PB1232 - Impact of anticoagulant function by the addition of heparinoid in vitro in the plasmas from patients with hemophilia

Background: Heparinoid (Hirudoid®) is used as topical treatments for sebum deficiency in Japan. But it has a structure similar to heparin, the package insert states the contraindication for hemorrhagic diseases. The influence of heparinoid on coagulant function in hemophilia patients remains to be investigated.

Aims: To examine the impact of anticoagulant function of heparinoid in vitro in the patients with hemophilia.

Methods: The maximum blood concentration from absorbed heparinoid was estimated to be 2.5 µg/mL, when heparinoid was applied to the skin as stated in package insert. Heparinoid (0-6.5 µg/mL) was added to normal plasma (NP), followed by measuring activated partial thromboplastin time (aPTT). A modified clot waveform analysis (CWA) was performed, followed by measuring clotting time (CT) and adjusted maximum coagulation velocity (Ad|min1|). Heparinoid was also added to the patients’ plasmas with Hemophilia A or B, followed by CWA assessment.

Results: The addition of 2.5 µg/mL heparinoid to NP prolonged aPTT (34.3 sec; 1.2-fold of control (no heparinoid)) and CT (36.3 sec; 1.2-fold of control), and decreased Ad|min1| (9.5; 0.96-fold of control), suggesting that heparinoid exhibited slight anticoagulant effect for NP. To examine the effect of heparinoid on hemophilia plasmas, recombinant (r) FVIII or rFIX (0-50 IU/dL) were added to FVIII- or FIX-deficient plasmas (3 lots each) together with heparinoid (0-6.3 µg/mL), respectively. The addition of heparinoid prolonged the CT and decreased the Ad|min1| at each concentration of FVIII and FIX dose-dependently. The addition of 2.5 µg/mL heparinoid showed modest anticoagulant effect for hemophilia A and B at each concentration of FVIII and FIX (CT; 1.3- and 1.5-fold of control, Ad|min1|; 0.82- and 0.87-fold of control).

Conclusion(s): The presence of heparinoid demonstrated mild anticoagulant effect in vitro in the plasmas of patients with hemophilia. It might be possible to apply the heparinoid-contained product as skin treatment for these patients.