Hyperhomocysteinemia and venous thromboembolic disease

Haematologica

Volumn 82, Issue 2, 1997, Pages 211-219

  D'Angelo, Armando ^a   Mazzola, Giuseppina ^a   Crippa, Luciano ^a   Fermo, Isabella ^a   D'Angelo, Silvana Viganò ^a  

^a SAN RAFFAELE HOSPITAL   (Italy)

Author keywords

Folio acid; Hyperhomocysteinemia; Thrombosis; Vitamin B12; Vitamin B6

Indexed keywords

AZAURIDINE; CONTRACEPTIVE AGENT; CYANOCOBALAMIN; FOLIC ACID; HOMOCYSTEINE; PYRIDOXINE;

DIET SUPPLEMENTATION; HUMAN; HYPERHOMOCYSTEINEMIA; MAJOR CLINICAL STUDY; REVIEW; THROMBOEMBOLISM; THROMBOGENESIS; THROMBOSIS PREVENTION; VEIN THROMBOSIS; VITAMIN DEFICIENCY; VITAMIN INTAKE;

HOMOCYSTEINE; HUMANS; RISK FACTORS; THROMBOPHLEBITIS;

EID: 0031454443     PISSN: 03906078     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (127)

1. Selhub J, Miller JW. The pathogenensis of homocysteinemia: interruption of the coordinate regulation by S-adenosylmethionine of the remethylation and transsulfuration of homocysteine. Am J Clin Nutr 1991; 55:131-8.
2. Mason JB, Miller JW. The effects of vitamin 812, B6 and folate on blood homocysteine levels. Ann NY Acad Sci 1992; 669:197-204.
3. Okada G, Teraoka H, Tsukada K. Multiple species of amammalian S-adenosylmethionine synchetase. Partial purification and characterization. Biochemistry 1981; 20:934-40.
4. Kraus JP, Le K, Swaroop M, et al. Human cystathionine-β-synthase cDNA: sequence. Alternative splicing and expression in cultured cells. Hum Mol Genet 1993; 2:1633-8.
5. Munke M, Kraus JP, Ohura T, Francke U. The gene for cystathionine β-synthase (CBS) maps to the subtelomeric region of human chromosome 21q and to proximal mouse chromosome 17. Am J Hum Genet 1988; 42:550-9.
6. Finkelstein JD, Martin JJ. Methionine metabolism in mammals. Distribution of homocysteine between competing pathways. J Biol Chem 1984; 259:9508-13.
7. Finkelstein JD, Kyle WE, Martin JJ, Pick A-M. Activation of cystathionine β-synthase by adenosylmethionine and adenosylethionine. Biochem Biophys Res Commun 1975; 66:81-87.
8. Roper MD, Kraus JP. Rat cystathionine β-synthase: expresison of four alternatively spliced isoforms in transfected cultured cells. Arch Biochem Biophys 1992; 298:514-21.
9. Kutzbach C, Stokstad ELR. Mammalian methylenetetrahydrofolate reductase: partial purification, properties and inhibition by S-adenosylmethionine. Biochim Biophys Acta 1971; 250:459-77.
10. Jencks DA, Matthews RG. Allosteric inhibition of methylenetetrahydrofolate reductase by adenosylmethionine. J Biol Chem 1987; 262:2485-93.
11. Finkelstein JD. Methionine metabolism in mammals. J Nutr Biochem 1990; 1:228-37.
12. Mudd SH, Levy HL, Skovby F. Disorders of transsulfuration. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular basis of inherited disease. New York: McGraw-Hill; 1995. p. 1279-327.
13. Hultberg B, Andersson A, Sterner G. Plasma homocysteine in renal failure. Clin Nephrol 1993; 40:230-5.
14. Fowler B, Kraus J, Packman S, Rosenberg LE. Homocystinuria: evidence for three distinct classes of cystathionine-β-synthase mutants in cultured fibroblasts. J Clin Invest 1978; 61:645-53.
15. Barber GW, Spaeth GL. The successful treatment of homocystinuria with pyridoxine. J Pediatr 1969; 75:463-78.
16. Sebastio G, Sperandeo MP, Panico M, de Franchis R, Kraus JP, Andria G. The molecular basis of homocystinuria due to cystathionine-β-synthase deficiency in Italian families and report of four novel mutations. Am J Hum Genet 1995; 56:1324-33.
17. Sperandeo MP, Panico M, Pepe A, et al. Molecular analysis of patients affected by homocystinuria due to cystathionine-β-synthase deficiency: report of a new mutation in exon 8 and a deletion in intron 11. J Inner Met Dis 1995; 18:211-4.
18. Levy HL, Mudd SH, Schulman JD, Dreyfus PM, Abeles RH. A derangement in B12 metabolism associated with homocystinemia, cystathioninemia, hypomethionemia and methylmalonic aciduria. Am J Med 1970; 48:390-7.
19. Goodman SI, Moe PG, Hammond KB, Mudd SH, Uhlendorf BW. Homocystinuria with methylmalonic aciduria: two cases in a sib-ship. Biochem Med 1970; 4:500-15.
20. Mudd SH, Levy HL, Morrow G. Deranged B12 metabolism: effects on sulfur amino acid metabolism. Biochem Med 1970; 4:193-214.
21. Mudd SH, Uhlendorf BW, Freeman JM, Finkelstein JD, Shih VE. Homocystinuria assiciated with decreased methylenetetrahydrofolate reductase activity. Biochem Biophys Res Commun 1972; 46:905-12.
22. Shih VE, Salam MZ, Mudd SH, Uhlendorf BW, Adams RD. A new form of homocystinuria due to 5,10-methylenetetrahydrofolate reductase deficiency. Pediatr Res 1972; 6:395.
23. Kanwar JS, Manaligod JR, Wong PWK. Morphologic studies in a patient with homocystinuria due to 5,10-methylenetetrahydrofolate reductase deficiency. Pediatr Res 1976; 10:598-609.
24. Kang SS, Zhou J, Wong PWK, Kowalisyn J, Strokosch G. Intermediate homocysteinemia: a thermolabile variant of methylenetetrahydrofolate reductase. Am J Hum Genet 1988; 43:414-21.
25. Erbe RW. Inborn errors of folate metabolism. In: Blakley RL, Whitehead VM, eds. Folate and pterins: nutritional, pharmacological and physiological aspects. New York: Wiley & Sons; 1986. p. 413-65.
26. Fenton WA, Rosenberg LE. Inherited disorders of cobalamin transport and metabolism. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular basis of inherited disease. New York: McGraw-Hill; 1995. p. 2065-82.
27. Rosenblatt DS. Inherited disorders of folate transport and metabolism. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular basis of inherited disease, New York: McGraw-Hill; 1995. p. 2049-64.
28. Goyette P, Sumner JS, Milos R, et al. Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification. Nature Genetics 1994; 7:195-200.
29. Goyette P, Frosst P, Rosenblatt DS, Rozen R. Seven novel mutations in the methylenetetrahydrofolate reductase gene and genotype/phenotype correlations in severe methylenetetrahydrofolate reductase deficiency. Am J Hum Genet 1995; 56:1052-9.
30. Kang SS, Wong PWK, Susmano A, Sora J, Norusis M, Ruggie N. Thermolabile methylenetetrahydrofolate reductase: an inherited risk factor for coronary artery disease. Am J Hum Genet 1991; 48:536-45.
31. Kang SS, Passen EL, Ruggie N, Wong PWK, Sora H. Thermolabile defect of methylenetetrahydrofolate reductase in coronary artery disease. Circulation 1993; 88:1463-69.
32. Engbersen AMT, Franken DG, Boers GHJ, Stevens EMB, Trijbels FJM, Blom HJ. Thermolabile 5,10-methylenetetrahydrofolate reductase as a cause of mild hyperhomocysteinemia. Am J Hum Genet 1995; 56:142-50.
33. Frosst P, Blom HJ, Milos R, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nature Genet 1995; 10:111-3.
34. Motulsky A. Nuritional ecogenetics: homocysteine-related arteriosclerotic vascular disease, neural tube defects, and folic acid. Am J Hum Genet 1996; 58:17-20.
35. Kluijtmans L, van den Heuvel L, Boers G, et al. Molecular genetic analysis in mild hyperhomocysteinemia: a common mutation in the 5,10-methylenetetrahydrofolate reductase gene is a genetic factor for cardiovascular disease. Am J Hum Genet 1996; 58:35-41.
36. de Franchis R, Mancini FP, D'Angelo A, et al. Elevated total plasma homocysteine (tHcy) and 677C→T mutation of the 5,10-methylenetetrahydrofolate reductase gene in thrombotic vascular disease. Am J Hum Genet 1996; in press.
37. D'Angelo A, Fermo I, Viganò D'Angelo S. Methionine loading, vitamin B6 status, and premature thromboembolic disease. Ann Intern Med 1996; 125:419-20.
38. Jacques PF, Bostom AG, Williams RR, et al. Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation 1996; 93:7-9.
39. Wilcken DEL, Wang XL, Siew Sim A, McCredie RM. Distribution in healthy and coronary populations of the methylenetetrahydrofolate reductase (MTHFR) C677T mutation. Arterioscl Thromb Vasc Biol 1996; 16:878-82.
40. Selhub J. Mild hyperhomocysteinemia and arterial occlusive disease. Haematologica 1997; 82:129-32.
41. D'Angelo A, Selhub J. Homocysteine and thrombotic disease. Blood 1997; in press.
42. Dillon MJ, England JM, Gompertz D, et al. Mental retardation, megaloblastic anaemia, methylmalonic aciduria and abnormal homocysteine metabolism due to an error in vitamin B12 metabolism. Clin Sci Molecular Med 1974; 47:43-61.
43. Brattstrom L, Israelsson B, Norrving B, et al. Impaired homocysteine metabolism in early onset cerebral and peripheral occlusive arterial disease - effects of pyridoxine and folic acid treatment. Atherosclerosis 1990; 81:51-60.
44. Dudman NPB, Wilcken DEL, Wang J, Lynch JF, Macey D, Lundberg P. Disordered methionine/homocysteine metabolism in premature vascular disease: its occurrence, cofactor therapy, and enzymology. Arterioscl Thromb 1993; 13:1253-60.
45. Brattstrom LE, Israelsson B, Jeppsson J-O, Hultberg BL. Folic acid - an innocuous means to reduce plasma homocysteine. Scand J Clin Lab Invest 1988; 48:215-21.
46. Wilcken DEL, Dudman NPB, Tyrrell PA, Robertson MR. Folic acid lowers elevated plasma homocysteine in chronic renal insufficiency: possible implications for prevention of vascular disease. Metabolism 1988; 37:697-701.
47. Kang SS, Wong PWK, Norusis M. Homocysteinemia due to folate deficiency. Metabolism 1987; 36:458-62.
48. Lindenbaum J, Healton EB, Savage DG, et al. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N Engl J Med 1988; 318:1720-8.
49. Kang SS, Wong PWK, Zhou J, et al. Thermolabile methylenetetrahydrofolate reductase in patients with coronary artery disease. Metabolism 1988; 37:611-3.
50. Stabler SP, Marcell PD, Podell ER, Allen RH, Savage DG, Lindenbaum J. Elevation of total homocysteine in the serum of patients with cobalamin or folate deficiency detected by capillary gas-chromatography-mass spectrometry. J Clin Invest 1988; 81:466-74.
51. Levy HL, Cardinale GJ. Sulfur amino acid abnormalities in experimental vitamin B12 deficiency. Fed Proceed 1970; 29:634.
52. Hollowell JG, Hall WK, Cryell ME, McPherson J, Hahn DA. Homocystinuria and organic aciduria in a patient with vitamin B12 deficiency. Lancet 1969; 2:1428.
53. Lin JY, Kang SS, Zhou J, Wong PWK. Homocysteinemia in rats induced by folic acid deficiency. Life Sciences 1989; 44:319-25.
54. Applegarth DA, Hardwick DF, Ingram F, Auckland NL, Bozoian G. Excretion of S-adenosylmethionine and S-adenosylhomocysteine in homocystinuria. N Engl J Med 1971; 285:1265-6.
55. Wilcken DEL, Gupta VJ, Betts AK. Homocysteine in the plasma of renal transplant recipients: effects of cofactors for methionine metabolism. Clin Sci 1981; 61:743-9.
56. Swift ME, Schultz TD. Relationship of vitamins B6 and B12 to homocysteine levels: risk for coronary heart disease. Nutr Reports Int 1986; 34:1-14.
57. Brattstrom L, Israelsson B, Lindgarde F, Hultberg B. Higher total plasma homocysteine in vitamin B12 deficiency than in heterozygosity for homocystinuria due to cystathionine-β-synthase deficiency. Metabolism 1988; 37:175-8.
58. Miller JW, Ribaya-Mercado JD, Russell RM, et al. Effect of vitamin B6 deficiency on plasma homocysteine concentrations. Am J Clin Nutr 1992; 55:1154-60.
59. Boers GHJ, Fowler B, Smals AGH, et al. Improved identification of heterozygotes for homocystinuria due to cystathionine synthase activity by the combination of methionine loading and enzyme determination in cultured fibroblasts. Hum Genet 1985; 69:164-69.
60. Sardharwalla IB, Fowler B, Robins AJ, Komrower GM. Detection of heterozygotes for homocystinuria. Arch Dis Child 1974; 49:553-9.
61. Smolin LA, Bebvenga NJ. Factors affecting the accumulation of homocyst(e)ine in rats deficient in vitamin B6. J Nutr 1984; 114:103-11.
62. Park YK, Linkswiler H. Effect of vitamin B6 depletion in adult man on the excretion of cystathionine and other methionine metabolites. J Nutr 1970; 100:110-6.
63. Miller JW, Nadeau MR, Smith D, Selhub J. Vitamin B6 deficiency vs folate deficiency: comparison of responses to methionine loading in rats. Am J Clin Nutr 1994; 59:1033-9.
64. Miller JW, Nadeau MR, Smith J, Smith D, Selhub J. Folate deficiency-induced homocysteinemia in rats: disruption of S-adenosylmethionine's coordinate regulation of homocysteine metabolism. Biochem J 1994; 298:415-9.
65. Bostom AG, Jacques PF, Nadeau MR, Williams RR, Ellison RC, Selhub J. Post-methionine load hyperhomocysteinemia in persons with normal fasting total plasma homocysteine - initial results from The NHLBI Family Heart Study. Atherosclerosis 1995; 116:147-51.
66. Mansoor MA, Svardal AM, Ueland PM. Determination of the in vivo redox status of cysteine, cysteinylglycine, homocysteine, and glutathione in human plasma. Anal Biochem 1992; 200:218-29.
67. Viganò D'Angelo S, Fermo I, D'Angelo A. The investigation of congenital thrombophilia: a critical evaluation. J Int Fed Clin Chem 1996, in press.
68. Fermo I, De Vecchi E, Arcelloni C, D'Angelo A, Paroni R. Methodological aspects of total plasma homocysteine measurement. Haematologica 1997; 82:246-50.
69. Fermo I, De Vecchi E, Viganò D'Angelo S, D'Angelo A, Paroni R. Total plasma homocysteine: influence of some common physiological variables. Amino Acids 1993; 5:17-21.
70. Jacobsen DW, Gatautis VJ, Green R, et al. Rapid HPLC determination of total homocysteine and other thiols in serum and plasma: sex differences and correlation with cobalamin and folate concentrations in healthy subjects. Clin Chem 1994; 40:873-81.
71. McGill JJ, Mettler G, Rosenblatt DS, Scriver CR. Detection of heterozygotes for recessive alleles. Homocyst(e)inemia: paradigm of pitfalls in phenotypes. Am J Med Genet 1990; 36:45-52.
72. Mansoor MA, Svardal AM, Scheede J, Ueland PM. Dynamic relation between reduced, oxidized and protein-bound homocysteine and other thiol components in plasma during methionine loading in healthy men. Clin Chem 1992; 38:1316-21.
73. Andersson A, Brattstrom L, Israelsson B, Isaksson A, Hultberg B. The effect of excess daily methionine intake on plasma homocysteine after loading tests in humans. Clin Chim Acta 1990; 192:69-76.
74. Bostom AG, Roubenoff R, Dellaripa P, et al. Validation of abbreviated oral methionine loading test. Clin Chem 1995; 41:948-9.
75. Mudd SH, Levy HL, Skovby F. The natural history of homocystinuria due to cystathionine β-synthase deficiency. Am J Hum Genet 1985; 37:1-31.
76. Hirsh J, Prins MH, Samama M. Approach to the thrombophilic patient. In: Colman RW, Hirsh J, Marder VJ, Salzman E, eds. Hemostasis and thrombosis: basic and clinical practice. Philadelphia: Lippincott Co.; 1994. p. 1543-61.
77. Brattstrom L, Tengborn L, Lagerstedt C, Israelsson B, Hultberg B. Plasma homocysteine in venous thromboembolism. Haemostasis 1991; 21:51-7.
78. Bienvenue T, Ankri A, Chadefauz B, Montalescot G, Kamoun P. Elevated total plasma homocysteine, a risk factor for thrombosis; relation to coagulation and fibrinolytic parameters. Thromb Res 1993; 70:123-9.
79. Falcon CR, Cattaneo M, Panzeri D, Martinelli I, Mannucci PM. High prevalence of hyperhomocysteinemia in patients with juvenile venous thrombosis. Arterioscler Thromb 1994; 14:1080-3.
80. Fermo I, Viganò D'Angelo S, Paroni R, Mazzola G, Calori G, D'Angelo A. Prevalence of moderate hyperhomocystelnemia in patients with early-onset venous and arterial occlusive disease. Ann Intern Med 1995; 123:747-53.
81. den Heijer M, Blom HJ, Gerrits WBJ, et al. Is hyperhomocystaeinemia a risk factor for recurrent thrombosis ? Lancet 1995; 345:882-5.
82. Bostom AG. Methionine loading, vitamin B6 status, and premature thromboembolic disease. Ann Intern Med 1996; 125:419.
83. den Heijer M, Koster T, Blom HJ, et al. Hyperhomocysteinemia as a risk factor for deep vein thrombosis. N Engl J Med 1996; 334:759-62.
84. Mandel H, Brenner B, Berant M, et al. Coexistence of hereditary homocystinuria and factor V Leiden - effect on thrombosis. N Engl J Med 1996; 334:763-8.
85. D'Angelo A, Fermo I, Viganò D'Angelo S. Coexistence of hereditary homocystinuria and factor V Leiden - effect on thrombosis. N Engl J Med 1996; 335:289.
86. Refsum H, Ueland PM. Clinical significance of pharmacological modulation of homocysteine metabolism. Trends Pharmacol Sci 1992; 11:411-6.
87. nd ed. Oxford: Blackwell; 1979.
88. Miller LT, Dow MJ, Kokkeler SC. Methionine metabolism and vitamin B6 status in women using oral contraceptives. Am J Clin Nutr 1978; 31:619-25.
89. Drell W, Welch AD. Azaribine-homocystieinemia-thrombosis in historical perspective. Pharmacol Ther 1989; 41:195-206.
90. Wilkinson JF. Megalocytic anaemias. Lancet 1949; i:249-55.
91. Wilcken DEL, Gupta VJ, Betts AK. Homocysteine in the plasma of renal transplant recipients: effects of cofactors for methionine metabolism. Clin Sci 1981 ; 61:743-49.
92. Soria C. Chadefaux B, Coude M, Gaillard O, Kamoun P. Concentrations of total homocysteine in plasma in chronic renal failure. Clin Chem 1990; 36:2137-8.
93. Bostom AG, Shemin D, Lapane KL, et al. Hyperhomocysteinemia and traditional cardiovascular disease risk factors in end-stage renal disease patients on dialysis: a case-control study. Atherosclerosis 1995; 114:93-103.
94. Parfrey PS, Harnett JD. Long-term cardiac morbidity and mortality during dialysis therapy. Adv Nephrol 1994; 23:311-7.
95. Chadefaux B, Rethore MO, Raoul O. Cystathionine β-synthase: gene dosage effect on trisomy 21. Biochem Biophys Res Commun 1986; 128:40-4.
96. Murdoch JC, Rodger JC, Rao SS, Fletcher CD, Dunnigan MG. Down's syndrome: an atheroma-free model. Br Med J 1977; 2:226-8.
97. Hla-Herttuala S, Luoma J, Nikkari T, Kivimaki T. Down's syndrome and atherosclerosis. Atherosclerosis 1989; 76:269-72.
98. Brattstrom L, Englund E, Brun A. Does Down syndrome support homocysteine theory of arteriosclerosis ? Lancet 1987; i:391-2.
99. Moss TJ, Augustin GE. Pre-atherosclerotic lesions in Down syndrome. J Ment Defic Res 1980; 24:137-41.
100. Harker LA, Harlan JM, Ross R. Effect of sulfinpyrazone on homocysteine-induced endothelial injury and arteriosclerosis in baboons. Circ Res 1983; 53:731-9.
101. Uhlemann ER, TenPas JH, Lucky AW, Schulman JD, Mudd SH, Shulamn NR. Platelet survival and morphology in homocystinuria due to cystathionine synthase deficiency. N Engl J Med 1976; 295:1283-6.
102. Hill-Zobel R, Pyeritz RE, Scheffel U, et al. Kinetics and distribution of 111-indium-labeled platelets in patients with homocystinuria. N Engl J Med 1982; 307:781-6.
103. Wall RT, Harlan JM, Harker LA, Striker GE. Homocysteine-induced endothelial cell injury in vitro: a model for the study of vascular injury. Thromb Res 1980; 18:113-21.
104. De Groot PG, Willems C, Boers GHJ, Gonsalves MD, van Aken WG, van Mourik JA. Endothelial cell dysfunction in homocystinuria. Eur J Clin Invest 1983; 13:405-10.
105. Starkebaum G, Harlan JM. Endothelial cell injury due to copper-catalyzed hydrogen peroxide generation from homocysteine. J Clin Invest 1986; 77:1370-6.
106. Wang J, Dudman NPB, Wilcken DE. Effects of homocysteine and related compounds on prostacyclin production by cultured human vascular endothelial cells. Thromb Haemostas 1993; 6:1047-52.
107. Rodgers GM, Kane WH. Activation of endogenous factor V by a homocysteine-induced vascular endothelial cell activator. J Clin Invest 1986; 77:1909-16.
108. Rodgers GM, Conn MT. Homocysteine, an atherogenic stimulus, reduces protein C activation by arterial and venous endothelial cells. Blood 1990; 75:895-901.
109. Lentz SR, Sadler JE. Inhibition of thrombomodulin surface expression and protein C activation by the thrombogenic agent homocysteine. J Clin Invest 1991; 88:1906-14.
110. Hajjar KA. Homocysteine-induced modulation of tissue plasminogen activator binding to its endothelial cell membrane receptor. J Clin Invest 1993; 91:2873-9.
111. Blann AD. Endothelial cell damage and homocysteine. Atherosclerosis 1992; 94:89-91.
112. Stamler JS, Osborne JA, Jaraki M, et al. Adverse vascular effects of homocysteine are modulated by endothelium-derived relaxing factor and related oxides of nitrogen. J Clin Invest 1993; 91:308-18.
113. 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; 13:1327-33.
114. Nishinaga M, Ozawa T, Shimada K. Homocysteine, a thrombogenic agent, suppresses anticoagulant heparan sulfate expression in cultured porcine aortic endothelial cells. J Clin Invest 1993; 92:1381-6.
115. Tsai J-C, Perrella MA, Yoshizumi M, et al. Promotion of vascular smooth muscle cell growth by homocysteine: a link to atherosclerosis. Proc Natl Acad Sci USA 1994; 91:6369-73.
116. Pathasarathy S. Oxidation of low-density lipoprotein by thiol compounds leads to its recognition by the the acetyl LDL receptor. Biochim Biophys Acta 1987; 917:337-40.
117. 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, atherogenesis and sulfhydryl compund metabolism. Proc Natl Acad Sci USA 1992; 89:10193-7.
118. Harker LA, Slichter SJ, Scott CR, Ross R. Homocysteinemia. Vascular injury and arterial thrombosis. N Engl J Med 1974; 291:537-43.
119. Giannini MJ, Coleman M, Innerfield I. Antithrombin activity on homocystinuria. Lancet 1974; 1:1094.
120. Maruyama I, Fukuda R, Kaszmama M, Abe T, Yoshida Y, Igata A. A case of homocystinuria with low antithrombin activity. Acta Haematol Jap 1977; 40:267-71.
121. Palareti G, Salardi S, Pizzi S, et al. Blood coagulation changes in homocystinuria: effects of pyridoxine and other specific therapy. J Pediatr 1986; 109:1001-6.
122. Merckz J, Kuntz F. Deficit en facteur VII et homocystinurie: association fortuite ou syndrome ? Nouv Presse Med 1981; 10:3769.
123. Munnich A, Saudbray JM, Dautzenberg MD, et al. Diet-responsive proconvertin (factor VII) deficiency in homocystinuria. J Pediatr 1983; 102:730-4.
124. Di Minno G, Davi G, Margaglione M, et al. Abnormally high thromboxane biosynthesis in homozygous homocystinuria. Evidence for platelet involvement and Probucol-sensitive mechanism. J Clin Invest 1993; 92:1400-6.
125. Di Minno G, Coppola A, D'Angelo A, et al. Does raised in vivo thromboxane A2 biosynthesis reflect a hypercoagulable state in homocystinuria due to homozygous cystathionine-β-synthase deficiency? Arterioscl Thromb Vasc Biol 1996; submitted.
126. Brattstrom L, Israelsson B, Tengborn L, Hultberg B. Homocysteine, factor VII and antithrombin III in subjects with different gene dosage for cystathionine-β-synthase. J Inher Metab Dis 1989; 12:475-82.
127. Boushey CJ, Beresford SAA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA 1995; 274:1049-57.