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- W2188662232 abstract "Background. We havedetermined invivotherelative antithrombotic efficacy andhemostatic safety ofcombining low-dose activated protein C (APC)andurokinase (urinary plasminogen activator, u-PA), twonatural proteins thatregulate thrombogenesis. Methods andResults. Tomodelacutethrombotic responsesofnative bloodunderconditions of arterial flow, thrombogenic segments ofDacronvascular graft (VG)wereincorporated intochronic exteriorized femoral arteriovenous (AV) accessshunts inbaboons. Thrombus formation onVG was determined bymeasuring1)thedeposition ofautologouslIn platelets using real-time scintillation camera imaging, 2)theaccumulation of125I fibrin, 3)segment patency byDoppler flowanalysis, and4)bloodtests forthrombosis, including plasma concentrations ofplatelet factor 4,,8-throm- boglobulin, fibrinopeptide A (FPA), andD-dimer. Treatments consisting oflow-dose andinterme- diate-dose APC (0.07 or0.25mg/kghr), u-PA(25,000 or50,000 IU/kghr), orthecombination wereadministered for1hourbycontinuous intravenous infusion. Inuntreated controls, platelets andfibrin accumulated rapidly, reaching plateau values at1hourof15.1+3.8x i09platelets and 7.8+2.2 mg fibrin. Although thelow-dose APC oru-PAalonedidnotdecrease either platelet or fibrin deposition significantly, thiscombination moderately reduced bothplatelet andfibrin accumulation (7.3 ±2.6x 109platelets, p 0.05). TheT;% clearance timeforAPCactivity was notaffected bytheconcurrent administration ofu-PA.u-PA alone increased theplasma levels ofD-dimer, FPA,and,interestingly, APC,implying thatduring pharmacological activation ofthefibnrnolytic system, thrombin activity was released, andthe protein C pathway was activated. Conclusions. A combination ofintermediate-dose APC andu-PAproduce substantial and efficient antithrombotic effects without impairing hemostatic function. (Circulation 1991; 84:2454-2462)" @default.
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- W2188662232 date "1991-01-01" @default.
- W2188662232 modified "2023-09-27" @default.
- W2188662232 title "Antithrombotic Effects ofCombining Activated Protein C andUrokinase in NonhumanPrimates" @default.
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