Fibrinolytic therapy

With alteplase, another endogenous plasminogen activator (tissue plasminogen activator, tPA) is available. With physiological concentrations this activator preferentially acts on plasminogen bound to fibrin. In concentrations needed for therapeutic fibrinolysis this preference is lost and the risk of bleeding does not differ with alteplase and streptokinase. Alteplase is rather short-Liillmann, Color Atlas of Pharmacology 

Inactivation of the fibrinolytic system can be achieved by plasmin inhibitors, such as -aminocaproic acid, p-aminomethylbenzoic acid (PAMBA), tranexamic acid, and aprotinin, which also inhibits other proteases. 

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Therapeutically t-PA and urokinase are the most important drugs for fibrinolytic therapy (myocardial infarction, stroke, massive pulmonary embolism). This treatment is associated with an enhanced risk of bleeding complications. 

Summarizing the fibrinolytic therapy, it should be emphasized that efficient treatment needs urgent application of plasminogen activator (within a few hours) to prevent the formation of crosslinks in the fibrin structure (Fig. 2) and to find the localization of thrombus to emerge plasmin on the surface of fibrin to prevent rapid inactivation of the enzyme by the inhibitor system of fibrinolysis (Fig. 3). 

Zeumer H, Ereitag HJ, Zanella E, Thie A, Arning C. Local intra-arterial fibrinolytic therapy in patients with stroke urokinase versus recombinant tissue plasminogen activator (r-TPA). Neuroradiology 1993 35 159-162. 

Sasaki O, Shigekazu T, Koike T, Koizumi T, Tanaka R. Fibrinolytic therapy for acute embolic stroke intravenous, intracarotid, and intra-arterial local approaches. Neurosurgery 1995 36 246-253. 

A reduction of at least 50% of the ST-segment elevation on follow-up ECG obtained 60-90 min after fibrinolytic therapy... 

Contraindications to Fibrinolytic Therapy in Patients With ST-Elevation Myocardial Infarction... 

Platelet dysfunction may be seen with fibrinolytic therapy... 

TABLE 5-3. Indications and Contraindications to Fibrinolytic Therapy per ACC/AHA Guidelines for Management of Patients with ST-Segment Elevation Myocardial Infarction3... 

In general, early pharmacotherapy of NSTE ACS (Fig. 5-3) is similar to that of STE ACS with three exceptions (1) fibrinolytic therapy is not administered (2) glycoprotein Ilb/IIIa receptor blockers are administered to high-risk patients for medical therapy as well as to PCI patients and (3) at this time, there are no standard quality indicators for patients with NSTE ACS who are not diagnosed with MI. 

Fibrinolytic therapy is not indicated in any patient with NSTE ACS, as increased mortality has been reported with fibrinolytics compared to controls in clinical trials in which fibrinolytics have been administered to patients with NSTE ACS (patients with normal or ST-segment depression ECGs).10... 

Ezura, M., Takahashi, A. and Yoshimoto, T. Evaluation of regional cerebral blood flow using single photon emission tomography for the selection of patients for local fibrinolytic therapy of acute cerebral embolism. Neurosurg. Rev. 19 231-236, 1996. 

It is not necessary to obtain the results of biochemical markers before initiating fibrinolytic therapy. 

Absolute contraindications to fibrinolytic therapy include (1) active internal bleeding (2) previous ICH at anytime (3) ischemic stroke within 3 months (4) known intracranial neoplasm (5) known structural vascular lesion (6) suspected aortic dissection and (7) significant closed head or facial trauma within 3 months. Primary PCI is preferred in these situations. 

GP Ilb/IIIa inhibitors may increase the risk of bleeding, especially if given in the setting of recent (<4 hours) administration of fibrinolytic therapy. An immune-mediated thrombocytopenia occurs in about 5% of patients. 

Fibrinolytics are not indicated in any patient with NSTE ACS, even those who have positive biochemical markers that indicate infarction. The risk of death from MI is lower in these patients, and the hemorrhagic risks of fibrinolytic therapy outweigh the benefit. 

Collen, D. (1998). Staphylokinase a potent, uniquely fibrin-selective thrombolytic agent. Nature Med. 4(3), 279-284. Collins, R. et al. (1997). Drug therapy—aspirin, heparin and fibrinolytic therapy in suspected acute myocardial infarction. N. Engl. J. Med. 336(12), 847-860. 

Fibrinolytic Therapy TriaUsts (FTT) Collaborative Group. Indications for fibrinolytic therapy in suspected acute myocardial infarction collaborative overview of early mortality and major morbidity results from aU randomised trials of more than 1000 patients. Lancet 1994 343(8893) 311-22. 

In contrast, intravenous fibrinolytic therapy is harmful without acute ST-segment elevation, a true posterior MI or a presumed new left bundle-branch block. 

The basic concept of prehospital care and patient transfer is carrying the patient to a facility capable of rapid revascularization, if fibrinolysis therapy is contraindicated. If the patient cannot be transferred to the facility capable of prompt intervention, fibrinolytic therapy is strongly recommended to start within 90 minutes of first medical contact. After such treatment, medical therapy will become important in managing the patient. 

As was said before, fibrinolytic therapy is recommended in many cases. It is recommended for patients with the onset of the STEMI within 12 hours, for patient with significant EGG changes having ST... 

Randomized comparison of direct thrombin inhibition versus heparin in conjunction with fibrinolytic therapy for acute myocardial infarction results from the GUSTO-lib Trial. Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO-lib) Investigators. J Am Coll Cardiol, 1998.31(7) 1493-8. 

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