Elevated plasma homocysteine leads to alterations in fibrin clot structure and stability: implications for the mechanism of thrombosis in hyperhomocysteinemia

• Published in: Journal of thrombosis and haemostasis 2003-02, Vol.1 (2), p.300-306
• Main Authors: Sauls, D. L., Wolberg, A. S., Hoffman, M.
• Format: Article
• Language: English
• Subjects: Animals; Blood Coagulation; cardiovascular disease; Fibrin - metabolism; Fibrin - ultrastructure; fibrinogen; Fibrinogen - isolation & purification; Fibrinogen - metabolism; Fibrinolysin - metabolism; fibrinolysis; homocysteine; Homocysteine - blood; Hyperhomocysteinemia - blood; Hyperhomocysteinemia - complications; In Vitro Techniques; Microscopy, Electron, Scanning; Rabbits; thrombosis; Thrombosis - blood; Thrombosis - etiology
• ISSN: 1538-7933; 1538-7836; 1538-7836
• DOI: 10.1046/j.1538-7836.2003.00053.x

Elevated plasma homocysteine is associated with an increased risk of atherosclerosis and thrombosis. However, the mechanisms by which homocysteine might cause these events are not understood. We hypothesized that hyperhomocysteinemia might lead to modification of fibrinogen in vivo, thereby causing altered fibrin clot structure. New Zealand White rabbits were injected intraperitoneally (i.p.) every 12 h through an indwelling catheter with homocysteine or buffer for 8 weeks. This treatment raised the plasma homocysteine levels to about 30 µmol L−1 compared with 13.5 µmol L−1 in control rabbits by the end of the treatment period. The fibrinogen levels were 3.2 ± 0.6 in homocysteine‐treated and 2.5 ± 1.1 mg mL−1 in control rabbits. The reptilase time was prolonged to 363 ± 88 for plasma from homocysteine‐treated rabbits compared with 194 ± 48 s for controls (P