Carbon monoxide releasing molecule-2 improves protamine-mediated hypocoagulation/hyperfibrinolysis in human plasma in vitro

Vance G. Nielsen, S. Nini Malayaman, Jack B. Cohen, Joshua M. Persaud

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Background: Protamine sulfate has been implicated as a possible cause of coagulopathy for over 20 y. Protamine has been demonstrated to decrease thrombin activity and to prolong bleeding. We tested the hypothesis that a new hemostatic agent, carbon monoxide releasing molecule-2 (tricarbonyldichlororuthenium (II) dimer; CORM-2), could attenuate protamine-mediated hypocoagulation/hyperfibrinolysis in plasma. Methods: Normal plasma was exposed to 0, 12.5, 25, or 50 μg/mL of protamine, with or without addition of 100 μM CORM-2. Tissue factor was used to initiate coagulation, and tissue type plasminogen activator was added in some experiments. Additional experiments were performed wherein plasma was exposed to protamine combined with 0% or 30% dilution with normal saline, with or without CORM-2 addition. Thrombelastography was performed until either stable clot strength or clot lysis occurred. Results: Protamine, in a concentration-dependent fashion, significantly prolonged the onset of coagulation, decreased the velocity of thrombus growth, and decreased clot strength in the absence or presence of tissue type plasminogen activator. Further, protamine significantly decreased the time to onset of fibrinolysis and decreased clot lysis time. CORM-2 exposure significantly diminished all aforementioned protamine-mediated effects on coagulation and fibrinolysis. Lastly, CORM-2 addition significantly increased the velocity of clot growth and strength in diluted, protamine-exposed plasma. Conclusions: CORM-2 attenuated protamine-mediated hypocoagulation/ hyperfibrinolysis at clinically encountered concentrations. Additional preclinical investigation is warranted to determine if CORM-2 administration will be efficacious in diminishing coagulopathy caused by protamine.

Original languageEnglish (US)
Pages (from-to)232-239
Number of pages8
JournalJournal of Surgical Research
Issue number2
StatePublished - Apr 2012


  • biochemistry
  • blood
  • coagulants
  • coagulation/anticoagulation
  • fibrin
  • thrombelastography

ASJC Scopus subject areas

  • Surgery


Dive into the research topics of 'Carbon monoxide releasing molecule-2 improves protamine-mediated hypocoagulation/hyperfibrinolysis in human plasma in vitro'. Together they form a unique fingerprint.

Cite this