Estudo dos polimorfismos dos sistemas de aloantigenos plaquetarios humanos (HPA) em doenças hemorragicas e tromboticas

AUTOR(ES)
DATA DE PUBLICAÇÃO

2000

RESUMO

Human platelet alloantigens (HP A) are polymorphic sequencies of the platelet membrane glycoproteins, which are associated to immune platelet disorders, such as neonatal alloimmune thrombocytopenia (NAIT), post-transfusion purpura (PTP), platelet transfusion reftactoriness and may be to related to occlusive vascular disease. Several distinct biallelic systems are known, and a heterogeneous distribution of HP A alleles has been described among distinct ethnic groups. In this study, the most trequently HP A systems involved in alloimmunization were determined by polymerase chain reaction, in three distinct ethnic groups which compose Brazilian population: Caucasians, Blacks and Indians. The HP A-I to -5 allele trequencies obtained between Caucasian and Blacks were similar. These data contrast with those reported for similar ethnic groups in other countries. Among the Indians, no b allele (low ftequency allele) ofthe HPA-l, -4 and -5 systems were identified. To evaluate the possible clinical impact of these data in the development of NAIT, we carried out a screening for neonatal thrombocytopenia and its relation to maternal-fetal genotype mismatch. Thrombocytopenia was determined in 1% of 12,714 uns~lected newborns trom Campinas in which 0.11% (13 cases) presented platelet count less than 50 x 109/L. Two newborns with thrombocytopenia developed a severe bleeding disorder, whereas the majority was asymptomatic. Maternal-fetal clinical conditions related to the development of thrombocytopenia were presented in almost half of the cases. The risk for neonatal thrombocytopenia due to alloimmunization to HP A systems was investigated by genotype mismatch between mother and newbom. The results showed that 50% of genotypes revealed a matemal-newbom mismatch in both control and thrombocytopenic group. The most common system likely to be associated with alloimmune thrombocytopenia is the HP A-3 system, followed by the HP A-2 system. In conelusion, neonatal thrombocytopenia is common among unselected newboms and the development of thrombocytopenia can not be predicted by the genotype mismatch.The role of HP A in the risk for an autoimmune platelet disease was carried out among adults with immune thrombocytopenic purpura (ITP). The result of this study was the detection of a two-fold higher ftequency of allele HP A-Sb among acute-ITP patients compared to a control group. These data suggest that the presence of HP A-Sb allele could be related to an increased risk of adults with acute ITP. Finally, we determined role of HP A-I system alleles as an inherited risk factor for venous or arterial disease. Platelet carrying the HPA-lb protein has a higher aggregation response to fibrinogen and may result in a elot resistant to physiological removal. Two groups of patients with venous thrombosis or arterial disease were evaluated. No association was found between HP A-I b allele and the risk for either venous thrombosis or arterial disease. Althóugh the prevalence ofHPA-lb alIeI e among 137 patients with myocardial infarction (1 1) did not differ ftom that observed in the control group (12.7% vs. 14.6%), the prevalence of the allele HP A-I b was higher among young patients than older patients (p=O.OI4). Unlike conventional risk factors, HPA-lb allele does not represent a riskfactor for venous thrombosis, systemic arterial disease or MI. The higher prevalence of HP A-I b allele among young patients with MI could result ftom a distinct pathogenesis of the early onset of the coronary artery disease

ASSUNTO(S)

população hematologia

ACESSO AO ARTIGO

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