vitamin-k-semiquinone-radical and Angina--Unstable

Older individuals contribute heavily to the percentage of deaths due to myocardial infarction (MI) and stroke. The incidence of venous thromboembolism (VTE) is highest in subjects > 65 years. Prospective intervention trials involving groups of clinically comparable subjects > or = 60 allow the following statements to be made with regard to the use of antithrombotic drugs in the elderly. Antiplatelet agents. To prevent recurrence of ischaemic stroke and MI in stable/unstable angina, MI, TIA/stroke or peripheral arterial disease, aspirin is the drug of choice. Clopidogrel is more effective than aspirin in this respect. Heparin. For the treatment of acute deep venous thrombosis (DVT) and pulmonary embolism (PE), intravenous standard heparin or subcutaneous standard heparin are effective (aPTT 1.5-2.0 times baseline values). As the risk of bleeding increases with age, low-molecular-weight heparins (LMWH) are preferable in the elderly. For the prophylaxis of VTE in general surgery in subjects at low-moderate risk, low-dose heparin or low doses of LMWH are effective. In subjects at high risk, adjusted-dose heparin plus physical devices or high-dose LMWH are recommended. The combination of heparin and aspirin is the standard treatment for unstable angina and non-Q wave MI. LMWH are as active as standard heparin in this indication. Vitamin K antagonists. For the chronic treatment of VTE, warfarin is also the treatment of choice (INR 2.0-3.0) in the elderly, though lower doses are needed due to their hypersensitivity to oral anticoagulants. For the prevention of thromboembolic stroke in patients > 75 with atrial fibrillation, warfarin is the drug of choice. Patients aged 65-75 may receive warfarin or aspirin. Thrombolytic agents. Thrombolytic agents are not recommended for treating DVT in the elderly because of their limited risk/benefit ratio and should be confined to massive PE. In the absence of contraindications, thrombolysis for MI may be considered in the elderly.

Topics: Aged; Angina, Unstable; Anticoagulants; Aspirin; Female; Fibrinolytic Agents; Heparin; Heparin, Low-Molecular-Weight; Humans; Lysine; Male; Practice Guidelines as Topic; Secondary Prevention; Thromboembolism; Veins; Vitamin K

Nine out of 47 (19%) patients on chronic anticoagulation with warfarin, as secondary prophylaxis after myocardial infarction, initially treated with streptokinase, had thromboembolic complications within 4 weeks after sudden (7/25) or gradual (2/22:NS) warfarin withdrawal. The biochemical effects of warfarin withdrawal were repeatedly studied in 20 of the patients during the first 14 days following drug cessation. During the first 4 days, the levels of coagulation factors VII and IX increased more rapidly than proteins C and S. Thus, a gap was created between the factors provoking and inhibiting the coagulation process. Furthermore, plasma concentrations of fibrinopeptide A (FPA) increased, reflecting activation of the coagulation system. These laboratory findings suggest that withdrawal of warfarin creates a transient hypercoagulable state, imposing a risk of thromboembolic events in patients given anticoagulant treatment as secondary prophylaxis following myocardial infarction.

Topics: Adult; Aged; Angina, Unstable; Blood Coagulation Disorders; Blood Coagulation Factors; Cerebrovascular Disorders; Drug Therapy, Combination; Female; Heparin; Humans; Male; Middle Aged; Myocardial Infarction; Peripheral Vascular Diseases; Streptokinase; Thromboembolism; Treatment Outcome; Vitamin K; Warfarin

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.

Topics: Acute Disease; Angina, Unstable; Coronary Thrombosis; Fibrinolytic Agents; Heparin; Humans; Myocardial Infarction; Syndrome; Thrombin; Thrombolytic Therapy; Vitamin K