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...

SummaryConflicting results of an association between the human platelet antigen 1b (HPA-1b or PlA2) allele and the risk of myocardial infarction and coronary artery disease have been reported. To assess the reason for this discrepancy, we determined the HPA-1 genotype in 298 men who had undergone coronary angiography, including 124 individuals with myocardial infarction, 83 individuals with coronary artery disease but no history of myocardial infarction, and 91 control patients. Among patients with acute or recent onset myocardial infarction (<1 year), the prevalence of HPA-1b was higher than among patients with coronary artery disease but without myocardial infarction (33 percent vs. 14 percent, p = 0.016). In patients under 60 years of age this difference was even more pronounced (45 percent vs. 15 percent, p = 0.003). Unlike conventional risk factors HPA-1b does not represent a risk factor for coronary artery disease itself but appears to be associated with increased platelet thrombogenicity.

In fetal alloimmune thrombocytopenia (FAIT) the fetus is threatened by intracranial haemorrhage (ICH); therefore early diagnostic and therapeutic intervention is required. We followed the clinical course of a 30-year-old woman during her fifth pregnancy after she had given birth to a child with alloimmune thrombocytopenia due to anti-Zwa. The fetus was monitored by 13 fetal blood samplings (FBS) always followed by transfusion of either maternal or compatible donor platelets. Intravenous immunoglobulin (ivIg) treatment of the mother was begun at 20 weeks of gestation when the fetal platelet count was 36 x 10(9)/l. The fetal platelets were typed Zwa positive by DNA analysis. Despite 11 weeks of maternal ivIg treatment fetal platelet counts progressively declined to 6 x 10(9)/l and ICH occurred. Subsequently, the fetus was successfully managed by intrauterine platelet transfusions at shorter intervals (3-5 days) and elective Cesarean section was carried out at 35 weeks of gestation. We conclude that maternal ivIg treatment does not prevent ICH in FAIT. The treatment of choice for severely affected cases is serial FBS combined with transfusion of compatible platelets.

Our data suggest that HLA-DR15 (B1*15011) might constitute an important genetic factor for the elimination of the hepatitis C virus in Germany.

As the host's immune response may determine the course of hepatitis C virus (HCV) infection, we studied the humoral and cellular immune responses to HCV-related antigens in subjects with different outcomes of HCV infection. Lymphoproliferative responses and circulating antibodies to a panel of HCV core- and E1-related 25-mer peptides were examined in 10 healthy anti-HCV-seropositive blood donors (group A) and in 29 patients with chronic hepatitis C (group B). In addition, cellular recognition of recombinant HCV proteins (core, NS3, NS4A, NS5A, NS5B) were investigated. In group A, stronger T-cell responses were detected against both HCV proteins (core, P = .03; NS4, P = .005; NS5B, P = .03) and peptides. Proliferation was induced by the same peptides in each group, defining at least five distinctive epitopes within core (amino acids [aa] of 20-44, aa 39-63, aa 79-103, aa 118-152 and aa 148-172) and three regions within E1(aa 198-252, aa 308-372, and aa 368-392). Subjects with strong T-cell responses had low or no detectable levels of peptide-specific antibodies, and vice versa. In particular, T-cell responses were more common in group A; B-cell responses were more common in group B. From our data, we conclude that a benign course of HCV infection may be the consequence of the effective activation of T-helper lymphocytes.