Thrombolytic functions

Therapeutic enzymes have a broad variety of specific uses, ie, as oncolytics, thrombolytics, or replacements for inherited deficiencies. Additionally, there is a growing group of miscellaneous enzymes of diverse function. 

Several clinical trials have been conducted with streptokinase adrninistered either intravenously or by direct infusion into a catheterized coronary artery. The results from 33 randomized trials conducted between 1959 and 1984 have been examined (75), and show a significant decrease in mortaUty rate (15.4%) in enzyme-treated patients vs matched controls (19.2%). These results correlate well with an ItaUan study encompassing 11,806 patients (76), in which the overall reduction in mortaUty was 19% in the streptokinase-treated group, ie, 1.5 million units adrninistered intravenously, compared with placebo-treated controls. The trial also shows that a delay in the initiation of treatment over six hours after the onset of symptoms nullifies any benefit from this type of thrombolytic therapy. Conversely, patients treated within one hour from the onset of symptoms had a remarkable decrease in mortaUty (47%). The benefits of streptokinase therapy, especially in the latter group of patients, was stiU evident in a one-year foUow-up (77). In addition to reducing mortahty rate, there was an improvement in left ventricular function and a reduction in the size of infarction. Thus early treatment with streptokinase is essential. 

After a baseline angiogram confirms the presence and location of the vascular occlusion, a microcatheter is navigated over a microwire into the occluded vessel, traversing the thrombus. Once the microcatheter is positioned immediately distal to the clot, thrombolytic infusion begins the microcatheter is then pulled back through the clot while dmg is infused. Dose adjustments and total dose calculations are made depending on the clinical circumstances, pretreatment dose of rt-PA received, degree of recanalization, and relative size and function of the territory at risk. 

Drag interactions Concomitant treatment with thrombolytic agents may increase the risk of bleeding comphcations and considerably enhance the effect of Refludan on aPTT prolongation. Concomitant treatment with coumarin derivatives (vitamin K antagonists) and drugs that affect platelet function may also increase the risk of bleeding. 

E. Therapeutic response Activase, and other thrombolytic agents, used in a timely manner during an evolving myocardial infarction, decrease mortality and improve left ventricular function. Resolution of chest pain, resolution of baseline EKG changes, reduced total creatine phospho-kinase (CPK) release, and preserved left ventricular function are evidence of cardiac reperfusion. Activase, administered within the first 3 hours of ischemic stroke onset, has been shown to improve recovery. 

All patients with acute myocardial infarction should be considered for intravenous thrombolytic therapy with streptokinase, tissue plasminogen activator (TPA), or anistreplase because these agents are effective in both preserving cardiac function and reducing mortality. 

Tissue plasminogen activator (tPA) is a protease with 527 amino acids and 4 glycosylation sites that acts in vivo as a thrombolytic agent. Its function is to proteolytically convert the zymogen, plasminogen, into active plasmin, which in turn degrades fibrin strands, thus dissolving the clots (Walsh, 2003). For this reason, recombinant tPA molecules... 

The ideal marker of myocardial injury should (1) provide early detection of injury, (2) allow rapid diagnosis of cardiac injury, (3) serve as a risk stratification tool in patients with ACS, (4) assess the success of reperfusion after thrombolytic therapy, (5) detect reocclusion and reinfarction, (6) determine the timing of an infarction as well as infarct size, and (7) detect procedural-related perioperative MI during cardiac or noncardiac surgery. At present, the perfect biomarker to satisfy all these needs does not exist. It is the function of the laboratory to provide advice to physicians about cardiac biomarker characteristics. 

RaoGHR, Wilson RF, White CW, White JG. Influence of thrombolytic agents on human platelet function. 

Azides affecting CNS function Azidomorphine and derivatives A zidobenzodiazepines Miscellaneous CNS-active azides Azides influencing cardiovascular activity Diuretic azidopyrimidines Azidoglycol renin inhibitors Miscellaneous antihypertensive azides Thrombolytic azidoquinolines... 

Balduini CL, Noris P, Bertolino G, Previtali M. Heparin modifies platelet count and function in patients who have undergone thrombolytic therapy for acute myocardial infarction. Thromb Haemost 1993 69(5) 522-3. 

Monoclonal antibodies to GPlIb/IIIa receptors are effective inhibitors of platelet function. Animal studies suggest that they may reduce both the dose, and the delay in onset of thrombolytic effect with streptokinase and similar agents when they are used in treating the sequelae of myocardial infarction. Early trials in humans suggest that these agents will be valuable for some specialist applications. 

The pathophysiology of contractile dysfunction observed in stunning and hibernation has been better characterized. Stunning may explain much delayed contractile recovery after thrombolytic therapy. Hibernation is searched for in efforts to improve left contractile function by revascularization. 

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