ALLOIMMUNE THROMBOCYTOPENIA

Michael F. McNamara, DO

Sanford Maternal Fetal Medicine

No disclosures

Platelet Disorders in Pregnancy

Gestational thrombocytopenia Idiopathic thrombocytopenia (ITP) Thrombotic thrombocytopenia (TTP) Alloimmune thrombocytopenia (NAIT)

Gestational Thrombocytopenia

Dilution effect Increase of platelet destruction No therapy needed

Idiopathic Thrombocytopenia

1-3 / 1000 pregnancies Pregnancy not usually altering disease

course Therapy

SteroidsIVIGSplenectomy

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

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

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

Case Study

Presented at 14 weeks gestation Genetic counseling, history reviewed Same paternity as previous infants Father of baby not available for testing

(zygosity)

Case Study

Diagnostic testing (platelet antigen) Maternal

Blood HPA 1b/1b Fetal

Amniotic fluid HPA 1a/1b

Case Study

Preventative therapy IVIG 1 gram / kg weekly Prednisone 1mg /kg daily

Case Study

Antenatal Course Gestational diabetes Severe headaches with IVIG therapy Elevated liver enzymes due to percocet

use secondary to headaches

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

Alloimmune thrombocytopenia

Also know as Neonatal Alloimmune throbocytopenia (NAIT)

Incidence 0.2 -1 per 1000 Caucasian births

Maternal antigens against fetal platelets

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)

NAIT

Affected pregnancies Most serious complication Intracranial hemorrhage 10-20 % of

cases 25-50 % cases diagnosed prenatally Ultrasound findings of intracranial

hematoma, porencephalic cysts

Antepartum Preventive Therapy

Extremely High Risk Previous baby ICH in second trimester

High riskPrevious baby ICH in third trimester

Moderate riskPrevious baby with thrombocytopenia but no

ICH

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

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

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

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

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

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

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

Summary

NAIT cause of neonatal thrombocytopenia

Index case possibly severe problems such as ICH

Decrease complications with in utero therapy, IVIG, prednisone