Abstract
Background: The timing for initiation of effective antithrombotic therapy relative to the onset of arterial thrombosis may influence outcomes. This report investigates the hypothesis that early administration of heparin anticoagulation relative to the onset of thrombotic occlusion will effect a reduction in occlusion. Methods: A standard rat model of experimental thrombosis induction was used, injuring the carotid artery exposure with FeCl3-saturated filter paper, followed by flow monitoring for onset of occlusion and subsequent embolization events. Intravenous heparin administration (200 units/mL) was timed relative to the initiation of injury or onset of near occlusion, compared with controls (no heparin administration). Results: No occlusion was found for delivery of heparin 5 min prior to thrombus induction, whereas all vessels occluded without heparin. Unstable (embolic) thrombi were seen with heparin given at or shortly after initial occlusion. Only 9% (1/11) of the vessels had permanent occlusion when heparin was given at the time of thrombotic onset (p < 0.0001 vs. unheparinized), while 50% occluded when heparin was delayed by 5 min (p > 0.05). Conclusions: These findings provide evidence that antithrombotic therapy may need to be administered prior to the onset of anticipated loss of patency, with less effectiveness when given after occlusion has occurred.
Highlights
The onset of arterial thrombosis leading to vascular occlusion and cardiac ischemia is often difficult to assess
We sought to address a simple aspect of these issues, using the timing of therapeutic heparin administration relative to the initiation of a vascular injury that leads to consistent thrombotic occlusion
A reflow event, indicative of an embolism, was recorded as the time to reflow (TTR) if the flow returned above 10% of baseline with a continued increase in flow beyond 25% of baseline
Summary
The onset of arterial thrombosis leading to vascular occlusion and cardiac ischemia is often difficult to assess. Antithrombotic therapies may be in place at the time of thrombus initiation; the specific timing of administration relative to when thrombogenesis is present may influence the development of an occlusive thrombus [1,2,3,4,5]. This is relevant in the above areas of practice where the decision to add an antithrombotic agent such as unfractionated heparin or bivalirudin may be made late, during or after reflow following an interventional procedure when thrombogenesis may well be underway [6,7]. Conclusions: These findings provide evidence that antithrombotic therapy may need to be administered prior to the onset of anticipated loss of patency, with less effectiveness when given after occlusion has occurred
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