Tinzaparin

Tinzaparin is a low molecular weight heparin produced by enzymatic depolymerisation. It prevents and treats venous thromboembolism and is dosed in anti Xa units for each kilogram once daily. It has a higher molecular weight than other low molecular weight heparins and accumulates less in kidney impairment, but a mortality signal was seen in older adults with creatinine clearance under 30 mL/min. It is rarely available in East Africa.

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

Mechanism. Binds antithrombin, speeding inactivation of factor Xa (anti Xa to anti IIa ratio about 1.9 to 1) and thrombin.

Pharmacodynamics. Peak anti Xa activity about 4 hours after subcutaneous injection; duration about 24 hours.

Pharmacokinetics. Subcutaneous bioavailability about 90%. Half life 3 to 4 hours (longer in kidney impairment). Cleared by the kidneys and reticuloendothelial system.

Prevention of venous thromboembolism, adult.

• Moderate risk surgery: 3500 units SC once daily (first dose 2 hours before surgery).

• High risk surgery (orthopaedic): 4500 units SC once daily (starting 12 hours before surgery).

• Continue for 7 to 10 days (longer in selected patients).

Treatment of deep vein thrombosis and pulmonary embolism, adult. 175 units/kg SC once daily for at least 6 days and until adequate oral anticoagulation is established (INR 2.0 or more for 24 hours).

Cancer associated thrombosis, adult (specialist). 175 units/kg SC once daily for 3 to 6 months.

Pregnancy. Weight based; prevention 4500 units once daily (adjust for weight); treatment 175 units/kg once daily with anti Xa monitoring.

Children. Not established.

Contraindications. Active major bleeding; history of heparin induced thrombocytopenia; haemorrhagic stroke; acute bacterial endocarditis; severe thrombocytopenia; recent neuraxial anaesthesia; hypersensitivity (including to pork products and sulphites).

Warnings. Bleeding; spinal haematoma; thrombocytopenia (days 4 to 14); hyperkalaemia; osteoporosis; accumulation in kidney impairment, with higher mortality reported in people over 70 years with creatinine clearance under 30 mL/min; 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 tinzaparin given (partial reversal).

Special groups.

• Pregnancy: safe; weight based dosing with anti Xa monitoring.

• Breastfeeding: safe.

• Patients of African ancestry: no dose change.

• Older adults: avoid treatment doses if creatinine clearance is under 30 mL/min.

• Kidney impairment: creatinine clearance 20 to 30 mL/min: caution with anti Xa monitoring; under 20 mL/min: use unfractionated heparin.

• Liver impairment: use with care.

Formulations. Prefilled syringes 3500, 4500, 10000, 14000, 18000 units; vials 20000 units/mL.

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, pregnancy, obesity (target 0.5 to 1.0 units/mL once daily). Creatinine every 3 months.

Stopping. Stop after the planned course or when oral anticoagulation is therapeutic; no taper.

Common prescribing errors. Using the prevention dose for treatment; full dose in older adults with creatinine clearance under 30 mL/min; confusing units with enoxaparin mg; missing platelet counts.