Combined heterozygous plasminogen deficiency and factor V Leiden defect inthe same kindred

Combined plasminogen deficiency and resistance to activated protein C defec t (factor V Leiden) have been described in a few families and associated wi th a variable occurrence of thrombotic events. Here we describe a new famil y with thrombophilia and the presence of hypoplasminogenemia and factor V L eiden mutation. In addition, a brief review of the literature is presented. Nine patients belonging to this kindred underwent coagulation study for he reditary thrombophilia, which included plasminogen antigen and activity ass ays, an activated protein C resistance test, and genetic analysis for facto r V Leiden mutation and for prothrombin variant 20210A. The proposita, a 40 -year-old asymptomatic female with a family history of thrombotic diathesis , was affected by heterozygous plasminogen deficiency. Hypoplasminogenemia was found also in her two sisters, in one instance associated with factor V Leiden mutation. The mother was the putative carrier of hypoplasminogenemi a, bur she refused to be studied. The symptomatic father was heterozygous f or factor V Leiden mutation, but presented with normal plasminogen levels. Among the available siblings investigated from the paternal side, resistanc e to activated protein C due to factor V Leiden mutation was found in three patients, one of whom experienced venous thromboembolism. Another uncle wi th a history of thrombotic disease showed no coagulation abnormalities. The se findings together with the data from literature confirm the role of fact or V Leiden as an independent risk factor for venous thromboembolism, where as isolated hypoplasminogenemia does not seem to increase the risk for thro mbosis. Their is no clear evidence that the coinheritance of these two defe cts may be associated with an additional risk for thrombosis compared with the presence of factor V Leiden mutation alone.