High prevalence of resistance to APC in young patients with retinal vein occlusion

Abstract

Resistance to activated protein C (APC) is among the coagulation disorders that have been implicated in retinal vein occlusion. However, since retinal vascular occlusions may be due to a combination of several mechanisms, the question of whether thrombophilic anomalies are pathogenic for this disorder remains controversial. In the current study, we investigated the prevalence of APC resistance in patients with retinal vein occlusion with reference to age and various cardiovascular risk factors. A cohort of 142 consecutive patients with retinal vein occlusion and a control group of 128 subjects matched for age, sex and several risk factors were screened for resistance to APC. Both cohorts were divided into two subgroups, according to the patient's age (< or =45 or >45 years) at the time of the retinal vein occlusion or a previous thromboembolic event. The proportion of individuals with resistance to APC was higher in the patient group (13 of 142; 9.1%) when compared to controls (6 of 128; 4.7%). Moreover, patient age < or =45 years by the time of the retinal vein occlusion or a previous thromboembolic event was significantly associated with a high prevalence of APC resistance (17%). By contrast, resistance to APC was present in 5 of 95 cases (5.3%) in the patient group >45 years and in 4 of 83 (4.8%) young controls. Our results indicate that APC resistance is highly prevalent in patients with retinal vein occlusion at age < or =45 years and/or with a history of thrombosis at this age. By contrast, the prevalence of APC resistance in patients who suffered a retinal vein occlusion when they were older than 45 years and had no history of thromboembolism appears to be similar to that seen in healthy control subjects or in the normal population. Selective screening may be helpful in identifying retinal vein occlusion patients with thrombophilic defects.

Selective Thrombophilia Screening in Young Patients with Retinal Artery Occlusion

“…Since thrombophilic disorders do not seem to be the singular causal agent for RAO and in view of the high costs involved in comprehensive screening, it moreover seems both reasonable and justifiable to limit screening for thrombophilic disorders in patients with RAO to individuals whose risk is elevated, i.e. who had already experienced thromboembolic events at a young age or have a family history of thrombosis [13,14,15,16]. However, to date, only very few studies have attempted to investigate the role of few thrombophilic disorders in patients with RAO.…”

Thrombophilic mutations and risk of retinal vein occlusion

“…The frequency of thrombophilic mutations in patients presenting RVO in previous studies range from 0% to 17% for the factor V Leiden (16)(17)(18)(19)(20) , from 0% to 10% for PT 20210A (16,19,(21)(22)(23)(24) and from 3% to 19% for MTHFR 677TT (25)(26)(27)(28)(29)(30) . These differences may be related to the racial background, selection of the control group, and study design.…”

“…Recently, a study (31) also suggested that the presence of factor V Leiden increases the risk of neo-vascular complications in patients presenting central RVO. However, despite being the thrombophilic abnormality most frequently associated with RVO, most studies have failed to show a role for this mutation in RVO (17)(18)(19)22,26,32) . In the present study, factor V Leiden was the only mutation with a higher frequency in patients than in controls (3.6% versus 0%).…”

18 Associations of Thrombophilia, Hypofibrinolysis, and Retinal Vein Occlusion.

“…Kuhli and coworkers evaluated resistance to activated protein C in 142 RVO cases and found APC resistance in 17% of cases age 45 or younger, versus 4.8% in young controls, and 5.3% in cases older than age 45 (28). Kuhli and colleagues suggested screening for resistance to activated protein C in RVO cases age 45 or younger (28). de Visser and associates reported that reduced sensitivity to activated protein C, not caused by the factor V Leiden mutation, is, itself, a risk factor for venous thrombosis (29).…”