Formulary
Heparin (Unfractionated): Uses, Dosing, Side Effects and Indian Brand Names
Unfractionated heparin is an indirect anticoagulant that potentiates antithrombin III to inhibit thrombin and factor Xa. It is used for acute thromboembolism, cardiac surgery, and is the anticoagulant of choice in pregnancy due to its inability to cross the placenta.
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Heparin (Unfractionated): Uses, Dosing, Side Effects and Indian Brand Names
Unfractionated heparin is an indirect anticoagulant that potentiates antithrombin III to inhibit thrombin and factor Xa. It is used for acute thromboembolism, cardiac surgery, and is the anticoagulant of choice in pregnancy due to its inability to cross the placenta.
NEET PG High-Yield: Heparin potentiates ANTITHROMBIN III (NOT a direct thrombin inhibitor). aPTT is the monitoring test (NOT PT/INR -- that is for warfarin). Protamine sulfate is the antidote. HIT type II: immune-mediated, paradoxically prothrombotic (not bleeding), occurs day 5-14. Heparin does NOT cross the placenta -- anticoagulant of choice in pregnancy. LMWHs (enoxaparin) primarily inhibit factor Xa (less thrombin inhibition) and are monitored by anti-Xa levels (NOT aPTT).
Clinical overview
Unfractionated heparin is a heterogeneous mixture of glycosaminoglycan chains (molecular weight 3,000-30,000 Da, mean ~15,000) and has been the most widely used parenteral anticoagulant since its discovery in 1916. It remains indispensable in acute coronary syndromes, pulmonary embolism, deep vein thrombosis, cardiac surgery (cardiopulmonary bypass), and haemodialysis. Its key advantages include a short half-life (60-90 minutes IV), complete reversibility with protamine sulfate, and monitoring capability via aPTT (activated partial thromboplastin time). The therapeutic target aPTT is 1.5-2.5 times control. In Indian clinical practice, UFH is widely used in hospital settings, particularly in cardiac care units and operation theatres. The major adverse effects are bleeding (managed with protamine) and heparin-induced thrombocytopenia (HIT). HIT type II is an immune-mediated paradoxical prothrombotic state (despite low platelets) caused by antibodies against heparin-platelet factor 4 complexes. It occurs in 1-5% of patients on UFH and requires immediate heparin cessation and initiation of a non-heparin anticoagulant (argatroban, fondaparinux). Unlike warfarin, heparin does NOT cross the placenta, making it the anticoagulant of choice during pregnancy.
Pharmacological class
Heparin (Unfractionated) belongs to the Indirect thrombin inhibitor (anticoagulant; glycosaminoglycan) class. Unfractionated heparin (UFH) binds to antithrombin III (AT-III) via a specific pentasaccharide sequence, inducing a conformational change that accelerates AT-III's inhibition of thrombin (factor IIa) and factor Xa by approximately 1000-fold. The heparin-AT-III complex inactivates factors IIa, Xa, IXa, XIa, and XIIa. For thrombin inhibition, heparin must simultaneously bind both AT-III and thrombin (requires a chain length of at least 18 saccharide units). For factor Xa inhibition, binding to AT-III alone is sufficient.
Indian brand names and formulations
Available as: Heparin Sodium (Biological E Limited), Caprin (Abbott India), Heparinol (Troikaa Pharmaceuticals), Beparin (Neon Laboratories).
Injection: 1000 IU/mL, 5000 IU/mL (multidose vials and single-dose ampoules), 25,000 IU/5 mL. For IV infusion and subcutaneous injection. Heparin flush (100 IU/mL for IV line patency). Heparinised saline for lock flush.
Regulatory status
Heparin (Unfractionated) is classified under Schedule H in India under the Drugs and Cosmetics Act, 1940. Schedule H prescription drug. Hospital use only (parenteral administration). Requires aPTT monitoring for dose adjustment. Protamine sulfate must be available for reversal.
Indications
- Deep vein thrombosis (DVT) -- treatment and prophylaxis
- Pulmonary embolism (PE) -- acute treatment
- Acute coronary syndromes (STEMI, NSTEMI, unstable angina -- as adjunct to PCI and thrombolytics)
- Cardiopulmonary bypass and cardiac surgery (intraoperative anticoagulation)
- Haemodialysis and extracorporeal circuits
- Disseminated intravascular coagulation (DIC -- low-dose, controversial)
- Venous thromboembolism prophylaxis (surgical patients)
- Anticoagulation during pregnancy (does not cross placenta)
Dosing
DVT/PE treatment: 80 units/kg IV bolus, then 18 units/kg/hour continuous infusion, adjusted to maintain aPTT 1.5-2.5x control (measured every 6 hours until stable, then daily). Prophylaxis: 5000 units SC every 8-12 hours. ACS: 60 units/kg IV bolus (max 4000 units), then 12 units/kg/hour (max 1000 units/hour). Cardiac surgery: 300-400 units/kg IV bolus (high-dose, monitored by ACT). Protamine reversal: 1 mg protamine neutralises approximately 100 units of heparin (dose adjusted for time since last heparin dose).
Contraindications
- Active major bleeding
- Severe thrombocytopenia (platelet count <50,000/mcL)
- History of heparin-induced thrombocytopenia (HIT type II)
- Severe uncontrolled hypertension
- Recent CNS surgery, spinal anaesthesia (within 24 hours)
- Bacterial endocarditis (relative -- increased ICH risk)
Adverse effects
- Bleeding (most common and most dangerous -- dose-dependent; reversed by protamine sulfate)
- Heparin-induced thrombocytopenia (HIT) -- Type I (benign, non-immune, transient) and Type II (immune-mediated, thrombotic, dangerous)
- Osteoporosis (with long-term use >3 months -- heparin inhibits osteoblasts)
- Hyperkalaemia (heparin inhibits aldosterone synthesis)
- Alopecia (reversible, with prolonged use)
- Skin necrosis at injection sites
- Hypersensitivity reactions
Drug interactions
- Antiplatelet agents (aspirin, clopidogrel) -- additive bleeding risk (but commonly co-prescribed in ACS with monitoring)
- Thrombolytics (streptokinase, alteplase) -- markedly increased bleeding risk
- NSAIDs -- increase bleeding risk through antiplatelet effect and GI toxicity
- Warfarin -- overlapped during transition but additive anticoagulation (monitor aPTT and INR separately)
- Nitroglycerin (IV) -- may reduce heparin's anticoagulant effect (mechanism unclear)
- Protamine sulfate -- specific antidote for heparin reversal
Pregnancy and lactation
Category C. Heparin does NOT cross the placenta (large molecular weight, negative charge) and does not cause fetal anticoagulation or teratogenicity. It is the anticoagulant of choice during pregnancy (for DVT, PE, mechanical heart valves, antiphospholipid syndrome). Warfarin is teratogenic (warfarin embryopathy) and is avoided in the first trimester and near term. LMWH (enoxaparin) has largely replaced UFH for outpatient management during pregnancy due to more predictable pharmacokinetics and easier administration.
Exam-style clinical scenario
A 55-year-old woman on IV heparin for DVT develops a platelet count drop from 250,000 to 80,000/mcL on day 7 of therapy, along with new-onset left leg DVT extension. What is the diagnosis and management? Answer: This is heparin-induced thrombocytopenia type II (HIT II) -- an immune-mediated condition caused by IgG antibodies against heparin-platelet factor 4 (PF4) complexes. Despite thrombocytopenia, HIT II is paradoxically prothrombotic (not haemorrhagic). Management: (1) STOP all heparin immediately (including heparin flushes and LMWH), (2) Start a non-heparin anticoagulant (argatroban IV or fondaparinux SC), (3) Do NOT give platelet transfusions (fuels thrombosis), (4) Test for anti-PF4/heparin antibodies. Warfarin should not be started until platelet count recovers (risk of warfarin-induced skin necrosis/venous limb gangrene in acute HIT).
Cost in India
INR 50-100 per vial (5000 IU/mL, 5 mL multidose vial); INR 30-60 per 5000 IU/mL single-dose ampoule
Clinical governance
Author: MedNext Editorial Team. Clinical reviewer: Awaiting clinical review. Jurisdiction: India (Drugs and Cosmetics Act, 1940). Sources: CIMS India, Indian Pharmacopoeia. Publication state: Awaiting clinical review. Correction: Report errors at support@mednext.academy.
Frequently Asked Questions
What is the difference between HIT type I and HIT type II?
HIT type I is a benign, non-immune, direct effect of heparin causing mild platelet aggregation (platelet count rarely falls below 100,000). It occurs in the first 2 days and resolves spontaneously even if heparin is continued. HIT type II is immune-mediated: IgG antibodies bind to heparin-PF4 complexes on platelet surfaces, causing platelet activation, aggregation, and consumption (count falls >50% or below 100,000, typically day 5-14). Paradoxically, HIT II causes thrombosis (not bleeding) and requires immediate heparin cessation and alternative anticoagulation.
Why does protamine sulfate reverse heparin?
Protamine is a strongly basic (positively charged) protein derived from fish sperm. Heparin is a strongly acidic (negatively charged) glycosaminoglycan. Protamine forms a stable ionic complex with heparin, neutralising its anticoagulant activity within 5 minutes of IV administration. Dose: 1 mg protamine reverses approximately 100 units of heparin given in the preceding hour. Excess protamine itself has mild anticoagulant properties, so precise dosing is important.
Why is LMWH (enoxaparin) preferred over UFH for many indications?
LMWH has several advantages: (1) more predictable dose-response (better bioavailability after SC injection), (2) longer half-life allowing once or twice daily dosing, (3) no routine aPTT monitoring needed, (4) lower risk of HIT type II, (5) lower risk of heparin-induced osteoporosis, (6) suitable for outpatient treatment of DVT. However, UFH is still preferred when rapid reversibility is needed (cardiac surgery, high bleeding risk), in severe renal failure (LMWH is renally cleared), and when aPTT monitoring is desirable (acute PE with haemodynamic instability).
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