Effect of Low-Dose Heparin Treatment on Fibrinolysis in Patients with Previous Myocardial Infarction

Abstract

The present study was designed to investigate whether medium-term, low-dose heparin treatment is able to affect the fibrinolytic system. In a randomized cross-over study 10 asymptomatic patients with previous (1-6 years) myocardial infarction underwent two sequential 15-day treatments, respectively, on heparin and on placebo (saline solution), preceded and separated by 10-day wash-out periods. Heparin (as calcium heparin, 12,500 IU in 0.5 ml) and saline (0.5 ml) were subcutaneously administered once a day at 8 a.m. Blood samples for fibrinolysis studies were withdrawn on the first and 15th day of each period immediately before and 4 h after heparin or saline administration before and after 10 min venous occlusion (VO) respectively. Four hours after the first heparin administration tissue plasminogen activator antigen (t-PA ag) levels significantly increased with respect to saline administration (p < 0.01 and p < 0.05, respectively). After 15-day heparin treatment a decrease in euglobulin lysis time (p < 0.05) and an increase in t-PA activity (act) (p < 0.05) and in t-PA ag (p < 0.01) in comparison with placebo were observed before VO. No statistically significant changes in plasminogen activator inhibitor-1 (PAI-1) levels were found. The variations of fibrinolytic system activity induced by heparin treatment were more marked when evaluated after VO. These results indicate that medium-term low-dose heparin treatment increases t-PA ag formation and/or release with consequent t-PA act increase.

Effects of Heparin Therapy on Fibrinolysis in Patients with Pulmonary Embolism

“…UFH administration led to a significant increase in the level of tPA:Ag. This effect of heparin on tPA:Ag levels has been generally recognized, however, the exact mechanism is unknown (8)(9)(10)12). Cell culture studies have shown that UFH can stimulate tPA secretion from the vascular endothelium, the main source of tPA (23.…”

“…Taking the diurnal variation of some fibrinolytic parameters into account, no significant increase in fibrinolytic activity was detected in most volunteers, who received a single bolus of 5,000 IU UFH intravenously or subcutaneously, and who were monitored up to 24 h (4-7). In contrast, other studies measured increasing tissue-type plasminogen activator antigen (tPA:Ag) plasma levels as early as 4 h after subcutaneous UFH administration of 7,500-12,500 IU in patients with unstable angina pectoris or previous myocardial infarction (8,9). Similar elevations of tPA:Ag concentrations have been observed in clinical Consecutive in-and outpatients, who underwent diagnostic work up for clinically suspected pulmonary embolism (PE) were eligible for the study.…”

Tissue factor and tissue factor pathway inhibitor levels in unstable angina patients during short‐term low‐molecular‐weight heparin administration

“…As far as the behaviour of fibrinolytic system during LMWH administration was concerned, a slight increase of t‐PA levels was observed, which was of a lesser degree than that reported after UFH administration (Prisco et al , 1993).…”

Evidence That Endogenous Heparin Activity Deficiency may be an Important Factor in Atherogenesis

“…Low doses of heparin increase fibrinolysis. 76 Heparin lowers elevated plasma fibrinogen levels. 77 A decrease of endothelial heparin activity would impair these effects and enhance the possibility of mural microthrombosis.…”