Resolution of Experimental Pulmonary Emboli with Heparin and Streptokinase in Different Dosage Regimens

Abstract

A B S T R A C T Thrombolytic agentsThe amount of residual embolus was 49% in control animals, 28% after heparin (200 U/kg loading dose and 800 U/kg/24 h maintenance dose), and 6% after high dose streptokinase (250,000 U loading dose and 100,000 U/h maintenance dose); it was 31% after low dose streptokinase (25,000 U loading dose and 10,000 U/h maintenance dose), 7% after low dose streptokinase with heparin, 14% after very low dose streptokinase (5,000 U/h without a loading dose) with heparin, and 9% after short course streptokinase (250,000 U loading dose and no maintenance dose) with heparin.The combination of heparin and low doses or brief courses of streptokinase appeared to be synergistic and produced as much resolution as did standard high dose streptokinase alone. The enhanced resolution of pulmonary emboli in heparin-treated animals may have been due to the prevention by heparin of further deposition of fibrin on the embolus. It appears that dosage regimens of thrombolytic therapy other than those in current use may be worthy of clinical examination.This work was presented in part at the 45th Scientific

Fibrinolytic Effects of Urokinase and Heparin in Acute Pulmonary Embolism: A Randomized Clinical Trial

“…The results after the first 24 h, however, showed a significantly greater angiograph ic and scintigraphic improvement in uro kinase-treated patients compared to he parin-treated patients. Heparin infusion during the diagnostic evaluation of all the patients before their random allocation to treatment groups may account for the dif ferences observed in the UPET study after 24 h. In fact, a synergistic effect between heparin and fibrinolytic agents has been postulated to explain the enhanced resolu tion by streptokinase of pulmonary em boli in heparin-treated animals [48]. The same effect is compatible with the findings of the UKEP study, in which embolus re solution appeared greater with an associa tion of moderate doses of urokinase and heparin than with high doses of urokinase alone [49], The observation of a fibrino lytic activity of heparin infusion alone in our patients may be related in some way to this effect observed in dogs [48] and patients [49].…”

Left Apical Pedunculated Thrombus with Normal Ventricular Function Mimicking an Intracardiac Tumor

“…However, as the mass failed to resolve on therapeutic heparin, and also, given the fact that there was no regional wall motion abnormality on echocardiography, the diagnosis of the mass being a tumor became more apparent. Most clots will resolve within 24 hours after initiating a heparin infusion as demonstrated by Cade and colleagues, unless organization has taken place 8 . However, once the mass was confirmed to be thrombus by histopathological examination, we can only speculate that a possible etiology might be a subendocardial infarct in the apex of the left ventricle, as the patient had a mildly elevated troponin I on admission.…”

Effect of Heparin on the Fibrinolytic Response to Plasminogen Activators

“…Adjunct heparin appears to potentiate the lytic response in a variety of published animal models ( Table 3). The effect is observed with SK, 14,15 u-PA, 17,18 t-PA, [16][17][18] low molecular weight heparin preparations, 18 and unfractionated heparin. It seems likely therefore that any beneficial effects of heparin can be attributed to action as an anticoagulant rather than as a cofactor in plasminogen activation.…”