Download PDF
Thromb Haemost 2008; 99(05): 925-929
DOI: 10.1160/TH07-11-0658
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

The prevalence of activated protein C (APC) resistance and factor V Leiden is significantly higher in patients with retinal vein occlusion without general risk factors

Case-control study and meta-analysis
Matus Rehak
1   Department of Ophthalmology, University Hospital Leipzig, Leipzig, Germany
2   Department of Ophthalmology, University Hospital Olomouc, Olomouc, Czech Republic
,
Jiri Rehak
2   Department of Ophthalmology, University Hospital Olomouc, Olomouc, Czech Republic
,
Marc Müller
3   Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig, Germany
,
Susanne Faude
1   Department of Ophthalmology, University Hospital Leipzig, Leipzig, Germany
,
Frank Faude
1   Department of Ophthalmology, University Hospital Leipzig, Leipzig, Germany
,
Annelie Siegemund
4   Intensive Care Unit, University Hospital Leipzig, Leipzig, Germany
,
Vera Krcova
5   Department of Haematology and Oncology, University Hospital Olomouc, Olomouc, Czech Republic
,
Ludek Slavik
5   Department of Haematology and Oncology, University Hospital Olomouc, Olomouc, Czech Republic
,
Dirk Hasenclever
6   Institute for Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Leipzig, Germany
,
Markus Scholz
6   Institute for Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Leipzig, Germany
,
Peter Wiedemann
1   Department of Ophthalmology, University Hospital Leipzig, Leipzig, Germany
› Author Affiliations
Further Information

Publication History

Received 04 November 2007

Accepted after major revision 24 March 2008

Publication Date:
30 November 2017 (online)

Also available at
    Permissions and Reprints

Summary

Several small case-control studies have investigated whether factor V Leiden (FVL) is a risk factor for retinal vein occlusion (RVO) and generated conflicting data. To clarify this question we performed a large two-centre case-control study and a meta-analysis of published studies. Two hundred seven consecutive patients with RVO and a control group of 150 subjects were screened between 1996 and 2006. A systematic meta-analysis was done combining our study with further 17 published European case-control studies. APC resistance was detected in 16 out of 207 (7.7%) patients and eight out of 150 (5.3%) controls. The odds ratio (OR) estimated was 1.49 with a (non-significant) 95% confidence interval (CI) of 0.62–3.57. The meta-analysis including 18 studies with a total of 1,748 patients and 2,716 controls showed a significantly higher prevalence of FVL in patients with RVO compared to healthy controls (combined OR 1.66; 95% CI 1.19–2.32). All single studies combined in the meta-analysis were too small to reliably detect the effect individually. This explains the seemingly contradictory data in the literature. In conclusion, the prevalence of APC resistance (and FVL) is increased in patients with RVO compared to controls, but the effect is only moderate. Therefore, there is no indication for general screening of factor V mutation in all patients with RVO. We recommend this test to be performed in patients older than 50 years with an additional history of thromboembolic event and in younger patients without general risk factors like hypertension.

Keywords

Retinal vein occlusion - factor V Leiden - APC resistance - activated protein C - meta-analysis
 

  • References

  • 1 The Eye Disease Case-Control Study Group: Risk factors for central retinal vein occlusion. Arch Ophthalmol 1996; 114: 545-554.
    CrossrefPubMedSearch in Google Scholar
  • 2 Weger M, Renner W, Steinbrugger I. et al. Role of thrombophilic gene polymorphisms in branch retinal vein occlusion. Ophthalmology 2005; 112: 1910-1915.
    CrossrefPubMedSearch in Google Scholar
  • 3 Cahill MT, Stinnett SS, Fekrat S. Meta-analysis of plasma homocysteine, serum folate, serum vitamin B(12), and thermolabile MTHFR genotype as risk factors for retinal vascular occlusive disease. Am J Ophthalmol 2003; 136: 1136-1150.
    CrossrefPubMedSearch in Google Scholar
  • 4 Janssen MC, de Heijer M, Cruysberg JR. et al. Retinal vein occlsuion: a form of venous thrombosis or a complication of atherosclerosis?. Thromb Haemost 2005; 93: 1021-1026.
    Thieme ConnectPubMedSearch in Google Scholar
  • 5 Leoncini G, Bruzzese D, Signorello MG. et al. Platelet activation by collagen is increased in retinal vein occlusion. Thromb Haemost. 2007; 97: 218-227.
    Thieme ConnectPubMedSearch in Google Scholar
  • 6 Fateh-Moghadam S, Gawaz M. Retinal vein occlusion disease and platelet activation: will antiplatelet therapy be a promising therapeutic strategy for patients with retinal vein occlusion disease in the future?. Thromb Haemost 2007; 97: 169-170.
    Thieme ConnectPubMedSearch in Google Scholar
  • 7 Lippi G, Franchini M, Targher G. Platelets and lipoprotein( a) in retinal vein occlusion: mutual targets for aspirin therapy. Thromb Haemost 2007; 97: 1059-1060.
    Thieme ConnectPubMedSearch in Google Scholar
  • 8 Gumus K, Kadayifcilar S, Eldem B. et al. Is elevated level of soluble endothelial protein C receptor a new risk factor for retinal vein occlusion?. Clin Experiment Ophthalmol 2006; 34: 305-311.
    CrossrefPubMedSearch in Google Scholar
  • 9 Arsene S, Delahousse B, Regina S. et al. Increased prevalence of factor V Leiden in patients with retinal vein occlusion and under 60 years of age. Thromb Haemost 2005; 94: 101-106.
    Thieme ConnectPubMedSearch in Google Scholar
  • 10 Albisinni R, Coppola A, Loffredo M. et al. Retinal vein occlusion and inherited conditions predisposing to thrombophilia. Thromb Haemost 1998; 80: 702-703.
    Thieme ConnectPubMedSearch in Google Scholar
  • 11 Marcucci R, Bertini L, Giusti B. et al. Thrombophilic risk factors in patients with central retinal vein occlusion. Thromb Haemost 2001; 86: 772-776.
    PubMedSearch in Google Scholar
  • 12 Larsson J, Hillarp A, Olafsdottir E. et al. Activated protein C resistance and anticoagulant proteins in young adults with central retinal vein occlusion. Acta Ophthalmol Scand 1999; 77: 634-637.
    CrossrefPubMedSearch in Google Scholar
  • 13 Greiner K, Peetz D, Winkgen A. et al. Genetic thrombophilia in patients with retinal vascular occlusion. Int Ophthalmol. 1999; 23: 155-160.
    CrossrefPubMedSearch in Google Scholar
  • 14 Gottlieb JL, Blice JP, Mestichelli B. et al. Activated protein C resistance, factor V Leiden, and central retinal vein occlusion in young adults. Arch Ophthalmol 1998; 116: 577-579.
    CrossrefPubMedSearch in Google Scholar
  • 15 Demirci FY, Güney DB, Akarcay K. et al. Prevalence of factor V Leiden in patients with retinal vein occlusion. Acta Ophthalmol Scand 1999; 77: 631-633.
    CrossrefPubMedSearch in Google Scholar
  • 16 Cruciani F, Moramarco A, Curto T. et al. MTHFR C677T mutation, factor II G20210A mutation and factor V Leiden as risks factor for youth retinal vein occlusion. Clin Ter 2003; 154: 299-303.
    PubMedSearch in Google Scholar
  • 17 Kalayci D, Gürgey A, Güven D. et al. Factor V Leiden and prothrombin 20210 A mutations in patients with central and branch retinal vein occlusion. Acta Ophthalmol Scand 1999; 77: 622-624.
    CrossrefPubMedSearch in Google Scholar
  • 18 Linna T, Ylikorkala A, Kontula K. et al. Prevalence of factor V Leiden in young adults with retinal vein occlusion. Thromb Haemost 1997; 77: 214-216.
    Thieme ConnectPubMedSearch in Google Scholar
  • 19 Kuhli C, Hattenbach LO, Scharrer I. et al. High prevalence of resistance to APC in young patients with retinal vein occlusion. Graefes Arch Clin Exp Ophthalmol 2002; 240: 163-168.
    CrossrefPubMedSearch in Google Scholar
  • 20 Larsson J, Sellman A, Bauer B. Activated protein C resistance in patients with central retinal vein occlusion. Br J Ophthalmol 1997; 81: 832-834.
    CrossrefPubMedSearch in Google Scholar
  • 21 Aras S, Yilmaz G, Alpas I. et al. Retinal vein occlusion and factor V Leiden and prothrombin 20210 G:A mutations. Eur J Ophthalmol 2001; 11: 351-355.
    CrossrefPubMedSearch in Google Scholar
  • 22 Bombeli T, Basic A, Fehr J. Prevalence of hereditary thrombophilia in patients with thrombosis in different venous systems. Am J Hematol 2002; 70: 126-132.
    CrossrefPubMedSearch in Google Scholar
  • 23 Marcucci R, Giusti B, Betti I. et al. Genetic determinants of fasting and post-methionine hyperhomocysteinemia in patients with retinal vein occlusion. Thromb Res 2003; 110: 7-12.
    CrossrefPubMedSearch in Google Scholar
  • 24 Gori AM, Marcucci R, Fatini C. et al. Impaired fibrinolysis in retinal vein occlusion: a role for genetic determinants of PAI-1 levels. Thromb Haemost 2004; 92: 54-60.
    Thieme ConnectPubMedSearch in Google Scholar
  • 25 Egger M, Smith GD, Schneider M. et al. Bias in meta-analysis detected by a simple, graphical test. Br Med J 1997; 315: 629-634.
    CrossrefPubMedSearch in Google Scholar
  • 26 Ihaka R, Gentleman RR. A language for data analysis and graphics. J Comp Graph Stat 1996; 5: 299-314.
    PubMedSearch in Google Scholar
  • 27 Bertina RM, Koelemann BPC, Koster T. et al. Mutation in blood coagulations factor V associated with resistance to activated protein C. Nature 1994; 369: 64-67.
    CrossrefPubMedSearch in Google Scholar
  • 28 Segers K, Dahlbäck B, Nicolaes GA. Coagulation factor V and thrombophilia: background and mechanisms. Thromb Haemost 2007; 98: 530-542.
    Thieme ConnectPubMedSearch in Google Scholar
  • 29 Dahlbäck B, Carlsson M, Svensson PJ. Familiar thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: predilection of a cofactor to activated protein C. Proc Natl Acad Sci USA 1993; 90: 1004-1008.
    CrossrefPubMedSearch in Google Scholar
  • 30 Trossaert M, Conard J, Horellou MH. et al. The modified APC resistance test in the presence of factor V deficient plasma can be used in patients without oral anticoagulant. Thromb Haemost 1996; 75: 521-522.
    Thieme ConnectPubMedSearch in Google Scholar
  • 31 Svensson PJ, Zoller B, Dahlback B. Evaluation of original and modified APC-resistance tests in unselected outpatients with clinically suspected thrombosis and in healthy controls. Thromb Haemost 1997; 77: 332-335.
    Thieme ConnectPubMedSearch in Google Scholar