COMPARATIVE EFFECTS OF STAPHYLOKINASE AND ALTEPLASE RABBIT BLEEDING-TIME MODELS

Background: The pathogenesis of bleeding associated with thrombolytic therapy remains largely unknown, although spontaneous bleeding appears to correlate with bleeding time prolongation. Here, the comparative e ffects an cuticle bleeding times (CBT) and ear puncture bleeding times (EBT) of recombinant staphylokinase (Sak) and alteplase (recombinant tissue-type plasminogen activator, rt-PA) at equivalent doses, alone a nd in combination with aspirin and heparin, were studied in rabbits. M ethods and Results: Groups of 4 to 9 rabbits were allocated to one of the 8 following intravenous infusions: saline; aspirin 15 mg/kg and he parin - 100 IU/kg bolus and 10 IU/kg infusion over one hour; 1.5 mg/kg rt-PA; 1.5 mg/kg rt-PA plus aspirin and heparin; 4.5 mg/kg rt-PA; 0.5 mg/kg Sak; 0.5 mg/kg Sak plus aspirin and heparin and 1.5 mg/kg Sak. Bleeding times were determined 30 and 15 min before and 5, 15, 30 and 60 min after the administration over one min of saline, rt-PA or Sak, by simultaneously severing a nail cuticle (CBT) and by puncturing the ear (EBT). Bleeding times were unaffected by saline and by both doses of Sak in monotherapy. Heparin-aspirin and low dose rt-PA significantl y lengthened EBT but not CBT. Both CBT and EBT were significantly prol onged (to a mean of >4 times pretreatment at 5 min) after high-dose rt -PA and after the combined administration of heparin and aspirin with either Sak or rt-PA. rt-PA provoked significantly longer bleeding than Sak in the CBT (p = 0.001; mean estimated difference = 23 min), but n ot in the EBT. rt-PA but not Sak degraded plasma fibrinogen dose-depen dently, CBT correlated inversely with fibrinogen (r = -0.66, p = 0.001 ) but EBT did not. Conclusions: At equivalent doses Sak displays a sig nificantly higher fibrin specificity and prolongs bleeding time less t han rt-PA, particularly in the nail cuticle bleeding time model in whi ch larger vessels are injured that require fibrinogen for hemostasis.