Heparin

Overview of Heparin

Heparin is an anticoagulant medication widely used in cardiac surgery, cardiopulmonary bypass (CPB), ECMO, dialysis, and other procedures requiring rapid and controllable inhibition of clot formation. It is classified as an indirect thrombin inhibitor and works by enhancing the activity of antithrombin III, which inactivates clotting factors IIa (thrombin), Xa, and others.

Heparin is essential in perfusion practice because it allows blood to circulate safely through extracorporeal circuits without clot formation.

Mechanism of Action

Heparin enhances the activity of antithrombin III (ATIII), a natural anticoagulant in the body.

Key effects:

• Inhibits thrombin (Factor IIa)
• Inhibits Factor Xa
• Reduces fibrin formation
• Prevents clot propagation in extracorporeal circuits

Heparin does not dissolve existing clots; it only prevents new clot formation and extension of existing clots.

Clinical Uses in Cardiac Surgery

Heparin is primarily used in situations where blood is exposed to non-endothelial surfaces:

• Cardiopulmonary bypass (CPB)
• Off-pump coronary artery bypass (OPCAB) support
• ECMO (Extracorporeal Membrane Oxygenation)
• Ventricular assist devices (VADs)
• Hemodialysis circuits
• Catheter-based cardiac procedures

Dosing and Administration

Heparin dosing is weight-based and highly protocol-driven in cardiac surgery.¹

Typical CPB dose:

• 300–400 units/kg IV bolus

Goal:

• Activated Clotting Time (ACT) ≥ 400–480 seconds before initiating bypass²³

Additional heparin may be given during CPB depending on:

• Circuit time
• ACT trends
• Patient response (heparin resistance)

Monitoring Anticoagulation

Heparin effect is monitored using the Activated Clotting Time (ACT).⁴⁵⁶⁷

ACT targets:

Phase	Target ACT
Baseline	70–120 sec89
Pre-bypass	≥ 400–480 sec2310
On CPB	Usually maintained > 400 sec45

Other monitoring methods:

• Anti-Xa levels (more common in ICU settings)
• aPTT (less common in surgical setting)

Heparin Resistance

Heparin resistance may occur when adequate anticoagulation cannot be achieved despite standard dosing.⁶

Common causes:

• Antithrombin III deficiency
• Prior heparin exposure
• Inflammation or critical illness
• High factor VIII levels

Management:

• Administer antithrombin III concentrate or FFP
• Increase heparin dose (less preferred)
• Evaluate for assay errors

Reversal of Heparin

Heparin is reversed using protamine sulfate.⁴⁵

Protamine dosing:

• 1 mg protamine per 100 units of heparin administered (approximate)

Important considerations:

• Rapid administration can cause hypotension
• Can cause pulmonary hypertension
• Allergic reactions possible (especially in Fish allergy, Prior exposure, Vasectomy, or NPH insulin use)

Heparin-Induced Thrombocytopenia (HIT)

Heparin-Induced Thrombocytopenia (HIT)¹¹ is an immune-mediated adverse reaction to heparin that results in paradoxical thrombosis despite low platelet counts.

Key features:

• Platelet drop >50% from baseline
• Thrombosis (arterial or venous)
• Occurs 5–10 days after exposure (can be earlier with prior exposure)

Management:

• Immediately discontinue all heparin
• Start alternative anticoagulant (Bivalirudin or Argatroban)
• Avoid platelet transfusion unless life-threatening bleeding

Complications of Heparin

• Bleeding¹²
• HIT (immune-mediated thrombosis)¹¹
• Osteoporosis (long-term use)
• Hyperkalemia (rare, via aldosterone suppression)
• Allergic reactions

Heparin in Cardiopulmonary Bypass

In CPB, heparin is critical to prevent clot formation in the circuit.¹⁴⁵

Key perfusion considerations:

• Ensure ACT is adequate before cannulation
• Monitor ACT every 30 minutes on bypass
• Adjust heparin as needed based on circuit response
• Confirm full reversal with protamine before leaving bypass

Recovery and Clearance

Heparin has a relatively short half-life:¹³

• 60–90 minutes in normal physiology
• Can be prolonged in hepatic dysfunction or high doses

Clearance occurs via:

• Reticuloendothelial system
• Renal excretion (minor pathway)

Summary

Heparin remains the cornerstone anticoagulant for cardiac surgery and extracorporeal circulation.¹ Safe use depends on appropriate dosing, frequent monitoring (ACT),⁶⁷ awareness of resistance, and prompt recognition of complications such as Heparin-Induced Thrombocytopenia (HIT).¹¹

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Perfusion Tidbits

ACT Targets: Why 480 Seconds?

The commonly cited Activated Clotting Time (ACT) target of 480 seconds during cardiopulmonary bypass originates from early studies in the 1970s, primarily by Bull et al.²³ and Young et al.¹⁰ These studies showed that clot formation could occur at ACT values around 300 seconds, leading investigators to recommend higher thresholds.

• Early data suggested:
  • ACT 300 sec → risk of fibrin formation¹⁰
  • ACT 400 sec → improved anticoagulation²³
• The 480 sec target was adopted as a safety margin, not because of strong evidence, but to account for:
  • Variability in early ACT devices
  • Differences in patient response to heparin
  • Lack of precise anticoagulation monitoring

Modern practice has evolved, and many centers now use ACT targets closer to 400 seconds, especially with:⁴⁵

• Heparin-bonded circuits
• Improved oxygenators
• More reliable monitoring techniques (Anti-Xa assays, heparin management systems (HMS))

The key takeaway is that the 480-second standard is largely a historical convention rather than a strictly evidence-based threshold, and appropriate ACT targets may vary depending on institutional protocols and technology.⁴⁵⁶

Emergency Re-initiation of Bypass (“Crashing Back On”)

In emergency situations where a patient must be rapidly returned to cardiopulmonary bypass such as hemodynamic collapse or cardiac arrest after coming off of bypass, there is often no time to calculate and verify a full weight-based heparin dose or wait for an ACT result.

In these scenarios, many perfusionists will just put 30,000 units of heparin in the pump to make sure the circuit does not clot while reinitiating. This is not generally considered a big issue, because it is better to have no clots, when heparin can just be reversed by protamine if needed.

Key points:

• This is for emergency situations only
• The goal is simply to get heparin on board fast enough to protect the circuit
• A formal ACT should be drawn as soon as the situation allows to guide ongoing anticoagulation management
• Full reversal with protamine should be recalculated based on total heparin administered once the patient is stable

Exam notes

• The book number of 480 seconds is considered the gold standard and should be selected when asked on exams.

• Protamine Reaction will cause Systemic Hypotension and Pulmonary Hypertension.

• 4 Main Concerns for Protamine Reaction NPH Insulin, Vasectomy, Previous Exposure, and Fish Allergy.

• HIT is an immune-mediated (Type II) reaction caused by IgG antibodies against the heparin–Platelet Factor 4 complex, leading to platelet activation and thrombosis.

• Approximately 1 mg of protamine per 100 units of heparin is needed to reverse the anticoagulation

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References

Footnotes

1. Gravlee GP, Davis RF, Stammers AH, Ungerleider RM, eds. Cardiopulmonary Bypass: Principles and Practice. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2008. ↩ ↩² ↩³

2. Bull BS, Korpman RA, Huse WM, Briggs BD. Heparin therapy during extracorporeal circulation. I. Problems inherent in existing heparin protocols. J Thorac Cardiovasc Surg. 1975;69(5):674–684. https://pubmed.ncbi.nlm.nih.gov/1127966/ ↩ ↩² ↩³ ↩⁴

3. Bull BS, Huse WM, Brauer FS, Korpman RA. Heparin therapy during extracorporeal circulation. II. The use of a dose-response curve to individualize heparin and protamine dosage. J Thorac Cardiovasc Surg. 1975;69(5):685–689. https://pubmed.ncbi.nlm.nih.gov/1127967/ ↩ ↩² ↩³ ↩⁴

4. Shore-Lesserson L, Baker RA, Ferraris VA, Greilich PE, Fitzgerald D, Roman P, Hammon JW. STS/SCA/AmSECT Clinical Practice Guidelines: Anticoagulation during Cardiopulmonary Bypass. J Extra Corpor Technol. 2018;50(1):5–18. https://pmc.ncbi.nlm.nih.gov/articles/PMC5850589/ ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶

5. Shore-Lesserson L, Baker RA, Ferraris VA, Greilich PE, Fitzgerald D, Roman P, Hammon JW. Clinical Practice Guidelines—Anticoagulation During Cardiopulmonary Bypass. Ann Thorac Surg. 2018;105(2):650–662. https://pubmed.ncbi.nlm.nih.gov/29362176/ ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶

6. Despotis GJ, Gravlee G, Filos K, Levy J. Anticoagulation monitoring during cardiac surgery: a review of current and emerging techniques. Anesthesiology. 1999;91(4):1122–1151. https://pubmed.ncbi.nlm.nih.gov/10519498/ ↩ ↩² ↩³ ↩⁴

7. Despotis GJ, Joist JH. Anticoagulation and anticoagulation reversal with cardiac surgery involving cardiopulmonary bypass: an update. J Cardiothorac Vasc Anesth. 1999;13(4 Suppl 1):18–29. https://pubmed.ncbi.nlm.nih.gov/10468245/ ↩ ↩²

8. Hattersley PG. Activated coagulation time of whole blood. JAMA. 1966;196(5):436–440. https://doi.org/10.1001/jama.1966.03100180108036 ↩

9. Dougherty KG, Gaos CM, Bush HS, Leachman DR, Ferguson JJ. Activated clotting times and activated partial thromboplastin times in patients undergoing coronary angioplasty who receive bolus doses of heparin. Cathet Cardiovasc Diagn. 1992;26(4):260–263. https://pubmed.ncbi.nlm.nih.gov/1423668/ ↩

10. Young JA, Kisker CT, Doty DB. Adequate anticoagulation during cardiopulmonary bypass determined by activated clotting time and the appearance of fibrin monomer. Ann Thorac Surg. 1978;26(3):231–240. https://pubmed.ncbi.nlm.nih.gov/699388/ ↩ ↩² ↩³

11. Greinacher A. Heparin-Induced Thrombocytopenia. N Engl J Med. 2015;373(3):252–261. https://pubmed.ncbi.nlm.nih.gov/26176382/ ↩ ↩² ↩³

12. Chest Physician Expert Panel. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):7S–47S. https://doi.org/10.1378/chest.1412S3 ↩

13. Heparin Sodium Injection [package insert]. Lake Forest, IL: Hospira, Inc. U.S. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/017029s049lbl.pdf ↩