Clara V. Hussey

ON THE COMPARATIVE PROTHROMBIC ACTIVITY OF HUMAN AND DOG BLOOD

Soon after the introduction of the oneand twostage methods for determining prothrombin, it was noted that while the results obtained by the two procedures generally agreed fairly well, marked discrepancies occurred in certain specific instances. Particularly puzzling has been the observation that the prothrombic activity of human blood as compared with dog blood, when measured by the two tests, is markedly different. Warner, Brinkhous and Smith (1) reported that the prothrombin concentration in dog blood is 350 units per cc. and in human blood 295 units. More recently Murphy and Seegers (2) found 190 to 205 units in dog and 290 to 315 in human blood. Mann and his associates (3, 4) reported that the average for dog blood is 183 units per cc. and for human blood 319 units. These findings indicate that the prothrombin concentration as measured by the two-stage method is approximately the same in the two species. When determined by the one-stage method, the prothrombic activity of dog blood, in marked contrast, is many-fold higher than in human blood (5). The reason for this divergency has not been satisfactorily explained, but obviously as long as this problem remains unsolved, a marked gap in the knowledge concerning prothrombin remains. In the present investigation human and dog bloods were studied by means of the prothrombin consumption test and by the adsorption and elution technique for determining prothrombin with the aim of obtaining new data that might be helpful in arriving at a better understanding of what constitutes prothrombic activity.

Prothrombin and the One-stage Prothrombin Time

We would like to thank Professor D. W. Smithers, of the Radiotherapy Department, and Professor W. V. Mayneord, of the Physics Department, and members of their staffs, for making this work possible. We are also grateful to numerous colleagues in this and other hospitals for referring cases to us, and in particular to Dr. P. E. T. Hancock. The earlier cases in the series were treated by Dr. R. J. Walton, to whom we acknowledge our debt.

Synergistic Action of Russell Viper Venom and Tissue Thromboplastin Extracts.

Summary As measured by one-stage prothrombin time, mixtures of various body tissues may have thromboplastin activity greater than that of either of the tissues in the mixture. A marked synergistic action as to thromboplastin activity occurs between body tissue extracts and Russell viper venom. This effect is absent if the plasma lacks either prothrombin or labile factor (factor V). The thromboplastin activity of Russell viper venom is not influenced by the lack of stable factor (factor VII) in contrast to the high sensitivity observed with rabbit brain thromboplastin.

Influence of Concentration of Thromboplastin on Prothrombin Time of Human and Dog Plasma.

Summary The amount of thromboplastin required for optimum prothrombin activity increases when human plasma is stored and the lost labile factor replaced. It decreases in dog plasma when the prothrombin level is reduced by means of Dicumarol or vitamin K deficiency. It is concluded that a direct relationship exists between the concentration of prothrombin and the amount of thromboplastin, for obtaining a minimal constant prothrombin time.

Is Hypoprothrombinemia Caused by Deficiency of Vitamin K Different from that of Dicumarol

Summary On mixing equal volumes of plasma obtained from a dog deprived of vit. K and plasma from a dog receiving Dicu-marol, the mixture has a prothrombin time that corresponds to the expected average based on the standard prothrombin time curve. It is concluded that in the dog the increased prothrombin time in both avitaminosis K and after Dicumarol is due to a decrease of prothromibin

Initiation of the clotting of blood.

Summary A minute amount of thrombin such as remains adherent to the wall of a test tube after repeated rinsing is enough to shorten markedly the clotting time of blood from a severe hemophiliac. Since the same effect is observed in platelet-rich but not in platelet-poor hemophilic plasma, it appears that although an extremely small quantity of thrombin can initiate clotting, platelets participate in accelerating the reaction.

Comparative Thromboplastin Activity of Acetone-Dehydrated Rabbit and Human Brain.

Summary Rabbit and human brains, when dehydrated with acetone, yield a product which has a high, constant and practically equal thromboplastic activity as measured by the one-stage prothrombin time and by prothrombin consumption time using hemophilic plasma as the assay medium. Serum prepared from normal platelet-poor plasma can be substituted for hemophilic plasma. Human brain extract differs from rabbit brain in that it has a greater inhibitory effect at high concentration and is more resistant to heat.

Prothrombin activity of blood of the newborn.

Summary When adult and newborn plasmas were mixed in varying proportions, the prothrombin time which was 12 seconds for each plasma remained unaltered in the series of mixtures. This suggests that the prothrombin activity i.e., the concentration of active prothrombin, is the same in the plasma of the newborn baby as in that of the adult.