The Plasma Concentration of the Antithrombotic Protein Annexin A5 Is Elevated in Sickle Cell Disease and Rises Further during Painful Crisis

Expression of phosphatidylserine (PS) on the membrane surface of red blood cells and circulating microparticles plays an important role in the etiology of the hypercoagulable state of sickle cell disease (SCD), as well as in the reduced red cell life span and adhesive interactions between red cells and endothelium. Annexin A5, an intracellular protein abundantly present in endothelial cells, exhibits high affinity for PS and has been shown to inhibit microparticle-induced PS-mediated thrombin generation. We determined plasma annexin A5 levels and microparticles in 17 sickle cell patients (12 HbSS and 5 HbSC) in steady state and at presentation with a painful crisis. Twenty five HbAA blood donors served as controls. Both annexin A5 levels and microparticle numbers were highest in HbSS patients (5.7 ng/mL IQR 3.7–7.6 and 37.9 nM, IQR 31.9–69.8) as compared to HbSC patients (1.8 ng/mL, IQR 1.7–7.6 and 20.9 nM IQR10.9–29.6) and healthy controls (2.5 ng/mL, IQR 1.4–4.4 and 13.1 nM, IQR 9.5–18.5) (p=0.01 and p<0.001, respectively). At presentation with a painful crisis, annexin V levels and microparticle numbers increased significantly in 16 of 17 patients (p=0.001) and 16 of 17 patients (p<0.001), respectively. Annexin V/microparticle ratio’s were lower at presentation with a painful crisis in 9 patients. In conclusion, sickle cell patients have elevated plasma concentrations of annexin V. The potential role of annexin V in modulating PS related pathophysiological processes in SCD is subject of further investigation.