Hemorrhage and the products of fibrinogen digestion after intracoronary administration of streptokinase.

Abstract

Hemorrhage was prospectively identified in 26 of 116 consecutive patients (23%) who were receiving intracoronary streptokinase for occlusive coronary thrombi producing infarction. Bleeding was not influenced by the dose of streptokinase or the method of cardiac catheterization. Before treatment, prothrombin time and partial thromboplastin time were normal in both bleeders and nonbleeders. Fibrinogen levels measured by bioassay after streptokinase (mean + SEM) were 62 29 mg/dl in patients with major bleeding, 1 11 ±+ 26 mg/dl in patients with minor bleeding, and 109 + 13 mg/dl in nonbleeders (p -NS). The regression slope b calculated from poststreptokinase fibrinogen time-concentration data in 71 patients was 4.7 mg/dl/hr. However, mean fibrinogen concentrations calculated at sequential 5 hr intervals revealed no net regeneration for the first 20 hr after thrombolysis. The apparent fibrinogen regeneration rate was less than normal (31 mg/kg/day) for more than 10 hr but subsequently increased to 94 10 mg/kg/day by the second day. The initial apparent latency of fibrinogen regeneration paralleled the sharp rise in fibrinogen degradation products, which began to decline after 20 hr of treatment but remained elevated well into the second day. Because of their anticoagulant effects, these products may interfere with the fibrinogen assay, causing spuriously low results. Thus, whether the early delay in fibrinogen regeneration is real or simply a reflection of the effects of fibrinogen degradation products on the bioassay, it signals the time for caution in initiating systemic-heparin therapy.

Clinical pharmacology in patients with evolving myocardial infarction of tissue-type plasminogen activator produced by recombinant DNA technology.

“…The short half-life of rt-PA and the lack of elaboration of functionally active fragments during the course of infusions of rt-PA probably contributed to the absence of prolonged adverse effects on the hemostatic system, in contrast to the case after infusion of conventional activators of the fibrinolytic system such as streptokinase." 17 Overall, in the group of patients given rt-PA, depletion of circulating fibrinogen was modest, depletion of circulating plasminogen was incomplete, and prolongation of the prothrombin time and/or protamine-corrected thrombin time was clinically insignificant.…”

Hemorrhagic complications associated with the use of intravenous tissue plasminogen activator in treatment of acute myocardial infarction

“…For this reason, the major impetus to the development of new thrombolytic agents has been the search for compounds with greater fibrin specificity. Older thrombolytic agents, such as streptokinase and urokinase, were known to be associated with significant bleeding complication rates [4,5], at least in part due to the systemic lytic state induced by the depletion of fibrinogen in the systemic circulation [6,7]. Early studies with the prototype fibrin-specific agent, tissue plasminogen activator (t-PA), suggested that although some systemic fibrinogen breakdown occurred, relative sparing of fibrinogen with a low bleeding complication rate was observed [8-lo].…”

Use of angioplasty in the management of complicated perioperative infarction following bypass surgery

“…While thrombolysis alone may remove the thrombus burden in occluded grafts or coronary arteries, the anatomic precipitant may remain. In addition, even lower doses [22] or intracoronary adminjstratjon [23] may precipitate systemic fibrinogenolysis and may be contraindicated in the perioperative period. We regard thrombolysis as adjunctive therapy to direct angioplasty in this setting and use it with caution.…”