Unfractionated Heparin (UFH): Uses, Dosage, Side Effects & Safety | DrugsAtlas
Authoritative Clinical Reference
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Therapeutic Class
Anticoagulant
Subclass
Indirect thrombin inhibitor (via antithrombin III potentiation)
Speciality
Haematology
Schedule (India)
Schedule H
Routes
Intravenous (IV), Subcutaneous (SC)
Formulations
- Injection: 5,000 IU/mL (1 mL, 5 mL vials/ampoules)
- Injection: 25,000 IU/5 mL (5 mL vials)
Adult indications
INDICATIONS + DOSING — FOR CLINICIAN USE ONLY
Primary Indications (Approved / Standard in India)
1. Venous Thromboembolism (VTE) Prophylaxis in High-Risk Patients
| Parameter | Recommendation |
|---|---|
| Starting dose | 5,000 IU SC |
| Titration | Not applicable |
| Usual maintenance dose | 5,000 IU SC every 8–12 hours |
| Maximum dose | 5,000 IU every 8 hours |
Clinical Notes:
- Initiate post-operatively once haemostasis is secured
- Continue until patient is ambulatory or transitioned to oral anticoagulation
- No aPTT monitoring required for prophylactic dosing
2. Treatment of Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE)
Weight-based Protocol (Preferred):
| Parameter | Recommendation |
|---|---|
| Starting dose | 80 IU/kg IV bolus |
| Titration | Adjust infusion rate every 6 hours based on aPTT (target: 1.5–2.5× control or 60–80 seconds) |
| Usual maintenance dose | 18 IU/kg/hour continuous IV infusion |
| Maximum dose | Titrate to therapeutic aPTT; no fixed ceiling |
Fixed-dose Protocol (Alternative):
| Parameter | Recommendation |
|---|---|
| Starting dose | 5,000–10,000 IU IV bolus |
| Titration | Adjust based on aPTT every 6 hours until stable |
| Usual maintenance dose | 1,000–1,500 IU/hour continuous IV infusion |
| Maximum dose | As per aPTT response |
Clinical Notes:
- Check aPTT 6 hours after initiation and after each dose adjustment
- Once stable, monitor aPTT daily
- Overlap with oral anticoagulant (warfarin) for minimum 5 days and until INR ≥2 for 24 hours
3. Acute Coronary Syndromes (Unstable Angina / NSTEMI)
| Parameter | Recommendation |
|---|---|
| Starting dose | 60–70 IU/kg IV bolus (maximum 5,000 IU) |
| Titration | Adjust infusion based on aPTT (target: 1.5–2.5× control) |
| Usual maintenance dose | 12–15 IU/kg/hour IV infusion (maximum 1,000 IU/hour) |
| Maximum dose | 1,000 IU/hour (higher doses increase bleeding without added benefit) |
Clinical Notes:
- Duration: 2–5 days or until revascularisation
- Co-administer with antiplatelet therapy (aspirin ± P2Y12 inhibitor) as per ACS protocol
- Monitor for bleeding complications at vascular access sites
4. Anticoagulation During Percutaneous Coronary Intervention (PCI)
| Parameter | Recommendation |
|---|---|
| Starting dose | 70–100 IU/kg IV bolus (without GP IIb/IIIa inhibitor) OR 50–70 IU/kg IV bolus (with GP IIb/IIIa inhibitor) |
| Titration | Additional boluses guided by ACT |
| Usual maintenance dose | Not applicable (bolus-only protocol) |
| Maximum dose | Guided by ACT (target: 250–350 seconds without GP IIb/IIIa; 200–250 seconds with GP IIb/IIIa) |
5. Anticoagulation During Cardiopulmonary Bypass (CPB)
| Parameter | Recommendation |
|---|---|
| Starting dose | 300–400 IU/kg IV bolus before cannulation |
| Titration | Additional boluses to maintain ACT >400–480 seconds |
| Usual maintenance dose | As per intra-operative ACT monitoring |
| Maximum dose | Guided by ACT; typically 600 IU/kg total may be required |
Clinical Notes:
- Protamine reversal required post-bypass
- Protamine dose: 1 mg per 100 IU of heparin administered
6. Anticoagulation During Haemodialysis
| Parameter | Recommendation |
|---|---|
| Starting dose | 1,000–2,000 IU IV bolus at initiation |
| Titration | Additional 500–1,000 IU if session prolonged |
| Usual maintenance dose | 500–1,000 IU/hour during dialysis |
| Maximum dose | Individualised based on clotting in circuit |
Clinical Notes:
- Reduce dose or use heparin-free dialysis in patients with high bleeding risk
- UFH preferred over LMWH in dialysis due to reversibility
Secondary Indications — Adults (Off-label, if any)
| Indication | Dose | Duration | Label Status | Evidence Basis |
|---|---|---|---|---|
| Disseminated Intravascular Coagulation (DIC) with predominant thrombotic features | 5,000 IU SC every 8–12 hours; adjust based on clinical and laboratory response | Until DIC resolution | OFF-LABEL; Specialist only | Indian specialist haematology practice; selected case series |
| Cerebral venous sinus thrombosis | Weight-based IV protocol as per DVT treatment | Until transition to oral anticoagulation | OFF-LABEL; Specialist only | AIIMS neurology protocols; international guidelines |
Paediatric indications
PAEDIATRIC DOSING (Specialist Only)
Primary Indications (Approved / Standard in India)
Treatment of DVT/PE in Children
| Age Group | Loading Dose (IV over 10 min) | Maintenance Infusion (IV) | Target aPTT |
|---|---|---|---|
| Neonates (<28 days) | 75–100 IU/kg | 28 IU/kg/hour | 60–85 seconds |
| Infants (28 days–1 year) | 75 IU/kg | 20 IU/kg/hour | 60–85 seconds |
| Children (>1 year) | 75 IU/kg | 18 IU/kg/hour | 60–85 seconds |
Titration Protocol:
- Check aPTT 4–6 hours after initiation
- Adjust infusion by 10–25% increments based on aPTT
- Recheck aPTT 4–6 hours after each dose change until stable
Safety Monitoring:
- Platelet count at baseline, day 3, and then every 2–3 days
- Monitor for signs of bleeding (mucosal, injection sites, intracranial in neonates)
- Anti-Xa levels may be used if aPTT unreliable (target: 0.35–0.7 IU/mL)
Secondary Indications — Paediatrics (Off-label, if any)
| Indication | Dose | Duration | Label Status | Evidence Basis |
|---|---|---|---|---|
| Central venous catheter patency (flush) | 10 IU/mL; flush every 8–12 hours | As long as catheter in situ | OFF-LABEL; Specialist only | Indian PICU practice; IAP recommendations |
| Kawasaki disease with coronary aneurysm | Weight-based therapeutic protocol | Until transition to LMWH or warfarin | OFF-LABEL; Specialist only | Indian paediatric cardiology practice |
Age Restriction: Not recommended in neonates except under specialist haematology or neonatology supervision with appropriate monitoring facilities.
Renal Adjustments
| Renal Function | Recommendation |
|---|---|
| Mild-to-moderate impairment (eGFR 30–89 mL/min) | No dose adjustment required |
| Severe impairment (eGFR <30 mL/min) | No dose adjustment; UFH preferred over LMWH in this population |
| Haemodialysis | Use as per dialysis anticoagulation protocol; preferred agent due to short half-life and reversibility |
| Peritoneal dialysis | Standard dosing; monitor for bleeding |
Clinical Note: Despite renal-independent clearance, monitor aPTT closely in severe renal impairment due to altered protein binding and comorbidities affecting bleeding risk.
Hepatic adjustment
Contraindications
- Active major bleeding (gastrointestinal, intracranial, retroperitoneal)
- Severe uncontrolled hypertension
- History of heparin-induced thrombocytopenia (HIT) type II
- Hypersensitivity to heparin or porcine-derived products
- Recent haemorrhagic stroke or intracranial haemorrhage
- Severe thrombocytopenia (platelet count <50,000/μL unless thrombotic emergency)
- Recent lumbar puncture or spinal anaesthesia (within 12–24 hours)
- Threatened abortion
Cautions
- Recent major surgery or trauma (within 7–14 days)
- Active peptic ulcer disease or history of GI bleeding
- Severe liver disease with coagulopathy
- Bacterial endocarditis
- Diabetic retinopathy with risk of vitreous haemorrhage
- Concurrent use of antiplatelet agents
- Indwelling epidural catheters
- Advanced age (>75 years) — increased bleeding risk
- History of allergy to beef or pork products
- Prior exposure to heparin within 100 days — increased HIT risk
Pregnancy
| Parameter | Recommendation |
|---|---|
| Safety status | Safe in pregnancy — does not cross placenta |
| Preferred use | Unidentified |
| Alternatives | LMWH is more commonly used due to convenient dosing; UFH preferred near delivery for reversibility |
| When to use | Throughout pregnancy; switch from LMWH to UFH at 36 weeks or before planned delivery |
| Monitoring | aPTT (therapeutic dosing); platelet count every 2–3 days; signs of bleeding; osteoporosis risk with prolonged use |
Lactation
| Parameter | Recommendation |
|---|---|
| Compatibility | Compatible with breastfeeding |
| Drug levels in milk | Negligible; large molecular weight prevents transfer |
| Preferred alternative | LMWH is equally safe; both acceptable |
| Infant monitoring | No specific monitoring required |
Elderly
- Starting dose: Use lower end of dosing range; consider 60 IU/kg bolus and 15 IU/kg/hour infusion for therapeutic anticoagulation
- Titration: More gradual; increase intervals between dose adjustments
- Extra risks:
-
- Increased bleeding risk due to age-related vascular fragility
- Reduced renal reserve affecting drug handling
- Higher incidence of falls and trauma
- Greater sensitivity to anticoagulant effect
- Polypharmacy increasing interaction risk
- Monitoring: More frequent aPTT checks; vigilant clinical monitoring for bleeding
Major drug interactions
| Interacting Drug/Class | Mechanism/Effect | Recommendation |
|---|---|---|
| Antiplatelet agents (aspirin, clopidogrel, prasugrel, ticagrelor) | Synergistic bleeding risk | Use cautiously; essential in ACS protocols but monitor closely |
| Oral anticoagulants (warfarin, acenocoumarol) | Additive anticoagulation | Overlap briefly during transition; monitor INR and aPTT |
| Direct oral anticoagulants (rivaroxaban, apixaban, dabigatran) | Excessive anticoagulation | Avoid concurrent use except during protocol-guided transitions |
| Thrombolytics (alteplase, streptokinase, tenecteplase) | Markedly increased bleeding | Use sequentially, not concurrently; heparin started after thrombolysis per protocol |
| GP IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban) | Synergistic bleeding | Reduce heparin dose during PCI; monitor ACT |
| Dextran | Additive anticoagulant effect | Avoid combination |
Moderate drug interactions
| Interacting Drug/Class | Mechanism/Effect | Recommendation |
|---|---|---|
| NSAIDs (diclofenac, ibuprofen, naproxen) | Increased GI bleeding risk; platelet inhibition | Monitor for bleeding; avoid if possible |
| SSRIs/SNRIs (fluoxetine, sertraline, venlafaxine) | Impaired platelet function | Monitor for bleeding |
| Nitroglycerin (IV) | May reduce heparin effect; mechanism unclear | May require higher heparin doses; monitor aPTT |
| Penicillins (high-dose piperacillin, ticarcillin) | Platelet dysfunction | Monitor bleeding time and clinical signs |
| Tetracyclines, antihistamines | May interfere with aPTT assay | Interpret aPTT cautiously |
Common Adverse effects
- Bleeding (injection site haematoma, gingival bleeding, epistaxis, haematuria)
- Injection site pain and erythema (SC administration)
- Mild transient thrombocytopenia (non-immune, within first 2 days)
- Elevated transaminases (mild, reversible)
- Bruising
Serious Adverse effects
- Heparin-induced thrombocytopenia (HIT) type II: Immune-mediated; platelet drop >50% from baseline typically day 5–10; paradoxically causes thrombosis — discontinue heparin immediately; initiate alternative anticoagulant (argatroban, fondaparinux)
- Major haemorrhage: Intracranial, retroperitoneal, GI — requires protamine reversal and supportive care
- Osteoporosis: With prolonged use (>1 month); vertebral fractures reported
- Skin necrosis: At injection sites; rare
- Hypersensitivity reactions: Urticaria, anaphylaxis (rare)
- Hyperkalaemia: Due to aldosterone suppression; monitor potassium in prolonged use
Monitoring requirements
| Timing | Parameters |
|---|---|
| Baseline | CBC with platelet count, aPTT, PT/INR, serum creatinine, LFTs |
| After initiation/dose change | aPTT every 6 hours until therapeutic and stable (2 consecutive values in range) |
| Ongoing (therapeutic dosing) | aPTT daily once stable; platelet count every 2–3 days for first 14 days (HIT surveillance) |
| Ongoing (prophylactic dosing) | Platelet count every 2–3 days; no routine aPTT required |
| Prolonged use (>1 month) | Consider bone density monitoring; serum potassium |
| Clinical | Daily assessment for bleeding, thrombosis, injection site reactions |
Brands in India
- Heparin Sodium Injection IP (Gland Pharma, Biological E, Gufic, VHB Lifesciences)
- Heparin Leo® (Leo Pharma)
- Beparine® (Troikaa)
- Hepaglan® (Gland Pharma)
- Multiple institutional and generic manufacturers
Price range (INR)
| Formulation | Approximate Price | Notes |
|---|---|---|
| 5,000 IU/mL (1 mL vial) | ₹15–40 per vial | NLEM-listed; price controlled |
| 25,000 IU/5 mL (5 mL vial) | ₹50–100 per vial | NLEM-listed; price controlled |
NLEM Status: Included in NLEM 2022; available through government supply under NHM and institutional procurement.
Clinical pearls
- UFH is preferred over LMWH in severe renal impairment (eGFR <30 mL/min), high bleeding risk situations, and when rapid reversibility is needed (surgery, delivery)
- Protamine sulfate reverses UFH: 1 mg neutralises approximately 100 IU of heparin given in the preceding hour; reduce dose for heparin given earlier
- HIT typically occurs day 5–14 of exposure; always check prior heparin exposure history — patients exposed within 100 days may develop rapid-onset HIT
- Weight-based dosing protocols achieve therapeutic aPTT faster and more reliably than fixed-dose protocols
- In obese patients, use actual body weight for bolus but consider dose-capping the infusion rate
- Never mix heparin with other IV medications unless compatibility is confirmed; use dedicated IV line or flush between drugs
Version
RxIndia v1.0 — 28 May 2025
Reference
-
- CDSCO product information
- Indian Pharmacopoeia
- NLEM 2022
- AIIMS Anticoagulation Guidelines
- API Textbook of Medicine
- ICMR/National Guidelines for Management of VTE
- Indian Society of Haematology and Blood Transfusion (ISHBT) protocols
- Cardiological Society of India (CSI) ACS management guidelines
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Clinical Responsibility
This platform is designed strictly for healthcare professionals. Data provided is synthesized from authoritative pharmacological sources and clinical registries. Do not use for consumer medical decisions. Always verify critical dosing and contraindications with official institutional protocols and peer-reviewed journals.
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