Reversibility of platelet thrombosis in vivo. Quantitative analysis in porcine carotid arteries.
Reversibility in vivo of acute platelet thrombosis in response to specific anticoagulants is analyzed with thrombi that develop in segments (1 cm) of porcine carotid arteries externally crushed with a hemostat. Most thrombi fill the lumens of the injured segments (ca. 1 cm x 3 mm, 1 x w) within 30 min and comprise masses of platelets interpenetrated with neutrophil-lined seepage channels of blood. Continuous quantitative assay of thrombus mass is provided by a gamma detector placed over the injured segments to collect counts from 111In-labeled platelets. Thrombi established 30 min after injury, otherwise stable for 6 h, clear during 30-60 min of continuous infusion of either hirudin, tick anticoagulant or activated porcine protein C, or intermittent activation of endogenous protein C with a latent thrombin reagent. Anticoagulant dose-dependence of thrombus clearance is established for hirudin between 0.01 and 1.0 mg/kg/min. Thrombi become progressively refractory to hirudin between 0.5 and 6 h after injury. Neither heparin no low-molecular-weight heparin in full (clinical) anticoagulant doses yield significant dethrombosis. It is concluded that, within time limits, controlled thrombin generation in platelet thrombi maintains platelet cohesion without catalyzing irreversible platelet aggregation or clotting of fibrinogen.
Wysokinski
W
W
Section of Hematology Research, Mayo Clinic and Foundation for Education and Research, Rochester, MN 55905, USA.
McBane
R
R
Chesebro
J H
JH
Owen
W G
WG
D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage*; D001777:Blood Coagulation / Q000187:drug effects; D002341:Carotid Artery Thrombosis / Q000188:drug therapy / Q000473:pathology; D006629:Hirudins / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D010974:Platelet Aggregation / Q000187:drug effects; D011486:Protein C / Q000008:administration & dosage*; D013552:Swine; D013997:Time Factors
D000925:Anticoagulants; D006629:Hirudins; D011486:Protein C