RESUMEN
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.
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Anemia de Células Falciformes/genética , Factor V/genética , /genética , Polimorfismo Genético , Enfermedades Vasculares Periféricas/etiología , Protrombina/genética , Alelos , Anemia de Células Falciformes/complicaciones , Marcadores Genéticos , Reacción en Cadena de la Polimerasa , Factores de RiesgoRESUMEN
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, beta-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.
Asunto(s)
Anemia de Células Falciformes/genética , Factor V/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Enfermedades Vasculares Periféricas/etiología , Polimorfismo Genético , Protrombina/genética , Adolescente , Adulto , Anciano , Alelos , Anemia de Células Falciformes/complicaciones , Femenino , Marcadores Genéticos , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Reacción en Cadena de la Polimerasa , Factores de RiesgoRESUMEN
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.
Asunto(s)
Adulto , Humanos , Masculino , Trombosis Intracraneal/microbiología , Trombosis de la Vena/microbiología , Tuberculosis del Sistema Nervioso Central/complicaciones , Imagen por Resonancia Magnética , Mutación Puntual , Protrombina/genéticaAsunto(s)
Trombosis Intracraneal/genética , Mutación Puntual , Protrombina/genética , Adulto , Brasil/epidemiología , Estudios de Casos y Controles , Factor V , Femenino , Humanos , Trombosis Intracraneal/epidemiología , Trombosis Intracraneal/etiología , Masculino , Epidemiología Molecular , Factores de Riesgo , Trombosis de la Vena/epidemiología , Trombosis de la Vena/etiología , Trombosis de la Vena/genéticaRESUMEN
Fasting total homocysteine (tHcy) and the methylenetetrahydrofolate reductase (MTHFR) C677T mutation were evaluated in 91 patients with venous thromboembolism and without acquired thrombophilia, and in 91 age-matched and sex-matched controls. Hyperhomocysteinemia was detected in 11 patients (12.1%) and in two controls (2.2%), yielding an odds ratio (OR) for venous thrombosis of 6.1 [95% confidence interval (CI), 1.3-28.4]. After excluding 21 patients and four controls with other known genetic risk factors for venous thrombosis, the OR was not substantially changed (7.0; 95% CI, 1.5-33.1). The prevalence of the MTHFR 677TT genotype was not significantly different in patients (9.9%) and in controls (5.5%), with an OR for venous thrombosis of 1.8 (95% CI, 0.6-5.8). Subjects with the MTHFR 677TT genotype showed higher levels of tHcy compared with the 677CC genotype in patients (P = 0.010) and in controls (P = 0.030). In conclusion, we found that fasting hyperhomocysteinemia is a risk factor for venous thrombosis in patients without known acquired thrombophilia and other genetic risk factors for venous thrombosis. Although tHcy levels are significantly higher in those homozygous for the MTHFR C677T mutation, this genotype does not increase the thrombotic risk in our study population.
Asunto(s)
Sustitución de Aminoácidos , Hiperhomocisteinemia/epidemiología , Mutación Missense , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH/genética , Mutación Puntual , Trombofilia/epidemiología , Trombosis de la Vena/epidemiología , Regiones no Traducidas 3'/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Niño , Ayuno/sangre , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Metilenotetrahidrofolato Reductasa (NADPH2) , Persona de Mediana Edad , Oportunidad Relativa , Polimorfismo Genético , Regiones Promotoras Genéticas/genética , Protrombina/genética , Factores de Riesgo , Trombofilia/sangre , Trombofilia/genética , Trombosis de la Vena/etiologíaRESUMEN
The authors report the case of a chronic myeloid leukemia (CML) patient submitted to allogenic bone marrow transplantation, who had probably never entered complete remission. The disease was reactivated as a granulocytic sarcoma, next to a platinum plate installed to correct a tibia fracture 11 years earlier. Its final event was a myeloid Ph1 + blastic crisis that was unsuccessfully treated with high doses of sc interferon and citarabine.
Asunto(s)
Trasplante de Médula Ósea/efectos adversos , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Adulto , Antineoplásicos/uso terapéutico , Crisis Blástica/tratamiento farmacológico , Citarabina/uso terapéutico , Resultado Fatal , Femenino , Humanos , Interferones/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/etiología , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Leucemia Mieloide/etiología , RecurrenciaRESUMEN
PURPOSE: To evaluate the response of 73 patients with antivitamin K (AVK) overdose to 3 different therapeutic regimens. METHODS: Seventy three patients were evaluated in 94 occasions: group A (N = 32), consisted of drug withdrawal for 2 days followed by reduced dosage; group B (N = 37), drug withdrawal and reassessment within 4 days; group C (N = 25), oral administration of vitamin K. Therapeutic range was set between INR-values of 2 and 4. RESULTS: Reversal regimens did not result in differences among 61 patients who had initial INR < 8 (chi 2 = 2.352, p = 0.671). There were more patients bellow therapeutic range in group C (N = 14) than group B (N = 19) (chi 2 = 9.998, p = 0.007). After intervention, 7 patients in group B still had INR > 4, but 5 of them were bellow 4.5, without increased bleeding risk. There were 10 patients in group C bellow therapeutic range, 6 of them with INR < 1.6, with risk of thromboembolism. Thirteen patients bled, but none required transfusion. CONCLUSION: Reversal of excessive oral anticoagulation can be safely performed by initial withdrawal of the drug, followed by lower doses. Vitamin K administration may lead to INR bellow the therapeutic range. This should be reserved for patients with high INR or in the presence of bleeding.
Asunto(s)
Anticoagulantes/efectos adversos , Hemorragia/prevención & control , Tromboembolia/tratamiento farmacológico , Vitamina K/antagonistas & inhibidores , Administración Oral , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Sobredosis de Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tromboembolia/prevención & controlRESUMEN
PURPOSE: To evaluate the clinical and laboratory management of patients taking anti-vitamin K drugs (AVK). METHODS: We studied retrospectively 952 visits of 100 outpatients taking AVK drugs for 7.6 months. There were 56 men and 44 women, 54 patients had acute arterial occlusion, 34 presented venous thromboembolism and 12 had cardiopathy. Anticoagulation level was estimated by the prothrombin time reported as international normalized ratio (INR). RESULTS: Seventy-three patients were considered stable, as they had one visit every at least 3 weeks, and their INR was within the therapeutic range in 59% of their visits, whereas 27 patients were less stable and had 36% of their visits within the therapeutic range. Insufficient anticoagulation was due to poor compliance (22%), vitamin K rich diet (19%) and underdosage (16%). Four patients presented minor bleedings, and there was no recurrence of thromboembolism. CONCLUSION: Careful clinical and laboratory management, using the INR, are necessary to avoid hemorrhage and thrombotic complications in patients taking oral anticoagulants.
Asunto(s)
Anticoagulantes/uso terapéutico , Coagulación Sanguínea/efectos de los fármacos , Tromboembolia/tratamiento farmacológico , Vitamina K/antagonistas & inhibidores , Administración Oral , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tiempo de Protrombina , Estudios RetrospectivosRESUMEN
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.
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Pacientes Ambulatorios , Anticoagulantes/uso terapéutico , Coagulación Sanguínea , Enfermedades Cardiovasculares/tratamiento farmacológico , Anciano de 80 o más Años , Estudios RetrospectivosRESUMEN
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.
Asunto(s)
Humanos , Adulto , Leishmaniasis Visceral/diagnóstico , Síndrome de Inmunodeficiencia Adquirida/diagnóstico , Tuberculosis/diagnóstico , Diagnóstico Diferencial , Leishmaniasis Visceral/patología , Infecciones OportunistasRESUMEN
This is a case report that describe an association of AIDS, visceral leishmaniasis and probable disseminated tuberculosis. Due to the spread of AIDS in developing areas worldwide this association would be more frequently, seen on subjects from endemic areas where this protozoonosis is prevalent. More than one opportunistic infection related with the endemic diseases of the developing regions can be associated with those immunocompromised patients.