自制活化凝血酶原复合物的安全性和有效性评价OA

Objective To evaluate the in vitro procoagulant efficacy and in vivo potential thrombogenic risk of self-pre-pared activated prothrombin complex concentrate(aPCC).Methods The preparation was administered at a dose of 0.5 IU per milliliter of plasma.For in vitro assays,the self-prepared aPCC concentrate was added to plasma spiked with factor Ⅷ(FⅧ)inhibitors.Calibrated automated thrombin generation(CAT),prothrombin time(PT),activated partial thrombo-plastin time(APTT),thrombin time(TT),and fibrinogen(Fib)quantification were performed.Normal saline and FEIBA® were set as controls to evaluate the procoagulant capacity of the self-prepared aPCC concentrate.For in vivo animal studies,the self-prepared aPCC concentrate was injected into rats via the jugular vein.A ferric chloride(FeCl3)filter pa-per patch was applied to induce carotid arterial thrombosis.Laser speckle blood flow imaging was used to continuously moni-tor thrombus formation in the rat carotid artery.Plasma samples were collected from rats for CAT,PT,APTT,TT and Fib testing,with normal saline and FEIBA® as controls to evaluate the potential thrombogenic risk of the self-prepared aPCC concentrate.Results Supplementation with aPCC significantly shortened APTT and PT values in inhibitor-spiked plasma(all P<0.001).There were no statistically significant differences in APTT and PT between FEIBA® and self-prepared aPCC(P>0.05).CAT results demonstrated that adding aPCC to inhibitor-containing plasma markedly increased endoge-nous thrombin potential(ETP)and peak thrombin concentration(Peak)(P<0.001),with both parameters higher than those of normal plasma(P<0.05).No significant intergroup difference in ETP was observed between self-prepared aPCC and FEIBA®(P>0.05).Carotid blood flow imaging in rats revealed that,compared with FEIBA®,thrombi induced by self-prepared aPCC were smaller and less stable,and all underwent spontaneous lysis,accompanied by better restoration of ca-rotid blood perfusion.Conclusion The self-prepared aPCC restores coagulation function in inhibitor-spiked plasma to a comparable extent as FEIBA®,while exhibiting a lower thrombogenic risk.