Antifibrinolytic Drugs and Haemostatics
July 4, 2017Fibrinolytic Drugs
July 4, 2017Parenteral Anticoagulants:
The main use of anticoagulants is to prevent thrombus formation or extension of an existing thrombus in the slower-moving venous side of the circulation, where the thrombus consists of a fibrin web enmeshed with platelets and red cells.
They are therefore widely used in the prevention and treatment of deep-vein thrombosis in the legs. Anticoagulants are of less use in preventing thrombus formation in arteries, for in faster-flowing vessels thrombi are composed mainly of platelets with little fibrin. They are used to prevent thrombi forming on prosthetic heart valves.
Heparin:
Indications: Heparin Sodium Injection is indicated for Anticoagulant therapy in prophylaxis and treatment of venous thrombosis and its extension; Low-dose regimen for prevention of postoperative deep venous thrombosis and pulmonary embolism in patients undergoing major abdominothoracic surgery or who, for other reasons, are at risk of developing thromboembolic disease.
Contraindications: haemophilia and other haemorrhagic disorders, thrombocytopenia (including history of heparin-induced thrombocytopenia), recent cerebral haemorrhage, severe hypertension; severe liver disease (including oesophageal varices), peptic ulcer; after major trauma or recent surgery to eye or nervous system; acute bacterial endocarditis; spinal or epidural anaesthesia with treatment doses of heparin; hypersensitivity to heparin or to low molecular weight heparins.
Dose and Administration:
Treatment of deep-vein thrombosis, pulmonary embolism, unstable angina, and acute peripheral arterial occlusion, by intravenous injection, loading dose of 5000 units or 75 units/kg (10 000 units in severe pulmonary embolism), followed by continuous intravenous infusion of 18 units/kg/hour or treatment of deep-vein thrombosis, by subcutaneous injection of 15 000 units every 12 hours.
Prophylaxis in general and gynaecological surgery (see notes above), by subcutaneous injection, 5000 units 2 hours before surgery, then every 8–12 hours for 7–10 days or until patient is ambulant (monitoring not needed); during pregnancy (with monitoring), 5000– 10 000 units every 12 hours.
Haemodialysis by intravenous injection initially 1000–5000 units, followed by continuous intravenous infusion of 250– 1000 units/hour
Low Molecular Weight Heparins:
Low molecular weight heparins are usually preferred over unfractionated heparin in the prevention of venous thromboembolism because they are as effective and they have a lower risk of heparin-induced thrombocytopenia. Also, the standard prophylactic regimen does not require monitoring. In orthopaedic practice Low molecular weight heparins are probably more effective than unfractionated heparin; fondaparinux can also be used. The duration of action of Low molecular weight heparins is longer than that of unfractionated heparin; once-daily subcutaneous dosage means that they are convenient to use.
Enoxaparin:
Indications: indicated for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE). Treatment of Acute Deep Vein Thrombosis. Prophylaxis of Ischemic Complications of Unstable Angina and NonQ-Wave Myocardial Infarction. Treatment of Acute ST-Segment Elevation Myocardial Infarction.
Contraindications: see under heparin.
Dose and Administration:
Prophylaxis of deep-vein thrombosis especially in surgical patients, by subcutaneous injection, moderate risk, 20 mg (2000 units) approx. 2 hours before surgery then 20 mg (2000 units) every 24 hours for 7–10 days; high risk (e.g. orthopaedic surgery), 40 mg (4000 units) 12 hours before surgery then 40 mg (4000 units) every 24 hours for 7–10 days.
Prophylaxis of deep-vein thrombosis in medical patients, by subcutaneous injection, 40 mg (4000 units) every 24 hours for at least 6 days and continued until patient ambulant (max. 14 days).Treatment of deep-vein thrombosis or pulmonary embolism, by subcutaneous injection, 1.5 mg/kg (150 units/kg) every 24 hours, usually for at least 5 days.Unstable angina and non-ST-segmentelevation myocardial infarction, by subcutaneous injection, 1 mg/kg (100 units/kg) every 12 hours usually for 2–8 days (minimum 2 days).
Tinzaparin:
Indications: indicated for the treatment of acute symptomatic deep vein thrombosis with or without pulmonary embolism when administered in conjunction with warfarin sodium.
Contraindications: contraindicated in patients with active major bleeding, in patients with (or history of) heparin-induced thrombocytopenia, or in patients with hypersensitivity to tinzaparin sodium.
Dose and Administration: Prophylaxis of deep-vein thrombosis, by subcutaneous injection, general surgery, 3500 units 2 hours before surgery, then 3500 units every 24 hours for 7–10 days; orthopaedic surgery (high risk), 50 units/kg 2 hours before surgery, then 50 units/kg every 24 hours for 7–10 days or 4500 units 12 hours before surgery, then 4500 units every 24 hours for 7–10 days. Treatment of deep-vein thrombosis and of pulmonary embolism, by subcutaneous injection, 175 units/kg once daily for at least 6 days (and until adequate oral anticoagulation established)
Treatment of thromboembolic disease in pregnancy [unlicensed indication], by subcutaneous injection, 175 units/kg once daily
Oral Anticoagulants:
Warfarin:
Indications: indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, and pulmonary embolism. indicated for the prophylaxis and/or treatment of the thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement. indicated to reduce the risk of death, recurrent myocardial infarction, and thromboembolic events such as stroke or systemic embolization after myocardial infarction.
Contraindications: peptic ulcer, severe hypertension; renal impairment (avoid if creatinine clearance less than 10 mL/minute); pregnancy
Dose and Administration: Whenever possible, the base-line prothrombin time should be determined but the initial dose should not be delayed whilst awaiting the result. For patients who require rapid anticoagulation the usual adult induction dose of warfarin is 10 mg on the first day; subsequent doses depend upon the prothrombin time, reported as INR (international normalised ratio). For patients who do not require rapid anticoagulation, a lower loading dose can be used over 3–4 weeks. The daily maintenance dose of warfarin is usually 3–9 mg (taken at the same time each day). The following indications and target INRs
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