The clinical impact of MTHFR polymorphism on the vascular complications of sickle cell disease

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 percent 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 percent) and there was no prothrombin G20210A variant. MTHFR 677TT polymorphism was detected in 1 patient (1.8 percent) and the heterozygous form 677TC was observed in 18 patients (34 percent, 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.

Tuberculosis: an uncommon cause of cerebral venous thrombosis?

Several infectious etiologies are related to cerebral venous thrombosis (CVT), but a review of literature showed only few cases related to tuberculosis (TB), and only one with neurological manifestations.We report an unusual case of CVT related to TB and mutation in prothrombin gene. A 38-man black presented abrupt right hemiparestesis, and hemiparesis. Investigations revealed CVT. Cerebral spinal fluid (CSF) examination evidenced an infection by Mycobacterium. He was heterozygous for G20210A prothrombin mutation. Probably, hypercoagulability mechanisms of TB, added to mutation of prothrombin gene increase the risk of CVT.

As mais variadas etiologias infecciosas estão relacionadas a trombose venosa cerebral (TVC), mas revisando-se a literatura há apenas poucos relatos de casos que se devem à tuberculose (TB), sendo que em apenas um deles havia manifestações no sistema nervoso central.Relatamos um caso de TVC associado a TB e a mutação do gene da protrombina. Homem 38 anos, negro, apresentou hemiparestesia de instalação súbita à direita, evoluindo com hemiparesia homolateral. Durante a internação, foi coletado líquor que evidenciou infecção por micobactéria. A pesquisa de trombofilias mostrou positividade somente para mutação do gene da protrombina(G20210A). Provavelmente os mecanismos de hipercoagulabilidade intrínsecos à tuberculose somados à mutação do gene da protrombina, potencializam o risco de TVC.

Avaliaçäo clínica e laboratorial de pacientes em uso de anticoagulantes orais / Clinical and Laboratory Management of Patients Under Oral Anticoagulation

Objetivo - Avaliar o acompanhamento clínico e laboratorial de pacientes em uso de drogas antivitamina K(AVK). MÉTODOS - Foram avaliados, retrospectivamente, 952 consultas ambulatoriais de 100 pacientes em uso de AVK, durante 7,6 meses. Havia 56 homens e 44 mulheres, 54 pacientes com obstruçäo arterial aguda, 34 com troboembolismo venoso e 12 com cardiopatia. O nível de anticoagulaçäo foi medido pelo tempo de protrombina expresso em razäo normalizada internacional (RNI). RESULTADOS - Nível adequado de anticoagulaçäo foi observado em 59 "por cento" das consultas dos 73 pacientes considerados estáveis, com intervalo entre consultas maior do que 3 semanas. Os 27 pacientes instáveis tinham 36 "por cento" das consultas com RNI adequado. Anticoagulaçäo insuficiente ocorreu por uso irregular (22 por cento), dieta rica em vitamina (19 por cento) e dose insuficiente (16 por cento). Quatro pacientes tiveram sangramento sem gravidade e näo houve recorrência da trombose durante o período de observaçäo. CONCLUSÄO - O controle clínico e laboratorial, através do RNI, é fundamental para evitar complicaçöes hemorrágicas ou trombóticas em pacientes que necessitam de anticoagulaçäo oral.

Leishmaniose visceral e sindrome da imunodeficiencia adquirida (SIDA): relato de um caso / Visceral leishmaniais and acquired immunodeficiency syndrome (AIDS) : case report

Os autores descrevem um caso de associacao de leishmaniose visceral, SIDA e provavel tuberculose disseminada. Discutem a possibilidade de associacao desta protozoonose e infeccao pelo virus da Imunodeficiencia Adquirida (VIH) principalmente pelo aumento de prevalencia de infeccao pelo VIH em areas endemicas para o calazar. A presenca de imunodepressao pelo VIH possibilita manifestacoes de agentes oportunistas muitas vezes associados e relacionados com as endemias prevalentes nestas regioes de subdesenvolvimento.