Comprehensive anticoagulant effect of heparinoid in blood samples from patients with hemophilia

Heparinoid (Hirudoid®), a topical heparin-like agent, is labeled as contraindicated in bleeding disorders, yet its propensity for clinically relevant systemic anticoagulation remains uncertain.

To assess heparinoid's anticoagulant potential in blood from healthy individuals and people with hemophilia (PwH).

In normal plasma exposed to heparinoid (≤ 6.5 μg/mL) or heparin, and in plasma from PwH supplemented with FVIII or FIX (0-50 IU/dL), we quantified activated partial thromboplastin time (APTT) and adjusted maximum coagulation velocity (Ad|min1|) by clot waveform analysis. In heparinoid-treated whole blood from healthy volunteers (≤ 9 μg/mL), clotting time (CT) and clot formation time (CFT) were assessed by rotational thromboelastometry.

In normal plasma, heparinoid dose-dependently prolonged APTT and reduced Ad|min1|; at the estimated C_max (2.5 μg/mL), APTT increased ~ 1.2-fold and Ad|min1| approximated the effect of ~ 0.2 IU/mL heparin. In FVIII- or FIX-supplemented plasma from PwH, Ad|min1| showed a mild, factor-level-dependent decrease (~ 85% of control). In whole blood, CT + CFT changed minimally at therapeutic concentrations. Heparin controls provided an internal benchmark for assay sensitivity.

At therapeutic levels, heparinoid exerts only mild anticoagulant effects in both normal and hemophilic matrices, supporting the view that topical use is unlikely to pose systemic bleeding risk in PwH.