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Homocysteine, coagulation, platelet function, and thrombosis.
Semin Thromb Hemost 2000; 26(3):243-54ST

Abstract

Over the last 30 years, a growing body of evidence has documented the role of hyperhomocysteinemia (HHcy) as an independent vascular risk factor. However, the mechanisms through which elevated circulating levels of homocysteine (Hcy) cause vascular injury and promote thrombosis remain elusive. Most findings have been achieved in in vitro studies employing exceedingly high concentrations of Hcy, whereas only a few studies have been carried out in vivo in humans. In homocystinuric patients, homozygotes for mutations of the gene coding for the cystathionine beta-synthase enzyme, abnormalities of coagulation variables reflecting a hypercoagulable state, have been reported. In vitro studies provide a biochemical background for such a state. In homocystinuric patients, an in vivo platelet activation has also been reported. The latter abnormality is not corrected by the bolus infusion of concentrations of hirudin, which determines a long-lasting impairment of the conversion of fibrinogen to fibrin by thrombin; in contrast, it appears at least in part lowered by the administration of the antioxidant drug probucol. During the autooxidation of Hcy in plasma, reactive oxygen species are generated. The latter initiate lipid peroxidation in cell membranes (potentially responsible for endothelial dysfunction) and in circulating lipoproteins. Oxidized low-density lipoproteins (LDL) may trigger platelet activation as well as some of the hemostatic abnormalities reported in such patients. Thus the oxidative stress induced by Hcy may be a key process in the pathogenesis of thrombosis in HHcy. Accumulation of adenosylhomocysteine in cells (a consequence of high circulating levels of homocysteine) inhibits methyltransferase enzymes, in turn preventing repair of aged or damaged cells. This mechanism has been recently documented in patients with renal failure and HHcy and provides an additional direction to be followed to understand the tendency to thrombosis in moderate HHcy.

Authors+Show Affiliations

Department of Clinical and Experimental Medicine, University of Naples Federico II, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

11011842

Citation

Coppola, A, et al. "Homocysteine, Coagulation, Platelet Function, and Thrombosis." Seminars in Thrombosis and Hemostasis, vol. 26, no. 3, 2000, pp. 243-54.
Coppola A, Davi G, De Stefano V, et al. Homocysteine, coagulation, platelet function, and thrombosis. Semin Thromb Hemost. 2000;26(3):243-54.
Coppola, A., Davi, G., De Stefano, V., Mancini, F. P., Cerbone, A. M., & Di Minno, G. (2000). Homocysteine, coagulation, platelet function, and thrombosis. Seminars in Thrombosis and Hemostasis, 26(3), pp. 243-54.
Coppola A, et al. Homocysteine, Coagulation, Platelet Function, and Thrombosis. Semin Thromb Hemost. 2000;26(3):243-54. PubMed PMID: 11011842.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Homocysteine, coagulation, platelet function, and thrombosis. AU - Coppola,A, AU - Davi,G, AU - De Stefano,V, AU - Mancini,F P, AU - Cerbone,A M, AU - Di Minno,G, PY - 2000/9/30/pubmed PY - 2001/3/3/medline PY - 2000/9/30/entrez SP - 243 EP - 54 JF - Seminars in thrombosis and hemostasis JO - Semin. Thromb. Hemost. VL - 26 IS - 3 N2 - Over the last 30 years, a growing body of evidence has documented the role of hyperhomocysteinemia (HHcy) as an independent vascular risk factor. However, the mechanisms through which elevated circulating levels of homocysteine (Hcy) cause vascular injury and promote thrombosis remain elusive. Most findings have been achieved in in vitro studies employing exceedingly high concentrations of Hcy, whereas only a few studies have been carried out in vivo in humans. In homocystinuric patients, homozygotes for mutations of the gene coding for the cystathionine beta-synthase enzyme, abnormalities of coagulation variables reflecting a hypercoagulable state, have been reported. In vitro studies provide a biochemical background for such a state. In homocystinuric patients, an in vivo platelet activation has also been reported. The latter abnormality is not corrected by the bolus infusion of concentrations of hirudin, which determines a long-lasting impairment of the conversion of fibrinogen to fibrin by thrombin; in contrast, it appears at least in part lowered by the administration of the antioxidant drug probucol. During the autooxidation of Hcy in plasma, reactive oxygen species are generated. The latter initiate lipid peroxidation in cell membranes (potentially responsible for endothelial dysfunction) and in circulating lipoproteins. Oxidized low-density lipoproteins (LDL) may trigger platelet activation as well as some of the hemostatic abnormalities reported in such patients. Thus the oxidative stress induced by Hcy may be a key process in the pathogenesis of thrombosis in HHcy. Accumulation of adenosylhomocysteine in cells (a consequence of high circulating levels of homocysteine) inhibits methyltransferase enzymes, in turn preventing repair of aged or damaged cells. This mechanism has been recently documented in patients with renal failure and HHcy and provides an additional direction to be followed to understand the tendency to thrombosis in moderate HHcy. SN - 0094-6176 UR - https://www.unboundmedicine.com/medline/citation/11011842/Homocysteine_coagulation_platelet_function_and_thrombosis_ L2 - http://www.thieme-connect.com/DOI/DOI?10.1055/s-2000-8469 DB - PRIME DP - Unbound Medicine ER -