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Although the existence of blood platelets had been known for many years it was not until 1882 that Bizzozero (1) called attention to the role of platelets in blood coagulation. Morawitz (2), twenty years later, was among the first to consider the specific chemical contribution of the platelet to the clotting process. Howell (3), in 1912, demonstrated the presence of an unsaturated phosphatide ("kephalin") in thromboplastic substances of tissue origin. Mills (4), in 1927, showed cephalin to be present in blood platelets, and the following year Haurowitz and Sladek (5) published results of chemical analysis of horse platelets, reporting a lipid content of 12 per cent of dry weight. The first convincing data relating the cephalin content of platelets to acceleration of coagulation were supplied by Chargaff, Bancroft and Stanley-Brown (6). These workers also reported at that time what has recently been emphasized again (7, 8): phosphatides from other natural sources (soy bean, yeast) also were capable of accelerating blood clotting in vitro. Erickson, Williams, Avrin and Lee (9), confirmed the results of Chargaff and associates relating to platelet phospholipid content. Wallach, Surgenor and Steele (10), identified phosphatidyl ethanolamine and phosphatidyl serine in human platelets. Subsequently the presence of inositol phosphatide was noted ( 11, 12). Wooldridge, in 1886 (13), demonstrated a coagulant effect of substances obtained from red cells by both aqueous and lipid solvents. With small doses of these extracts administered intravenously to dogs, Wooldridge also observed a hypocoagulable

THROMBOPLASTIC FACTORS IN PLATELETS AND RED BLOOD CELLS: OBSERVATIONS ON THEIR CHEMICAL NATURE AND FUNCTION IN IN VITRO COAGULATION *