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

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 Thrombocytopenia Purpura (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 Alloimmune throbocytopenia (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