Heparin (Unfractionated) | Medication Reference

Bedside Snapshot

Unfractionated heparin (UFH) is a rapid-on/rapid-off parenteral anticoagulant used for acute venous thromboembolism (VTE), ACS, bridging around procedures, and line/circuit anticoagulation (CRRT, ECMO).
Mechanism: binds to antithrombin (AT) and greatly accelerates inactivation of thrombin (IIa) and factor Xa (and IXa, XIa, XIIa). Requires AT as a cofactor; does not dissolve existing clots but prevents extension and new clot formation.
ED/ICU advantages over LMWH: IV titratable, short half-life (~1–2 h), reversible with protamine, less accumulation in renal impairment. Disadvantage: more lab monitoring and risk of heparin-induced thrombocytopenia (HIT).
Typical VTE/PE treatment (adult): 80 units/kg IV bolus (max ~10,000 units) then 18 units/kg/h IV infusion, adjusted to aPTT or anti-Xa per institutional nomogram.
Typical ACS/NSTEMI treatment (adult): 60–70 units/kg IV bolus (max ~4,000 units) then 12–15 units/kg/h IV infusion (max ~1,000 units/h), titrated to institutional targets.
DVT prophylaxis: 5,000 units SC q8–12h; some protocols use 7,500 units SC q8h in morbid obesity if bleeding risk acceptable.
Major risks: bleeding, immune-mediated HIT (Type II) with paradoxical thrombosis, long-term high-dose use → osteoporosis, plus rare hyperkalemia (hypoaldosteronism).

Brand & Generic Names

Generic Name: Heparin sodium (unfractionated)
Brand Names: Heparin, various generics

Medication Class

Parenteral anticoagulant; indirect thrombin inhibitor (antithrombin III–mediated); unfractionated heparin (UFH)

Pharmacology

Mechanism of Action:

UFH is a heterogeneous mixture of sulfated glycosaminoglycan chains (3,000–30,000 Da) derived from porcine intestinal mucosa
Binds to antithrombin (AT) causing a conformational change that increases AT's ability to inactivate clotting factors, particularly thrombin (IIa) and factor Xa, and to a lesser extent IXa, XIa, and XIIa
Only heparin chains ≥18 saccharides long can form the ternary complex bridging AT and thrombin, so UFH inhibits both IIa and Xa, whereas LMWH is relatively more anti-Xa selective
Does not lyse existing clots; instead, stabilizes clot burden and prevents propagation while endogenous fibrinolysis works
Binding to plasma proteins and cells (endothelium, macrophages, platelets) leads to variable pharmacokinetics and dose–response, necessitating lab-guided titration (aPTT or anti-Xa)

Pharmacokinetics (IV/SC):

Onset: Immediate with IV bolus; SC onset ~1–2 hours
Half-life: Dose-dependent, roughly 30–90 minutes at therapeutic doses; prolonged in hepatic dysfunction, severe illness, or with high doses
Bioavailability: IV 100%; SC ~30–70% (variable). For full therapeutic control, IV infusion is preferred in ED/ICU
Distribution: Largely intravascular; extensive binding to plasma proteins, macrophages, and endothelial cells
Elimination: Primarily via rapid reticuloendothelial system uptake (saturable), with slower renal excretion of smaller fractions; accumulation possible in renal failure at high doses but less pronounced than LMWH

Indications

Initial treatment of acute DVT/PE (especially in high-bleeding-risk, morbidly obese, or renal failure patients where rapid reversibility is helpful)
ACS (NSTEMI/unstable angina, STEMI with fibrinolysis) as part of antithrombotic regimen with antiplatelets and/or fibrinolytics
Bridging therapy around procedures in patients with mechanical valves or high-risk atrial fibrillation when warfarin or DOACs are held (per cardiology/hematology guidance)
Anticoagulation of CRRT circuits, ECMO, and sometimes hemodialysis circuits
Line patency and thrombus prevention (low-dose heparin flushes for central lines and some arterial catheters, depending on institutional practice)
VTE prophylaxis in medical and surgical patients at risk for thromboembolism

Dosing & Administration

Available Forms:

IV/SC vials: multiple strengths, commonly 1,000 units/mL, 5,000 units/mL, and premixed infusion bags (e.g., 25,000 units in 250 mL = 100 units/mL)
Heparin lock/flush solutions: often 10 units/mL or 100 units/mL for catheter patency (not for systemic anticoagulation)

Critical Safety: Always double-check vial/infusion concentrations to avoid 10× dosing errors.

Dosing – Unfractionated Heparin (Adult; always follow local nomogram/protocol):

Indication / Scenario	Typical Dose	Route / Administration	Notes
Acute DVT/PE – therapeutic anticoagulation	80 units/kg IV bolus (max ~10,000 units), then 18 units/kg/h	Continuous IV infusion; titrate to aPTT or anti-Xa	Use weight-based nomogram; check aPTT/anti-Xa ~6 h after start or dose changes
NSTEMI/unstable angina – UFH regimen	60–70 units/kg IV bolus (max 4,000 units), then 12–15 units/kg/h (max 1,000 units/h)	Continuous IV infusion	Dose and target aPTT/anti-Xa per ACS protocol; adjust for concurrent antiplatelets
STEMI treated with fibrinolysis	60 units/kg IV bolus (max 4,000 units), then 12 units/kg/h (max 1,000 units/h)	Continuous IV infusion for at least 24–48 h	Used with alteplase/TNK per STEMI lytic protocols
VTE prophylaxis – general medical/surgical	5,000 units SC q8–12h	Subcutaneous (usually abdomen)	No routine aPTT monitoring; adjust for bleeding risk and obesity
VTE prophylaxis – obesity (example)	7,500 units SC q8h	Subcutaneous	Used in some protocols for BMI ≥40; balance against bleeding risk
CRRT/ECMO circuit anticoagulation (examples only)	10–30 units/kg/h (no bolus or small bolus)	Infusion into extracorporeal circuit	Dosing highly protocolized; titrate to circuit anti-Xa/ACT targets
Central line patency (flush)	10–100 units per flush (e.g., 3–5 mL of 10–100 units/mL)	Intracatheter instillation	Do not confuse with therapeutic heparin; verify concentration carefully
Reversal – major bleeding or urgent procedure	Protamine 1 mg per 100 units UFH (given in last 2–3 h; max ~50 mg)	Slow IV over 10–15 min	Neutralizes ~1 mg:100 units; excess protamine has its own anticoagulant effect

Contraindications

Absolute/Strong Contraindications:

Active major bleeding (e.g., intracranial, significant GI bleed, ongoing hemoperitoneum/hypotension)
Recent intracranial hemorrhage or major neurosurgery with high rebleed risk
History of heparin-induced thrombocytopenia (HIT) (Type II) from UFH or LMWH – avoid all heparin products unless cleared by hematology
Severe thrombocytopenia (e.g., platelet count <50,000/µL) when full-dose anticoagulation is not absolutely essential
Inability to monitor/mitigate bleeding risk in a high-bleed-risk patient

Major Precautions:

Recent surgery, trauma, or invasive procedures – adjust dosing/targets and coordinate with surgeons
Uncontrolled hypertension, history of intracranial pathology (tumor, AVM, prior ICH) – higher ICH risk
Patients with renal or hepatic dysfunction, elderly, and low body weight – increased bleeding risk; favor careful titration and closer monitoring
Baseline coagulopathy (INR elevation, thrombocytopenia) or concurrent use of other anticoagulants/antiplatelets (warfarin, DOACs, dual antiplatelet therapy)
Spinal/epidural catheters – risk of spinal epidural hematoma with anticoagulation; follow neuraxial anesthesia guidelines for timing of dosing and catheter manipulation

HIT Warning: History of heparin-induced thrombocytopenia (HIT Type II) is an absolute contraindication to all heparin products. Always screen for prior HIT before initiating therapy.

Adverse Effects

Common:

Minor bleeding (bruising, oozing from lines, epistaxis, gingival bleeding)
Injection-site discomfort with SC injections
Mild, transient thrombocytopenia (non-immune Type I) early in therapy

Serious:

Major bleeding: Including GI bleed, retroperitoneal hemorrhage, hemopericardium, and intracranial hemorrhage
Heparin-induced thrombocytopenia (HIT) Type II: Immune-mediated; typically onset 5–10 days after start (or earlier with prior exposure), characterized by platelet drop >50% and new thrombosis (arterial or venous). This is a medical emergency requiring immediate heparin cessation and alternative anticoagulation
Osteoporosis: With prolonged high-dose therapy (e.g., in pregnancy or long-term bridging); increased risk of spontaneous fractures
Hyperkalemia: Due to heparin-induced hypoaldosteronism, particularly in patients with renal dysfunction or on ACEi/ARB
Alopecia, transaminitis, and hypersensitivity reactions (less common)

HIT Alert: Suspect HIT if platelet count drops >50% from baseline or new thrombosis develops during heparin therapy. Stop all heparin immediately and start alternative anticoagulation (argatroban, bivalirudin, fondaparinux).

Special Populations

Elderly:

Increased bleeding risk; use lower end of dosing ranges and monitor closely
May have unpredictable pharmacokinetics due to changes in protein binding and renal function

Renal Impairment:

UFH is often preferred over LMWH in severe renal impairment (CrCl <30 mL/min) due to less accumulation
Monitor aPTT or anti-Xa closely; some dose reduction may be needed in severe renal failure
Short half-life and protamine reversibility make UFH safer in dialysis-dependent patients

Hepatic Impairment:

Severe hepatic dysfunction may prolong heparin half-life and increase bleeding risk
Baseline coagulopathy common; correct INR and platelet count before initiating if possible

Obesity:

Use actual body weight for bolus and infusion calculations per most weight-based nomograms
Some institutions cap maximum bolus doses; verify local protocol
VTE prophylaxis may require higher doses (7,500 units SC q8h) in morbid obesity

Pregnancy & Lactation:

UFH does not cross the placenta and is safe for use in pregnancy when anticoagulation is needed
Preferred over warfarin for pregnant patients requiring anticoagulation
Long-term use (>1 month) associated with osteoporosis risk; monitor bone density if prolonged therapy needed
Does not enter breast milk in significant amounts; safe during breastfeeding

Monitoring

Baseline Labs (before full-dose therapy):

CBC (Hgb/Hct, platelets)
PT/INR, aPTT
Creatinine (assess renal function)
Baseline anti-Xa if using that assay for monitoring

Therapeutic Monitoring:

aPTT or anti-Xa level: Check ~6 hours after starting or changing infusion rate, then adjust per nomogram. Once stable, spacing labs to q24h is common
Target ranges: aPTT 1.5–2.5× control (typically 60–80 seconds) OR anti-Xa 0.3–0.7 units/mL for therapeutic anticoagulation
If aPTT and anti-Xa disagree, anti-Xa is generally more reliable (aPTT affected by lupus anticoagulant, factor deficiencies, acute phase reactants)

Serial CBC:

Monitor at least daily for hemoglobin drop (occult bleeding) and platelet count
Screen for HIT, especially days 4–14 of therapy
Calculate 4Ts score if platelets drop or thrombosis occurs; order HIT antibody testing if intermediate or high probability

Clinical Bleeding Surveillance:

Monitor for hematuria, melena/hematochezia, coffee-ground emesis
Assess for new flank/abdominal pain (retroperitoneal bleed)
Neurologic checks for signs of ICH (headache, focal deficits, altered mental status)
Inspect IV/arterial line sites, surgical sites, and any invasive procedure sites

Electrolytes:

Monitor potassium periodically, especially in patients with renal dysfunction or on ACEi/ARB (risk of heparin-induced hyperkalemia)

Clinical Pearls

Use Weight-Based Nomograms: Use your institution's weight-based nomogram rather than ad hoc dosing; it reduces both under- and over-anticoagulation and improves therapeutic time-in-range.

aPTT vs. Anti-Xa: If aPTT and anti-Xa disagree, trust anti-Xa in most cases. aPTT is influenced by factor deficiencies, lupus anticoagulant, and acute phase reactants, making it less reliable in critically ill patients.

Renal Failure Advantage: In renal failure or in patients likely to need procedures, UFH is often preferable to LMWH/DOACs because of short half-life and protamine reversibility. This allows rapid cessation before urgent procedures.

HIT Monitoring: Do not forget HIT monitoring – falling platelets or new thrombosis on heparin should immediately trigger a HIT workup and switch to an alternative (e.g., argatroban, bivalirudin, fondaparinux per local protocol). Never re-challenge with heparin if HIT is confirmed.

Protamine Reversal: Protamine reversal is helpful but not perfect (neutralizes ~60–100% of heparin effect depending on timing). Always address the underlying bleeding source, coagulopathy, and mechanical issues in parallel. Give protamine slowly (over 10–15 min) to avoid hypotension and anaphylactoid reactions.

Concentration Confusion: Heparin comes in multiple concentrations (10, 100, 1,000, 5,000 units/mL). Always perform an independent double-check when drawing up or programming infusions to prevent 10× or 100× dosing errors.

Bridging Therapy: When bridging patients off warfarin for procedures, stop heparin 4–6 hours before procedure (allowing ~3–5 half-lives) and check aPTT/anti-Xa to confirm normalization. Resume 12–24 hours post-procedure if hemostasis adequate.

References

1. Lexicomp. (2025). Heparin (systemic): Drug information. Wolters Kluwer.
2. Agnelli, G., & Becattini, C. (2010). Acute pulmonary embolism. New England Journal of Medicine, 363(3), 266–274.
3. Kearon, C., Akl, E. A., Ornelas, J., et al. (2016). Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest, 149(2), 315–352.
4. Linkins, L.-A., Dans, A. L., Moores, L. K., et al. (2012). Treatment and prevention of heparin-induced thrombocytopenia. Chest, 141(2 Suppl), e495S–e530S.
5. EMCrit Project. (2023). Anticoagulation in critical illness (IBCC). https://emcrit.org/