Fibrinolytic therapy dosing

Efficacy and safety oftenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin the ASSENT-3 randomized trial in acute myocardial infarction. Lancet 2001 358 605. LincoffAM, Califf RM, Van De WerfE etal. Mortality at I year with combination platelet glycoprotein llb/llla inhibition and reduced-dose fibrinolytic therapy vs conventional fibrinolytic therapy for acute myocardial infarction GUSTO V randomized trial. JAMA 2002 288 2130. 

Typically, patients with confirmed CVST are treated with intravenous heparin even in the presence of intracerebral hemorrhage. Although there is only one placebo-controlled, double-blind study showing a significant advantage of intravenous dose-adjusted unfractionated heparin therapy in patients with CVST (Einhaupl et al. 1991), heparin as the first-line treatment is recommended because of its efficacy, safety and feasibility (Ameri and Bousser 1992 Bousser 1999). Only in rare cases may fibrinolytic therapy or thrombectomy be considered as alternative treatment options. 

Experience with thrombolysis in children is limited but the need for this procedure has increased because of the need to treat complications of cardiac catheterization and systemic arterial intervention. Agents used include urokinase and rtPA. Effective dose schedules for children have been extrapolated from adult studies. Coagulation and fibrinolysis are probably different in pediatrics, particularly in neonates. Plasminogen levels are known to be low in neonates, and it has been proposed that plasminogen or fresh plasma be given to enhance fibrinolytic therapy. Most centers favor iTPA, and this may be locally delivered via a selective catheter. Local low-dose therapy is unlikely to produce systemic... 

Although intrapleural streptokinase does not cause systemic fibrinolytic effects, there can be local fibrinolytic effects. In a case series describing the use of intrapleural streptokinase or urokinase in 26 patients, one developed major oozing from rib fractures sustained 1 month before therapy (89). This local bleeding required two thoracotomies. It is not clear from the report if streptokinase or urokinase was used in this patient, but streptokinase was used in most of patients in this series. Furthermore, the dose used was also not clear, with streptokinase doses of 100 000-750 000 lU. 

Combination reperfusion therapy with reduced-dose fibrinolytic and a glycoprotein Ilb/IIIa inhibitor for patients with a large quantity of anterior myocardium at risk and at low risk for bleeding. 

Figure 10.2 The emergence of pharmacoinvasive therapy in practice is evident by comparing the approaches actually used in CAPTIM and DANAMI-2 (11,12). There was >10-fold difference in the use of urgent PCI after full-dose thrombolytics in CAPTIM compared with the earlier DANAMI-2 trial. Favorable results in CAPTlM s fibrinolytic arm may be directly related to the high nse of early PCI subsequently.

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