Protein C and protein S deficiency and activated protein C resistance have been associated with retinal vascular occlusions and other thromboembolic phenomena. Proteins C and S inhibit clot formation. Inherited deficiencies in antithrombin, protein C, or protein S are the most commonly reported causative hematological factors in patients with retinal vascular occlusions.

Protein C is a vitamin K-dependent serine protease. Activated protein C (APC) regulates blood coagulation by degrading factors Va and VIIIa. Protein S is a cofactor to APC in factor Va degradation, whereas factor VIIIa degradation is potentiated by the synergistic APC-cofactor activity of protein S and factor V.

The prevalence of protein C deficiency, an autosomal dominant trait, in young patients with thrombotic events ranges from 2.5% to 4%. Decreased protein C activity is associated with CRVO. Kruger and Anger (cited in 1) reported a 52-year-old woman with CRVO with protein C activity reduced to 32% of normal.

Familial protein S deficiency has autosomal dominant transmittance, with a prevalence of 1% to 5% among young patients with thrombosis. It has been reported more commonly in patients with central retinal artery occlusion than among patients with retinal vein occlusions.

Activated protein C (APC) resistance is a dominantly inherited disorder caused largely by an Arg 506 to Gln mutation in the factor V gene (Leiden mutant). The prevalence of APC resistance, which ranges from 2% to 7% in the general population, is higher than that of protein C or S deficiency and is reported to be 12.5% to 26% among patients with CRVO. There is some controversy regarding the importance of APC resistance as a cause of retinal venous occlusive disease, however. One study found that only 1 (4.7%) of 21 patients with CRVO, who were younger than 50 years, had APC resistance and factor V Leiden mutant. A study of CRVO in patients older than 50 years found that about 10% of patients and controls had APC resistance. Identification of APC using a commercial assay (Chromogenix) does not necessarily indicate the presence of factor V Leiden mutant. Thus, previous assessments of the prevalence of the Leiden mutant among patients with retinal vein occlusion may be incorrect.