Methylene blue for neutralization of heparin

Elaine M. Sloand, Craig M. Kessler, Charles L. McIntosh, Harvey G. Klein

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Patients with protamine allergy present a difficult dilemma when reversal of heparin is required for excessive bleeding. Premedication with steroids and antihistamines has not been shown to effectively prevent anaphylactic reactions in patients with hypersensitivity to protamine. Other heparin antagonists are either not available or are too toxic for human use. This report describes a patient in whom methylene blue was used effectively to neutralize heparin and decrease bleeding due to heparinization. In vitro testing was then done to further define the interaction of heparin and methylene blue. This testing demonstrated that methylene blue neutralized heparin levels of 1 u/ml as well as 10 u/ml. Methylene blue acted as an anticoagulant when present at levels of 3000 μg/ml. However, it acted as a coagulant when present in intermediate levels of 800 μg/ml and 1600 μg/ml. The plasma levels necessary for neutralization of heparin levels of 1 unit/ml (the levels achieved in patient therapeutically anticoagulated) are easily achieved using doses routinely used in treatment of methemoglobinemia. Although the toxicity of methylene blue has been well defined at the lower doses of 2-4 mg/Kg, work still needs to be done to determine safety of the drug at the higher doses necessary to neutralize heparin levels achieved in bypass patients.

Original languageEnglish (US)
Pages (from-to)677-686
Number of pages10
JournalThrombosis Research
Issue number6
StatePublished - Jun 15 1989
Externally publishedYes


  • allergy
  • cardiopulmonary bypass
  • heparin
  • Methylene Blue
  • protamine

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Hematology


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