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Two cases of hypoprothrombinemia of unknown cause are presented. In each case there was a marked hemorrhagic diathesis which, in Case 1, led to death. In each there were additional findings (clinical or necropsy) which suggested that the prothrombin deficiency was only one manifestation of a generalized disease. The pertinent literature is reviewed and a classification of the previously reported cases of "idiopathic hypoprothrombinemia" into "congenital" and "acquired" types is offered. Both of our cases fall into the "acquired" group. The treatment of the condition is discussed and it is pointed out that vitamin K1 oxide in large doses restored the prothrombin time to normal after the apparent failure of large doses of water soluble menadione. A rationale for this difference in response is suggested.

Interest has recently been revived concerning the efficacy and safety of crystalline trypsin (Enzar) administered intravenously in the treatment of intravascular thrombosis. This has followed reports by Innerfield, Schwartz, and Angrist 1 stating that trypsin intravenously induces lytic effects upon artificially formed intravascular thrombi in rabbits and dogs. They also claim that with certain amounts of trypsin "complete dissolution" of such clots may be obtained "with restoration of circulatory integrity." These observations have led them to administer trypsin intravenously to patients with what they claim to have been gratifying results. 2 As the attempted dissolution of an intravascular protein thrombus with a proteolytic enzyme would appear to be an empiric but rational procedure, further consideration and investigation seemed mandatory. The concomitant possibility that it might activate the profibrinolysin system of the plasma had also to be considered. Reference to the literature, however, revealed that in certain amounts trypsin will, in

Recent investigations of the value of anticoagulants in myocardial infarction have indicated the need for a critical analysis of the blood-clotting mechanism in this disease. 1 Observations have been reported 2 which suggest that there is an increased tendency toward a coagulation associated with coronary thrombosis. Certain studies have yielded evidence that "hyperprothrombinemia" (in reality a summation of factors producing a shortening of the prothrombin time) is one of the factors responsible for the increased clotting tendency. 3 The importance of careful inquiry into whether such a state actually exists in patients with coronary thrombosis becomes obvious when the use of the anticoagulant drugs for both treatment and prophylaxis is being considered. Opportunity to observe daily prothrombin times in patients in whom coronary occlusion with myocardial infarction developed was afforded us during studies of the use of bishydroxycoumarin (dicumarol®) in this syndrome. The data obtained from observations of a group

1.1. The blood clotting time is not altered by the oral administration of cream. 2.2. When one syringe is reused for successive venepunctures, the blood clotting time is accelerated, irrespective of whether the subject has ingested cream, eaten breakfast or is in the fasting state. This is true whether the subject is active or is in a basal state. 3.3. Evidence of thrombin activity has been demonstrated on the surface of reused glass syringes. 4.4. The practice of reusing a glass syringe for the determination of the blood clotting time without heat sterilization of the syringe between each venepuncture is inaccurate and should not be used. 5.5. These findings raise doubt as to whether the ingestion of fat in the form of dairy products affects the incidence of thrombosing conditions by immediate direct action on the clotting mechanism of the blood.

The exact mechanism by which bishydroxycoumarin (dicumarol®) affects the blood coagulation system is still unknown. The similarity in the chemical structure of 3-substituted 4-hydroxycoumarins to vitamin K led the original workers1to suggest that bishydroxycoumarin might act by blocking or competing with vitamin K in maintaining prothrombin activity. This hypothesis was supported by animal experiments which demonstrated the similarity of vitamin K deficiency to the biologic response to bishydroxycoumarin2and the ability of vitamin K to reverse the action of this drug.3However, it was clearly shown that the levels of 2-methyl-1, 4-naphthoquinone necessary to counteract the action of the anticoagulant are considerably larger