Indirect thrombin and factor Xa inhibitor via antithrombinREQUIRES MONITORINGNARROW THERAPEUTIC INDEX

Heparin (unfractionated)

Heparin LEO · Heparin Panpharma

The anticoagulant to choose when the ability to reverse rapidly matters: the half-life is one to two hours, the effect can be measured in real time with APTT, and it can be neutralised completely with protamine within minutes. This is why unfractionated heparin is the first choice in severe renal failure, in the bleeding-prone patient, and when surgery or thrombolysis may become necessary at short notice. The disadvantages are continuous infusion, an unpredictable dose–response relationship due to binding to plasma proteins, and the risk of heparin-induced thrombocytopenia.

BOXED WARNING

A platelet fall of 50 % or a platelet count below 100 × 10⁹/l during heparin treatment is heparin-induced thrombocytopenia until proven otherwise — all heparin must be stopped immediately, including flushes and LMWH, and replaced with non-heparin-based anticoagulation. Giving a platelet transfusion or merely pausing the infusion worsens the thrombotic course.

Dosing in adults

By indicationuppdaterad 2026-08-22

Indication	Regimen	Comment
Venous thromboembolism, bolus	5 000 IU iv (1 ml Heparin 5 000 IU/ml)	2 500 IU in patients aged over 85, weight below 40 kg, or eGFR below 20; 7 500 IU at weight above 90 kg
Venous thromboembolism, infusion	500 IU/kg per day iv in infusion at 100 IU/ml	started within one hour of the bolus; maximum 45 000 IU per day
Venous thromboembolism, high bleeding risk	200–400 IU/kg per day	advanced age, renal or hepatic failure, thrombocytopenia, postoperative, after thrombolysis
Acute coronary syndrome without PCI	60 IU/kg iv bolus (maximum 4 000 IU) followed by 12 IU/kg per hour (maximum 1 000 IU per hour)	APTT-guided, target 1,5–2,5 times baseline
During PCI	70–100 IU/kg iv bolus, 50–70 IU/kg with concurrent GPIIb/IIIa inhibitor	guided by ACT in the laboratory, not by APTT

Renal impairment

No dose adjustment is required — heparin is eliminated predominantly via the reticuloendothelial system and not renally. This is the entire reason unfractionated heparin is chosen over low molecular weight heparin at eGFR below 30 ml/min and in dialysis. The bolus dose is reduced at eGFR below 20 ml/min due to bleeding risk.

Hepatic impairment

No formal dose adjustment, but hepatic failure with coagulopathy carries increased bleeding risk — start in the lower part of the dose range (200–400 IU/kg per day) and keep APTT in the lower part of the target range.

Children

Used in children with weight-based dosing and a lower APTT target range than in adults. Neonates have low antithrombin levels and may show relative heparin resistance. Dosing and monitoring in consultation with a paediatric coagulation unit.

Pitfall

Do not calculate the protamine dose on the full daily heparin dose — only the heparin given in the past two to three hours remains in circulation, and excessive protamine has anticoagulant effects of its own and can trigger severe hypotension, bradycardia, and pulmonary hypertension. Never give heparin to a patient with previous HIT, not even as a catheter flush: re-exposure can trigger thrombosis within hours.

Pharmacokinetics

BIOAVAIL.: 100 % iv, approximately 30 % subcutaneously
Vd: approximately 40–70 ml/kg (plasma volume)
t½: 1–2 h, dose-dependent
PROTEIN BINDING: High and variable (acute-phase proteins, PF4)
METABOLISM: Reticuloendothelial system, heparinase
EXCRETION: Renal only at high doses
MECHANISM: Potentiates antithrombin approximately 1 000-fold
ONSET: Immediate iv

Adverse effects by frequency

≥ 10 %

Bleeding from puncture sites and mucous membranes, bruising, mild transaminase elevation

1–10 %

Thrombocytopenia (non-immunological type I), haematoma, hyperkalaemia through aldosterone inhibition, injection site reaction

< 1 %

Heparin-induced thrombocytopenia type II with arterial and venous thrombosis, intracranial or retroperitoneal haemorrhage, skin necrosis, osteoporosis with long-term treatment, anaphylaxis

Monitoring schedule

APTT, target 50–90 sec: 4–6 hours after start and after each dose change, then daily
Platelet count: daily in the acute phase — HIT typically occurs on days 5–14
Haemoglobin and clinical signs of bleeding: daily
Anti-factor Xa 0,3–0,7 kIU/l and antithrombin: on suspicion of heparin resistance, lupus anticoagulant, or overdose

Interaction burden

18clinically significant

2 contraindicated · 8 major · 8 moderate. Additive bleeding risk with platelet inhibitors, NSAIDs, thrombolytics, direct oral anticoagulants, and warfarin. High-dose nitroglycerin infusion has been reported to reduce the heparin effect. Antithrombin deficiency — hereditary or acquired in sepsis, massive thrombosis, and cancer — causes heparin resistance because heparin has no intrinsic effect without antithrombin.

Formulation & cost

Injection solution: 5 000 IU/ml, 5 ml vial
Infusion preparation: 5 ml Heparin 5 000 IU/ml in 245 ml NaCl 9 mg/ml = 100 IU/ml, stable for 12 hours
Antidote: protamine sulfate: 1 mg neutralises approximately 100 IU heparin; maximum 50 mg per dose, given slowly iv