The suprapharmacologic dosing of antithrombin concentrate for Staphylococcus aureus-induced disseminated intravascular coagulation in guinea pigs: substantial reduction in mortality and morbidity.

摘要: An animal model of gram-positive septicemia was developed to evaluate the effects antithrombin (AT) concentrates on morbidity, mortality, and laboratory consequences disseminated intravascular coagulation (DIC). DIC induced in guinea pigs by infusing Staphylococcus aureus (SA) isolated from blood cultures patients with (DIC-SA) or without (non-DIC-SA). The non-DIC-SA animals infused sterile saline served as controls. Varying doses AT were administered either 30 minutes 24 hours after infusion SA. confirmed within 4 changes prothrombin time, activated partial thromboplastin fibrinogen, fibrinogen-fibrin degradation products, activity. Clinical bleeding also evident. Mortality untreated DIC-SA 36% up 75% 72 hours. Intervention any dose between 125 1,000 IU/kg associated 100% survival (P < = .05 250 group) sustained increases activity fibrinogen concentrations .05). When combination low molecular weight heparin (LMWH) if LMWH adminstered alone, mortality slightly, but not significantly reduced compared DIC-SA. Gross hemorrhage observed premortem at autopsy all substantially fewer that received .001 250, 500, groups). In contrast, groups treated LMWH, alone AT, experienced appeared develop pathologic DIC. Fibrin formation end-organs detected group alone. prevented fibrin could reverse pre-existing histopathologic evidence favorably affected survival, which reached statistical significance .025). summary, suprapharmacologic concentrate decreased morbidity ameliorated adverse measures this pig untoward hemorrhagic complications. These findings provide justification for studying use therapy