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Alloimmune Thrombocytopenia

Michael F. McNamara, DO Sanford Maternal Fetal Medicine. Alloimmune Thrombocytopenia. No disclosures. Platelet Disorders in Pregnancy. Gestational thrombocytopenia Idiopathic thrombocytopenia (ITP) Thrombotic thrombocytopenia (TTP) Alloimmune thrombocytopenia (NAIT).

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Alloimmune Thrombocytopenia

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  1. Michael F. McNamara, DO Sanford Maternal Fetal Medicine Alloimmune Thrombocytopenia

  2. No disclosures

  3. Platelet Disorders in Pregnancy • Gestational thrombocytopenia • Idiopathic thrombocytopenia (ITP) • Thrombotic thrombocytopenia (TTP) • Alloimmune thrombocytopenia (NAIT)

  4. Gestational Thrombocytopenia • Dilution effect • Increase of platelet destruction • No therapy needed

  5. Idiopathic Thrombocytopenia • 1-3 / 1000 pregnancies • Pregnancy not usually altering disease course • Therapy • Steroids • IVIG • Splenectomy

  6. Thrombotic ThrombocytopeniaPurpura (TTP) • TTP/HUS, may be confused with pre eclampsia • Microangiopathic hemolytic anemia • Thrombocytopenia • Neurologic changes (headache, lethargy) • Thrombotic occlusions in multiple small vessels • Therapy plasma exchange, platelet transfusions

  7. Alloimmune Thrombocytopenia • Also known as Neonatal Alloimmune Thrombocytopenia (NAIT) • 0.2 -1 per 1000 deliveries • Low fetal platelets due to maternal antibodies • Index case usually affected • Antenatal diagnosis often by ultrasound with findings of intracranial hemorrhage

  8. Case Study • 25 year old female • Gravida 5, para 2 • Two previous term vaginal deliveries • Petechiae, bruising, platelets < 10,000 • Counseled on further pregnancies, need of treatment

  9. Case Study • Presented at 14 weeks gestation • Genetic counseling, history reviewed • Same paternity as previous infants • Father of baby not available for testing (zygosity)

  10. Case Study • Diagnostic testing (platelet antigen) • Maternal • Blood HPA 1b/1b • Fetal • Amniotic fluid HPA 1a/1b

  11. Case Study • Preventative therapy • IVIG 1 gram / kg weekly • Prednisone 1mg /kg daily

  12. Case Study • Antenatal Course • Gestational diabetes • Severe headaches with IVIG therapy • Elevated liver enzymes due to percocet use secondary to headaches

  13. Case Study • Antenatal steroids at 33 weeks gestation • Elected cesarean for delivery with tubal ligation • Vaginal delivery if umbilical cord sampling performed with normal fetal platelet count • Delivery at 37 weeks, uncomplicated • Female infant 5 lbs, 4 oz

  14. Alloimmune thrombocytopenia • Also know as Neonatal Alloimmunethrobocytopenia (NAIT) • Incidence 0.2 -1 per 1000 Caucasian births • Maternal antigens against fetal platelets

  15. NAIT • Platelet antigens classified at HPA 1a (PLA1) and HPA 1b (PLA2) • 97% adults phenotype HPA 1a (positive for 1a) • 69% adults homozygous HPA 1a (1a/1a) • 28 % adults heterozygous HPA 1a (1a/1b) • 3 % adults homozygous HPA 1b (1b/1b)

  16. NAIT • Affected pregnancies • Most serious complication • Intracranial hemorrhage 10-20 % of cases • 25-50 % cases diagnosed prenatally • Ultrasound findings of intracranial hematoma, porencephalic cysts

  17. Antepartum Preventive Therapy • Extremely High Risk • Previous baby ICH in second trimester • High risk • Previous baby ICH in third trimester • Moderate risk • Previous baby with thrombocytopenia but no ICH

  18. NAIT • Recurrence risk up to 100% • Thrombocytopenia is severe and happens earlier in subsequent pregnancies • Previous ICH is risk factor for severe thrombocytopenia in next pregnancy • Low platelet count goes lower in subsequent pregnancies without treatment in utero

  19. NAIT – antenatal therapy • IVIG – very uncommon for ICH with IVIG treatment (11/411 for 2.7%) • Prednisone (additionally) – no better than IVIG alone • Umbilical cord sampling – procedure / bleeding risk • Platelet transfusions – unknown efficacy

  20. IVIG Mechanism of Action • Provision of missing immunoglobulins or neutralizing antibodies, restoration of immune function, and/or suppression of inflammatory and immune-mediated processes • Increase the effect of regulatory T cells, contributing to the maintenance of immunologic self-tolerance • Prevention of reticuloendothelial uptake of autoantibody-coated blood cells (eg, platelets, red cells) through blockade of macrophage Fc-receptors

  21. Case Study #2 • Preconception Counseling • Gravida 3, Para 3 with recent neonatal demise from ICH delivered at 38 weeks • Low platelet count • Paternal 1a/1b • Maternal 1b/1b

  22. Case Study #2 • Pregnancy #4, amniocentesis • Fetus - male1b/1b, normal pregnancy • Pregnancy #5, amniocentesis • Fetus – male,1a/1b, affected • IVIG, prednisone, cord sampling • Cesarean at 37 weeks gestation

  23. Case Study #2 • First two pregnancies vaginal deliveries with no complications • Oldest is a male, second oldest female • Recent testing of the female (now an adult), 1b/1b

  24. Case Study #2 • Platelet antigens classified at HPA 1a (PLA1) and HPA 1b (PLA2) • 97% adults phenotype HPA 1a (positive for 1a) • 69% adults homozygous HPA 1a (1a/1a) • 28 % adults heterozygous HPA 1a (1a/1b) • 3 % adults homozygous HPA 1b (1b/1b) • 83% chance of having a baby with 1a/1b

  25. Summary • NAIT cause of neonatal thrombocytopenia • Index case possibly severe problems such as ICH • Decrease complications with in utero therapy, IVIG, prednisone

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