Summary
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 × 3 mm, 1 × 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 nor 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.
