Thrombocytopenia caused by NAIT is associated with a high risk of intracranial hemorrhage (10-20%); therefore, all infants with NAIT should be investigated for intracranial hemorrhage with either ultrasound or computed tomography scan. Treatment is recommended for a platelet count lower than 30 × 109/L or less than 100 × 109/L in infants with severe hemorrhage. Optimal treatment includes transfusion of HPA-compatible platelets, which can be washed irradiated maternal platelets or collected from an antigen-negative donor. Random donor platelets should be given if antigen-negative platelets are unavailable since platelet count increments have been documented with this approach. Additionally, IVIG and methylprednisolone may decrease the rate of platelet destruction and can be used as adjunctive therapy. Regardless of treatment, NAIT usually resolves within two to four weeks.

Specific testing for NAIT, including platelet antigen typing and antibody identification, can confirm the diagnosis; however, treatment should be instituted even if results of testing are unavailable. NAIT testing is important because of the implications for subsequent pregnancies, where the risk of severe thrombocytopenia is higher and can occur as early as the second trimester. Prenatal management should be undertaken in conjunction with a high-risk obstetrician.

Several strategies can be used to manage NAIT in subsequent pregnancies. Serial fetal blood sampling and intrauterine platelet transfusions, as well as weekly maternal IVIG, with or without additional corticosteroid therapy, are common options. Most studies have found comparable outcomes regarding the occurrence of intracranial hemorrhage, regardless of the antenatal management strategy applied: fetal blood sampling, intrauterine platelet transfusions, or IVIG with or without corticosteroids. However, noninvasive management in pregnant mothers who have had a previous neonate with NAIT is effective without the relatively high rate of adverse outcomes seen with invasive strategies. IVIG decreases placental transfer of antibodies and reduces cellular destruction in the fetus. There is no consistent evidence for the value of adding steroids to IVIG.


  1. Bussel J. Diagnosis and management of the fetus and neonate with alloimmune thrombocytopenia. J Thromb Haemost. 2009;7 Suppl 1:253-257.
  2. Peterson JA, McFarland JG, Curtis BR, et al. Neonatal alloimmune thrombocytopenia: pathogenesis, diagnosis and management. Br J Haematol. 2013;161:3-14.
  3. Winkelhorst D, Murphy MF, Greinacher A, et al. Antenatal management in fetal and neonatal alloimmune thrombocytopenia: a systematic review. Blood. 2017;129:1538-1547.
  4. Lieberman L, Greinacher A, Murphy MF, et al. Fetal and neonatal alloimmune thrombocytopenia: recommendations for evidence-based practice, an international approach. Br J Haematol. 2019;185:549-562.

Case submitted by Sara Taveras Alam, MD, Baylor College of Medicine, Houston, TX.