Combined heterozygous plasminogen deficiency and factor V Leiden defect in the same kindred

Combined plasminogen deficiency and resistance to activated protein C defect (factor V Leiden) have been described in a few families and associated with a variable occurrence of thrombotic events. Here we describe a new family with thrombophilia and the presence of hypoplasminogenemia and factor V Leiden mutation. In addition, a brief review of the literature is presented. Nine patients belonging to this kindred underwent coagulation study for hereditary thrombophilia, which included plasminogen antigen and activity assays, an activated protein C resistance test, and genetic analysis for factor 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 hypoplasminogenemia, but she refused to be studied. The symptomatic father was heterozygous for factor V Leiden mutation, but presented with normal plasminogen levels. Among the available siblings investigated from the paternal side, resistance to activated protein C due to factor V Leiden mutation was found in three patients, one of whom experienced venous thromboembolism. Another uncle with a history of thrombotic disease showed no coagulation abnormalities. These findings together with the data from literature confirm the role of factor V Leiden as an independent risk factor for venous thromboembolism, whereas isolated hypoplasminogenemia does not seem to increase the risk for thrombosis. There is no clear evidence that the coinheritance of these two defects may be associated with an additional risk for thrombosis compared with the presence of factor V Leiden mutation alone.