The thrombogenic mechanism of homocystinemia was defined by determination of the relative involvement of platelets, coagulation and fibrinolysis and by characterization of the vascular effects of homocystine infusion in a primate model. Nineteen survival and turnover measurements of ⁵¹Cr-platelets, ¹³¹I-fibrinogen and ¹²⁵I-plasminogen in four homocystinuric patients demonstrated uniformly a threefold increase in platelet consumption with only a 20 per cent parallel increase in fibrinogen and plasminogen utilization. Platelet consumption was interrupted by pyridoxine-induced clearing of plasma homocystine or by dipyridamole inhibition of platelet function but not by heparin anticoagulation. Measurements of platelet function in untreated patients and homocystinemic animals were normal.

Experimental homocystinemia in baboons caused patchy desquamation of vascular endothelium and appearance of circulating endothelial cells, selective platelet consumption and arterial thrombosis. Platelet utilization was prevented by inhibition of platelet function with dipyridamole or sudoxicam. We conclude that arterial thrombus formation in homocystinuric patients results from sustained, homocystine-induced, endothelial injury. (N Engl J Med 291:537–543, 1974)