Microparticles in Stored RBC as Potential Mediators of Transfusion Complications

NCT01185600 | Completed Results DMC

• 2 other identifiers: 20090685R01HL098031
• Study Type: interventional
• Target: 177
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Coronary Artery Bypass

Keywords

transfusion complications; washed RBC; microparticles; storage lesion

Outcome Measures

Primary Outcomes (7)

• In Hospital Mortality

  The number of participants who expired during hospital stay after CABG surgery

  Within 30 days after CABG surgery

• One-year Mortality

  Number participants who expired within one year after CABG surgery

  Within one year after CABG surgery

• Occurrence of at Least One Serious Adverse Event (SAE)

  Comparison of the two groups with respect to occurrence or not of at least one SAE including sepsis, respiratory failure, multi-organ failure, anaphylactic shock, transfusion-related acute lung injury, MI, stroke, cardiac arrest.

  within 30 days after CABG surgery

• Difference in Levels of Circulating CD41+ Platelet-derived Microparticles 1 Hour Post-surgery

  Difference in levels of circulating CD41+ platelet microparticles between at pre-surgery and at 1hour post-surgery, i.e. level at 1hour post-surgery - level at pre-surgery

  interval between presurgery and 1 hour post-surgery

• Difference in Levels of Circulating Annexin V+ Microparticles 1 Hour Post- Surgery

  Difference in levels of circulating Annexin V+ microparticles between at pre-surgery and 1 hour post-surgery, i.e. level of Annexin V+ microparticles at 1 hour post-surgery - level of Annexin V+ microparticles at pre-surgery

  Interval between pre-surgery and 1 hour post-surgery

• Difference in Levels of Circulating CD62E+ Endothelial Microparticles 1 Hour Post-surgery

  Difference in levels of circulating CD62E+ endothelial microparticles between 1 hour post-surgery and at pre-surgery, i.e. level at 1 hour post-surgery - level at pre-surgery

  Interval between pre-surgery and 1 hour post-surgery

• Difference in Levels of Circulating CD235a+ Red Cell Microparticles 1 Hour Post-surgery

  Difference in levels of circulating CD235a+ red cell microparticles between at 1 hour post-surgery and at pre-surgery, i.e. levels at 1 hour post-surgery - level at pre-surgery

  Interval between pre-surgery and 1 hour post-surgery

Secondary Outcomes (1)

• Each Participant's Number of Non-serious Adverse Events

  Within 30 days after CABG surgery

Study Arms (2)

Transfusion with washed RBC

ACTIVE COMPARATOR

Subject assigned to this arm will be transfused with washed RBC

Biological: Washed RBC

Transfusion with unwashed RBC

ACTIVE COMPARATOR

Subjects assigned to this arm will be transfused with unwashed RBC

Biological: Unwashed RBC

Interventions

Washed RBC BIOLOGICAL

There is no pre-set dosage, frequency and duration for transfusion with washed RBC. It all depends on the conditions of patients during and after surgery. As circumstances arise, the physician will request needed washed RBC for the subject.

Also known as: Washed packed cells

Transfusion with washed RBC

Unwashed RBC BIOLOGICAL

There is no pre-set dosage, frequency and duration for transfusion with unwashed RBC. It all depends on the conditions of patients during and after surgery. As circumstances arise, the physician will request needed unwashed RBC for the subject.

Also known as: Unwashed packed cells

Transfusion with unwashed RBC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Patients will be ineligible for the study if they (1) are unable or unwilling to give informed consent; (2) are unable or unwilling to follow the study protocol; (3) are less than 21 years of age; (4) require emergency procedures; (5) require cardiopulmonary bypass (pump) during the operation; (6) require other surgical procedures in addition to coronary artery bypass; (7) have a proven coagulation or platelet disorder; (8) are unwilling to receive blood transfusions; (9) are pregnant; or (10) have cognitive impairment.

Sponsors & Collaborators

• University of Miami: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Jackson Memorial Hospital

Miami, Florida, 33136, United States

Location

Related Publications (7)

• 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.

  PMID: 10439058 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.

  PMID: 14977533 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.

  PMID: 18354101 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.

  PMID: 17118501 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.

  PMID: 17261534 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.

  PMID: 17723839 BACKGROUND

• 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.

  PMID: 25524686 DERIVED

Limitations and Caveats

A major limitation of the present study is its small sample size and its restriction to CABG surgery. Larger-scale controlled studies comparing transfusion with washed vs. unwashed PCs are warranted.

Results Point of Contact

• Title: Wenche Jy, PhD, Research Associate Professor, Principal Investigator
• Organization: University of Miami

wjy@med.miami.edu

305-243-6617

Study Officials

• Wenche Jy, PhD

  University of Miami

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Associate Professor

Study Record Dates

• First Submitted: August 17, 2010
• First Posted: August 20, 2010
• Study Start: July 1, 2010
• Primary Completion: April 1, 2014
• Study Completion: May 1, 2015
• Last Updated: July 2, 2017
• Results First Posted: November 23, 2016

Record last verified: 2017-06

Locations

US (1)