Thromb Haemost 1997; 77(03): 466-471
DOI: 10.1055/s-0038-1655990
Clinical Studies
Schattauer GmbH Stuttgart

Mild Hyperhomocysteinemia and Hemostatic Factors in Patients with Arterial Vascular Diseases

G Freyburger
1   The Laboratoire d'Hèmatologie, Hôpital Pellegrin, Bordeaux, France
,
S Labrouche
1   The Laboratoire d'Hèmatologie, Hôpital Pellegrin, Bordeaux, France
,
G Sassoust
3   The Service de Chirurgie Vasculaire, Hôpital Pellegrin, Bordeaux, France
,
F Rouanet
4   The Service de Neurologie, Hôpital Pellegrin, Bordeaux, France
,
S Javorschi
1   The Laboratoire d'Hèmatologie, Hôpital Pellegrin, Bordeaux, France
,
F Parrot
2   The Laboratoire de Biochimie, Hôpital Pellegrin, Bordeaux, France
› Author Affiliations
Further Information

Publication History

Received 16 July 1996

Accepted after resubmissions. 07 November 1996

Publication Date:
11 July 2018 (online)

Summary

Mild hyperhomocysteinemia, due to genetic or to environmental factors, is now recognized as a risk factor for premature arterial disease, including peripheral arterial occlusion, thrombotic stroke and myocardial infarction. It is defined by either an increased level of fasting homocysteine or by an increased level after loading with methionine, which is more frequently altered than the former. We studied the hemostatic parameters in 88 patients with premature arterial disease (mean age 43 ± 11 years). We confirmed previously known hemostatic alterations described in vascular patients when compared to controls, but found that, among patients, some of these parameters were more altered in hyperhomocysteinemic patients. When fasting homocysteine was increased, higher alterations were found in factors VIIIc, von Wille- brand and thombin-antithrombin complexes were more elevated. When post-methionine load homocysteine was increased, alterations in fibrinolytic parameters were more pronounced.

 
  • References

  • 1 Gibson JB, Carson NAJ, Neill DW. Pathological findings in homocystinuria. J Clin Pathol 1964; 17: 427-437
  • 2 Shimke RN, McKusik VA, Huang T. Homocystinuria:studies of 20 families with 38 affected members. JAMA 1965; 193: 711-719
  • 3 Boers GH, Smals AG, Trijbels FJ, Fowler B, Bakkeren JA, Schoonderwaldt HC, Kleijer WJ, Kloppenborg PWC. Heterozygosity for homocystinuria in premature peripheral and cerebral occlusive arterial disease. N Engl J Med 1985; 313: 709-715
  • 4 Genest JJ, McNamara JR, Upson B, Salem DN, Ordovas JM, Schaefer EJ, Malinow MR. Prevalence of familial hyperhomocysteinemia in men with premature coronary artery disease. Arterioscler Thromb 1991; 11: 1129-1136
  • 5 Den Heijer M, Koster T, Blom HJ, Bos GMJ, Briet E, Reitsma PH, Vanden-broucke JP, Rosendaal FR. Hyperhomocysteinemia as a risk factor for deep-venous thrombosis. N Engl J Med 1996; 334: 759-762
  • 6 Stamler JS, Slivka A. Biochemical chemistry of thiols in the vasculature and in vascular-related disease. Nut Rev 1996; 54: 1-30
  • 7 Lentz SR, Sadler JE. Inhibition of thrombomodulin surface expression and protein C activation by the thrombogenic homocysteine. J Clin Invest 1991; 88: 1900-1904
  • 8 Stamler JS, Loscalzo J. Glutathione dramatically alters the activity of tissue plasminogen activator. Clin Res 1990; 38: 246 A
  • 9 Harpel PC, Chang VT, Borth W. Homocysteine and other sulfhydryl compounds enhance the binding of lipoprotein(a) to fibrin:a potential biochemical link between thrombosis, atherosclerosis, and sulfhydryl compound metabolism. Proc Natl Acad Sci USA 1992; 89: 10193-10197
  • 10 Lentz SR, Sadler E. Homocysteine inhibits von Willebrand factor processing and secretion by preventing transport from the endoplasmic reticulum. Blood 1993; 81: 683-689
  • 11 Fryer RH, Wilson BD, Gubler DB, Fitzgerald LA, Rodgers GM. Homocysteine, a risk factor for premature vascular disease and thrombosis, induces tissue factor activity in endothelial cells. Arterioscler Thromb 1993; 13 9: 1327-1333
  • 12 Rodgers GM, Kane W. Activation of endogenous factor V by a homocysteine-induced vascular endothelial cell activator. J Clin Invest 1986; 77: 1909-1916
  • 13 Palareti G, Coccheri S. Lowered antithrombin III activity and other clotting changes in homocystinuria:effects of a pyridoxine-folate regimen. Haemostasis 1989; 19S: 24-28
  • 14 Stamler JS, Osborne JA, Jaraki O, Rabbani LE, Mullins M, Singel D, Loscalzo J. Adverse effects of homocysteine are modulated by endothelium-derived relaxing factor and related oxides of nitrogen. J Clin Invest 1993; 91: 308-318
  • 15 Ueland PM. Homocysteine species as components of plasma redox thiol status. Clin Chem 1995; 41: 340-343
  • 16 Brattstrӧm L, Israelsson B, Lindgärde F, Hultberg B. Higher total plasma homocysteine in vitamin B12 deficiency than in heterozygoty for homocystinuria due to cystathionine ß-synthase deficiency. Metabolism 1988; 37: 175-178
  • 17 Zӧller B, Dahlbäck B. Linkage between inherited resistance to activated protein C and factor V gene mutation in venous thrombosis. Lancet 1994; 344: 1536-1538
  • 18 Kluft C, Brachman P, Verdhuyzen-Stolk EC. Screening of fibrinolytic activity in plasma euglobulin fractions on the fibrin plate. In: Progress in chemical fibrinolysis and thrombolysis. Davidson JF, Samama MM, Desnoyers PC. eds New-York: Raven Press; 1976. 2. pp 57-65
  • 19 Cortes HJ. High performance liquid chromatography of inorganic and organic anions using ustraviolet detection and an amino column. J Chrom-atogr 1982; 234: 517-520
  • 20 Freyburger G, Bilhou-Nabera C, Javorschi S, Dief S, Labrouche S, Lere-beller MJ, Boisseau MR. Technical and biological conditions influencing the functional APC resistance test. Thromb Haemost 1996; 75: 460-465
  • 21 Heinrich J, Schulte H, Schonfeld R, Kohler E, Assmann G. Association of variables of coagulation, fibrinolysis and acute-phase with atherosclerosis in coronary and peripheral arteries and those arteries supplying the brain. Thromb Haemost 1995; 73: 374-379
  • 22 Herren T, Strieker H, Haeberli A, Do DD, Straub PW. Fibrin formation and degradation in patients with atherosclerotic disease. Circulation 1994; 90: 2679-2686
  • 23 Genest JJ, Cohn JS. Clustering of cardiavascular risk factors:targeting high-risk individuals. Am J Cardiol 1995; 76: 8A-20A
  • 24 Freyburger G, Janvier G, Dief S, Boisseau MR. Fibrinolytic and Hemorheologic alterations during and after elective aortic graft surgery. Anesth Analg 1993; 76: 504-512
  • 25 Blann AD. Is raised vonWillebrand factor a marker of endothelial cell damage?. Med Hypotheses 1993; 41: 419-424
  • 26 Van den Berg M, Stehouwer CDA, Boers GHJ, Rauwerda JA, Kluft C. Arterial disease in hyperhomocysteinaemia and the effect of treatment:a pilot study. Fibrinolysis 1994; 8: 88-90
  • 27 Mudd SH, Havlick R, Levy HL, McKusick VA, Feinlieb M. A study of cardiovascular risk in heterozygotes for homocystinuria. Am J Hum Genet 1981; 33: 883-893