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
- Systematic Review Examining Impact of Leukoreduction on Various Adverse Outcomes of PRBC Transfusion (Cochrane Database Syst Rev, 2015) [MEDLINE]
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
- Prospective Trial of Premedication for Leukoreduced Transfusions (Transfusion, 2008) [MEDLINE]
- Agents
- Acetaminophen (Tylenol) (see Acetaminophen, [[Acetaminophen]])
- Diphenhydramine (Benadryl) (see Diphenhydramine, [[Diphenhydramine]])
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
- 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)
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
- Allogeneic transfusion of lymphocytes/leukocytes (lymphocytes may circulate in the
-
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
- 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
- Systematic Review Examining Impact of Leukoreduction on Various Adverse Outcomes of PRBC Transfusion (Cochrane Database Syst Rev, 2015) [MEDLINE]
- 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
- Prospective Trial Examining Efficacy of Premedication for Leukoreduced Transfusions (Transfusion, 2008) [MEDLINE]
- Leukoreduction: although it is thought that this may decrease the risk of acute febrile non-hemolytic transfusion reaction, the results from trials are conflicting
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
- Posterior Reversible Encephalopathy Syndrome (PRES) (see Posterior Reversible Encephalopathy Syndrome, [[Posterior Reversible Encephalopathy Syndrome]])
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]