NEONATAL IMMUNE THROMBOCYTOPENIA M.Hashemieh,M.D Pediatric hematologist SBMU

Immune thrombocytopenia occurs due to the passive transfer of antibodies from the maternal to the fetal circulation. There are two distinct types of immune-mediated thrombocytopenia: (1) neonatal alloimmune thrombocytopenia (NAIT) (2) neonatal autoimmune thrombocytopenia(NATP)

Neonatal alloimmune thrombocytopenia (NAIT) NAIT is the most common cause of severe thrombocytopenia in the newborn Typically resolves in 2-4 weeks First-born infants are 25-50% of those affected Subsequent affected pregnancies have increasingly severe presentation and require antenatal treatment

Pathophysiology NAIT can be thought of as a platelet analog of Rh incompatibility. In NAIT, the antibody is produced in the mother against a specific human platelet antigen(HPA) present in the fetus but absent in the mother. The antigen is inherited from the father of the fetus. The anti-HPA antibody produced in the maternal serum crosses the placenta and reaches the fetal circulation.

In autoimmune thrombocytopenia, the antibody is directed against an antigen on the mother's own platelets (autoantibody) as well as on the baby's platelets. The maternal autoantibody also crosses the placenta, resulting in destruction of fetal platelets.

The most common antigen involved is HPA-1a(75% ) Sensitization to HPA-5b( 10-20% of cases) HPA-4 is important in Asian populations Mothers who possess the HLA-DR type DRB30101 represent more than 90% of cases of sensitization to HPA-1a

Clinical Features Typically infants are otherwise healthy full-term babies, who manifest symptomatic thrombocytopenia. Affected neonates have rates of ICH up to 10-20%. ICH tends to be severe and intraparenchymal. Death in utero may occur. Cases of HPA-5b incompatibility are milder.

suspect NAIT 1- platelet count <50,000/mm 2-No clinically apparent etiology of thrombocytopenia 3- Family history of transient neonatal thrombocytopenia It is important to investigate and establish the diagnosis because of the impact on subsequent pregnancies and hence their management

Lab: Laboratory evaluation should include: screening for HPA-1, 3, and 5 antibodies as well as HPA-4 antibodies in those of Asian descent HPA-9 and 15 are the next most common antigen incompatibilities

Other criteria: Additional useful clinical criteria for the diagnosis include: Normal non-pregnant maternal platelet count and negative history of maternal ITP Exclusion of alternate diagnoses Recovery of normal platelet count within 2-3 weeks History of NAIT in a prior pregnancy Increased megakaryocytes in bone marrow examination (if performed)

Treatment Platelet transfusion Intravenous immunoglobulin (IVIG) Methylprednisolone Head ultrasound follow-up until the platelet count is within the normal range

Guidelines for Platelet Transfusion <30,000: Transfuse all 30,000-49,000: Transfuse if: BW <1,500 g and ≤7 days old Clinically unstable

Recent diagnosis of NEC Concurrent coagulopathy Previous major hemorrhage (i.e., grade 3 or 4 IVH) Prior to surgical procedure Postoperative period (72 hours)

50,000-100,000 Transfuse if: Active bleeding NAIT with intracranial bleed Before or after neurosurgical procedures

Neonatal Autoimmune Thrombocytopenia NATP is due to a passive transfer of autoantibodies from mothers with ITP to their fetus. It may also be seen in association with SLE and lymphoproliferative states. NATP can be confusing with gestational thrombocytopenia(GTP).

GTP GTP is almost always mild is not associated with neonatal thrombocytopenia the maternal platelet count normalizes after delivery.

Thrombocytopenia in infants with NATP is usually less severe than NAIT . There is a lower risk of bleeding and ICH. The platelet count may be near normal at delivery but then fall to a clinically significant nadir over the next 13 days. The most frequently targeted antigens are the GPIIB/IIIA or GPIb/IX complexes.

Diagnosis Pregnant women with the following conditions may give birth to a neonate with autoimmune thrombocytopenia: History of previously affected infant. Mother who was previously splenectomized for ITP Mother with SLE, hypoythyroidism, preeclampsia—HELPP syndrome (hemolytic anemia, elevated liver enzymes, and low platelets). Maternal drug ingestion (e.g., thiazide) treatment

Treatment Treatment is required when the infant’s platelet count falls below 30,000/mm3 or if significant bleeding is present. The regimen is similar to that of NAIT, utilizing IVIG and IV methylprednisolon. The duration of neonatal thrombocytopenia is usually about 3 weeks.