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[Antithrombin therapy in acute coronary syndromes]
A Maseri1, F Andreotti, L M Biasucci
1Istituto di Cardiologia, Università Cattolica del Sacro Cuore, Roma.
Insights
Intracoronary thrombosis is key in acute coronary syndromes. Thrombin inhibitors, like heparin and newer direct agents, aim to prevent pathological thrombus formation, with new drugs showing promise but needing more study.
Area of Science:
- Cardiology
- Hematology
- Pharmacology
Context:
- Intracoronary thrombosis underlies acute coronary syndromes.
- Thrombin generation is critical for thrombus formation and progression.
- Current treatments like heparin have limitations in inhibiting clot-bound thrombin.
Purpose:
- To review the role of thrombin inhibition in acute coronary syndromes.
- To compare the efficacy and limitations of heparin versus newer direct thrombin inhibitors.
- To discuss the clinical indications for antithrombin therapies.
Summary:
- Heparin, a primary antithrombin, enhances antithrombin III's effect but doesn't inhibit clot-bound thrombin and requires monitoring.
- Newer direct thrombin inhibitors (hirudin, hirulog, argatroban) offer potential advantages like reduced monitoring and inhibition of clot-bound thrombin.
- Clinical studies suggest newer agents may be more effective but carry a higher risk of bleeding in acute myocardial infarction patients receiving thrombolysis.
Impact:
- Heparin remains indicated for unstable angina and myocardial infarction with rt-PA.
- Direct thrombin inhibitors show promise but require further clinical evaluation for safety and efficacy.
- Understanding thrombin's role guides the development of more effective antithrombotic strategies.
Abstract:
Intracoronary thrombosis is fundamental in the pathogenesis of acute coronary syndromes, although the causes of thrombosis are still unclear. As thrombin generation is crucial for thrombus formation, the inhibition of thrombin is a primary aim to prevent the evolution of an initial repair process into a pathological thrombus. Thrombin inhibition can be achieved by several drugs. Heparin is the principal antithrombin drug currently used in acute syndromes; it acts mainly by binding to antithrombin III and increasing its inhibitory effect on thrombin and other coagulation factors. The heparin-antithrombin III complex, however, does not inhibit thrombus-bound thrombin; moreover, iv heparin requires frequent laboratory monitoring and dose adjustments. Despite these limitations, continuous infusion of i.v. heparin has been found to be effective in unstable angina and in myocardial infarction, especially when treated with accelerated rt-PA. New antithrombin drugs that selectively and directly inhibit thrombin are hirudin, its synthetic derivate hirulog, and argatroban. These drugs have several theoretical advantages over heparin: greater stability of the aPTT--with the need for less laboratory monitoring--and greater efficacy--associated mainly with its capacity to inhibit clot-bound thrombin. Clinical pilot studies seem to indicate a greater antithrombotic efficacy compared with heparin, but a greater number of hemorrhagic events in patients with acute myocardial infarction receiving thrombolysis. In conclusion, the use of heparin is certainly indicated in patients with unstable angina and persistent ischemia and in acute myocardial infarction treated with accelerated rt-PA. The use of new antithrombin drugs, although promising, requires further clinical evaluation.