Heparin inhibits fibrin, but not leukocytes, in a model of deep-vein thrombosis.
Previous studies with models of deep-vein thrombosis (DVT) have demonstrated that leukocyte (PMN)-mediated vein injury may be an initiating event in DVT (14, 17). Since heparin (H) can prevent DVT, we studied its effect on vascular injury and thrombosis in our model. Three groups of rabbits were treated with H either sc (73 and 147 U/kg) or iv (662 U/kg). Scanning electron microscopy revealed that the 73 U/kg sc dose was ineffective. All veins had PMN accumulation, fibrin deposition and complex thrombus formation. There was no increase in anti-Xa activity; activated partial thromboplastin times (APTT) and whole blood clotting times were normal. The 147 U/kg sc and the intravenous dose did not inhibit PMN-mediated vein injury. The endothelium was sloughed by migrating PMNs, basement membrane was exposed, and platelets adhered to it. Thrombosis was completely absent in the iv dose group. This correlated with increased anti-Xa activity and prolonged APTT and whole blood clotting times. Our results indicate that heparin does not inhibit the PMN adhesion and migration which produces vascular injury. However, the anticoagulant activity of heparin effectively reduces fibrin deposition and complex thrombus formation.
Simmons
C A
CA
Atherosclerosis & Thrombosis Research, Upjohn Company, Kalamazoo, Michigan 49001.
Burdick
M D
MD
Schaub
R G
RG
D000818:Animals; D005337:Fibrin / Q000096:biosynthesis*; D006493:Heparin / Q000008:administration & dosage / Q000627:therapeutic use*; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008855:Microscopy, Electron, Scanning; D009504:Neutrophils / Q000502:physiology*; D011817:Rabbits; D013924:Thrombophlebitis / Q000188:drug therapy* / Q000473:pathology; D014680:Veins / Q000648:ultrastructure
D005337:Fibrin; D006493:Heparin