Blood: Extracellulation histogen can replace clotting enzyme primary initiation to promote in-vascular clotting!

The production of clotting enzymes is essential for the formation of physiological clots in the blood and the pathological development of dispersive in-vascular clotting (DIC).
in critical diseases, extensive cell damage releases histogens into the bloodstream, which can increase the production of clotting enzymes and lead to DIC, but its molecular mechanisms are unclear.
normally, clotting enzymes are produced by clotting enzyme complexes and consist of active X-factors (FXa), active cofactors V (FVa) and phospholipids, which can be lysed in the presence of calcium.
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on clotting enzyme lysis and clotting enzyme production In this study, researchers found that in the presence of extracellular histogens, even without FVa and phospholipids, an alternative clotting enzyme could be formed.
histogen directly binds to clotting enzyme fragment F1 and fragment F2 binds directly to clotting enzyme fragment F1 and fragment F2 specific binding, promotes clotting enzyme original FXa cleavage to explain the release of active clotting enzyme, unlike FVa requires phospholipid surface anchoring classic clotting enzyme primary complex.
infusion of histoproteins into mice can induce DIC, but infusion of clotting enzyme fragments F1-F2 before infusion of histogens can eliminate histogen-induced DIC.
DIC, where the original fragment of coagulation enzyme F1 plus F2 reduces histoprotein-induced DIC, significantly increased circulating histoprotein levels in patients with sepsis in a group of intensive care units (ICU) (n-144).
data suggest that histogen-induced phospholipid-free alternative clotting enzymes can lead to in-blood clotting, revealing new molecular mechanisms for clotting enzyme production and DIC.
addition, histoprotein significantly reduced the need for FXa in the clotting cascades, enabling blood clots to form in mice where the clotting factor VIII (FVIII) and FIX were lacking plasma, as well as in mice where FVIII was lacking.
, this study emphasizes a new coagulation mechanism, which has certain therapeutic potential in treating systemic clotting activation and correcting the deficiency of coagulation factors.