Atrial fibrillation (AF) renders individual patients at risk for development of an atrial thrombus. The aim of this study was to determine clinical and echocardiographic factors influencing the risk of left atrial thrombosis (LAT) in patients with persistent nonvalvular AF. Genetic variants encoding haemostatic factors have been also assessed for putative association with LAT. In the cross-sectional study, a total of 212 patients (132 males and 80 females) with nonvalvular persistent AF (duration range 48 h-90 days) have been selected. LAT was visualized by transesophageal echocardiography. The FGB G(-455)A, PAI-1 4G/5G, F5 C(-224)T, and F5 R506Q genetic markers were tested using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. To reveal independent factors contributing to the thromboembolic risk in AF, a multivariate logistic model was applied. LA thrombi were found in 44 out of 212 subjects (21%). LAT was more frequently observed in patients at age >75 years (P 75 years, LVEF
Adaptation to hypoxia is critical for survival and regulates multiple processes, including erythropoiesis and vasculogenesis. Chuvash polycythemia is a hypoxia-sensing disorder characterized by homozygous mutation (598C>T) of von Hippel-Lindau gene (VHL), a negative regulator of hypoxia sensing. Although endemic to the Chuvash population of Russia, this mutation occurs worldwide and originates from a single ancient event. That VHL 598C>T homozygosity causes elevated normoxic levels of the transcription factor hypoxia inducible factor-1alpha (HIF-1alpha), serum erythropoietin and hemoglobin is known, but the disease phenotype has not been documented in a controlled manner. In this matched cohort study, VHL 598C>T homozygosity was associated with vertebral hemangiomas, varicose veins, lower blood pressures, and elevated serum vascular endothelial growth factor (VEGF) concentrations (P T homozygotes than in controls, erythropoietin response to hypoxia was identical. Thus, Chuvash polycythemia is a distinct VHL syndrome manifested by thrombosis, vascular abnormalities, and intact hypoxic regulation despite increased basal expression of hypoxia-regulated genes.
AIM: To identify prothrombotic risk profiles in children and adolescents referred to a regional coagulation centre in southern Sweden for a first thrombotic event. METHODS: One hundred and twenty-eight consecutive children and adolescents (newborn to 20 y) referred for evaluations of a first episode of venous thrombosis were investigated. Clinical data were collected retrospectively, and the following variables were investigated: protein C, protein S, antithrombin; resistance to activated protein C; the genotypes FV-G1691A, F II-G20210A, MTHFR-C677T, MTHFR- A1298C; coagulation factors VIII and XI. RESULTS: 104/128 subjects (81%) had identifiable acquired risk factors, most often indwelling catheters and hormone therapy. Predisposing genetic factors related to thromboembolic events were revealed in 53/83 (64%) of subjects who agreed to follow-up blood sampling, and 17/83 (20%) had two or more inherited risk factors. Combinations of genetic and acquired risk factors were identified in 45/83 (54%) of the subjects, and 77/83 (93%) had at least one such risk factor. Both sexes had one peak in frequency at less than 1 y of age and then an increase during adolescence, more in females than in males. Plasma values for coagulation factors VIII and XI were age appropriate and showed a normal Gaussian distribution. CONCLUSION: This study identified prothrombotic risk profiles in almost all children and adolescents with venous thrombosis, which underlines the importance of careful evaluation of genetic and acquired risk factors.