Transcript Alloimmune Thrombocytopenia

Michael F. McNamara, DO
Sanford Maternal Fetal Medicine
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No disclosures
Platelet Disorders in Pregnancy
Gestational thrombocytopenia
 Idiopathic thrombocytopenia (ITP)
 Thrombotic thrombocytopenia (TTP)
 Alloimmune thrombocytopenia (NAIT)
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Gestational Thrombocytopenia
Dilution effect
 Increase of platelet destruction
 No therapy needed
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Idiopathic Thrombocytopenia
1-3 / 1000 pregnancies
 Pregnancy not usually altering disease
course
 Therapy
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 Steroids
 IVIG
 Splenectomy
Thrombotic Thrombocytopenia
Purpura (TTP)
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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
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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
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Case Study
Presented at 14 weeks gestation
 Genetic counseling, history reviewed
 Same paternity as previous infants
 Father of baby not available for testing
(zygosity)
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Case Study
Diagnostic testing (platelet antigen)
 Maternal
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 Blood HPA 1b/1b
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Fetal
 Amniotic fluid HPA 1a/1b
Case Study
Preventative therapy
 IVIG 1 gram / kg weekly
 Prednisone 1mg /kg daily
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Case Study
Antenatal Course
 Gestational diabetes
 Severe headaches with IVIG therapy
 Elevated liver enzymes due to percocet
use secondary to headaches
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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
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Alloimmune thrombocytopenia
Also know as Neonatal Alloimmune
throbocytopenia (NAIT)
 Incidence 0.2 -1 per 1000 Caucasian
births
 Maternal antigens against fetal platelets
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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)
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NAIT
Affected pregnancies
 Most serious complication
 Intracranial hemorrhage 10-20 % of
cases
 25-50 % cases diagnosed prenatally
 Ultrasound findings of intracranial
hematoma, porencephalic cysts
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Antepartum Preventive Therapy
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Extremely High Risk
 Previous baby ICH in second trimester
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High risk
 Previous baby ICH in third trimester
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Moderate risk
 Previous 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
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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
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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
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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
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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
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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
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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
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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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