Hyperhomocysteinemia due to folate deficiency is thrombogenic in rats.
Although hyperhomocysteinemia (HH) appears to be an independent risk factor for thrombosis, the pathophysiologic mechanisms seen in thrombus formation are largely unresolved. The aim of the present study was to investigate whether HH is accompanied by thrombogenic alterations as assessed by whole blood thromboelastographic profiles. Severe (111 micro mol/L) and intermediate (42 micro mol/L) HH were induced in two series of rats by feeding them a folate-depleted diet. Each group was compared with a separate control group. In rats suffering severe HH (n = 30), initiation of the coagulation was protracted, with a clotting time of 79.7 s (95% CI, 76.2-83.4) compared with 70.4 s (95% CI, 66.5-74.6) in controls (P = 0.001). The velocity of the propagation of coagulation was increased, reaching 0.119 mm/s (95% CI, 0.111-0.127) in HH rats compared with 0.104 mm/s (95% CI, 0.099-0.108) in controls (P < 0.001). The maximum clot firmness also was increased, i.e., 41.9 mm (95% CI, 40.5-43.4) in HH rats compared with 37.6 mm (95% CI, 36.5-38.7) in controls (P < 0.001). The resting thrombin-antithrombin complex concentration in plasma tended to be lower in HH rats [5.60 micro g/L (95% CI, 3.76-8.34) than in controls [8.56 micro g/L (95% CI, 6.44-11.37)] (P = 0.074). In the series of rats with intermediate HH (n = 16), the changes in the whole blood coagulation profile (WBCP) were similar to those in rats with severe HH although only the prolongation of the initiation phase was significant. In conclusion, our study revealed that the WBCP was influenced by high plasma homocysteine by 1) prolonging the initiation phase, 2) increasing the velocity of the coagulation propagation and 3) increasing the maximum clot firmness. These changes in WBCP may contribute to the increased risk of thrombosis in hyperhomocysteinemic individuals.
Ebbesen
Liselotte Sabroe
LS
Institute of Experimental Clinical Research, Department of Clinical Biochemistry, University Hospital of Aarhus/Skejby, Brendstrupgaardsvej, DK-8200 Aarhus N, Denmark. lse@dadlnet.dk
Christiansen
Kirsten
K
Ingerslev
Jørgen
J
D000818:Animals; D001835:Body Weight; D005494:Folic Acid Deficiency / Q000150:complications*; D006710:Homocysteine / Q000097:blood*; D020138:Hyperhomocysteinemia / Q000150:complications*; D008297:Male; D051381:Rats; D011921:Rats, Inbred WKY; D013927:Thrombosis / Q000209:etiology*
D006710:Homocysteine