The effect of cyanate on the clotting proteins and platelet function.
Cyanate reacts with unchanged amino groups of various proteins in a specific irreversible carbamylation reaction. The effect of this molecule on the clotting process and the effects of carbamylation on the clotting proteins and platelet functions were investigated in vitro. An immediate effect on the clotting proteins, not related to pH, was seen in the screening tests prothrombin time, partial thromboplastin time and thrombin time at the highest concentration (100 mM), to a lesser degree at the lower concentration (10 mM). These changes reflected decreases of 19 and 36% respectively in Factor V and X activity, an inhibition of 63-75% of Factors VII, IX, X and XI activity, and 80% inhibition of thrombin activity. The inhibitory changes of carbamylation increased with time. No changes were seen in the activity of Factors I and VIII. Platelet function studies revealed no inhibition of Factor III release; aggregation was abnormal only at high concentrations with epinephrine and collagen induction and partially reversible by resuspension in normal plasma.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000293:Adolescent; D001779:Blood Coagulation Factors / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects*; D002219:Carbamates; D003094:Collagen / Q000494:pharmacology; D003485:Cyanates / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology; D005164:Factor IX / Q000378:metabolism; D005165:Factor V / Q000378:metabolism; D005167:Factor VII / Q000378:metabolism; D005170:Factor X / Q000378:metabolism; D005172:Factor XI / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D011516:Prothrombin / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism; D013997:Time Factors
D001779:Blood Coagulation Factors; D002219:Carbamates; D003485:Cyanates; D000244:Adenosine Diphosphate; D005165:Factor V; D005167:Factor VII; D011516:Prothrombin; D005164:Factor IX; D005170:Factor X; D003094:Collagen; D005172:Factor XI; D013925:Thromboplastin; D013917:Thrombin; D004837:Epinephrine