Familial clustering of high factor VIII levels in patients with venous thromboembolism

High levels of factor VIII (FVIII) but not von Willebrand factor (vWF) are known to increase the risk for venous thromboembolism, Whether high FVIII l evels originate from hereditary defects or from acquired conditions remains unanswered. The objective of our study was to investigate whether there is evidence for familial clustering of elevated FVIII levels in families in w hich greater than or equal to1 member has been affected by a thromboembolic event and had reproducibly high FVIII levels. We investigated FVIII levels in 361 patients with previous venous thromboembolism. FVIII levels were me asured by a chromogenic assay; the cutoff value was defined as the 98th per centile of FVIII plasma levels of 266 blood donors. vWF levels were determi ned by an enzyme immunoassay. After exclusion of known causes of FVIII elev ation, such as the acute thrombotic event itself; inflammation; malignancy; liver, renal, or vascular disease; surgery; or pregnancy, we included 17 p atients with unexplained, reproducibly high FVIII levels. The investigation was also extended to these patients' relatives. Multiple regressive analys is of blood donors and asymptomatic family members showed that the affiliat ion with a family in which 1 member suffered from venous thromboembolism an d had reproducibly high FVIII levels is the second most important predictor for FVIII levels. Familial clustering was analyzed by the Houwing-Duisterm aat familial aggregation test. After adjustment for the influence of age, s ex, blood group, and vWF, FVIII levels were significantly (P=0.038) cluster ed within families. In conclusion, FVIII levels seem to be familially deter mined in families in which a member showed high FVIII levels after previous venous thromboembolism.