Management of Heparin Resistance

Definition and Diagnosis

• Heparin resistance is defined as the inability to achieve an Activated Clotting Time (ACT) >300 seconds after administration of >600 U/kg heparin, often caused by antithrombin III (AT III) deficiency, preoperative heparin treatment, extreme thrombocytosis, septicemia, and hypereosinophilic syndrome 1
• Neonates and infants typically have lower levels of AT III (20-80% of adult levels) until approximately 6 months of age 1

Treatment Approach

• The recommended dose of Fresh Frozen Plasma (FFP) for treating heparin resistance is 10-15 ml/kg of body weight, which typically corresponds to 2-4 units of FFP for an average adult, as recommended by the American College of Cardiology and the American Society of Anesthesiologists (ASA) 2, 3
• Patients receiving FFP for heparin resistance should be monitored for transfusion reactions, which occur in approximately 5% of patients 2
• FFP contains approximately 1 unit/ml of antithrombin III (AT III) and appears to "normalize" the heparin-ACT dose-response curve in heparin-resistant patients, although the evidence comes primarily from observational studies and case reports 2

Special Considerations

• Patients with hereditary AT III deficiency may require higher doses of FFP or preferably AT III concentrate 1
• In massive transfusion protocols for trauma patients, a high-ratio transfusion strategy is recommended, with at least one unit of plasma per two units of packed red blood cells (1:2 FFP:RBC ratio), and in some cases, a plasma-first approach using an inverse ratio of 2 FFP to 1 RBC can be adopted 4, 5

Efficacy and Safety

• FFP should be ABO compatible with the patient, and if blood group is unknown, group AB FFP is preferred (contains no anti-A or anti-B) 3
• Once thawed, FFP can be used for up to 24 hours if stored at 4°C, and when removed from refrigeration, it must be used within 30 minutes 3
• The average volume per bag of FFP is approximately 300 ml 3

Indications and Contraindications

• FFP should only be used in specific clinical scenarios, including replacement of coagulation factors during major hemorrhage (trauma, obstetrics), acute disseminated intravascular coagulation (DIC) with bleeding, and actively bleeding patients with INR > 1.5, as recommended by the American Society of Anesthesiologists (ASA) 3, 6
• FFP can also be used for immediate reversal of warfarin-induced hemorrhage when PCC is unavailable, thrombotic thrombocytopenic purpura (usually with plasmapheresis), and replacement of coagulation factors when specific factors are unavailable 3
• FFP should not be used for routine circulatory volume replacement, management of mild-moderate coagulation abnormalities in non-bleeding patients, routine use in patients with cirrhosis/liver disease unless significant coagulopathy is identified, and correction of INR < 1.5 in non-bleeding patients, as recommended by the American Society of Anesthesiologists (ASA) 3, 6

Fibrinogen Replacement

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• The recommended dosage for FFP is 10-15 ml/kg to achieve minimum 30% plasma factor concentration, and for cryoprecipitate, typically 1 unit per 7-10 kg body weight, as recommended by the American Society of Anesthesiologists (ASA) 6, 7
• The American Society of Anesthesiologists (ASA) recommends measuring fibrinogen level whenever possible before administering blood products, and considering clinical context (active bleeding, planned procedure, etc.) 6

Monitoring and Precautions

• Transfused platelets and fibrinogen may have very short lifespans in patients with vigorous coagulation activation, according to the Journal of Thrombosis and Haemostasis 8
• FFP is not indicated solely for augmentation of plasma volume or albumin concentration, and cryoprecipitate is preferred for isolated low fibrinogen levels (< 80-100 mg/dL) with excessive microvascular bleeding, according to the American Society of Anesthesiologists (ASA) 6, 7