Studies on Thrombin-induced Platelet

The importance of morphologic alteration, clumping, and subsequent fusion of blood platelets in hemostasis and thrombosis is well known. The mechanisms underlying these platelet changes, often referred to as agglutination and viscous metamorphosis, are poorly understood. Since the early work of Wright and Minot (1), many studies have suggested that thrombin may be involved. Widely divergent conclusions, however, have been reached regarding the role of thrombin in bringing about these platelet changes. These conclusions have ranged from the proposal that thrombin acts directly to cause platelet agglutination, to denial that it is concerned in a vital way with the process (2). In some studies, serum containing thrombin caused platelet agglutination (3-8). In other studies, thrombin preparations rather than serum have been employed. While a few of the data suggest that thrombin may act directly to agglutinate platelets (9-11), most investigators have found that thrombin by itself is inactive (3, 12-18). Other data have indicated that inadequately washed platelets were agglutinated by thrombin, but that no clumping occurred if the platelets were first thoroughly washed (17, 18). Washed platelets suspended in serum (5), plasma (3, 18), or any of several buffers (3) have also been reported to be clumped by the addition of thrombin. Sharp (19), however, could not confirm such direct action of thrombin, and he has questioned if thrombin is concerned with the earlier stages of platelet agglutination. Many studies have indicated that one or more cofactors are needed for the agglutination of platelets by thrombin. We have previously reported (20) that a combination of thrombin and calcium is highly active in producing agglutination of carefully washed platelets, no other cofactors being necessary. Other workers have observed that thrombin together with calcium will not agglutinate washed platelets (16) unless certain additional cofactors are present (3, 4, 10, 13-15). This list of cofactors includes glucose and other monosaccharides as