Abstract
Heparin is a widely used anticoagulant in hemodialysis (HD) for patients with chronic kidney disease (CKD); however, it entails the risk of thrombus formation due to heparin-induced thrombocytopenia. Indeed, CKD patients on HD are associated with excessive mortality from cardiovascular disease due to their prothrombotic profile. Therefore, it would be a significant breakthrough to develop a thrombolytic adjuvant that facilitates heparin to achieve its proper anticoagulant efficiency at a much lower dose for greater safety. Nattokinase (NK), a valuable dietary supplement possessing strong fibrinolytic and thrombolytic activity, was reported to interact with heparin and thereby the beneficial efficacy of NK-heparin was investigated herein. NK-heparin induced a synergistic enhancement of clotting time both in vitro and in vivo evaluations, whereas the overall fibrinolytic activity was only marginally enhanced. Moreover, it was demonstrated for the first time that NK induced potent degradation of all three chains of fibrinogen. In particular, NK-heparin markedly reinforced the fibrinolysis activity of NK, which may underlie, at least in part, the mechanism by which NK-heparin benefited their overall thrombolytic and anticoagulant activity. Collectively, we clarified the beneficial combination efficacy of NK and heparin for greater safety, providing a powerful impetus for physicians to administer heparin to a larger portion of patients with CKD.
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