Association of Protein Z Deficiency with Retinal Artery and Vein Occlusion.

Central retinal vein occlusion (CRVO) and central retinal artery occlusion (CRAO) are common disorders mainly associated with traditional risk factors for atherosclerosis. There is no clear correlation between thrombophilia and CRVO. However it was suggested that hyperhomocysteinemia and the presence of antiphospholipid antibodies are risk factors for the development of CRAO. Protein Z is a vitamin K dependent cofactor for the inactivation of activated factor X (Xa) by the protein Z dependent protease inhibitor (ZPI). Protein Z deficiency presumably promotes thrombosis, in particular arterial thrombosis, as suggested by an association between low plasma protein Z levels and ischemic stroke. The similarity between risk factors for ischemic stroke and CRVO / CRAO and the fact that low protein Z levels are associated with an increased risk for ischemic stroke has led us to assess protein Z levels in patients with CRVO and CRAO. Plasma samples from 29 patients with CRVO and 7 patients with CRAO (total study group= 36, mean age 60±11) were screened for protein Z levels by ELISA. Study group was also screened for the presence of lupus anticoagulant (LAC) by the kaolin clotting time (KCT) index and the dilute Russells’ viper venum test (DRVVT), for activated protein C resistance (APCR) and anticardiolipin antibodies (ACA). Levels of protein Z were compared with a control group of 42 healthy individuals (mean age 43±11). Patients with CRAO and history of ischemic stroke or an embolic source were excluded. Thirty patients in the study group had traditional risk factors for atheroscalerosis including hypertension, diabetes mellitus, hyperlipidemia and smoking and 6 patients had none. There was no significant difference in protein Z levels between the whole study group patients and controls (1995±810 vs. 2010±603 ng/ml p=0.922). However, patients with no risk factors for CRVO/CRAO had significantly lower protein Z levels than controls (1379±682 vs. 2010±603 ng/ml p=0.022) and patients with risk factors (1379±682 vs. 2118±785 ng/ml p=0.04). In the study group three patients had abnormal APCR and 6 had positive LAC. There was no correlation between low protein Z levels and the presence of LAC, APCR or ACA, or a correlation between low protein Z levels and the specific diagnosis (CRVO or CRAO) or age. The data show that low protein Z levels may be an additional risk factor for CRVO and CRAO in patients without traditional risk factors for these disorders. The association should be explored in a larger group of patients.