Primary open-angle glaucoma patients have superactivated platelets: A sticky conundrum

Abstract

Purpose: Hemorrhages on the optic nerve head and in the nailfold capillary bed characterize primary open-angle glaucoma (POAG). Exactly why hemorrhages occur and the wherefore of hemorrhages is enigmatic. Recent studies of patients with Alzheimer’s disease, transient ischemic attacks and intracerebral hemorrhages have documented an increase in superactivated platelets. Notably, superactivated platelets are hypercoagulable. The purpose of this study is to determine if POAG patients display an upregulated phenotype of superactivated platelets.

Methods: Blood samples from age-matched control (n=3), POAG (n=3), and normal tension glaucoma (NTG; n=3) patients were obtained in acid citrate dextrose tubes; platelet rich plasma was isolated by centrifugation. Platelets were labeled with anti-CD41-PE (platelet glycoprotein IIb, alpha 2b intregin) and anti-PAC1-FITC (recognizes an activated glycoprotein IIb/IIIa epitope) and challenged with two agonists: thrombin (via protease-activated receptors [PARs]) and convulxin (via activation of glycoprotein VI receptor). Superactivated platelets are identified by the inability to bind PAC1, because its target receptor is tightly bound by fibrinogen, and phosphatidylserine exposure. After 10 minutes of incubation at 37°C the platelets were fixed with 1.5% formalin and analyzed on a Beckman Coulter Cyan ADP flow cytometer.

Results: Platelets from controls, POAG, and NTG were challenged with agonists and characterized by forward scatter and PAC1-FITC intensity. In this initial study, notably, POAG patients contained 59.4% superactivated platelets which was highly significant (P<0.001) compared to controls (29.1%). Although NTG patients displayed lower levels of super activated platelets (31.3%), this was not statistically significant when compared to POAG patients.

Conclusions: Conceivably, platelets of POAG patients are intrinsically “primed” and readily activated by agonists compared to controls. Platelet hypercoagulability may represent an etiological factor in optic nerve hemorrhages, provide a new therapeutic target, and establish a final common pathway in vascular diseases, including Alzheimer’s disease.

Keywords: 436 blood supply • 615 neuroprotection • 749 vascular occlusion/vascular occlusive disease