Carbon monoxide releasing molecule-2 enhances coagulation and diminishes fibrinolytic vulnerability in plasma exposed to heparin or argatroban.
BACKGROUND
It has been recently demonstrated that a carbon monoxide releasing molecule (tricarbonyldichlororuthenium [II] dimer; CORM-2) enhances coagulation and attenuates vulnerability to fibrinolysis in normal and hemophiliac human plasma. We tested the hypothesis that plasma anticoagulated with heparin or argatroban would demonstrate improved coagulation and decreased fibrinolytic vulnerability after exposure to CORM-2.


METHODS
Normal plasma was anticoagulated with 0 to 0.1 U/mL unfractionated heparin or 0 to 1 μg/mL argatroban. Samples were subsequently exposed to 0 or 100 μM CORM-2 and activated with tissue factor. Additional samples with the same anticoagulant and CORM-2 exposure schema were incubated with 100 U/mL tissue-type plasminogen activator (tPA) to assess fibrinolytic vulnerability. Thrombelastographic data were collected until either clot strength stabilized or clot lysis occurred as appropriate.


RESULTS
In the absence of tPA, CORM-2 significantly increased the velocity of clot growth in heparin (75%) and argatroban-exposed (40%) samples. Clot strength was also significantly increased in heparin (69%) and argatroban-exposed (72%) samples. In the presence of tPA, CORM-2-treated samples had even greater (94%-731%) increases in velocity of growth and strength after exposure to either anticoagulant and significantly increased clot lysis time (103%-200%).


CONCLUSIONS
CORM-2 exposure resulted in faster-growing, stronger, longer-lived thrombi after anticoagulation with heparin or argatroban. Additional preclinical investigation is warranted to determine whether CORM-2 administration will be useful in attenuating bleeding complications associated with thromboprophylaxis.
Department of Anesthesiology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, USA. vance.nielsen@drexelmed.edu
Vance G
VG
Nielsen
Ejaz S
ES
Khan
James K
JK
Kirklin
James F
JF
George
D000925:Anticoagulants / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives; D001777:Blood Coagulation / Q000187:drug effects*; D003029:Coagulants / Q000494:pharmacology*; D005342:Fibrinolysis / Q000187:drug effects*; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D009942:Organometallic Compounds / Q000494:pharmacology*; D010875:Pipecolic Acids / Q000494:pharmacology*; D013449:Sulfonamides; D013916:Thrombelastography; D013925:Thromboplastin / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000378:metabolism
D000925:Anticoagulants; D003029:Coagulants; D009942:Organometallic Compounds; D010875:Pipecolic Acids; D013449:Sulfonamides; C447082:tricarbonyldichlororuthenium (II) dimer; D006493:Heparin; D013925:Thromboplastin; D001120:Arginine; D010959:Tissue Plasminogen Activator; C031942:argatroban