Why the study?
Activation of the intrinsic pathway of coagulation contributes to the pathogenesis of arterial and venous thrombosis, but advances from studying its factors and targeted inhibitors needed synthesis.
Does targeting components of the intrinsic coagulation pathway (FXI, FXII, PKK) reduce thrombosis without increasing bleeding in preclinical models?
Does targeting components of the intrinsic coagulation pathway (FXI, FXII, PKK) reduce thrombosis without increasing bleeding in preclinical models?
Development of inhibitors of activated FXI and FXII may offer a novel anticoagulant strategy that reduces thrombosis with minimal bleeding risk compared to current therapies.
May support clinical trials of FXI/FXII inhibitors; leaves open translation to reduced bleeding in patients.
Activation of the intrinsic pathway of coagulation contributes to the pathogenesis of arterial and venous thrombosis. Critical insights into the involvement of intrinsic pathway factors have been derived from the study of gene-specific knockout animals and targeted inhibitors. Importantly, preclinical studies have indicated that targeting components of this pathway, including FXI (factor XI), FXII, and PKK (prekallikrein), reduces thrombosis with no significant effect on protective hemostatic pathways. This review highlights the advances made from studying the intrinsic pathway using gene-specific knockout animals and inhibitors in models of arterial and venous thrombosis. Development of inhibitors of activated FXI and FXII may reduce thrombosis with minimal increases in bleeding compared with current anticoagulant drugs.
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Grover et al. (2019) studied this question.
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