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Plasma annexin A5 and microparticle phosphatidylserine levels are elevated in sickle cell disease and increase further during painful crisis.
Biochem Biophys Res Commun 2009; 390(1):161-4BB

Abstract

Expression of phosphatidylserine (PS) on the membrane surface of red blood cells and circulating microparticles (MP) plays an important role in 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 and platelets, exhibits high affinity for PS and has been shown to inhibit several of these PS-mediated pathophysiological processes. We determined plasma annexin A5 levels and MP-associated procoagulant activity, a measure of MP-PS exposure, 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 and MP-PS 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, IQR 10.9-29.6) 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 A5 and MP-PS had increased in 16 of 17 patients (p=0.001 and p<0.001, respectively). Most interestingly, in 7 HbSS patients the proportional increase in MP-PS exposure was higher than the proportional increase in plasma annexin A5 concentration, leading to lower annexin A5/MP-PS ratio of HbSS patients during crisis than HbAA controls (0.0027 (0.0017-0.0049) vs 0.0048 (0.0027-0.0085), p=0.05). In conclusion, patients with SCD have elevated plasma levels of annexin A5- and PS-exposing MP. During crisis both levels increase, but in most HbSS patients MP-PS exposure increases more than annexin A5. Future studies must address a potential role of annexin A5 in modulating PS-related pathophysiological processes in SCD.

Authors+Show Affiliations

Department of General Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. B.vantits@aig.umcn.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19799864

Citation

van Tits, L J., et al. "Plasma Annexin A5 and Microparticle Phosphatidylserine Levels Are Elevated in Sickle Cell Disease and Increase Further During Painful Crisis." Biochemical and Biophysical Research Communications, vol. 390, no. 1, 2009, pp. 161-4.
van Tits LJ, van Heerde WL, Landburg PP, et al. Plasma annexin A5 and microparticle phosphatidylserine levels are elevated in sickle cell disease and increase further during painful crisis. Biochem Biophys Res Commun. 2009;390(1):161-4.
van Tits, L. J., van Heerde, W. L., Landburg, P. P., Boderie, M. J., Muskiet, F. A., Jacobs, N., ... Schnog, J. B. (2009). Plasma annexin A5 and microparticle phosphatidylserine levels are elevated in sickle cell disease and increase further during painful crisis. Biochemical and Biophysical Research Communications, 390(1), pp. 161-4. doi:10.1016/j.bbrc.2009.09.102.
van Tits LJ, et al. Plasma Annexin A5 and Microparticle Phosphatidylserine Levels Are Elevated in Sickle Cell Disease and Increase Further During Painful Crisis. Biochem Biophys Res Commun. 2009 Dec 4;390(1):161-4. PubMed PMID: 19799864.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Plasma annexin A5 and microparticle phosphatidylserine levels are elevated in sickle cell disease and increase further during painful crisis. AU - van Tits,L J, AU - van Heerde,W L, AU - Landburg,P P, AU - Boderie,M J, AU - Muskiet,F A J, AU - Jacobs,N, AU - Duits,A J, AU - Schnog,J B, Y1 - 2009/09/30/ PY - 2009/09/21/received PY - 2009/09/25/accepted PY - 2009/10/6/entrez PY - 2009/10/6/pubmed PY - 2009/12/16/medline SP - 161 EP - 4 JF - Biochemical and biophysical research communications JO - Biochem. Biophys. Res. Commun. VL - 390 IS - 1 N2 - Expression of phosphatidylserine (PS) on the membrane surface of red blood cells and circulating microparticles (MP) plays an important role in 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 and platelets, exhibits high affinity for PS and has been shown to inhibit several of these PS-mediated pathophysiological processes. We determined plasma annexin A5 levels and MP-associated procoagulant activity, a measure of MP-PS exposure, 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 and MP-PS 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, IQR 10.9-29.6) 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 A5 and MP-PS had increased in 16 of 17 patients (p=0.001 and p<0.001, respectively). Most interestingly, in 7 HbSS patients the proportional increase in MP-PS exposure was higher than the proportional increase in plasma annexin A5 concentration, leading to lower annexin A5/MP-PS ratio of HbSS patients during crisis than HbAA controls (0.0027 (0.0017-0.0049) vs 0.0048 (0.0027-0.0085), p=0.05). In conclusion, patients with SCD have elevated plasma levels of annexin A5- and PS-exposing MP. During crisis both levels increase, but in most HbSS patients MP-PS exposure increases more than annexin A5. Future studies must address a potential role of annexin A5 in modulating PS-related pathophysiological processes in SCD. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/19799864/Plasma_annexin_A5_and_microparticle_phosphatidylserine_levels_are_elevated_in_sickle_cell_disease_and_increase_further_during_painful_crisis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(09)01919-6 DB - PRIME DP - Unbound Medicine ER -