New clotting disorders that cast new light on blood coagulation and may play a role in clinical practice

Recently several variants of clotting factors have shown a peculiar behavior so that they appear as new defects. The factors involved are FII, FV and FIX. Prothrombin deficiency is usually associated with bleeding. Recently a few prothrombin abnormalities involving Arg396 mutations, have been demonstrated to show antithrombin resistance with the consequent appearance of a thrombophilic state and venous thromboses in young age. The same is true for an abnormal FIX (FIX Padua). The thrombotic manifestations in the latter condition are also venous. The abnormal FIX (FIX Padua) is characterized by a great increase in FIX activity whereas FIX antigen is only slightly increased. The condition is due to an Arg338Lys mutation. The increased intrinsic clotting activity of this abnormal FIX is being investigated as a useful therapeutic approach in homophile B patients. Another new clotting disorder is represented by two abnormal FV (FV East Texas and FV Amsterdam). These are characterized by a deletion of part of the B domain of FV resulting in a “short” FV. The condition is characterized by a mild bleeding tendency due to high levels of Tissue Factor pathway inhibitor. The “short” factor V is in fact resistant to the action of Tissue Factor pathway inhibitor which is sharply increased in these patients. These new clotting entities have again demonstrated that the study of patients who show a tendency to venous thrombosis or a mild bleeding condition that cannot be explained on the basis of our current concepts of blood coagulation, may represent “new” coagulation disorders. All persons interested in thrombotic or hemorrhagic disorders should be informed about these new clinical and laboratory conditions.