We have compared the relative antithrombotic and antihemostatic effects of the very low molecular weight heparin CY222 with standard unfractionated heparin (SH) in a baboon model of platelet-dependent thrombosis. Thrombus formation was induced by placement of a thrombogenic device in an exteriorized femoral arteriovenous shunt under conditions of intermediate-shear blood flow. The device consisted of a collagen-coated cannular segment positioned proximal to two regions of expanded diameter exhibiting disturbed flow and stasis. Thrombus formation was measured in real time by indium 111-labeled platelet imaging. The collagen-coated surface accumulated thrombi composed largely of platelets, and the regions of disturbed flow were morphologically rich in fibrin and red cells. SH and CY222 were administered by continuous infusion for 1 hour. Although both heparin preparations abolished thrombus formation in the low-shear fibrin-rich regions at plasma levels less than 0.5 anti-Xa U/ml, platelet deposition onto the collagen surface was not reduced by either SH or CY222 at that dosage. These findings were consistent with previously observed therapeutic benefits of this level of anti-Xa activity in venous, but not arterial, thrombosis. Platelet deposition on the collagen was reduced in a dose-dependent manner by both SH and CY222 administered at doses between 1 and 5 anti-Xa U/ml. It is important to note that although heparin preparations produced profound and equivalent antithrombotic effects for platelet-dependent thrombus formation at comparable levels of anti-Xa activity, SH prolonged both the coagulation time and the bleeding time substantially more than did CY222.(ABSTRACT TRUNCATED AT 250 WORDS)