Selektives Thrombophiliescreening junger Patienten mit venösen retinalen Gefäßverschlüssen

Zusammenfassung

Hintergrund: Die Bedeutung thrombophiler Gerinnungsstörungen für die Entstehung venöser retinaler Gefäßverschlüsse wird immer noch kontrovers diskutiert. Patienten und Methoden: In einer prospektiven Fall-Kontroll-Studie untersuchten wir 74 junge Patienten (≤ 45 Jahre zum Zeitpunkt des retinalen Gefäßverschlusses oder eines früheren thromboembolischen Ereignisses) mit retinalem Zentral-, Hemizentral- oder Astvenenverschluss und 74 gesunde Probanden auf thrombophile Gerinnungsstörungen und kardiovaskuläre Risikofaktoren. Ergebnisse: 38 der 74 Patienten (51,4 %) wiesen thrombophile Gerinnungsstörungen auf, während lediglich bei 8 der 74 Probanden Koagulopathien aufgedeckt werden konnten (p < 0,0001). Darüber hinaus konnten wir thrombophile Gerinnungsstörungen signifikant häufig bei Patienten mit einer auffälligen Familienanamnese hinsichtlich thromboembolischer Komplikationen (p < 0,0001) und bei Patienten ohne kardiovaskuläre Risikofaktoren nachweisen (p = 0,0025). Schlussfolgerung: Unsere Ergebnisse weisen daraufhin, dass Gerinnungsstörungen neben kardiovaskulären Risikofaktoren bei jungen Patienten mit venösen retinalen Gefäßverschlüssen eine pathogenetische Bedeutung zukommt. Eine positive Eigen- oder Familienanamnese hinsichtlich thromboembolischer Ereignisse sowie das Fehlen kardiovaskulärer Risikofaktoren weisen signifikant häufig auf eine zugrunde liegende Thrombophilie hin.

Abstract

Background: The potential impact of coagulation abnormalities on retinal vascular occlusive diseases, individually and in combination with cardiovascular risk factors, remains unclear. Patients and Methods: In a prospective case-control study a cohort of 74 young patients with central, hemicentral or branch retinal vein occlusion (RVO) (≤ 45 years at the time of the RVO or a previous thromboembolic event) and 74 subjects matched for age and sex were prospectively screened for thrombophilic risk factors. Results: Overall, thrombophilic defects were found to be present in 38 of the 74 patients (51.4 %) and in 8 of 74 (10.8 %) controls (p < 0.0001). We found a strong association between the presence of thrombophilic disorders and a family history of thromboembolism (p < 0.0001). Patients without cardiovascular risk factors had a statistically significant higher frequency of coagulation disorders than patients with these risk factors (p = 0.0025). Conclusions: Our results indicate that thrombophilic disorders are associated with the development of retinal vein occlusion. Selective screening of young patients, patients with a personal or family history of thromboembolism, and patients without cardiovascular risk factors may be helpful in identifying retinal vein occlusion patients with thrombophilic defects.

Schlüsselwörter

Thrombophilie - APC-Resistenz - Antiphospholipidantikörper - retinale venöse Gefäßverschlüsse

Key words

thrombophilia - resistance to APC - antiphospholipid antibodies - retinal vein occlusion

Literatur

• 1 Abu el-Asrar A M, al-Momen A K, al-Amro S. et al . Prothrombotic states associated with retinal venous occlusion in young adults.  Int Ophthalmol. 1996 – 1997;  20 197-204
• 2 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
• 3 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
• 4 Cushman M. Inherited Risk Factors for Venous Thrombosis.  Hematology Am Soc Hematol Educ Program. 2005;  452-457
• 5 De Stefano V, Rossi E, Paciaroni K. et al . Screening for inherited thrombophilia: indications and therapeutic implications.  Haematologica. 2002;  87 1095-1108
• 6 Dori D, Beiran I, Gelfand Y. et al . Multiple retinal arteriolar occlusions associated with coexisting primary antiphospholipid syndrome and factor V Leiden mutation.  Am J Ophthalmol. 2000;  129 106-108
• 7 Glueck C J, Bell H, Vadlamani L. et al . Heritable thrombophilia and hypofibrinolysis. Possible causes of retinal vein occlusion.  Arch Ophthalmol. 1999;  117 43-49
• 8 Gottlieb J L, Blice J P, 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
• 9 Graham S L, 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
• 10 Green W R, Chan C C, Hutchins G M. et al . Central retinal vein occlusion: a prospective histopthalogic study of 29 eyes in 28 cases.  Trans Am Ophthalmol Soc. 1981;  79 371-422
• 11 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
• 12 Hattenbach L O, Klais C, Scharrer I. Heparin cofactor II deficiency in central retinal vein occlusion.  Acta Ophthalmol Scand. 1998;  76 758-759
• 13 Kearon C, Ginsberg J S, Kovacs M J. et al . Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism.  N Engl J Med. 2003;  349 631-639
• 14 Krüger K, Witt I. Inhibitors of blood coagulation in vascular occlusion of the retina and optic nerve.  Fortschr Ophthalmol. 1990;  78 178-181
• 15 Kuhli C, Hattenbach L O, 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
• 16 Kuhli C, Scharrer I, Koch F. et al . Recurrent retinal vein occlusion in a patient with increased plasma levels of histidine-rich glycoprotein.  Am J Ophthalmol. 2003;  135 232-234
• 17 Lahey J M, 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
• 18 Lane D A, Manucci P M, Bauer K A. et al . Inherited thrombophila: Part 1.  Thromb Haemost. 1996;  75 651-662
• 19 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
• 20 Laurell C B. Elektroimmuno Assay.  Scand J Clin Lab Invest. 1972;  124 21-37
• 21 The Eye Disease Case-Control Study Group . Risk factors for branch retinal vein occlusion.  Am J Ophthalmol. 1993;  116 286-296
• 22 The Eye Disease Case-Control Study Group . Risk factors for central retinal vein occlusion.  Arch Ophthalmol. 1996;  114 545-554
• 23 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
• 24 Schulman S, Granqvist S, Holmström M. et al . The duration of oral anticoagulant therapy after a second episode of venous thromboembolism.  N Engl J Med. 1997;  336 393-398
• 25 Scott J A, Arnold J J, Currie J M. et al . No Excess of Factor V: Q 506 Genotype but High Prevalence of Anticardiolipin Antibodies without Antiendothelial Cell Antibodies in Retinal Vein Occlusion in Young Patients.  Ophthalmologica. 2001;  215 217-221
• 26 Vine A K. Retinal vascular occlusion and deficiencies in the protein C pathway.  Am J Ophthalmol. 2000;  129 113-115
• 27 Vine A K, Samama M M. The role of abnormalities in the anticoagulant and fibrinolytic systems in retinal vascular occlusions.  Surv Ophthalmol. 1993;  37 283-292
• 28 Vossen C Y, Walker I D, Svensson P. et al . Recurrence Rate After a First Venous Thrombosis in Patients With Familial Thrombophilia.  Arterioscler Thromb Vasc Biol. 2005;  25 1992-1997
• 29 Weger M, Stanger O, Deutschemann H. et al . Hyperhomocyst(e)inemia, but not methylenetetetrahydrofolate reductase C 677T mutation, is a risk factor in branch retinal vein occlusion.  Ophthalmology. 2002;  109 1105-1109
• 30 Williamson T H, Rumley A, Lowe G DO. Blood viscosity, coagulation, and activated protein C Resistance in central retinal vein occlusion: a population controlled study.  Br J Ophthalmol. 1996;  80 203-208
• 31 Wu O, Robertson L, Twaddle S. et al . The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study. Screening for thrombophilia in high-risk situations: a meta-analysis and cost-effectiveness analysis.  Br J Haematol. 2005;  131 80-90