New data on FII, FV, FIX and thrombomodulin defects: blood keeps clotting in normal and in peculiar ways

Abstract

ABSTRACTObjective: To present the clinical and laboratory implications of defects or variants of some clotting factors and of thrombomodulin that were discovered during the past few years.Methods: Data concerning new aspects of FII, FV, FIX and thrombomodulin defects were investigated. This involved the dysprothrombinemias, the East Texas or short FV disorder, a FIX defect and a thrombomodulin abnormality.Results: the recently reported clotting defects or variants are: (1) the thrombophilic dysprothrombinemias due to Arg596 mutations (Prothrombin Yukuhashi, Belgrade and Padua 2) which are characterized by absence of bleeding and presence of venous thrombosis; (2) the short FV defects due to Ser356Gly (FV East Texas) or Ala863Gly (FV Amsterdam) mutations characterized by a mild bleeding tendency with normal FV and other clotting factors, increased TFPI and no thrombosis; (3) the abnormal FIX (FIX Padua) due to the Arg338Leu mutation which is associated with high levels of FIX activity, lack of bleeding and venous thrombosis; (4) the thrombomodulin Cys537Stop mutation associated with a mild bleeding tendency despite normal clotting factors but increased plasma levels of soluble thrombomodulin and no thrombosis.Conclusions: these new coagulation defects have great implications in the clinical and laboratory approach to the coagulation disorders. They have demonstrated that a prothrombin defect may be associated with thrombosis, that a mild bleeding tendency may occur despite normal Factor V levels and that high levels of plasmatic thrombomodulin may be associated with mild bleeding.