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Updated: Aug 6, 2026
Ferric Chloride-induced Murine Thrombosis Models
Published on: September 5, 2016
Prolonged antithrombin activity of low-molecular-weight heparins. Clinical implications for the treatment of
1Istituto di Medicina Interna e di Medicina Vascolare, Università di Perugia, Italy.
Background:
The mechanism for the efficacy of once- or twice-daily subcutaneous injections of low-molecular-weight heparins (LMWHs) for the treatment of venous thromboembolism has been difficult to explain. The confusion exists because the observation from experimental studies that the antithrombin activity of LMWHs is necessary for their antithrombotic effect is inconsistent with the reported short half-life of the antithrombin activity of LMWHs. Previous pharmacokinetic studies were performed with lower doses of LMWHs than have been used in contemporary trials, and antithrombin activity was assessed with the barely sensitive chromogenic assay.
Methods And Results:
We performed a pharmacokinetic study to compare the relative half-lives of prophylactic and therapeutic doses of LMWHs assessing antithrombin activity with both the chromogenic and a more sensitive assay (plasma thrombin neutralization assay). An eight-way cross-over randomized study in healthy volunteers was performed. Enoxaparin (20 and 40 mg and 1 and 2 mg/kg) and nadroparin (7500 and 10,000 ICU and 225 and 450 ICU/kg) were administered subcutaneously. The maximal peak activity for aPTT ratio was 1.7. A dose-dependent peak activity was found for both antifactor Xa and antithrombin activities. Disappearance time of these activities after the highest dose of both LMWHs was longer than 16 hours. Overall mean antifactor Xa activity half-life was 4.6 hours. Overall mean antithrombin activity half-life was longer than 4 hours.
Conclusions:
Our results provide an explanation for the effectiveness of LMWHs administered either once or twice daily. High and sustained plasma antithrombin activity is achieved when LMWHs are administered in therapeutic doses used in contemporary trials with only a moderate prolongation of the aPTT.
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