heparin

anticoagulant· Brands: Calciparine, Hep-Lock, HeparinIVSC

Mechanism of action

Heparin is a glycosaminoglycan that binds to antithrombin III, producing a conformational change that greatly increases its ability to inactivate thrombin (factor IIa) and factor Xa. This action inhibits the coagulation cascade and prevents thrombus formation. Unfractionated heparin has a higher ratio of anti-IIa to anti-Xa activity compared with low molecular weight heparins.

Pharmacokinetics

Heparin is poorly absorbed orally and is administered parenterally. It binds extensively to plasma proteins, contributing to variability in anticoagulant response. Heparin is metabolised in the liver and by the reticuloendothelial system, and its elimination half-life is dose-dependent, typically 1 to 2 hours at therapeutic doses. Some metabolites are excreted in urine, and renal impairment may prolong the effect.

Indications & dosing

Treatment of acute venous thromboembolism (DVT/PE)

Follow with continuous IV infusion of 18 units/kg/hr, adjusted to aPTT.

adult · IV: 80 units/kg once · Follow with continuous IV infusion of 18 units/kg/hr, adjusted to aPTT.

Prophylaxis of venous thromboembolism

Given 2 hours before surgery and continued until patient is mobile or at risk resolved.

adult · SC: 5000 units every 8-12 hours · Given 2 hours before surgery and continued until patient is mobile or at risk resolved.

Acute coronary syndromes (unstable angina/NSTEMI/STEMI)

Then 12 units/kg/hr infusion. Maximum initial bolus 4000 units.

adult · IV: 60 units/kg once · Then 12 units/kg/hr infusion. Maximum initial bolus 4000 units.

Contraindications & precautions

Active major bleeding · Heparin is contraindicated in patients with active major bleeding or a blood clotting disorder.
Severe thrombocytopenia · Particularly if platelet count is below 100 x 10^9/L, including a history of heparin-induced thrombocytopenia.
Hypersensitivity to heparin or porcine products · Avoid in patients with a history of heparin-induced thrombocytopenia or severe allergic reactions to heparin.
Recent or planned surgery of the central nervous system or eye · Increased risk of bleeding; consider alternative anticoagulation in the perioperative period.
Active peptic ulcer disease or oesophageal varices · Bleeding risk may be high; use with caution and monitor closely.
Monitor activated partial thromboplastin time (aPTT) regularly and adjust the dose to achieve the therapeutic range.
Monitor platelet count periodically, at baseline and every 2 to 3 days initially, to detect heparin-induced thrombocytopenia.
Use with caution in patients with renal impairment, as accumulation may occur.
Avoid intramuscular injections, as they risk haematoma formation in anticoagulated patients.
Have protamine sulfate available for reversal in case of major bleeding or overdose.

Adverse effects

Bleeding (any site, including gastrointestinal, intracranial, retroperitoneal)serious
Heparin-induced thrombocytopenia (HIT)serious
Injection site pain, bruising and haematoma
Osteoporosis with long-term use (more than 3 months)serious
Hyperkalaemia due to aldosterone suppression
Alopecia (reversible on discontinuation)

Renal & hepatic adjustment

eGFR 0–30: No specific dose adjustment defined; monitor aPTT closely and adjust dosing in severe renal impairment. Consider lower dose and increased bleeding risk.
Hepatic impairment (moderate): Use with caution; monitor coagulation parameters and adjust dose as needed.
Hepatic impairment (severe): Avoid; increased risk of bleeding. (avoid)

Monitoring, pregnancy & toxicity

aPTT · Baseline, then 6 hours after starting or dose adjustment, and daily once therapeutic
Platelet count · Baseline and every 2-3 days during therapy
Haemoglobin and haematocrit · Baseline and regular intervals
Potassium · Baseline and periodically
Pregnancy: Heparin is the anticoagulant of choice in pregnancy; it does not cross the placenta and is safe for the fetus. Use when anticoagulation is required.
Toxicity: Haemorrhage · Stop heparin; give protamine sulfate. Dose: 1 mg protamine per 100 units of heparin given in the previous 2-3 hours, max 50 mg.
Toxicity: Heparin-induced thrombocytopenia (HIT) · Discontinue heparin; start alternative anticoagulant such as argatroban or danaparoid.

Antidotes & reversal

Protamine sulfate · 1 mg per 100 units of heparin given in the preceding 2-3 hours (max 50 mg).

Clinical notes

Heparin is used for the prophylaxis and treatment of venous thromboembolism, and for anticoagulation during procedures such as haemodialysis or cardiopulmonary bypass. It requires monitoring of the activated partial thromboplastin time (aPTT) and can be reversed with protamine sulfate. Major adverse effects include bleeding and heparin-induced thrombocytopenia (HIT). Low molecular weight heparins are often preferred for many indications due to more predictable pharmacokinetics.

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BNF; local formulary