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199 Red Cell Rejuvenation Targets Inflammatory Microparticles, free Haemoglobin and Redox Active Iron: Key Mediators of Transfusion Related Acute Lung Injury in Cardiac Surgery
  1. Saqib Qureshi1,
  2. Nishith Patel2,
  3. Marcin Wozniak1,
  4. Rebecca Cardigan3,
  5. Gavin Murphy1
  1. 1University of Leicester
  2. 2National Heart and Lung Institute, Imperial College London, Hammersmith Hospital Campus
  3. 3Component Development Laboratory, NHS Blood and Transplant

Abstract

Background Using porcine model of TRALI, we have previously demonstrated that red cell washing prior to transfusion fails to protect against organ injury after cardiac surgery. Red cell rejuvenation however, eliminated all metabolic, biochemical and histological features of TRALI. In current study we investigate the mechanisms that drive endothelial dysfunction and organ injury in response to stored RBC transfusion.

Method Recipient swine of allogenic blood were randomised as: Sham (n = 6), transfusion of: 1-day old RBC (n = 8), 14-day old RBC (n = 6), 14-day old RBC washed (n = 8) and rejuvenated-washed 14-day stored RBC (n = 8). Microparticles (MP), free haemoglobin and iron levels were measured in plasma and serum by flow cytometry and colorimetric methods. Expression of heme oxygenase-1 was assessed by RT-PCR. Parallel serial analysis of human stored, washed and rejuvenated RBC packs was conducted to co-relate with porcine data. Data was analysed using and t-tests. The data are reported as mean ± SE.

Results Removing inflammatory MP by washing suppressed leucocyte adhesion in lung but increased serum free haemoglobin and serum/pulmonary iron levels (see Table 1). That in turn activated endothelium through a non-standard pathway, which lead to higher in-vivo pulmonary vascular resistance index and reduced renal vasodilation (see table). Rejuvenation eliminated generation of free haemoglobin and iron, prevented endothelial dysfunction and functional and histopathological features of TRALI.

Abstract 199 Table 1

Effect of red cell storage, washing and Rejuvenation-washing on measures of inflammation and endothelial function in recipient swine. Sham (Crystalloid infusion), D14 Tx (14 days stored blood transfusion to swine), D14 Washed Tx (14 day stored and washed Tx) and D14 washed-Rejuvenation Tx (14 day stored blood rejuvenated and washed prior to transfusion to swine)

Conclusions We identified two components of stored blood transfusion that contribute to organ injury. MP activate leukocytes and are removed by RBC washing. Free iron and haemoglobin is generated during washing and is eliminated by Rejuvenation.

  • Organ injury
  • Red cell transfusion
  • Inflammation

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