Prothrombin Molise: a "new" congenital dysprothrombinemia, double heterozygosis with an abnormal prothrombin and "true" prothrombin deficiency

A family with a new congenital dysprothrombinemia is described. The propositus was a 36-yr-old female from the Molise region of Italy who presented with epistaxis, easy bruising, and menometrorrhagia. The main laboratory features of the defect included slight prolongation of prothrombin time, Thrombotest, Normotest, PP test, and partial thromboplastin time. Prothrombin activity was approximately 10% in several one- and two-stage systems employing tissue thromboplastins as activating agents. Using several viper venoms as activating agents low prothrombin levels were also obtained. However, the staphylocoagulase-complexed prothrombin level and immunologic methods yielded levels of about 50%. A line of identity between normal and abnormal prothrombin was seen on immunodiffusion. The migration of the abnormal prothrombin was normal in single and bidimensional immunoelectrophoresis systems. A single abnormal serum fragment was seen on bidimensional immunoelectrophoresis. The brother of the propositus was also affected and presented a similar pattern. Family studies revealed that the mother had approximately 50% prothrombin activity and antigen, whereas the father had 65% prothrombin activity and 100% prothrombin antigen. The propositus's first son showed approximately 50% prothrombin activity and antigen. A second child showed approximately 50% prothrombin activity but normal antigen. We suggest that the propositi are heterozygous for an abnormal prothrombin and heterozygous for “true” prothrombin deficiency. The father and the second child are heterozygous for abnormal prothrombin. The mother and the first child are heterozygous for “true” prothrombin deficiency. The term prothrombin Molise is proposed for this peculiar prothrombin abnormality.