Comparison of the effects of CORM-2, CORM-3 and CORM-A1 on coagulation in human plasma.

Carbon monoxide derived from the catalytic action of heme oxygenase-1 or carbon monoxide-releasing molecules (CORMs) has been found to potentially be an anticoagulant or procoagulant agent. Of interest, two water-soluble CORMs, CORM-3 and CORM-A1, recently became commercially available. Thus, the purpose of the present study was to assess and compare the effects of the previously well studied CORM-2 to the effects of CORM-3 and CORM-A1 on coagulation in citrated human plasma with thrombelastography. Plasma exposed to CORMs was incubated at 37°C for at least one carbon monoxide release half-time, and then tissue factor-activated coagulation was commenced with calcium addition. CORM-2 and CORM-3 enhanced the velocity of clot formation and thrombus strength in a similar manner, whereas CORM-A1 did not affect coagulation. However, CORM-A1 did diminish tissue-type plasminogen activator initiated fibrinolysis. The similarity in effect on coagulation by CORM-2 and CORM-3 was likely secondary to the relatively inert effect of their ruthenium-containing carrier molecule, whereas the boron-containing CORM-A1 may have had no effect secondary to boron binding to fibrinogen, preventing carbon monoxide-mediated changes in fibrinogen protein structure via attached heme group(s). Future investigations with CORMs should have special attention to confounding effects of the carrier molecule.