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

3. 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)

4. 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

5. 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.

6. 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.

7. 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

8. 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.

9. 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

10. 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

11. 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)

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

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

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

15. 50, ,000
Transfuse if:
Active bleeding
NAIT with intracranial bleed
Before or after neurosurgical procedures

16. 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).

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

18. 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.

19. 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

20. 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.