International journal of hematology · 2025
Comprehensive anticoagulant effect of heparinoid in blood samples from patients with hemophilia.
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Miyatake Tomoya, Takeyama Masahiro, Horiuchi Kaoru, Furukawa Shoko, Ogiwara Kenichi, Nogami Keiji
Аннотация
BACKGROUND: Heparinoid (Hirudoid®), a topical heparin-like agent, is labeled as contraindicated in bleeding disorders, yet its propensity for clinically relevant systemic anticoagulation remains uncertain.
AIM: To assess heparinoid's anticoagulant potential in blood from healthy individuals and people with hemophilia (PwH).
METHODS: 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.
RESULTS: In normal plasma, heparinoid dose-dependently prolonged APTT and reduced Ad|min1|; at the estimated Cmax (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.
CONCLUSION: 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.
AIM: To assess heparinoid's anticoagulant potential in blood from healthy individuals and people with hemophilia (PwH).
METHODS: 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.
RESULTS: In normal plasma, heparinoid dose-dependently prolonged APTT and reduced Ad|min1|; at the estimated Cmax (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.
CONCLUSION: 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.