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-X_a 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.

LMW heparin

LMW heparins are now preferred for treatment of DVT and PE and prophylaxis. They appear to have superior efficacy, a better safety profile and to be more cost-effective than unfractionated heparin. LMW heparins cause less bleeding and a lower incidence of thrombocytopenia and osteoporosis. The more predictable dose response precludes the need for routine monitoring and the long half-life allows once or twice daily subcutaneous administration. Where monitoring is indicated (e.g. in renal failure), the anti-Xa effect is measured. LMW heparin treatment allows outpatient management of uncomplicated DVT.

Fondaparinux is a synthetic form of the heparin pentasaccharide molecule with a specific anti-Xa effect. It has similar indications to LMW heparin.