title: Folate deficiency-induced hyperhomocysteinemia attenuates, and folic acid supplementation restores, the functional activities of rat coagulation factors XII, X, and II.
abstract: 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.
authors.affiliation: Clinical Institute and Center for Hemophilia and Thrombosis, Department of Clinical Biochemistry, University Hospital of Aarhus (Skejby Sygehus), Denmark. lse@dadlnet.dk
authors.forename: Liselotte Sabroe
authors.initials: LS
authors.lastname: Ebbesen
authors.forename: Jørgen
authors.initials: J
authors.lastname: Ingerslev
mesh_terms: 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
chemical_list: D011516:Prothrombin; D005170:Factor X; D005174:Factor XII; D005492:Folic Acid