A new approach to treating heparin-induced thrombocytopenia has been developed by Japanese researchers.
Heparin-induced thrombocytopenia (HIT) is the rapid and sometimes fatal clotting which occurs in up to 3% of people treated with heparin. The numbers of patients with this side-effect have increased globally, due to the increased use of heparin to treat severe COVID during the pandemic.
The anti-coagulant drugs used to treat HIT block a clotting protein called thrombin. However, these drugs sometimes lead to severe bleeding, and there are currently no effective strategies to prevent this.
So Dr Keitaro Yoshimoto and colleagues, from the University of Tokyo, set out to create an improved treatment for HIT.
Writing in the journal Molecular Therapy - Nucleic Acids, they explain that they “devised a potent thrombin inhibitor based on bivalent aptamers with a higher safety profile”.
It involves specific anti-thrombin DNA molecules called ‘aptamers’, that act as an anticoagulant. The team showed in lab tests on human cells and in mice that their new aptamers had improved binding ability to thrombin.
The anticoagulant activity of this approach “significantly surpassed that of an approved drug for heparin-induced thrombocytopenia treatment, argatroban,” they report.
What’s more, the anti-coagulant activity could be rapidly neutralised with the medication protamine sulfate, which is commonly used to reverse the effects of heparin and prevent severe bleeding.
Their novel drugs “will be promising candidates for heparin-induced thrombocytopenia treatment with a higher safety profile,” the authors conclude.
Dr Yoshimoto said: “The best treatment for heparin-induced thrombocytopenia is an infusion of what are called thrombin inhibitors, but current drugs can lead to severe bleeding and there is no antidote to avoid this.
“We need a new low-risk thrombin inhibitor to replace current drugs. My team and I have created such an anticoagulant and have demonstrated it in mice and also in human blood plasma.”
Source:
Nagano M, Kubota K, Sakata A, Nakamura R, Yoshitomi T, Wakui K, Yoshimoto K. (2023) “A neutralizable dimeric anti-thrombin aptamer with potent anticoagulant activity in mice.” Molecular Therapy - Nucleic Acids, doi: 10.1016/j.omtn.2023.07.038
Link: https://www.cell.com/molecular-therapy-family/nucleic-acids/fulltext/S2162-2531(23)00211-1
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