1. The Effect of blood Storage Time Before & After Transfusion Ahmad Sh. Silmi Staff Specialist in Hemayology

2. Recruit Transfuse blood Screen Donor Pretransfusion Testing Collect & Prepare Monitor & evaluate Infections/disease tests Medical Decision to transfuse Blood Safety Transfusion Safety Transfusion Safety in the Hospital Transfusion Sept 2003

3. Storage lesion Storage lesion is an amalgamation of reversible and irreversible changes that begin after 2 to 3 weeks of storage

4. Problems with stored pRBC’s 1.Reduced ability of Hgb to release bound oxygen at tissue level (2,3 DPG)

5. 2,3 DPG levels become undetectable after two weeks of storage. Levels are restored within 72 hours after transfusion Does red blood cell storage affect clinical outcome? When in doubt, do the experiment. Transfusion Vol 49 July 2009

6. “storage lesion”

7. Problems with stored pRBC’s 1.Reduced ability of Hgb to release bound oxygen at tissue level (2,3 DPG). 2.Reduced RBC deformability = potential to block capillary beds

8. “storage lesion”

9. RBC squeezing through a capillary bed

10. Problems with stored pRBC’s 1.Reduced ability of Hgb to release bound oxygen at tissue level (2,3 DPG).. 2.Reduced RBC deformability = potential to block capillary beds 3.Storage lesion (age dependent defect) = potential to block capillary beds

14. Problems with stored pRBC’s 1.Reduced ability of Hgb to release bound oxygen at tissue level (2,3 DPG) 2.Reduced RBC deformability = potential to block capillary beds 3.Storage lesion (age dependent defect) = potential to block capillary beds 4.Activation of recipients immune system

15. Transfusions & Infection Each unit of blood increases the risk of a nosocomial infection by up to 50%! Transfusion increases the risk of postoperative infections after cardiovascular surgery J Am Coll Surg 2006 Jan;202 An alternative scoring system to predict risk for surgical site infection complicaating coronary artery bypass graft surgery Infect Control Hosp Epidemiol 2007 Oct; Transfusion of red cells is associated with increased incidence of bacterial infection after colorectal surgery; a prospective study Transfusion Feb 2003 Impact of allogenic packed red blood cell transfusion on nosocomial infection rates in the critically ill patient Crit Care Med 2002 Vol 30 #10 Transfusion Practice and Blood Stream Infections in Critically Ill Patients Chest 2005:127 Blood transfusions correlate with infections in trauma patients in a dose-dependant manner Am Surg 2002:68

16. Storage Depletes RBC Nitric Oxide Bioactivity

17. Altered parameters in Stored RBC Biochemical Metabolic BiomechanicalOxidative SNO-Hb ↓ RBC Storage Lesions Tatsuro Yoshida PhD Presentation to AABB

19. 42-Day Post-storage pRBC Characteristics Vox Sang 1998;75:212-217 CharacteristicPre-storagePost-storage pH6.86.4 ATP (μmol/g Hb) 4.12.9 DPG (μmol /g Hb) 9.00.3 Potassium (mEq/L) 2.463 Glucose (mg/dl) 608402 Plasma Hb (mg/dl) 39372 Hemolysis (%) -- --0.61

20. Byproducts of Stored RBC’s 1.Released heme and iron from ruptured cells 2.Shed microvesicles 3.Loss of lipid and protein products from damaged RBC’s 4.Activated RBC adhesins Properties of stored red blood cells: understanding immune and vascular reactivity Spinella et.al Transfusion 2011

21. FDA Requirements Membrane fragments (lipids) shed from almost all cell types. They have been implicated in immune suppression.

22. Byproducts of Stored RBC’s “All of these materials and activities are normal parts of the RBC life cycle, but they are concentrated in space and time by the RBC storage and transfusion process.” Properties of stored red blood cells: understanding immune and vascular reactivity Spinella et.al Transfusion 2011

23. The effect of red-cell age on outcomes Inverse association between changes in gastric intramucosal pH and the age of transfused blood for patients who received red cells stored for more than 15 days evidence of splanchnic ischemia developed in patients given older blood Marik PE,. Effect of stored blood transfusion on oxygen delivery in patients with sepsis. JAMA 1993

24. Blood Transfusion Morbidity Study of 12,000 CAB patients at Cleveland Clinic Post-Op ComplicationNon-Transfused patientsTransfused patients New onset of renal failure requiring dialysis 0%1.81% Post-op ventilator support > 72 hours.44%9.14% Serious post-op infection (includes sepsis and mediastinitis).24%5.03% Cardiac Morbidity (Includes Low Cardiac Index ( 4 hrs, post-op MI with IABP or VAD).05%3.03% Neurologic Morbidity.37%2.41% Morbidity and mortality risk associated with red blood cell and blood-component transfusion in isolated coronary artery bypass grafting – Koch, et al.,Critical Care Medicine 2006

25. Blood Transfusion Morbidity Study of 12,000 CAB patients at Cleveland Clinic Morbidity and mortality risk associated with red blood cell and blood-component transfusion in isolated coronary artery bypass grafting – Koch, et al.,Critical Care Medicine 2006 “Transfusion is the single factor most reliably associated with increased postoperative morbid events. Each unit of red cells transfused is associated with incrementally increased risk for adverse outcome.”

26. So what do we do with all of this?

27. FDA Requirements 1.Hemolysis must be no greater than 1% at the end of storage, and 2.RBC recovery rates must be greater than 75% one day after transfusion Does the storage duration of blood products affect outcomes in critically ill patients Spinella et al, Transfusion August 2011

28. First proposed in 1942 and based on studies that defined “peak” oxygen delivery in animals 10/30 Rule* *Keep Hgb at 10gm and Hct at 30%

29. 10/30 Rule* *Keep Hgb at 10gm and Hct at 30%

30. How low can we go?

31. In animal studies, ECG ST segment changes are observed once Hgb falls below 5 g/dL Both human and animal studies have demonstrated that Hgb’s < 3 g/dL are “maximally life-threatening.” Time course and etiology of death in patients with severe anemia Transfusion Vol 49 July 2009

32. So what does this mean? 1.Understand that transfusions may lead to worse outcomes.

33. So what does this mean? 1.Understand that transfusions may lead to worse outcomes. 2. It is reasonable to infer that older stored blood may lead to worse outcomes!

34. So what does this mean? 1.Understand that transfusions may lead to worse outcomes. 2. It is reasonable to infer that older stored blood may lead to worse outcomes! 3. Washing older stored blood may reduce morbidity.