Microparticles in Stored RBC as Potential Mediators of Transfusion Complications

Summary

INTRODUCTION. Cell-derived microparticles (MP) are released in cell activation, apoptosis and other processes. MP derived from red cells (RMP) are known to be released from stored packed red blood cells (PRBC), and their number increases with storage time. This constitutes one aspect of the storage lesion. Adverse transfusion events are known to increase with time of PRBC storage. The explanation for this is not known. HYPOTHESIS. Based on their findings and those of others, the investigators propose to test the hypothesis that MP in stored PRBC contribute to adverse effects of transfusion. Specifically, MP in stored blood: (1) increase procoagulant activity, expression of pro-inflammatory mediators, immune suppression, and endothelial disturbance; and (2) increase the risk of transfusion and post-operative complications in patients undergoing coronary artery bypass grafting (CABG). AIMS \& PROCEDURES. The aim of this study is to assess the clinical significance of MPs in PRBC-related transfusion complications utilizing washed PRBC. Packed red blood cells (PRBC) will be washed at the blood bank to obtain MP depleted PRBC (PRBC-MP). A total of 500 patients undergoing CABG will be initially randomized to 2 groups: one to receive PRBC-MP, and the other conventional PRBC (PRBC+MP). Using a panel of lab tests/biomarkers selected for high sensitivity the investigators will compare the 2 groups with respect to subclinical physiologic host responses including (i) endothelial disturbances, (ii) inflammatory, and (iii) procoagulant responses. In addition, clinically evident transfusion complications and short term (\<=30 days) surgical complications will be assessed and compared. Patients who are randomized but end up not requiring transfusion at surgery will serve as controls. Laboratory and clinical results will also be evaluated to elucidate which tests are significantly associated with clinically adverse effects. SIGNIFICANCE. This study will shed new light on the biochemical and clinical effects of transfusion of MP. The findings of this investigation could significantly improve transfusion practice and safety.

Timeline

Start

2010-07

Primary completion

2014-04

Completion

2015-05

Publications

• Background Horstman LL, Ahn YS. Platelet microparticles: a wide-angle perspective. Crit Rev Oncol Hematol. 1999 Apr;30(2):111-42. doi: 10.1016/s1040-8428(98)00044-4. No abstract available.
• Background Horstman LL, Jy W, Jimenez JJ, Ahn YS. Endothelial microparticles as markers of endothelial dysfunction. Front Biosci. 2004 May 1;9:1118-35. doi: 10.2741/1270.
• Background Koch CG, Li L, Sessler DI, Figueroa P, Hoeltge GA, Mihaljevic T, Blackstone EH. Duration of red-cell storage and complications after cardiac surgery. N Engl J Med. 2008 Mar 20;358(12):1229-39. doi: 10.1056/NEJMoa070403.
• Background Piccin A, Murphy WG, Smith OP. Circulating microparticles: pathophysiology and clinical implications. Blood Rev. 2007 May;21(3):157-71. doi: 10.1016/j.blre.2006.09.001. Epub 2006 Nov 22.
• Background Biro E, Nieuwland R, Tak PP, Pronk LM, Schaap MC, Sturk A, Hack CE. Activated complement components and complement activator molecules on the surface of cell-derived microparticles in patients with rheumatoid arthritis and healthy individuals. Ann Rheum Dis. 2007 Aug;66(8):1085-92. doi: 10.1136/ard.2006.061309. Epub 2007 Jan 29.
• Background van den Goor JM, Nieuwland R, van Oeveren W, Rutten PM, Tijssen JG, Hau CM, Sturk A, Eijsman L, de Mol BA. Cell Saver device efficiently removes cell-derived microparticles during cardiac surgery. J Thorac Cardiovasc Surg. 2007 Sep;134(3):798-9. doi: 10.1016/j.jtcvs.2007.02.042. No abstract available.
• Jy W, Gomez-Marin O, Salerno TA, Panos AL, Williams D, Horstman LL, Ahn YS. Presurgical levels of circulating cell-derived microparticles discriminate between patients with and without transfusion in coronary artery bypass graft surgery. J Thorac Cardiovasc Surg. 2015 Jan;149(1):305-11. doi: 10.1016/j.jtcvs.2014.10.042. Epub 2014 Oct 14.

Drugs

Indications

No indication recorded.