Download PDF
Thromb Haemost 1998; 80(04): 566-569
DOI: 10.1055/s-0037-1615421
Rapid Communication
Schattauer GmbH

Hyperhomocysteinemia Is a Risk Factor of Recurrent Venous Thromboembolism

S. Eichinger
1   From the Department of Internal Medicine I, University of Vienna
,
A. Stümpflen
2   From the Department of Internal Medicine II, University of Vienna
,
M. Hirschl
3   From the Hanuschkrankenhaus, Vienna
,
C. Bialonczyk
4   From the Wilhelminenspital, Vienna
,
K. Herkner
5   From the Department of Pediatrics, University of Vienna
,
M. Stain
1   From the Department of Internal Medicine I, University of Vienna
,
B. Schneider
6   From the Department of Medical Statistics, University of Vienna, Austria
,
I. Pabinger
1   From the Department of Internal Medicine I, University of Vienna
,
K. Lechner
1   From the Department of Internal Medicine I, University of Vienna
,
P. A. Kyrle
1   From the Department of Internal Medicine I, University of Vienna
› Author Affiliations
Further Information

Publication History

Received 30 April 1998

Accepted after revision 29 June 1998

Publication Date:
08 December 2017 (online)

Also available at
    Permissions and Reprints

Summary

Hyperhomocysteinemia is a risk factor of venous thromboembolism. The risk of recurrence in patients with hyperhomocysteinemia is unknown, and the optimal therapy for these patients after acute venous thromboembolism is uncertain.

In a multicenter study, 264 patients with an objectively documented single episode of idiopathic venous thromboembolism were prospectively followed after discontinuation of oral anticoagulants. Patients were classified as hyperhomocysteinemic if their homocysteine levels exceeded the 95th percentile of the controls. The outcome events studied were objectively confirmed deep-vein thrombosis and/or pulmonary embolism.

Homocysteine levels were elevated in 66 patients (25%) and normal in 198 patients (75%). Recurrent venous thromboembolism occurred in 12 of 66 patients with hyperhomocysteinemia (18.2%) and in 16 of 198 patients without hyperhomocysteinemia (8.1%). The cumulative probability of recurrence 24 months after discontinuation of oral anticoagulants was 19.2 percent (95 percent confidence interval 8.7-27) in patients with hyperhomocysteinemia and was 6.3 percent (95 percent confidence interval 2.4-10.1; p = 0.001) in those without hyperhomocysteinemia. The relative risk of recurrent thrombosis was higher in patients with hyperhomocysteinemia [RR 2.7 (1.3-5.8), p = 0.009].

Patients with hyperhomocysteinemia are at high risk of recurrent venous thromboembolism. The high prevalence of hyperhomocysteinemia in thrombosis patients together with the increased risk of recurrence warrants extended patient screening. The impact on the risk of recurrence of prolonged anticoagulation, supplementation of folate and vitamin B12, or both have to be investigated.

 

  • References

  • 1 Prandoni P, Lensing AWA, Cogo A, Cuppini S, Villalta S, Carta M, Cattelan A, Polistena P, Bernardi E, Prins MH. The long-term clinical course of acute deep venous thrombosis.. Ann Intern Med 1996; 125: 1-7.
    CrossrefPubMedGoogle Scholar
  • 2 Nordström M, Lindblad B, Bergqvist D, Kjellström TA. A prospective study of the incidence of deep vein thrombosis with a defined urban population.. J Intern Med 1992; 232: 155-60.
    CrossrefPubMedGoogle Scholar
  • 3 Anderson FA, Wheeler HB, Goldberg RJ, Hosmer DW, Patwardhan NA, Jovanovic B, Forcier A, Dalen JE. A population based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism: the Worcester DVT Study.. Arch Intern Med 1991; 151: 933-8.
    CrossrefPubMedGoogle Scholar
  • 4 Khamashta MA, Cuadrado MJ, Mujic F, Taub NA, Hunt BJ, Hughes GRV. The management of thrombosis in the antiphospholipid-antibody syndrome.. N Engl J Med 1995; 332: 993-7.
    CrossrefPubMedGoogle Scholar
  • 5 Simioni P, Prandoni P, Lensing AWA, Scudeller A, Sardella C, Prins MH, Villalta S, Dazzi F, Girolami A. The risk of recurrent venous thromboembolism in patients with an Arg506→Gln mutation in the gene for factor V (factor V Leiden).. N Engl J Med 1997; 336: 399-403.
    CrossrefPubMedGoogle Scholar
  • 6 Eichinger S, Pabinger I, Stümpflen A, Hirschl M, Bialonczyk C, Schneider B, Mannhalter C, Minar E, Lechner K, Kyrle PA. The risk of recurrent venous thromboembolism in patients with and without factor V Leiden.. Thromb Haemost 1997; 77: 624-8.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Ridker PM, Miletich JP, Stampfer MJ, Goldhaber SZ, Lindpaintner K, Hennekens CH. Factor V Leiden and risks of recurrent idiopathic venous thromboembolism.. Circulation 1995; 92: 2800-2.
    CrossrefPubMedGoogle Scholar
  • 8 Brattström L, Tengborn L, Israelsson B, Hultberg B. Plasma homocysteine in venous thromboembolism.. Haemostasis 1991; 21: 51-7.
    PubMedGoogle Scholar
  • 9 Falcon CR, Cattaneo M, Panzeri D, Martinelli I, Mannucci PM. High prevalence of hyperhomocyst(e)inemia in patients with juvenile venous thrombosis.. Arterioscler Thromb 1994; 14: 1080-3.
    CrossrefPubMedGoogle Scholar
  • 10 Fermo I, D’Angelo SV, Paroni R, Mazzola G, Calori G, D’Angelo A. Prevalence of moderate hyperhomocysteinemia in patients with early-onset venous and arterial occlusive disease.. Ann Intern Med 1995; 123: 747-53.
    CrossrefPubMedGoogle Scholar
  • 11 den Heijer M, Koster T, Blom HJ, Bos GMJ, Briet E, Reitsma PH, Vandenbroucke JP, Rosendaal FR. Hyperhomocysteinemia as a risk factor for deep-vein thrombosis.. N Engl J Med 1996; 334: 759-62.
    CrossrefPubMedGoogle Scholar
  • 12 Simioni P, Prandoni P, Burlina A, Tormene D, Sardella C, Ferrari V, Benedetti L, Girolami A. Hyperhomocysteinemia and deep-vein thrombosis – a case control study.. Thromb Haemost 1996; 76: 883-6.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 den Heijer M, Blom HJ, Gerrits WBJ, Rosendaal FR, Haak HL, Wijermans PW, Bos GMJ. Is hyperhomocysteinaemia a risk factor for recurrent venous thrombosis?. Lancet 1995; 345: 882-5.
    CrossrefPubMedGoogle Scholar
  • 14 The PIOPED Investigators.. Value of the ventilation/perfusion scan in acute pulmonary embolism.. JAMA 1990; 263: 2753-9.
    CrossrefPubMedGoogle Scholar
  • 15 Bertina RM, Koeleman BPC, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velden PA, Reitsma PH. Mutation in blood coagulation factor V associated with resistance to activated protein C.. Nature 1994; 369: 64-7.
    CrossrefPubMedGoogle Scholar
  • 16 Pabinger I, Brücker S, Kyrle PA, Schneider B, Korninger HC, Niessner H, Lechner K. Hereditary deficiency of antithrombin III, protein C, and protein S: prevalence in patients with a history of venous thrombosis and criteria for rational patient screening.. Blood Coagul Fibrinolysis 1992; 3: 547-53.
    CrossrefPubMedGoogle Scholar
  • 17 Brandt JT, Triplett DA, Alving B. Scharrer I on the behalf of the Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the ISTH.. Criteria for the daignosis of lupus anticoagulants: an update.. Thromb Haemost 1995; 74: 1185-90.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Kalbfleisch JD, Prentice RL. The statistical analysis of failure time data.. John Wiley and Sons,; 1980
    PubMedGoogle Scholar
  • 19 Kaplan EL, Meier P. Nonparametric estimation from incomplete observations.. J Am Stat Assoc 1958; 53: 457-81.
    CrossrefPubMedGoogle Scholar
  • 20 Koeleman BP, Reitsma PH, Allart CF, Bertina RM. Activated protein C resistance as an additional risk factor for thrombosis in protein C-deficient families.. Blood 1994; 84: 1031-5.
    PubMedGoogle Scholar
  • 21 Zöller B, Berntsdotter A, Garcia de Frutos P, Dahlbäck B. Resistance to ac tivated protein C as an additional genetic risk factor in hereditary deficiency of protein S.. Blood 1995; 85: 3518-23.
    PubMedGoogle Scholar
  • 22 van Boven HH, Reitsma PH, Rosendaal FR, Baiston TA, Chowdhury V, Bauer KA, Scharrer I, Conard J, Lane DA. Factor V Leiden (FV R506Q) in families with inherited antithrombin deficiency.. Thromb Haemost 1996; 75: 417-21.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 23 Schulman S, Rhedin AS, Lindmarker P, Carlsson A, Lärfars G, Nicol P, Loogna E, Svensson E, Ljungberg B, Walter H, Viering S, Nordlander S, Leijd B, Jönsson K, Hjorth M, Linder O, Boberg J. and the Duration of Anticoagulation Trial Study Group.. A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism.. N Engl J Med 1995; 332: 1661-5.
    CrossrefPubMedGoogle Scholar
  • 24 Ridker PM, Hennekens CH, Selhub J, Miletich JP, Malinow MR, Stampfer MJ. Interrelation of hyperhomocyst(e)inemia, factor V Leiden, and the risk of future venous thromboembolism.. Circulation 1997; 95: 1777-82.
    CrossrefPubMedGoogle Scholar
  • 25 Ubbink JB, Vermaak WJ, van der Merwe A, Becker PJ. Vitamin B-12, vitamin B-6, and folate nutritional status in men with hyperhomocysteinemia.. Am J Clin Nutr 1993; 57: 47-53.
    CrossrefPubMedGoogle Scholar
  • 26 Stampfer MJ, Willett WC. Homocysteine and marginal vitamin deficiency: the importance of adequate vitamin intake.. JAMA 1993; 270: 2726-7.
    CrossrefPubMedGoogle Scholar
  • 27 Selhub J, Jacques PF, Wilson PWF, Rush D, Rosenberg IH. Vitamin status and intake as primary determinants of homocysteinemia in an elderly population.. JAMA 1993; 270: 2693-8.
    CrossrefPubMedGoogle Scholar