BCC 2011 David Oh, MD Chief Medical Officer San Diego Blood Bank

Blood refrigerators are not time capsules

Blood Expiration

• Maximum allowable storage time – 75% of transfused RBCs in recipient’s circulation at

24 hours

Red Cell Preservative Expiration CPD or CP2D 21 days

CPDA-1 35 days

With Additive Solution (AS-1, AS-3, AS-5)

42 days

After washing 24 hours

RBC metabolism

Storage Lesion of Red Cells

• Reversible Changes (in vivo) – pH decreases – ATP decreases – 2,3-DPG decreases – Plasma K+ increases – Nitric Oxide (NO) decreases (probably reversible)

• Irreversible Changes – % of viable cells decreases – Plasma hemoglobin increases

Oxygen Dissociation Curve of Hemoglobin

Stored Blood Controversies

• Possible increase in TRIM – Transfusion related immunomodulation – ? Increased risk of infection?

• Possible MOF – Multiple Organ Failure

• Possible ARDS/TRALI risk – Respiratory Complications

• Possible poorer tissue perfusion/oxygenation – NO/2,3-DPG

NO: Nature’s Third Respiratory Gas

• NO represents 3/4ths of the Earth atmosphere

• Normally think of Hemoglobin as transporting O2 and CO2

• Hemoglobin binds to NO in oxygenated blood and discharges it in hypoxic tissue

• NO is a potent vasodilator allowing increased RBC flow into hypoxic areas

Nitric Oxide (NO)

Dzik. Transfusion Vol 42. Dec 2002.

Original Article Duration of Red-Cell Storage and Complications

after Cardiac Surgery

Colleen Gorman Koch, M.D., Liang Li, Ph.D., Daniel I. Sessler, M.D., Priscilla Figueroa, M.D., Gerald A. Hoeltge, M.D., Tomislav Mihaljevic, M.D., and Eugene H.

Blackstone, M.D.

N Engl J Med Volume 358(12):1229-1239

March 20, 2008

Study Overview

• Stored red cells undergo progressive structural and functional changes over time

• In a study of 6002 patients undergoing cardiac surgery at a single institution, those who received blood stored for 14 days or less had lower rates of complications and death than those who received blood stored for more than 14 days

Number of Red-Cell Units Transfused in Relation to the Percentage of Patients Receiving Transfusion and Box Plots of the Duration of Storage of Blood

Koch CG et al. N Engl J Med 2008;358:1229-1239

Characteristics of Transfused Blood and Demographic and Clinical Features of the Patients

Koch CG et al. N Engl J Med 2008;358:1229-1239

Postoperative Complications, According to the Duration of Blood Storage

Koch CG et al. N Engl J Med 2008;358:1229-1239

Statistical Model Showing Dose-Response Relationship between the Maximum Number of Days of Storage of All the Red-Cell Units Each Patient Received and the Probability of the

Composite Outcome

Koch CG et al. N Engl J Med 2008;358:1229-1239

Results

Older Blood Newer Blood p value In-hospital mortality 2.8% 1.7% 0.004 Ventilatory support 9.7% 5.6% < 0.001 Renal failure 2.7% 1.6% 0.003 Sepsis 4.0% 2.8% 0.01 Multisystem organ failure 0.7% 0.2% 0.007 1 yr survival 89.0% 92.6% < 0.001

Kaplan-Meier Estimates of Survival and Death

Koch CG et al. N Engl J Med 2008;358:1229-1239

Conclusion

• In patients undergoing cardiac surgery, transfusion of red cells that had been stored for more than 2 weeks was associated with a significantly increased risk of postoperative complications as well as reduced short-term and long-term survival

Stored Blood Controversies

• van de Watering study (Transfusion 2006) – 2732 patients with CABG

• <18 days storage (median 13 days)

• >18 days storage (median 24 days)

– Multivariate analysis conclusion: RBC storage time had no affect

• Mortality

• Length of hospital stay

Transfusion Aug 2011

• Does the storage duration of blood products affect outcomes in critically ill patients? – Is there a role for Fresh Whole Blood?

– “In summary, the current body of literature evaluating blood product storage duration appears insufficient to either spport or change current regulations or allocations policies”

– Ongoing randomized controlled studies • ABLE – Age of Blood Evaluation

• RECESS – Red Cell Storage Study

Fresh Whole Blood

• US Military: Blood stored at 20 to 24 C for < 24 hrs

• Civilian: Blood stored at 2 to 6 C for <48 hrs( or less than 5 days by others)

• Potential advantages – Increased Hb, coag factors, PLTs relative to

reconstitution of individual components

– Limited impact of processing on function

– Lessening of storage lesion defects

Fresh Whole Blood

• Disadvantages – FWB is typically NOT leukoreduced

• Febrile reactions, CMV

– INFECTIOUS DISEASE TESTING

– Inventory management related to ABO

Editorial Summary

• Challenging times for Transfusion Medicine – Must provide a scarce resource in high demand

– Support physicians who approach transfusion practice with great diversity

– Frequently practice is not evidence based

• In the absence of regulatory requirement for direct efficacy and safety data… we lack incentive for industry to invest the resources necessary to acquire this information

Editorial Summary

• In an era of quality improvement, evidence based medicine, and significant cost constraints, determining the optimal transfusion approach for critically ill patients with shock and/or coagulopathy is difficult, but worthy of pursuit.

To Transfuse or Not To Transfuse?

Detection of Bacterial Contamination in Platelets

• Culture has decreased incidence of bacterial contamination of platelets, but it has not been eliminated

• Between 2005-2009, the third leading cause of transfusion related fatalities reported to FDA (12% or 33/267 fatalities)

• Bacterial contamination is known to be underrecognized and underreported

Detection of Bacterial Contamination in Platelets

• Culture may not detect small amounts of bacteria due to sampling

• Bacterial load increases over time

• Screening with PGD test may better indicate presence of bacteria on day of transfusion

Detection of Bacterial Contamination in Platelets

• Pan Genera Detection test (Verax)

• Current online issue of Transfusion – 9 of 27620 (1:3069) apheresis PLT Blood Center

Culture Negative • 6/9: Coag negative staphylococcus

• 2/9: Bacillus sp

• 1/9: Enterococcus

• Day 3: 4/9

• Day 4: 2/9

• Day 5: 1/9

Detection of Bacterial Contamination in Platelets

• 3 contaminated doses had nonreactive PGD tests

• 0.51% of tests were false positives

Article first published online: Jacobs MR. Detection of bacterial contamination in prestorage culture-negative apheresis platelets on day of issue with the Pan Genera Detection test. Transfusion. 29 AUG 2011 DOI: 10.1111/j.1537-2995.2011.03308.x

Detection of Bacterial Contamination in Platelets

• “… interdiction of … contaminated units in the US apheresis PLT supply has the potential to prevent more than 300 transfusion reactions and several fatalities per year, and use of the PGD test has the potential to detect the majority of these cases”