Dalteparin

Dalteparin is a low molecular weight heparin used to prevent and treat venous thromboembolism, to treat acute coronary syndromes, and to treat cancer associated thrombosis. It is dosed in units of anti Xa activity. It accumulates less than enoxaparin in kidney impairment but still needs monitoring when creatinine clearance is under 30 mL/min. Availability in East Africa is limited.

Classification. Low molecular weight heparin; indirect factor Xa inhibitor.

Mechanism. Binds antithrombin, speeding the inhibition of factor Xa (anti Xa to anti IIa ratio about 2.7 to 1) and, less, thrombin.

Pharmacodynamics. Peak anti Xa activity 4 hours after subcutaneous injection; duration up to 24 hours. Little effect on aPTT.

Pharmacokinetics. Subcutaneous bioavailability about 87%. Half life 3 to 5 hours (longer in kidney impairment). Cleared mainly by the kidneys.

Prevention of venous thromboembolism, adult.

• Moderate risk surgery or medical patients: 2500 units SC once daily (first dose 1 to 2 hours before surgery).

• High risk surgery: 5000 units SC once daily (evening before surgery), or 2500 units 1 to 2 hours before and 2500 units 8 to 12 hours after surgery.

• Duration 5 to 14 days (up to 35 days after hip surgery or cancer surgery).

Treatment of venous thromboembolism, adult. 200 units/kg SC once daily (maximum 18000 units) or 100 units/kg every 12 hours for at least 5 days and until the INR is 2.0 or more for 24 hours.

Cancer associated thrombosis, adult. 200 units/kg once daily (maximum 18000 units) for the first month, then 150 units/kg once daily (maximum 18000 units) for months 2 to 6.

Unstable angina and non ST elevation myocardial infarction, adult. 120 units/kg SC every 12 hours (maximum 10000 units each dose) with aspirin for 5 to 8 days.

Pregnancy. Weight based prevention (usually 5000 units daily in the second and third trimester, adjusting for weight); treatment 100 units/kg every 12 hours with anti Xa monitoring.

Children (specialist). Treatment: 100 units/kg every 12 hours (adjust to anti Xa); prevention: 100 units/kg once daily.

Contraindications. Active major bleeding; history of heparin induced thrombocytopenia; haemorrhagic stroke; acute bacterial endocarditis; severe thrombocytopenia; recent neuraxial anaesthesia within 12 hours of a dose; hypersensitivity (including to pork products).

Warnings. Bleeding; spinal haematoma (needle placement 12 hours after a prophylactic dose and 24 hours after a treatment dose); thrombocytopenia (check platelets days 4 to 14); hyperkalaemia; osteoporosis in long term use; accumulation in kidney impairment; mechanical heart valves.

Adverse effects. Bleeding, injection site haematoma, thrombocytopenia, raised liver enzymes, hyperkalaemia.

Interactions. Aspirin, antiplatelet drugs, non steroidal anti-inflammatory drugs, warfarin, direct oral anticoagulants, thrombolytics: bleeding.

Reversal. Protamine sulphate 1 mg for each 100 anti Xa units of dalteparin given (about 60% neutralisation).

Special groups.

• Pregnancy: safe; use weight based dosing.

• Breastfeeding: safe.

• Patients of African ancestry: no dose change.

• Older adults: adjust for kidney function.

• Kidney impairment: creatinine clearance under 30 mL/min: use anti Xa monitoring (target 1.0 units/mL at 4 hours) and reduce the dose; avoid if under 15 mL/min.

• Liver impairment: use with care.

Formulations. Prefilled syringes 2500, 5000, 7500, 10000, 12500, 15000, 18000 units.

Administration. Deep SC injection into the abdomen; alternate sides.

Baseline. Platelet count, haemoglobin, creatinine clearance, liver function, weight.

Monitoring. Platelet count every 2 to 3 days from days 4 to 14. Anti Xa level at 4 hours after the third dose in kidney impairment, obesity, pregnancy and children. Creatinine every 3 months in long treatment.

Stopping. Stop after the planned course; no taper.

Common prescribing errors. Using the wrong strength syringe (units differ from enoxaparin mg); full dose in kidney impairment; omitting weight; forgetting the dose reduction after one month in cancer thrombosis.