Pharmacodynamics of multi-dose low molecular weight heparin in healthy horses.
Authors: Whelchel Dorothy D, Tennent-Brown Brett S, Giguère Steeve, Epstein Kira L
Journal: Veterinary surgery : VS
Summary
This 2013 crossover trial investigated optimal dosing schedules for low molecular weight heparin (dalteparin) in healthy horses, comparing once-daily versus twice-daily subcutaneous administration at 50 U/kg over three consecutive days. Six adult mares underwent coagulation monitoring including anti-factor Xa activity (the primary marker of LMWH efficacy), partial thromboplastin time, platelet counts, packed cell volume, and antithrombin activity across both treatment protocols. Twice-daily dosing maintained anti-factor Xa activity within the therapeutic thromboprophylactic range (0.1–0.2 U/mL) throughout the 24-hour dosing interval, whilst once-daily administration allowed levels to fall below this threshold approximately 16 hours post-injection; neither regimen caused clinically significant changes in haematological parameters or prolonged PTT beyond normal limits. For practitioners considering LMWH in cases requiring sustained anticoagulation—such as horses with thromboembolism risk or during critical illness—these findings suggest that twice-daily dalteparin dosing provides more consistent therapeutic coverage, whereas once-daily dosing may leave a therapeutic window where protection is suboptimal, particularly in the latter hours before the next injection.
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Practical Takeaways
- •Use twice-daily LMWH dosing (50 U/kg SC q12h) to maintain consistent thromboprophylactic coverage; once-daily dosing leaves a 16-hour window below therapeutic levels
- •LMWH accumulates with repeated dosing, so therapeutic levels improve with continuation of treatment despite no dose increase
- •LMWH at these doses is safe for equine use with no clinically significant effects on blood cell counts or coagulation parameters over short courses
Key Findings
- •Twice daily LMWH (dalteparin 50 U/kg) maintained anti-factor Xa activity within thromboprophylactic range (0.1-0.2 U/mL) for 24 hours, while once daily dosing fell below therapeutic range at 16 hours post-administration
- •No adverse effects on packed cell volume, platelet count, or antithrombin activity were detected with either dosing frequency over 3 days
- •Area under the curve for anti-factor Xa activity was significantly greater after the final dose compared to the first dose, suggesting drug accumulation with repeated administration
- •Both dosing regimens appeared safe in healthy adult horses, with PTT values increasing but remaining within normal reference intervals