What to do with supratherapeutic heparin (unfractionated heparin) therapy?

From the Guidelines

For super therapeutic heparin, immediately stop the heparin infusion and notify the healthcare team to prevent serious bleeding complications, as evidenced by the most recent guidelines 1. The management of super therapeutic heparin involves careful monitoring of the patient for signs of bleeding and adjusting the anticoagulation therapy as needed.

• Check the aPTT or anti-Xa level to determine the degree of anticoagulation, with a target aPTT ratio of 1.5 to 2.5, which approximates heparin levels of 0.3 to 0.7 IU/mL measured by an anti-Xa assay 1.
• If there is serious bleeding, administer protamine sulfate as the antidote, typically at a dose of 1 mg per 100 units of heparin received in the previous 2-3 hours, with a maximum single dose of 50 mg, as recommended by previous studies 1.
• Protamine should be administered slowly intravenously over 10 minutes to avoid hypotension and anaphylactoid reactions.
• If there is no active bleeding, simply stopping the heparin may be sufficient as its half-life is relatively short (60-90 minutes), and resume heparin at a lower dose once levels return to therapeutic range, if continued anticoagulation is needed. Super therapeutic heparin levels can occur due to overdosing, decreased clearance in renal impairment, or drug interactions, and can lead to dangerous bleeding complications including intracranial hemorrhage, gastrointestinal bleeding, or retroperitoneal bleeding, highlighting the importance of careful monitoring and management 1.

From the FDA Drug Label

Fatal hemorrhages have occurred in pediatric patients due to medication errors in which 1 mL Heparin Sodium Injection vials were confused with 1 mL “catheter lock flush” vials. Avoid using heparin in the presence of major bleeding, except when the benefits of heparin therapy outweigh the potential risks. Hemorrhage can occur at virtually any site in patients receiving heparin.

The management of super therapeutic heparin involves careful monitoring and potential dose adjustment.

• Key considerations:
  • Bleeding risk: High risk of bleeding, especially in patients over 60 years of age, and those with conditions that increase the risk of hemorrhage.
  • Monitoring: Regular monitoring of platelet counts, hematocrit, and occult blood in stool is necessary.
  • Dose adjustment: The heparin dose may need to be adjusted based on frequent blood coagulation tests.
  • Alternative anticoagulants: If the platelet count falls below 100,000/mm3 or if recurrent thrombosis develops, consider discontinuing heparin and administering an alternative anticoagulant 2 2.
• Interactions with other medications:
  • Oral anticoagulants: Heparin sodium may prolong the one-stage prothrombin time, so a period of at least 5 hours after the last intravenous dose or 24 hours after the last subcutaneous dose should elapse before blood is drawn 2.
  • Platelet inhibitors: Drugs that interfere with platelet-aggregation reactions may induce bleeding and should be used with caution in patients receiving heparin sodium 2.

From the Research

Monitoring Therapeutic Heparin

• The management of therapeutic heparin involves monitoring to ensure that the patient's blood is within the therapeutic range, neither too prone to clotting nor too prone to bleeding.
• Two common methods for monitoring unfractionated heparin (UFH) are the activated partial thromboplastin time (aPTT) and the antifactor Xa heparin assay (anti-Xa) 3, 4, 5, 6, 7.

Comparison of Monitoring Methods

• Studies have compared the performance of aPTT and anti-Xa protocols in adult patients, with results indicating that anti-Xa monitoring can provide a more accurate measure of anticoagulation and achieve therapeutic range more rapidly 3, 6, 7.
• The use of anti-Xa levels has been associated with fewer dose adjustments and less variability in test results compared to aPTT monitoring 4, 6.
• However, the choice of monitoring method may depend on various factors, including the specific clinical context and the availability of laboratory resources 5.

Clinical Implications

• The discordance between aPTT and anti-Xa values can have significant clinical implications, including an increased risk of bleeding complications in patients with high aPTT to normal anti-Xa values 3.
• The transition from aPTT to anti-Xa monitoring has been shown to be safe and efficacious in certain patient populations, including veterans 4.
• Further research is needed to fully understand the advantages and disadvantages of each monitoring method and to determine the optimal approach for specific patient groups 5, 7.