A study of the cation- and pH-dependent stability of factors V and VIII in plasma.

The in vitro lability of factors V and VIII in plasma has been studied. In agreement with previous reports, an increase in anticoagulant concentration renders both factors more labile (cation-deficient decay), as does an increase in the pH above 7.3 (alkaline-decay). Calcium appears to be the plasma cation which protects factors V and VIII against in vitro loss of activity. The protection obtained by the addition of other divalent cations depended on the type of plasma used. When resin-EDTA plasma was made cation free by dialysis at 4 degrees C and then incubated at 37 degrees C, the rapid loss of factors V and VIII activity could be prevented by prior addition of strontium, manganese and magnesium. In oxalate plasma, nickel, manganese, cadmium and strontium were effective. The alkaline decay of both factors V and VIII is irreversible. Partial reversibility of the cation-deficient decay was demonstrated for factor V, but not for factor VIII. The temperature coefficient for both the cation-deficient and alkaline decay is 2-3, suggesting an enzymatic rather than a physical reaction. There was no evidence to implicate thrombin, plasmin or trypsin since inhibitors of these enzymes failed to modify either type of decay.