Folate deficiency-induced hyperhomocysteinemia attenuates, and folic acid supplementation restores, the functional activities of rat coagulation factors XII, X, and II.
Hyperhomocysteinemia (HH) constitutes a risk marker for thrombosis, but the pathophysiological mechanisms in thrombus formation are still unresolved. We investigated the influence of HH on single coagulation factor functions and evaluated the platelet GpIIb/IIIa receptor function in HH-induced changes in whole-blood coagulation profiles (WBCP). Three groups of 12 rats were investigated: control rats, folate deficient-HH (FD-HH) rats, and treated rats. Plasma total homocysteine was 7.1 micromol/L in controls, 31.3 micromol/L in FD-HH rats, and 7.6 micromol/L in treated rats. Factor (F) II:C, FX:C, and FXII:C were reduced in FD-HH rats compared with controls and normalized in treated rats (P < 0.05). FVII:C activity did not differ among the groups. Factor VIII:C activity was greater in FD-HH rats than in controls (P < 0.05). Blockage of the platelet GpIIb/IIIa receptor by Integrilin (Schering-Plough A/S) did not abolish the FD-HH-induced increase in whole-blood coagulation velocity, irrespective of the dosage of Integrilin. In conclusion, FD-HH reduced the functional activities of FXII:C, FX:C and FII:C, whereas FVII:C was unchanged and FVIII:C increased. These findings may partially explain the prolonged initiation phase of WBCP in FD-HH rats. The changes in single coagulation factor functions and WBCPs in FD-HH rats were reversed by treatment with folic acid.
Ebbesen
Liselotte Sabroe
LS
Clinical Institute and Center for Hemophilia and Thrombosis, Department of Clinical Biochemistry, University Hospital of Aarhus (Skejby Sygehus), Denmark. lse@dadlnet.dk
Ingerslev
Jørgen
J
D000818:Animals; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005170:Factor X / Q000187:drug effects / Q000378:metabolism*; D005174:Factor XII / Q000187:drug effects / Q000378:metabolism*; D005492:Folic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D005494:Folic Acid Deficiency; D020138:Hyperhomocysteinemia / Q000139:chemically induced*; D008297:Male; D011516:Prothrombin / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011921:Rats, Inbred WKY
D011516:Prothrombin; D005170:Factor X; D005174:Factor XII; D005492:Folic Acid