Antithrombotic efficacy of low-molecular-weight heparin in deep arterial injury.
Low-molecular-weight heparin subfractions more specifically inhibit factor Xa than thrombin, and they may have advantages over unfractionated heparin in arterial thrombosis. The antithrombotic efficacy of four dosages of a low-molecular-weight heparin (CY216 at 100, 200, 400, or 500 Institute Choay units/kg) was compared with unfractionated calcium heparin (100 US Pharmacopeia units/kg) and placebo during deep arterial injury produced by balloon dilatation of the carotid artery in the pig. The acute thrombotic end points were 111In-labeled platelet and 125I-labeled fibrinogen/fibrin deposition and macroscopic mural thrombosis; these were related to the anti-factor Xa and antithrombin effects of the heparin preparations. Platelet deposition in segments with deep arterial injury was 42 +/- 28, 22 +/- 5, 29 +/- 12, 9 +/- 2, 9 +/- 2, and 11 +/- 3 x 10(6)/cm2 (mean +/- SEM) for pigs treated with placebo, with 100, 200, 400, and 500 units/kg CY216, and with 100 units/kg unfractionated heparin, respectively. Fibrinogen/fibrin deposition was 35 +/- 8, 19 +/- 2, 19 +/- 4, 21 +/- 3, 14 +/- 4, and 12 +/- 3 molecules x 10(12)/cm2, respectively; deposition was significantly reduced in pigs given 100 units/kg unfractionated heparin compared with placebo (p less than 0.05). Mural thrombosis was present in 74%, 45%, 30%, 14%, 5%, and 9% of deeply injured arterial segments, respectively (p = 0.02). Plasma anti-factor Xa activity and prolongation of the activated partial thromboplastin time (aPTT) with 100 units/kg unfractionated heparin were similar to that produced by 200 units/kg and 500 units/kg CY216, respectively. Thus, low-molecular-weight heparin, which predominantly inhibits factor Xa activity, was only moderately effective at reducing platelet thrombus deposition. It was less effective than 100 units/kg unfractionated heparin, except at high dosages, producing similar prolongation of the aPTT and the thrombin time.(ABSTRACT TRUNCATED AT 250 WORDS)
Heras
M
M
Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, Rochester, Minn 55905.
Chesebro
J H
JH
Webster
M W
MW
Mruk
J S
JS
Grill
D E
DE
Fuster
V
V
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000209:etiology; D001158:Arteries / Q000293:injuries* / Q000378:metabolism; D001780:Blood Coagulation Tests; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D005340:Fibrinogen / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D006801:Humans; D013552:Swine; D013927:Thrombosis / Q000209:etiology
D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D005340:Fibrinogen