Anticoagulation and thrombolytic therapy


Anticoagulation and thrombolytic therapy

Two major classes of drugs are commonly used in the management of thromboembolic disease. The anticoagulants heparin and warfarin are used to prevent thrombosis and limit the extension of an established clot, while thrombolytic agents such as streptokinase are used to dissolve thrombus.



Unfractionated heparin is a naturally occurring glycosaminoglycan produced by mast cells. Low molecular weight (LMW) heparin is prepared by controlled depolymerisation of the unfractionated form. Both unfractionated and LMW heparin exert their anticoagulant properties by binding to antithrombin (AT) and potentiating its activity. AT is a normal circulating anticoagulant which inhibits the actions of factor Xa and thrombin. LMW heparin differs from unfractionated heparin in having a relatively greater anti-Xa than antithrombin activity.

Unfractionated heparin

Standard unfractionated heparin may be used therapeutically to treat established thrombosis (usually intravenously at higher dosage) or prophylactically to prevent thrombosis (usually subcutaneously at lower dosage). Most common indications for therapeutic use are deep vein thrombosis (DVT) and pulmonary embolism (PE) (Fig 40.1). A typical regimen is an intravenous loading dose of 5000 units followed by an infusion of 1000–2000 units/hour. The anticoagulant response varies as the drug binds non-specifically to plasma and cellular proteins. Laboratory monitoring using the APTT (see p. 20) is required; the therapeutic range is usually 1.5–2.5, these values being the ratio of the patient’s APTT to a control sample. As the half-life is short, high APTTs are managed by stopping the heparin but in the event of bleeding (in up to 7% of cases) the antidote protamine can be given. When the APTT is too low the heparin dose should be promptly increased. Heparin is normally continued until oral anticoagulation is therapeutic.

Prophylactic heparin is most commonly given to prevent DVT and PE in patients undergoing surgery. It is particularly indicated in patients with known risk factors for venous thrombosis (see p. 78) and in major procedures. A typical prophylactic regimen is 5000 units subcutaneously preoperatively and 5000 units 8- to 12-hourly after surgery, for 7 days or until the patient is mobile. No laboratory monitoring is necessary in routine cases – where required anti-Xa assays are used.

Apart from haemorrhage, patients on heparin may develop thrombocytopenia (see p. 69) and prolonged use can cause osteoporosis. It should be prescribed cautiously where there is any bleeding tendency.

Jun 12, 2016 | Posted by in HEMATOLOGY | Comments Off on Anticoagulation and thrombolytic therapy
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