Thrombolytic fibrin specificity influences activated partial thromboplastin time prolongation in vitro

Despite limited comparative data, guidelines suggest the same concomitant unfractionated heparin (UFH) dose for all fibrin-specific thrombolytic agents in acute myocardial infarction. Since a supratherapeutic activated partial thromboplastin time (aPTT) correlates with adverse outcomes, clarifying effects of various agents on aPTT are needed. The present in vitro study evaluated the influence of alteplase (rt-PA), reteplase (r-PA), and tenecteplase (TNK) on aPTT prolongation. Blood samples from healthy volunteers (n = 12) were treated with equipotent concentrations of rt-PA, r-PA, and TNK, with and without UFH. Samples of each treatment group were incubated at 37 degrees C; aPTT and fibrinogen activity were measured after 4 h. Mean aPTT values for rt-PA alone and r-PA alone were prolonged versus those of TNK alone (P = 0.001 for both). Combined with UFH, rt-PA and r-PA increased the aPTT versus UFH alone (P < 0.05 for both). Interestingly, TNK + UFH reduced the aPTT versus UFH alone (P < 0.001). A negative correlation existed between fibrinogen activity and aPTT for all treatments, except TNK alone. The present investigation illustrates that an agent with maximal fibrin specificity (TNK) has minimal effect on the aPTT, while agents with less fibrin specificity are more likely to prolong the aPTT, with and without UFH present.