Increase in Thrombin Generation after Coronary Thrombolysis with rt-PA or Streptokinase with Simultaneous Heparin versus Heparin Alone

Abstract

This study compares the extent of inhibition of thrombin generation and activity achieved in patients with acute myocardial infarction receiving fibrinolytic treatment (streptokinase SK, or rt-PA) and concomitant intravenous heparin treatment adjusted to the patients’ weight with that achieved with the same heparin regimen but without fibrinolytic therapy. The study involved 90 patients, grouped according to their treatment: SK+heparin; rt-PA+heparin, and heparin without thrombolytic agents. Prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), fibrinopeptide A (FPA) and activated partial thromboplastin time were measured. Patients treated with SK+heparin or rt-PA+heparin and higher F1+2 plasma levels than the patients treated with heparin alone at 12, 48 and 72 h in the case of SK+heparin, and at 12, 24, 48 and 72 h in that of rt-PA+heparin. Compared to baseline, the plasma levels of FPA were decreased in the three treatment groups at 24–48 h. There were no significant changes in TAT and FPA plasma levels among the three treatment groups at the different times. After thrombolytic therapy with both SK and rt-PA, there was an increase in thrombin generation, although high-dose intravenous heparin inhibited the different increases in thrombin associated with the thrombolytic agents to the same extent.

Local proCPU (TAFI) Activation during Thrombolytic Treatment in a Dog Model of Coronary Artery Thrombosis can be Inhibited with a Direct, Small Molecule Thrombin Inhibitor (Melagatran)

“…The CPU generation in the present dog model coincides with thrombus formation (when thrombin is generated) and an increase in thrombin generation after coronary thrombolysis with t-PA (22). The link between thrombin generation and proCPU activation is further strengthened by the observation that inhibition of thrombin by melagatran attenuates CPU generation (Figure 3).…”

RNAi Targeting Embryonic Myosin Heavy Chain Isoform Inhibited Bound Thrombin-Induced Migration of Vascular Smooth Muscle Cells

“…The residual thrombin in clot has been called postclotting thrombin (bound thrombin). After percutaneous transluminal coronary angioplasty, levels of fibrinopeptide A, thrombin-antithrombin III complex and prothrombin fragments 1+2 were significantly increased in many patients, indicating coronary thrombosis by procoagulant activity [6, 7]. It was reported that the coronary thrombosis by procoagulant activity was resistant to the treatment by high doses of heparin [8, 9].…”

A Monoclonal Antibody Against Bovine Thrombin Reacting to the C-Terminal Side of Thrombin

“…(15) In addition, reocclusion and restenosis of blood vessels usually occurs after PTCR (16,17) and the cause of the restenosis could be correlated to the activity of the generated thrombin (postclotting thrombin) from fibrin clot and fibrin thrombin. (18)(19)(20) We therefore attempted to produce a MAb against thrombin to measure the thrombin concentration and postclotting thrombin concentration. A discussion took place regarding which of the MAbs against thrombin could recognize the structure of thrombin.…”