Antigen-positive platelet transfusion in neonatal alloimmune thrombocytopenia (NAIT)

Abstract

Neonatal alloimmune thrombocytopenia (NAIT) is a fetomaternal incompatibility most commonly induced by maternal anti-HPA-1a, IgG alloantibodies against a polymorphic epitope of the glycoprotein IIb/ IIIa complex in approximately 97.5% of white patients. Current guidelines recommend transfusion of immunologically compatible platelets to prevent cerebral hemorrhage, the most severe complication in affected newborns. Such platelet concentrates, however, are often not readily available. In a retrospective analysis in German and Canadian centers, 27 newborns with NAIT were identified who received platelets from random donors. Unexpectedly, 24 of 27 newborns showed an increase above a threshold of 40 ؋ 10 9 platelets per liter, with moderate (n ‫؍‬ 8) or significant (n ‫؍‬ 16) platelet count increments (more than 80 ؋ 10 9 /L). We conclude that transfusion of platelet concentrates from random donors is an appropriate strategy in the management of unexpected, severe NAIT predominantly in first pregnancies, pending the availability of compatible platelets. IntroductionNeonatal alloimmune thrombocytopenia (NAIT) is an immunemediated fetomaternal incompatibility. It occurs after maternal alloimmunization against polymorphic epitopes on fetal platelet glycoproteins (GPs) and diaplacental transfer of maternal IgG alloantibodies to the fetus. Alloantibodies implicated in NAIT are directed against antigens on GP IIb/IIIa, Ib/IX, Ia/IIa, and CD109. The most common antibody is anti-HPA-1a (originally referred to as anti-Zw(a) 1 ), which accounts for about 75% of cases. 2 A leucine-proline polymorphism of GP IIIa of amino acid 33 is the molecular basis of the HPA-1a/1b polymorphism. 3 NAIT has an incidence of 1:1000 to 1:2000 births in white populations and may occur if a pregnant, HPA-1b/1b homozygous woman is immunized with HPA-1a-positive platelets by her fetus. 4,5 NAIT is a self-limiting and transient disorder with an excellent prognosis in the absence of cerebral bleeding. Approximately 42% of newborns with NAIT are born to primiparous women. 6 Prenatal screening for maternal platelet-specific alloantibodies has not been established, 5 and the birth of a first affected child therefore occurs unexpectedly. Because a significant proportion of untreated newborns with NAIT (approximately 7% to 14% 6,7 ) are affected by cerebral hemorrhage in the first days of life, a liberal attitude toward platelet transfusion of the severely thrombocytopenic newborn is considered appropriate. 8 While intravenous ␥-globulin (IVIG) has been shown to be of some benefit in the antenatal management of alloimmune thrombocytopenia, 9 high-dose IVIG can only be recommended as a complementary treatment modality in the management of NAIT because of the delayed rise in platelet counts and limited evidence from a small series of cases. 10,11 Currently, antigen-negative platelets are considered optimal for the prevention of hemorrhage in newborns with suspected NAIT. 8,12 To meet this need, transfusion services have attempted to stock HPA-1a-negative an...

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“…(2, 40) may be more efficient than fetal platelet transfusion. Platelet transfusion, however, may be critical to controlling bleeding after birth, as suggested from both clinical and animal studies (1,3,17,62). These findings may shift the prevailing view and advance our understanding of the pathogenesis of FNAIT and may contribute markedly to improvements in the clinical management of this life-threatening disease.…”

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Inhibition of HPA-1a alloantibody-mediated platelet destruction by a deglycosylated anti–HPA-1a monoclonal antibody in mice: toward targeted treatment of fetal-alloimmune thrombocytopenia

“…4,8 After delivery, FNAIT can be treated by platelet transfusion. 9,10 However, in almost 50% of affected cases, intracranial hemorrhage occurs before delivery, sometimes as early as in the 20th week of gestation. 8,11,12 This makes antenatal treatment essential to avoid deleterious consequences.…”