Latest news – News about Thrombolytic Therapy

The indications for thrombolytic therapy are for patients presenting with chest discomfort within 12 hours of onset and with ST segment elevation 1mm in at least two limb leads and 2mm in two or more contiguous precordial leads suggestive of STEM or new left bundle branch block. To achieve optimal benefit from thrombolytic therapy, the lytic drugs should be started as early as possible based on the electrocardiogram ECG criteria, without waiting for the creatinine kinase CK or troponin enzyme result. A 30 day overall 7% mortality rate achieved by thrombolytic therapy is well proven in large randomized trials. The current lytic agents are divided into two groups, the fibrin selective and the less fibrin selective agents. The drugs that lack or have less fibrin specificity such as streptokinase SK, urokinase and lanoteplase n-PA, activate plasminogen indiscriminately whether it is physically bound with fibrin inside the thrombus or free in the circulation. So they induce a systemic lytic state, evidenced by depletion of circulating plasminogen, degradation of fibrinogen, which causes a high level of fibrinogen degradation products FDP’s and a decreased level of alpha antiplasmin. This low level of fibrinogen and high level of FDP’s with anticoagulant properties helps to sustain the process of thrombotic dissolution so there is no need for unfractioned heparin UFH. The fibrin selective agents are tissue plasminogen activators t-PA such as alteplase, duteplase or saruplase single chain urokinase, tenecplase TNK tPA and staphylokinase. They activate fibrin associated plasminogen preferentially at the clot surface, cleaving plasminogen to plasmin. Since this plasmin is already bound to fibrin at the lysine binding sites, this opens up new binding sites, that can bind more of the fibrinolytic and more plasminogen, thus fasciliating continued lysis of the clot. By this mechanism, the fibrin selective agents induce thrombolysis without causing a systemic lytic state or depletion of fibrinogen in the circulation so they need UFH and cause less intracranial hemorrhage ICH. The biochemical characteristics of any ideal lytic drug are to have slow plasma clearance to be more fibrin specific and to be resistant to plasminogen activator inhibitor I. As the plasma clearance is slower, the half life of the drug is longer. Then it can be given as a simple intravenous bolus which can decrease substantially the delay in the process of administration. If the drug is more fibrin binding, its efficacy should be improved and it can be given in a smaller dose. To be effective, thrombolytic therapy requires dissolution of the fibrin network of a thrombotic clot, complete suppression of further thrombin generation and platelet aggregation. With current results, the advantage of thrombolytic therapy is by earliest restoration of flow due to its quick and simple intravenous administration. It does not resolve full epicardial or microvascular flow to the majority of patients, nor sustain its patent thereafter. Because of the incomplete results of thrombolytic therapy and ineligibility of many patients at first ballon angioplasty POBA was performed on patients with STEM. In the primary coronary angioplasty with Thrombolysis PCAT study, the results showed clearly the short and long term mortality reduction of POBA over thrombolytic therapy.