Effect of phospholipases on factor-VIII activity.

The effect of the enzymes phospholipases C and D on Factor VIII were investigated. Phospholipase D was found to activate the partially purified intact Factor-VIII molecule maximally at a final concentration of 0.6 U/ml. Neither the dissociated small molecular weight component nor the high molecular weight component were activated. Phospholipase C, on the other hand, inactivated both the intact and the dissociated Factor-VIII molecule. Phospholipase D, however, had no effect on the haemophilic cryoprecipitate or the partially purified haemophilic Factor VIII. The implications of these results for the genetic control of the Factor-VIII molecule are discussed. In this connection, haemophilia A is hypothesized to be caused by an X-linked enzyme effect that impairs phospholipid assembly of the Factor-VIII protein, whereas von Willebrand's disease might be due to a structural defect of the Factor-VIII protein.