Retinal Vein Thrombosis
Scientific update, 1/11/99, Cholesterol Center, Jewish Hospital
E-mail: glueckch@healthall.com or cglueck@fuse.net
Fax: 513-585-7950
Background:
Retinal vein occlusion (RTV) is severely debilitating, often causing reduced visual acuity, blindness,
and neovascular glaucoma. It may occur in both eyes in up to 25% of cases, and is among common causes of blindness.
New Data:
Glueck CJ, Bell H, Vadlamani L, et al. Heritable thrombophilia and hypofibrinolysis: Possible
pathoetiologies of retinal vein occlusion. Archives of Ophthalmology, 1/11/99
Objectives:
Our specific aim was to determine whether heritable thrombophilias and hypofibrinolyses were
pathoetiologic risk factors for retinal vein occlusion.
Design:
Measures of thrombophilia (increased likelihood of thrombus formation) included anticardiolipin antibodies
(IgG, IgM), the Lupus anticoagulant (including dilute Russel's Viper venom time [DRVVT]), antigenic proteins C and S, and homocysteine. Polymerase chain
reaction (PCR) assays were performed for 3 thrombophilic gene mutations (Factor V Leiden, methylenetetrahydrofolate reductase, prothrombin gene). Measures
of hypofibrinolysis (reduced ability to lyse thrombi) included lipoprotein (a) [Lp(a)], plasminogen activator inhibitor activity (PAI-Fx), and PCR
analysis of the hypofibrinolytic 4G/5G polymorphism of the PAI-1 gene. These coagulation measures were performed in 17 patients with retinal vein
occlusions with comparison to serologic coagulation measures and PCR assays in 40 and 234 healthy normal controls, respectively.
Results:
Of 14 retinal vein occlusion patients with measures of dilute Russel's viper venom time, a thrombophilic
antiphospholipid antibody, 6 (43%) were abnormal (>38.8 sec) vs 1/30 (3.3%) controls p=.002. Three of 17 vein occlusion patients (18%) were
heterozygous for the thrombophilic Factor V Leiden G1691A mutation versus 7 of 233 controls (3%), p=.023. Two of 17 vein occlusion patients (12%) had
normal alleles (5G/5G) for the plasminogen activator inhibitor (PAI) gene promoter; 88% were heterozygous or homozygous for the 4G polymorphism which is
associated with hypofibrinolysis. Of 234 controls, 85 (36%) had 5G/5G; 149 (64%) were heterozygous or homozygous for the 4G polymorphism, p=.03. Vein
occlusion patients were more likely to have high levels of the major determinant of hypofibrinolysis, plasminogen activator inhibitor activity (PAI-Fx).
PAI-Fx was high (>22 U/L) in 6/16 vein occlusion patients (38%) vs 1/40 controls (2.5%), X2=12.8, p=.001. Vein occlusion patients were more
likely (8/16, 50%) to have high levels of hypofibrinolytic Lp(a) (>35 mg/dl) than controls (5/40, 13%), X2=9, p=.003. Median Lp(a) in vein
occlusion patients with the 4G/4G genotype was 62 mg/dl vs 5.3 in 4G/4G controls (p=.048).
Conclusions:
Thrombophilia and hypofibrinolysis are possible pathoetiologies for retinal vein occlusion. Since
patients with retinal vein thrombosis are also at high risk for venous and arterial blood clots (thrombi) in their legs, hearts, or brains, every patient
with retinal vein thrombosis should have blood testing for thrombophilia and hypofibrinolysis.
Speculation:
Thrombophilic mutations which predispose to thrombosis may be major risk factors for retinal vein
thrombosis.
TAKE ACTION:
Patients with retinal vein thrombosis should be tested for markers of thrombophilia and
hypofibrinolysis. These tests should include PCR cDNA tests for the most common thrombophilic mutations, Factor V Leiden and MTHFR, and for the most
common hypofibrinolytic mutation (4G/4G mutation of the PAI-1 gene), and blood coagulation tests for the Lupus anticoagulant, and Lp(a). Call
MDRC Lab (513-475-6631) or email (fontaine@MDRCLAB.COM) to arrange for the PCR cDNA tests.
Molecular Diagnosis of Risk Factors for venous and arterial thrombi, and for atherosclerosis. Jewish Hospital Cholesterol Center and Molecular Diagnostics Laboratories (MDL)
E-mail: glueckch@healthall.com
or cglueck@fuse.net
Fax: 513-585-7950
