Packed Red Blood Cells (PRBC)

Epidemiology of Packed Red Blood Cell (PRBC) Transfusion

  • Incidence of Packed Red Blood Cell Transfusion (2011): approximately 13.8 million units of whole blood or red blood cells were transfused -> this represents an 11.6% decrease from 2008

Pharmacology of Packed Red Blood Cells (PRBC)

Characteristics of Packed Red Blood Cells (PRBC)

  • Hematocrit of a Unit of PRBC: approximate Hct 70% (+/-5%)
  • Volume of One Unit of PRBC: 180-300 ml
  • Iron Content of One Unit PRBC: 200-250 mg of elemental iron

Storage of Packed Red Blood Cells

Storage Additives

  • Citrate Phosphate Dextrose (CPD) Solution: allows packed red blood cell storage for up to 21 days
  • Citrate Phosphate Dextrose-Adenine (CPD-Adenine): allows packed red blood cell storage for up to 35-days
  • Current Additives: allow packed red blood cell storage up to 45 days

Effects of Storage on Packed Red Blood Cells (PRBC)

  • Apoptosis of WBC: results in hemolysis and potassium leakage -> possible immunomodulation and increased risk of infection
  • Decreased 2,3-Diphosphoglycerate: results in shift of oxygen dissociation curve to the left -> decreased oxygen delivery to tissues
  • Decreased Adenosine 5′-Triphosphate: results in altered shape and imapred function -> microvascular occlusion and potential organ failure
  • Decreased Antioxidants: results in oxidative damage to hemoglobin with conversion to methemoglobin -> decreased oxygen delivery to tissues

Leukoreduction

  • Indications
    • All Potential Solid Organ/Hematopoietic Cell Transplant Recipients
    • CMV Seronegative Patients At-Risk Patients for Whom Seronegative Components are not Available
    • Patients Undergoing Cardiac Surgery
    • Patients With Previous Febrile Non-Hemolytic Transfusion Reactions
    • Patients With Solid Organ/Hematopoietic Cell Transplants
    • Patients Who Require Chronic Transfusions
  • Rationale
    • *Leukoreduction Prevents HLA Alloimmunization (Which May Interfere with Future Bone Marrow Transplant/Stem Cell Transplant): HLA alloimmunization against class I antigens does not occur if PRBC contains <10,000,000 (10 to the 6th power) leukocytes
    • Leukoreduction Markedly Decreases the Risk of CMV Transmission (see Cytomegalovirus, [[Cytomegalovirus]])
  • Technique
    • Leukoreduction Filter: optimal to filter as close to collection time as possible
  • Cost Considerations: if cost were not as issue, all PRBC transfusions should probably be leukoreduced
  • Clinical Efficacy
    • Systematic Review Examining Impact of Leukoreduction on Various Adverse Outcomes of PRBC Transfusion (Cochrane Database Syst Rev, 2015) [MEDLINE]
      • Leukoreduction did not decrease the incidence of TRALI, death (from any cause), infection from any cause, fever, or other non-infectious complications

Irradiation

  • Indications
    • Immunocompromised Hematopoietic Stem Cell/Organ Transplant Recipients
    • Neonates Requiring Exchange Transfusion
    • Patients Requiring Intrauterine Transfusion
    • Patients with Hematologic Disease Requiring Imminent Bone Marrow/Stem Cell Transplantation
    • Premature, Low Birthweight Neonates
    • Other Patients Receiving Fludarabine (see Fludarabine, [[Fludarabine]])
    • Patients with 5′-Nucleotidase Deficiency
    • Patients with Chronic Lymphocytic Leukemia (CLL) (see Chronic Lymphocytic Leukemia, [[Chronic Lymphocytic Leukemia]])
    • Patients with Congenital Cell-Mediated Immunodeficiencies
    • Patients with Hematologic Malignancies Other than Hodgkin’s Disease: probable indication
    • Patients with Hodgkin’s Disease (see Hodgkin’s Disease, [[Hodgkins Disease]])
    • Patients with Leiner’s Disease
    • Patients with Solid Tumors Treated with Cytotoxic Chemotherapy: probable indication
    • Patients with Thymic Hypoplasia (DiGeorge syndrome)
    • Patients with Wiskott-Aldrich Syndrome
    • Recipients of Directed Donations from Biologic Relatives
    • Recipients of Donation from HLA-Matched Donors
    • Recipients Who are Heterozygous at an HLA Locus for Which the Conor is Homozygous and Shares an Allele: most common in genetically homogeneous populations
  • Rationale
    • Irradiation Depletes T-Cells, Preventing Graft vs Host Disease (see Graft vs Host Disease, [[Graft vs Host Disease]]): irradiation prevents the donor T-cells from dividing in the recipient
  • Adverse Effects
    • Decreased Red Blood Cell Viability (Due to Damage to RBC Membrane): decreases the shelf-life to maximum of 28 days
    • Potassium Leakage from Red Blood Cells

Administration

  • IV: administer PRBC at 1-2 mL/min through a standard 170-260 micron filter (filter removes clots and aggregates)
    • Uncrossmatched Blood (For Unknown Blood Type): use Type O (“universal donor” for blood)

Premedication to Prevent Potential Febrile Non-Hemolytic/Allergic Transfusion Reactions

  • Clinical Efficacy
    • Prospective Trial of Premedication for Leukoreduced Transfusions (Transfusion, 2008) [MEDLINE]
      • Premedication did not decrease the overall risk of all types transfusion reactions
      • However, premedication decreased the rate of febrile non-hemolytic transfusion reactions
  • Agents

Potential Strategies to Decrease Packed Red Blood Cell (PRBC) Transfusion in the ICU

Erythropoeitin (see xxxx, [[xxxx]])

  • Decreases PRBC use in the ICU (although it’s not clear if this is cost-effective)
  • Recombinant human erythropoietin (rHuEPO): in critically ill patients has been shown to be effective in reducing the number of PRBC units required
    • Prospective, randomized, double-blind placebo-controlled multicenter trial. Three hundred U/kg of rHuEPO were given subcutaneously on the third ICU day and the drug was administered for a total of 5 consecutive days; it was then given every other day. More recently, there are data to suggest that a weekly dose of 600 U/kg of rHuEPO is as efficacious in critically ill patients.

Restrictive Transfusion Thresholds

  • Clinical Efficacy
    • Canadian Critical Care Trials Group Transfusion Requirements in Critical Care (TRICC) Trial (NEJM, 1999): trial comparing transfusion cut-offs of Hb 7g/dL vs 10 g/dL (trial excluded: acute myocardial infarction and unstable angina)
      • No overall difference in 30-day mortality: however, less acutely ill (APACHE score of ≤20) and <55 y/o groups had lower mortality rates with the restrictive transfusion strategy
      • Decreased hospital mortality rate with restrictive transfusion strategy
    • Transfusion Requirements in Septic Shock (TRISS) Trial (NEJM, 2014) [MEDLINE]: Danish multi-center RCT (n = 998) comparing hemoglobin of 7 g/dL vs 9 g/dL in septic shock (trial excluded: acute myocardial ischemia, acute burn injury, previous PRBC transfusion, and acute life-threatening bleeding) -> primary outcome: 90-day mortality
      • No difference in mortality (and rates of ischemic events, transfusion reactions, and use of life support) between the groups: however, the 7 g/dL group had lower PRBC utilization

Pre-Operative Autologous Blood Donation

  • Decreases (allogeneic) PRBC use in the ICU
  • Only useful for those undergoing elective surgeries

Use of Aprotinin in Cardiac Surgery (see Aprotinin, [[Aprotinin]])

  • Decreases PRBC use in the ICU
  • Protease inhibitor that modulates the systemic inflammatory response associated with cardiopulmonary bypass surgery
  • Inhibits pro-inflammatory response cytokine release and maintains glycoprotein homeostasis
  • Demonstrated to decrease the need for allogeneic PRBC
  • Demonstrated to decrease bleeding
  • Demonstrated to decrease the need for mediastinal re-exploration for bleeding

Blood-Conservation Devices (CellSaver, etc)

  • Technique
    • Reinfuse leftover blood back into patient (after requisite blood for testing has been taken)
    • However, these decrease the amount of blood drawn and these patients have higher Hb levels
  • Clinical Efficacy
    • No impact on PRBC use in the ICU

Parenteral Iron

  • Agents
    • Deferasirox (xxx) (see xxxx, [[xxxx]])
    • Ferrous Sulfate (see Ferrous Sulfate, [[Ferrous Sulfate]])
    • xxx
    • xxx
  • Clinical Efficacy
    • No impact on ICU PRBC transfusions
    • Used commonly in chronic dialysis patients

  • Possible Mechanisms of Immunomodulatory Effects of PRBC’s (as RBC’s themsleves do not appear to be involved in the immunomodulatory mechanism)

    • Allogeneic transfusion of lymphocytes/leukocytes (lymphocytes may circulate in the
      recipient for years)
    • Allogeneic transfusion of cytokines
    • Pplasticizer from the containers of the blood
    • Viruses in the blood
    • High levels of plasma protein in the transfused blood
  • Physiologic Effects in Recipient: these changes may persist for months after the transfusion

    • Decreased numbers of circulating lymphocytes
    • Modifications in the T-cell helper/suppressor ratio
    • Changes in B-cell function
    • Down-regulation of antigen presenting cells
    • Activation of immune cells as measured by a number of cell surface markers
  • Clinical Effects in Recipient:

    • Immunomodulatory changes are associated with increased tumor growth in certain patients
    • Immunomodulatory changes are associated increased incidence of postoperative infections
    • Transfusion-associated GVHD

Adverse Effects of Packed Red Blood Cell Transfusion

Allergic/Immunologic Adverse Effects

Anaphylaxis (see Anaphylaxis, [[Anaphylaxis]])

  • Physiologic Mechanisms
    • IgE-Mediated Mast Cell Activation
    • Non-IgE-Mediated Mast Cell Activation: rare cases of patients with very low levels of IgA and anti-IgA Ab’s, may develop anaphylaxis upon receiving blood with IgA present (these patients need IgA-deficient blood products)

Angioedema (see Angioedema, [[Angioedema]])

  • Physiologic Mechanisms
    • IgE-Mediated Mast Cell Activation
    • Non-IgE-Mediated Mast Cell Activation: rare cases of patients with very low levels of IgA and anti-IgA Ab’s, may develop anaphylaxis upon receiving blood with IgA present (these patients need IgA-deficient blood products)

Urticaria (see Urticaria, [[Urticaria]])

  • Physiologic Mechanisms
    • IgE-Mediated Mast Cell Activation
    • Non-IgE-Mediated Mast Cell Activation: rare cases of patients with very low levels of IgA and anti-IgA Ab’s, may develop anaphylaxis upon receiving blood with IgA present (these patients need IgA-deficient blood products)

Cardiovascular Adverse Effects

Fluid Overload/Congestive Heart Failure (CHF) (see Congestive Heart Failure, [[Congestive Heart Failure]])

  • xxx

Hematologic Adverse Effects

Acute Granulocytic Febrile Transfusion Reaction (see Acute Granulocytic Febrile Transfusion Reaction, [[Acute Granulocytic Febrile Transfusion Reaction]])

  • Epidemiology: most common type of transfusion reaction
  • Physiology: believed to be associated with class I HLA antibodies (or sometimes granulocyte specific antibodies) directed against the contaminating leukocytes in the transfused blood product
    • However, such antibodies are not always found
  • Associated Blood Products
    • Packed Red Blood Cells
    • Platelets: may be contaminated with leukocytes
  • Onset: 1-6 hrs after transfusion of red blood cells or platelets
  • Clinical
    • Chills
    • Fever (see Fever, [[Fever]])
    • Mild Dyspnea (see Dyspnea, [[Dyspnea]])
  • Treatment
    • Stop the Transfusion
    • Rule Out a Acute Hemolytic Transfusion Reaction (see Acute Hemolytic Transfusion Reaction, [[Acute Hemolytic Transfusion Reaction]])
    • Anti-Pyretics: aspirin should be avoided in the setting of thrombocytopenia
    • Meperidine (Demerol) (see Meperidine, [[Meperidine]]): for severe chills and rigors
  • Prognosis: usually resolves without sequelae
  • Risk of Recurrence
    • Approximately 40% of Patients Experiencing a Febrile Non-Hemolytic Transfusion Reaction will Experience Another Febrile Non-Hemolytic Transfusion Reaction [MEDLINE]: 24% will experience it on their next transfusion
  • Prevention
    • Leukoreduction: although it is thought that this may decrease the risk of acute febrile non-hemolytic transfusion reaction, the results from trials are conflicting
      • Systematic Review Examining Impact of Leukoreduction on Various Adverse Outcomes of PRBC Transfusion (Cochrane Database Syst Rev, 2015) [MEDLINE]
        • Leukoreduction did not decrease the incidence of TRALI, death (from any cause), infection from any cause, fever, or other non-infectious complications
    • Premedication with Acetaminophen (Tylenol) and Diphenhydramine (Benadryl) (see Acetaminophen, [[Acetaminophen]] and Diphenhydramine, [[Diphenhydramine]])
      • Prospective Trial Examining Efficacy of Premedication for Leukoreduced Transfusions (Transfusion, 2008) [MEDLINE]
        • Premedication did not decrease the overall risk of all types transfusion reactions
        • However, premedication decreased the rate of febrile non-hemolytic transfusion reactions

Acute Hemolytic Transfusion Reaction (see Acute Hemolytic Transfusion Reaction, [[Acute Hemolytic Transfusion Reaction]])

  • xxxx

Coagulopathy (see Coagulopathy, [[Coagulopathy]])

  • xxxx

Delayed Hemolytic Transfusion Reaction (see Delayed Hemolytic Transfusion Reaction, [[Delayed Hemolytic Transfusion Reaction]])

  • xxxx

Iron Overload (see Hemochromatosis, [[Hemochromatosis]])

  • xxxx

Post-Transfusion Purpura (see Post-Transfusion Purpura, [[Post-Transfusion Purpura]])

  • xxxx

Serum Sickness (see Serum Sickness, [[Serum Sickness]])

  • xxxx

Thrombocytopenia (see Thrombocytopenia, [[Thrombocytopenia]])

  • xxxx

Transfusion-Associated Graft vs Host Disease (see Transfusion-Associated Graft vs Host Disease, [[Transfusion-Associated Graft vs Host Disease]])

  • xxx

Infectious Adverse Effects

Babesiosis (see Babesiosis, [[Babesiosis]])

  • Risk:

Cytomegalovirus (CMV) (see Cytomegalovirus, [[Cytomegalovirus]])

  • Risk:

Hepatitis B Virus (see Hepatitis B Virus, [[Hepatitis B Virus]])

  • Risk: 1 in 63-200k

Hepatitis C Virus (see Hepatitis C Virus, [[Hepatitis C Virus]])

  • Risk: 1 in 1.6 million

Human Immunodeficiency Virus (HIV) (see Human Immunodeficiency Virus, [[Human Immunodeficiency Virus]])

  • Risk (for HIV-1 or HIV-2): 1 in 2 million

Human T-Lymphotropic Virus I (HTLV-I) (see Human T-Lymphotropic Virus I, [[Human T-Lymphotropic Virus I]])

  • Risk: 1 in 641k

Malaria (see Malaria, [[Malaria]])

  • Risk: 1 in 1 million

Other Bacteria

  • Risk: variable

Prion Disease

  • Risk: no proven risk
  • xxxx (see xxxx, [[xxxx]])

Syphilis (see Syphilis, [[Syphilis]])

  • Risk: 1 in 1 million

Neurologic Adverse Effects

Pulmonary Adverse Effects

Transfusion-Associated Acute Lung Injury (TRALI) (see Acute Respiratory Distress Syndrome, [[Acute Respiratory Distress Syndrome]])

  • Incidence: occurs in 0.014-0.08% of blood component transfusions
  • Clinical
    • xxx

Other Adverse Effects

  • Increased Mortality: mortality is higher in those who receive PRBC (even when matched for degrees of organ impairment)

References

  • Efficacy of recombinant human erythropoietin in the critically-ill patient: a randomized, double-blind, placebo-controlled trial. Crit Care Med 1999; 27: 2346-2350
  • Transfusion medicine: first of two parts: Blood transfusion. N Engl J Med 1999; 340:438-447
  • A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med 1999; 340:409-417
  • Immunomodulatory aspects of transfusion; a once and future risk? Anesthesiology 1999; 91:861-865
  • A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med 1999;340:409-417 [MEDLINE]
  • Benefits of leukocyte-reduced blood transfusions in surgical patients. Curr Opin Hemat 1998; 5:376-380
  • Transfusion medicine: first of two parts: Blood transfusion. N Engl J Med 1999; 340:438-447
  • Anemia and blood transfusion in critically ill patients. JAMA 2002; 288:1499-1507.
  • Efficacy of recombinant human erythropoietin in the critically ill patient: a randomized, double blind placebo controlled trial. Crit Care Med 1999; 27:2346-2350.
  • Comparison of blood-conservation strategies in cardiac surgery patients at high risk for bleeding. Anesthesiol 2000; 92:674-682.
  • Parenteral iron use in the management of anemia in end-stage renal disease patients. Am J Kidney Dis 2000; 35:1-12
  • A prospective, randomized, double-blind controlled trial of acetaminophen and diphenhydramine pretransfusion medication versus placebo for the prevention of transfusion reactions. Transfusion. 2008;48(11):2285 [MEDLINE]
  • Reports on clinical transfusion medicine in the early days of transfusion. Transfusion. 2010;50(5):963 [MEDLINE]
  • Packed Red Blood Cell Transfusions in Critically Ill Patients. Critical Care Nurse. 2011; 31[1]:25-34
  • Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med. 2014 Oct 9;371(15):1381-91. doi: 10.1056/NEJMoa1406617. Epub 2014 Oct 1 [MEDLINE]
  • Blood product transfusions and reactions. Emerg Med Clin North Am. 2014 Aug;32(3):727-38. doi: 10.1016/j.emc.2014.04.012. Epub 2014 Jun 12 [MEDLINE]
  • Leukoreduction for the prevention of adverse reactions from allogeneic blood transfusion. Cochrane Database Syst Rev. 2015 Dec 3;12:CD009745. doi: 10.1002/14651858.CD009745.pub2 [MEDLINE]