The effect of heparin on the early stages of blood coagulation.

From experiments reported it is concluded that heparin combines with and inactivates Christman factor (C.F.) to form reversibly a heparin-C.F. complex. Apart from the effect of heparin on C.F. and on thrombin, heparin in moderate concentrations was not shown to inactivate any other coagulation factors."Available" heparin is defined as heparin in such a state that it can delay some clotting systems. Heparin was rendered "unavailable" or inactive by plasma C.F. and especially by serum C.F., by platelet protein (but not intact platelets), and by platelet-like activity of serum (P.L.A.S.). These three proteins uniquely among all the plasma and serum proteins inactivate heparin. If an appropriate concentration of heparin is added to whole blood the clotting time is prolonged, due presumably to the inactivation of C.F. by heparin: "available" heparin disappears during clotting and none is found in the serum. The interactions summarized above probably account for these findings. The disappearance of available heparin would also account for the normal thrombin generation and prothrombin consumption observed when heparinized blood clots. Some properties of P.L.A.S. are reported and its possible role in normal coagulation is considered. Heparin is known to become attached preferentially to one protein rather than another. Some plasma and serum fractions can be arranged in order of their increasing affinity for heparin thus: beta Lipoproteins<thrombin clotting system<C.F.<platelet protein<protamine sulphate.