Coagulation disorders and the risk of retinal vein occlusion

Claudia Kuhli-Hattenbach; Inge Scharrer; Marc Lüchtenberg; Lars-Olof Hattenbach

doi:10.1160/TH09-05-0331

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2010; 103(02): 299-305
DOI: 10.1160/TH09-05-0331

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Coagulation disorders and the risk of retinal vein occlusion

A subgroup analysis

Claudia Kuhli-Hattenbach

¹Klinik für Augenheilkunde, Klinikum der Johann-Wolfgang-Goethe-Universität Frankfurt am Main, Germany

,

Inge Scharrer

²Medizinische Klinik I, Klinikum der Johann-Wolfgang-Goethe-Universität Frankfurt am Main, Germany

³III. Medizinische Klinik, Johannes-Gutenberg-Universität, Mainz, Germany

,

Marc Lüchtenberg

¹Klinik für Augenheilkunde, Klinikum der Johann-Wolfgang-Goethe-Universität Frankfurt am Main, Germany

,

Lars-Olof Hattenbach

¹Klinik für Augenheilkunde, Klinikum der Johann-Wolfgang-Goethe-Universität Frankfurt am Main, Germany

⁴Augenklinik des Klinikums Ludwigshafen, Ludwigshafen, Germany

› Author Affiliations

Abstract

Summary

Over the past years, there has been a dramatic increase in the number of identifiable causes of thrombophilia. However, to date, there are no large, prospective studies to assess an optimal, cost-effective approach with regard to screening and case finding for thrombophilic risk factors in patients presenting with retinal vessel occlusion. Two hundred twenty-eight patients with retinal vein occlusion (RVO) and 130 age-matched healthy controls were prospectively screened for thrombophilic risk factors. Both cohorts were divided into three subgroups, depending on the patients‘ age at the time of the RVO or a previous thromboembolic event. Patient age ≤45 years was associated with a high prevalence of coagulation disorders (p<0.0001). Among patients ≤45 years and >45 to ≤60 years, a family history of thromboembolism was strongly associated with the presence of thrombophilic disorders. The absence of cardiovascular risk factors was found to be a strong predictor for the presence of coagulation disorders in all patient groups (≤45 years, p=0.003; >45 to ≤60 years, p=0.0008; >60 years, p=0.001). Multivariate analysis revealed the presence of resistance to activated protein C (p=0.014), antiphospholipid antibodies (p=0.022), and deficiency of the anticoagulant proteins (p=0.05) as independent risk factors for the development of RVO among patients ≤45 years. Our results indicate that thrombophilic disorders are associated with the development of retinal vein occlusion in patients ≤45 years by the time of the RVO or a previous thromboembolic event, in patients with a family history of thromboembolism, or in patients without cardiovascular risk factors.

Keywords

Retinal vein occlusion - APC resistance - thrombophilia - inherited coagulation disorders - risk factors

Full Text

References

References
1 Simioni P, Prandoni P, Zanon E. et al. Deep venous thrombosis and lupus anticoagulant. A case-control study. Thromb Haemost 1996; 76: 187-189.
2 Brouwer JL, Lijfering WM, Ten Kate MK. et al. High long-term absolute risk of recurrent venous thromboembolism in patients with hereditary deficiencies of protein S, protein C or antithrombin. Thromb Haemost 2009; 101: 93-99.
3 Vossen CY, Walker ID, Svensson P. et al. Recurrence rate after a first venous thrombosis in patients with familial thrombophilia. Arterioscler Thromb Vasc Biol 2005; 25: 1992-1997.
4 Greiner K, Hafner G, Dick B. et al. Retinal Vascular Occlusion and Deficiencies in the Protein C Pathway. Am J Ophthalmol 1999; 128: 69-74.
5 Hattenbach LO, Klais C, Scharrer I. Heparin cofactor II deficiency in central retinal vein occlusion. Acta Ophthalmol Scand 1998; 76: 758-9.
6 Kuhli C, Hattenbach LO, Scharrer I. et al. High Prevalence of resistance to APC in young patients with retinal vein occlusion. Graefe`s Arch Clin Exp Ophthalmol 2002; 240: 163-168.
7 Rehak M, Rehak J, Müller M. et al. 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. Thromb Haemost 2008; 99: 925-929.
8 Weger M, Stanger O, Deutschemann H. et al. Hyperhomocyst(e)inemia, but not methylenetetetrahydrofolate reductase C677T mutation, is a risk factor in branch retinal vein occlusion. Ophthalmology 2002; 109: 1105-1109.
9 Glueck CJ, Bell H, Vadlamani L. et al. Heritable thrombophilia and hypofibrinolysis. Possible causes of retinal vein occlusion. Arch Ophthalmol 1999; 117: 43-49.
10 Albisinni R, Coppola A, Loffredo M. et al. Retinal vein occlusion and inherited conditions predisposing to thrombophilia. Thromb Haemost 1998; 80: 702-703.
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.
12 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.
13 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.
14 Graham SL, Goldberg I, Murray B. et al. Activated protein C resistance – low incidence in glaucomatous optic disc haemorrhage and central retinal vein occlusion. Aust NZ J Ophthalmol 1996; 24: 199-205.
15 D´Angelo A, Tavola A, Fermo I. et al. Moderate hyperhomo-cysteinemia and central retinal vein occlusion. Thromb Haemost 2002; 87: 1078-1079.
16 Koizumi H, Ferrara DC, Brué C. et al. Central retinal vein occlusion case-control-study. Am J Ophthalmol 2007; 144: 858-863.
17 Wong TY, Marino Larsen EK, Klein R. et al. Cardiovascular risk factors for retinal vein occlusion and arteriolar emboli. The atherosclerosis risk in communities & casdiovascular health study. Ophthalmology 2005; 112: 540-547.
18 Wu O, Robertson L, Twaddla S. et al. for The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study. Br J Haematol 2005; 131: 80-90.
19 Laurell CB. Elektroimmuno Assay. Scand J Clin Lab Invest 1972; 124: 21-37.
20 Larsson J, Olafsdottir E, Bauer B. Activated protein C resistance in young adults with central retinal vein occlusion. Br J Ophthalmol 1996; 80: 200-202.
21 Scott JA, Arnold JJ, Currie JM. et al. No Excess of Factor V:Q506 Genotype but High Prevalence of Anticardiolipin Antibodies without Antiendothelial Cell Antibodies in Retinal Vein Occlusion in Young Patients. Ophthalmologica 2001; 215: 217-221.
22 Kuhli C, Scharrer I, Koch F. et al. Factor XII Deficiency: a Thrombophilic Risk Factor for Retinal Vein Occlusion. Am J Ophthalmol 2004; 137: 459-464.
23 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.
24 Salomon O, Moissiev J, Rosenberg N. et al. Analysis of genetic polymorphisms related to thrombosis and other risk factors in patients with retinal vascular occlusion. Blood Coagul Fibrinolysis 1998; 9: 617-622.
25 Janssen MCH, den Heijer M, Cruysberg JRM. et al. Retinal vein occlusion: A form of venous thrombosis or a complication of atherosclerosis?. Thromb Haemost 2005; 93: 1021-1026.
26 Ehrenforth S, von Depka Prondsinki M, Aygören-Pürsün E. et al. Study of the prothrombin gene 20210 GA variant in FV:Q506 carriers in relationship to the presence or absence of juvenile venous thromboembolism. Arterioscler Thromb Vasc Biol 1999; 19: 276-280.
27 Arséne 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.
28 Lahey JM, Tunc M, Kearnea J. et al. Laboratory evaluation of Hypercoagulable states in patients with central retinal vein occlusion who are less than 56 years of age. Ophthalmology 2002; 109: 126-131.
29 Abu el-Asrar AM, al-Momen AK, al-Amro S. et al. Prothrombotic states associated with retinal venous occlusion in young adults. Int Ophthalmol 1996–97 20: 197-204.
30 Ates O. The deficiencies of protein C, protein S and antithrombin III in patients with retinal vein occlusion: a Turkish sample. Clin Lab Haematol 2006; 28: 391-392.
31 Kearon C, Gent M, Hirsh J. et al. A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. N Engl J Med 1999; 340: 901-907.
32 Cosmi B, Palareti G. Extended treatment for venous thromboembolism: how long is long enough?. Curr Hematol Rep 2004; 3: 375-381.
33 Ridker PM, Miletich JP, Stampfer MJ. et al. Factor V Leiden and the risks of recurrent idiopathic venous thromboembolism. Circulation 1995; 92: 2800-2802.
34 Simioni P, Prandoni P, Lensing AW. et al. 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.
35 De Stefano V, Martinelli I, Mannucci RM. et al. The risk of recurrent deep venous thrombosis among heterozygous carriers of both factor V Leiden and the G20210A prothrombin mutation. N Engl J Med 1999; 341: 801-806.
36 Anaya DA, Nathens AB. Thrombosis and coagulation: deep vein thrombosis and pulmonary embolism prophylaxis. Surg Clin North Am 2005; 85: 1163-1177.
37 Wu O, Robertson L, Langhorne P. et al. Oral contraceptives, hormone replacement therapy, thrombophilia and risk of venous thromboembolism: a systematic review. The Thrombosis Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study. Thromb Haemost 2005; 94: 17-25.