Shifts in redox/thiol balance differentially affect intrinsic and extrinsic coagulation pathways, suggesting a mechanism for selective modulation of clotting factors.
Differential redox sensitivity of coagulation pathways may inform targeted antithrombotic strategies; leaves open human translation from this animal model.
The biological chemistry that underlies and regulates the blood coagulation cascade is not fully understood. To begin to understand this, we performed clotting assays under various redox conditions. By varying the amount of oxidant and/or antioxidant in these assays, we observed that both the intrinsic/tenase complex and the extrinsic pathways were susceptible to shifts in the thiol/redox balance. We established a dichotomy where blood clotting via the intrinsic pathway was sensitive to oxidation whereas the tissue factor or extrinsic pathway was more sensitive to reduction. These differential inhibitory effects present a conceptual mechanism for selective modulation of the activities of clotting factors specific for the respective pathways. These data also suggest that blood clotting may be influenced by unidentified redox or thiol equilibria.
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Bayele et al. (2001) studied this question.
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