Familial clustering of defective release of t‐PA

91 unrelated patients with idiopathic or familial deep vein thrombosis (DVT) and 72 (34 with DVT) relatives from 26 families were screened for hypofibrinolysis by measuring tissue plasminogen activator antigen (t-PA:Ag) after venous occlusion (VO) for 10 and 20 min and by measuring t-PA inhibitor activity (PAI) at rest. 21 healthy subjects served as controls. Defective release of t-PA:Ag was found in eight out of the 91 patients (9%). A partial family study of six of these eight patients was performed. This study included 10 family members with and 21 without DVT. A defective release of t-PA:Ag was found in 50% (5/10) of the family members with DVT, which is significantly more frequent than the 9% (8/91) prevalence in the unrelated patients (P less than 0.001). Furthermore, 24% (5/21) of asymptomatic members of these families also had defective release of t-PA:Ag. In the 18 families where the propositus had a normal level of t-PA:Ag, none of the 24 studied family members with DVT had defective release of t-PA:Ag. In contrast to the defective release of t-PA:Ag, increased basal level of PAI did not show familial clustering. In conclusion, low release of t-PA during VO shows familial clustering in a proportion of the cases.