Sickle cell disease (SCD) is one of the most common inherited diseases in the world and the patients present notorious clinical heterogeneity. It is known that patients with SCD present activation of the blood coagulation and fibrinolytic systems, especially during vaso-occlusive crises, but also during the steady state of the disease. We determined if the presence of the factor V gene G1691A mutation (factor V Leiden), the prothrombin gene G20210A variant, and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism may be risk factors for vascular complications in individuals with SCD. We studied 53 patients with SCD (60% being women), 29 with SS (sickle cell anemia; 28 years, range: 13-52 years) and 24 with SC (sickle-hemoglobin C disease; 38.5 years, range: 17-72 years) hemoglobinopathy. Factor V Leiden, MTHFR C677T polymorphism, and prothrombin G20210A variant were identified by PCR followed by further digestion of the PCR product with specific endonucleases. The following vascular complications were recorded: stroke, retinopathy, acute thoracic syndrome, and X-ray-documented avascular necrosis. Only one patient was heterozygous for factor V Leiden (1.8%) and there was no prothrombin G20210A variant. MTHFR 677TT polymorphism was detected in 1 patient (1.8%) and the heterozygous form 677TC was observed in 18 patients (34%, 9 with SS and 9 with SC disease), a prevalence similar to that reported by others. No association was detected between the presence of the MTHFR 677T allele and other genetic modulation factors, such as alpha-thalassemia, ß-globin gene haplotype and fetal hemoglobin. The presence of the MTHFR 677T allele was associated with the occurrence of vascular complications in SCD, although this association was not significant when each complication was considered separately. In conclusion, MTHFR C677T polymorphism might be a risk factor for vascular complications in SCD.

A deficiência de antitrombina III (ATIII) é observada na hepatopatia grave e pode ser decorrente da redução de síntese ou de consumo aumentado, o que poderia ser compensado com o uso de concentrado de ATIII. OBJETIVO. Avaliar a eficiência da administração de uma dose fixa de concentrado de ATIII, em pacientes com hepatopatia descompensada com distúrbio da hemostasia. CASUÍSTICA E MÉTODO. Foram avaliados seis pacientes, com idade média de 44 anos, variando de 14 a 63 anos, portadores de cirrose (quatro de etiologia alcoólica, um viral e um doença de Wilson), com alteração de pelo menos dois dos parâmetros da hemostasia (TP > 1,40, TTPA > 1,25, fibrinogênio < 1,5g/L, plaquetas < 80.000/mm³). A média do nível de albumina foi de 2,6g/dL (1,9 a 3,8g/dL). O concentrado de ATIII (Kybernin®) foi administrado na dose de 50U/kg, em dias alternados. Foi colhido sangue antes da primeira infusão, 4 horas após e, depois, diariamente, antes da infusão do dia, para medida da ATIII plasmática (amidolítico). Nenhum paciente recebeu hemoderivados. RESULTADOS.As médias da dosagem de ATIII foram: inicial = 35,8%, 4 horas = 56,2%*, 2 dias = 48,7%*, 4 dias = 45,7%* e 8 dias = 42,3%. Após a infusão houve elevação significante dos níveis de ATIII (* = p < 0,02, teste de Friedman), que se manteve até o 4º dia. Não houve alteração dos demais parâmetros de coagulação. CONCLUSÕES. O uso de concentrado de ATIII na dose utilizada é suficiente para elevar os níveis desse inibidor na hepatopatia; entretanto, com essa dose não se obteve normalização de seus níveis. Esses dados sugerem que doses mais elevadas devem ser usadas em pacientes com hepatopatias graves, que apresentam não apenas redução de síntese, mas aumento de consumo dos fatores da coagulação e de seus inibidores.

BACKGROUND. Patients with severe hepatic failure present acquired deficiency of antithrombin III (ATIII) owing to reduced synthesis associated with intravascular activation of blood coagulation, which may be corrected by ATIII infusion. OBJECTIVE. The aim of this uncontrolled trial was to verify the effect of a standard dose of ATIII concentrate (Kybernin™ ), that is, 50U/kg of body weight per day, every 2 days, on ATIII levels in patients with severe hepatic failure and hemostatic imbalance. PATIENTS AND METHODS. Six cirrhotic patients were studied: mean age of 44 years (14 to 63 years), who presented at least 2 abnormal coagulation tests (PT > 1.40, APTT > 1.25, Fibrinogen < 1.5g/dL, Platelet count < 80,000/mm³). Mean serum albumin was 2.6g/dL (1.9 to 3.8g/dL). Blood was drawn before infusion, 4h after the first infusion, and just before the next infusion. ATIII levels were measured by amidolytic method. RESULTS. Mean ATIII levels were: initial = 35.8%, 4th h = 56.2%*, 2th d = 48.7%*, 4 d th = 45.7%*, and 8th d = 42.3%. ATIII levels increased significantly after infusion of this standard dose in all patients, although they have not been fully corrected (Friedman test, * p < 0.02), which has been sustained till the 4th day. There was no improvement on the clinical outcome. CONCLUSIONS. These findings suggest that doses of ATIII concentrate higher than 50U/kg/infusion must be administered to patients with severe hepatic failure, to guarantee normal levels of the inhibitor, in order to verify its influence on the hemostatic mechanism.