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A. Red Blood Cell (RBC) Transfusions [6] navigator

  1. Indications
    1. Elective Surgery: often autologous transfusion
    2. Acute blood loss
    3. Anemia in critical care patients
    4. Chronic anemia unresponsive to other interventions
  2. Autologous Transfusion [2,6]
    1. Patient donates blood prior to surgery which be used if needed
    2. Can reduce most, but not all, risks
    3. May increase risks of ischemia if patient begins surgery with reduced hematocrit
    4. Must give plenty of supplemental iron
    5. Alternative is acute hemodilution and collection of blood just prior to surgery
    6. Erythropoietin (EPO) and iron supplements before surgery reduced need for transfusion [20]
  3. Acute Blood Loss
    1. Acute reduction in hemoglobin (Hb) from 13gm/dL to 5gm/dL in resting young persons did not significantly affect tissue oxygenation [11]
    2. However, this study was carried out in healthy, resting, young persons
    3. Suggests that young persons undergoing elective surgery can tolerate blood loss
    4. Minimum Hb levels which would not affect tissue oxygenation in trauma and acute disease setting and in persons with atherosclerosis are not currently known
    5. Bleeding diathesis with active bleeding may require additional transfusions
  4. Anemia in Critical Care Patients [16]
    1. Most recommendations have suggested transfusion for Hb 9.0gm/dL
    2. However, restricting transfusions until Hb <7.0gm/dL had better outcomes
    3. Consider restrictive strategy for transfuion (<7.0gm/dL) except in cardiac ischemia
  5. Transfusion Levels
    1. Packed RBC are 250-300mL in volume, derived from ~500mL of whole blood
    2. Each unti of RBC expected to raise Hb levels in an adult by ~1gm/dL
    3. This effect is very variable in practice
  6. Blood Substitutes [30]
    1. Goal is to replace RBC with infusible liquid that does not require special handling
    2. This infusible liquid would allow oxygen carriage, at least in acute/subacute setting
    3. Would not be subject to compatibility issues (see below)
    4. Polymerized bovine Hb has been used under effectively compassionate guidelines [19]
    5. Several Hb-based blood substitutes are available with modest to moderate efficacy
    6. Overall, these Hb-based blood substitutes increased myocardial infarction risk 2.7X and risk of death by 1.3X [30]
    7. These risks are likely due to "unprotected" Hb reacting with nitric oxide in circulation

B. Overview of Blood Compatility [6] navigator

  1. Blood transfusion requires compability between donor and recipient
  2. Non-major histocompatility (MHC) associated antigens play a key role in the process
    1. These are called "systems" or blood-group antigens
    2. Compability in the ABO system is the most important
    3. Compability in the Rh (D) system is also critical
  3. Anti-Globin and Anti-Complement tests should be run also (Direct Coombs' Test)
  4. Antibody Screen (Indirect Coombs' Test)
    1. Use patient's serum with ABO similar RBC from another person
    2. Add complement to the serum-exposed RBC and analyze for lysis
  5. Leukoreduction (white cell removal) can reduce fever, antibiotic use, mortality after RBC transfusions [15]
  6. RBC substitutes (based on Hb) with no compability issues have been developed [30]

C. ABO System [18]navigator

  1. Carbohydrate antigens, very simple structures
  2. A and B are actual antigens produced by addition of sugars to RBC surface proteins
    1. Core of A and B antigens is called "H" Antigen
    2. O type is absence of sugar-linkage and so is "naked" H antigen
    3. Sugar transferases for formation of A and B antigens found on chromosome 9
    4. Type A produced by N-acetyl-galactosamine linkage to H antigen
    5. Type B produced by galactose linkage to H antigen
    6. Some people have both sugar transferases (maternal/paternal), and these are AB
  3. The A and B antigens are found on many organisms, including bacteria
    1. Therefore, humans develop anti-A and/or anti-B antibodies from exposure to bacteria
    2. Anti-self antibodies are not produced
    3. Thus, A persons have anti-B; B have anti-A; AB have neither Ab; O have anti-A and B
    4. These antibodies are only of the IgM (complement fixing, not cross placenta) class
  4. Donors and Recipients
    1. RBC are "washed" prior to transfusion, so no serum components are transferred
    2. Thus, Type O blood is the universal donor but can only receive Type O blood
    3. Type AB blood is the universal recipient; can only donate to type AB
    4. Type A blood can be donated to A or AB; receive only A or O blood
    5. Type B blood can be donated to B or AB; receive only B or O blood
    6. All transfusions should be mateched at the Rh locus as well

D. Rh (D) (Rh) And Other Systemnavigator

  1. Rh (D) System
    1. One of many minor systems, but is most immunogenic of all minor systems
    2. Rh proteins have sequence homology to transporters, but have unknown function
    3. Most people are Rh positive
    4. Rh negative is universal donor (assuming ABO compatibility)
    5. Rh positive can sensitive Rh negative recipients and should be avoided
    6. Rh positive fetus in Rh negative mother can develop hemolytic disease
  2. Kell Antigens [12]
    1. Major antigenic systems in human red blood cells
    2. 23 known antigens reside on one 93K transmembrane protein (chr 7q33)
    3. Antigen is expressed on erythroid progenitor cells and mature erythroid cells
    4. Antibodies to Kell specifically inhibit progenitor cells as well as causing RBC lysis
    5. These anti-Kell Abs lead to reduced reticulocytes and hemolytic anemia
  3. Duffy
  4. Lewis - incompability at this locus is generally not severe
  5. These all represent antigenic determinants on the surface of RBC's
  6. These antigens are polymorphic in the human population
  7. Main significance is in maternal-fetal hemolytic diseases

E. Acute Transfusion (Hemolytic) Reactionnavigator

  1. Anaphylotoxins are produced with Ag-Ab complexes
    1. Most commonly from ABO mismatches
    2. Other antigens are very rarely involved (for example, Rh Antigen)
  2. Symptoms
    1. Pain at intravenous insertion site (phlebitis)
    2. Shakes, Rigors
    3. Fevers
    4. Back Pain (renal failure from Ag-Ab complexes and/or acute tubular necrosis)
  3. Lab Analysis
    1. Urine for hemoglobin, Casts (Acute Tubular Necrosis)
    2. Serum Bilirubin and Haptoglobin
    3. Blood Smear
    4. Electrolytes and renal function tests
  4. Treatment
    1. Discontinue transfusion
    2. Acetaminophen, diphenhydramine, hydrocortisone
    3. Meperidine (Demerol®) for rigors
    4. IV Fluids to patients with renal damage, maintain good urine output
  5. Prognosis
    1. 10-20% Mortality - correlates with amount of blood given
    2. Disseminated Intravascular Coagulopathy (DIC)
    3. Renal Failure
  6. Delayed reaction - with mixed bilirubins can be seen several weeks post-transfusion

F. Infectious Complications of RBC Transfusion [1]navigator

  1. HIV 1 and 2 risk is ~1 in 2 million
  2. HTLV 1 and 2 risk is ~1:70,000 to ~1 in 2 million
  3. Parvovirus B19 risk is 1:10,000
  4. Hepatitis B Virus - risk is 1:63,000-200,000
  5. Hepatitis C Virus - risk is ~1:150,000
  6. Syphilis is ruled out completely - RPR or microhemaglutinin for Treponema pallidum
  7. Bacterial contamination of red cells - risk is ~1:500,000
  8. Aggregate risk of some infection: ~1:34,000 (88% accounted for by hepatitis)
  9. West Nile Virus (WNV) [14]
    1. Risk of transfusion with RBC, platelets, FFP
    2. Routine testing with WNV RNA detection completely prevented new WNV infections [24,25]
    3. Individual donor testing, rather than minipool testing, in endemic regions, reduced the collection of blood with low levels of WNV RNA [25]
    4. Prior to routine testing, ~50% of infected patients developed symptoms
    5. Over 40% of transmissions prior to testing occurred in immunocompromised recipients
  10. Other Infectious Diseases [1]
    1. Chagas Disease, Babesia, Yersinia
    2. Cytomegalovirus (~70% of persons are CMV positive) - important in transplantation
    3. Parenterally transferred SEN D or SEN H can cause post-transfusion hepatitis [22]
  11. Prion-Related Diseases [27,28]
    1. Variant Creutzveld-Jacob Disease (vCJD) reported after blood transfusion in humans [5,8]
    2. Bovine spongiform encephalopathy prion from cattle can cause a CJD-like illness in humans
    3. Agent is transmissible with blood transfusion
    4. In UK, 3 of 66 exposed persons have developed vCJD within 6 years of transfusion [27]
    5. Early psychiatric symptoms progressing to dementia, ataxia, death
    6. Resins which absorb prion proteins and reduce prion infectivity have been developed for treatment of blood products [4]

G. Febrile Transfusion Reactionnavigator

  1. Usually due to WBC in blood, with Abs to HLA on WBC surface
  2. Patients with this are at much higher risk for respiratory failure
  3. Must be concerned with acute transfusion reaction
  4. Treat with acetaminophen ± diphenhydramine
  5. Use WBC poor products (filtered) in future

H. Other Transfusion Risks [1]navigator

  1. Acute Transfusion / Hemolytic Reaction ~ 1:500,000
  2. Delayed Hemolytic reactions ~1:1,000
  3. Transfusion Related Acute Lung Injury (TRALI) [23]
    1. Reported in ~1:5000 transfusions but may be underrecognized
    2. Third leading cause of transfusion-related mortality
    3. Dyspnea, hypoxemia, hypotension, fever
    4. Bilateral pulmonary edema on chest radiography
    5. 100% requrie oxygen; ~70% require mechanical ventilation
    6. Associated with presence of various antibodies (HLA Class I and II, granulocyte)
    7. Also associated with specific lipids in donor plasma
  4. Transfusion Associated Graft Versus Host Risks (WBC free components must be used)
    1. All irradiated blood products
    2. Seen in Hodgkin's Disease, Bone Marrow Transplant, severe combined immunodeficiency
  5. No increased risk of cancer after transfusions from donors with subclinical cancer [3]
  6. In cardiac surgery patients, transfusion of RBC stored >2 weeks associated with increased postoperative complications and reduced survival [29]

I. Immunological Effects of Blood Transfusion navigator

  1. Major Immunologic Effects of Allogeneic Red Cell Transfusion
    1. Increased alloantibody formation to HLA-A,B (MHC Class I Proteins)
    2. Increased generalized antibody formation
    3. Decreased cutaneous delayed type hypersensitivity (DTH)
    4. Decreased T cell proliferation and natural killer cell function
  2. Clinical Consequences of Blood Cell Transfusion
    1. Alloantibody generation may make future organ transplantation (matches) difficult
    2. Once transplanted, engraftment and long term outcomes improved with transfusions
    3. Reduction in symptoms of some autoaimmune disease (such as Crohn Disease)
    4. Increase in recurrence rates in certain kinds of cancer including gastric, head and neck
    5. Increase in perioperative infections (only with allogeneic blood products [8])
  3. Pathophysiology of Effects
    1. Appears that allogeneic transfusion stimulates a Th2-helper cell phenotype
    2. Transfusion also reduces Th1-helper functions
    3. Thus, IL10 and IL4 are increased; IL-12 and IL-2 are decreased
    4. This would explain improved organ engraftment and increase in certain cancers
    5. Also explains predisposition for transfused patients to make antibodies
  4. Unclear if autologous transfusion or use of leukocyte-depleted blood has same effects

J. Platelet Transfusions [7] navigator

  1. Two-Step Purification from Whole Blood
    1. Whole blood centrifuged at slow speed: RBC/WBC sediment, platelets with plasma on top
    2. Platelet rich plasms (PRP) is then centrifuged at high speed to sediment platelets
    3. Supernatent (platelet-free plasma) removed and platelets resuspended in 50-70mL plasma
    4. A standard platelet dose for an adult (300-600 billion platelets) requires 4-8 of these concentrates to be combined
    5. Apheresis can also be used to obtain platelets in an automated proceedure
  2. Storage at room temperature with stirring is required to prevent aggregation
  3. Manipulation of Platelets
    1. WBC depletion - irradiation (UVB treatment), filtration (high losses)
    2. Goal is to reduce alloimmunization which is caused by contaminating donor lymphocytes
    3. HLA Matching
    4. Overall alloimmunization risk is 3-5% with leukocyte depleted platelets [9]
    5. Risk of platelet associated infection (sepsis) is ~1:12,000 transfusions [1]
  4. Unit definition: ~4x10exp(11) platelets per 6 random units or 1 pheresis unit
  5. Indications
    1. Platelet counts <5K/µL - platelet transfusion should always be given
    2. Counts 5-30K/µL - given for prophylaxis or for active bleeding
    3. Chemotherapy prophylaxis - given for platelet counts <10K/µL (as safe as <20K/µL) [10]
    4. Major surgery prophylaxis - given for platelet counts <50K/µL
    5. Enhanced platelet destruction - given at 50K/µL with microvascular bleeding
    6. Contraindicated in TTP generally
    7. Platelet dysfunction - aspirin effects, uremia, vWF deficiency (consider DDAVP), others
  6. Adverse Effects
    1. Platelets can transmit disease such as HIV, HBV, HCV (all tested for) and CMV
    2. Bacterial contamination - due to storage at room temperature
    3. Febrile transfusion reactions - particularly with leukocyte rich platelets
    4. Rh alloimmunization - RhD mismatches
    5. Graft versus host disease activity - due to accompanying leukocytes, mainly in patients with severe immunosuppression or congenital immunodeficiency
    6. Transfusion related acute lung injury - soluble CD40 ligand, HLA antibodies, others have implicated in this reaction (see below)
  7. Fevers and Rigors to Platelets [21]
    1. May be life threatening and include acute lung injury
    2. Storage of platelets leads to accumulation of soluble CD40L (CD154)
    3. Soluble CD40L is an immune stimulant and can cause cytokine release
    4. Leukoreduction before platelet transfusion does not remove soluble CD40L
  8. Platelet growth and development factors are being investigated for clinical use

K. Fresh-Frozen Plasma (FFP) [13] navigator

  1. Plasma separated from RBC and platelets, frozen at less than -18°C within 8 hours
  2. Shelf life ~12 months
  3. Each unit (1 bag) contains 250mL with all clotting factors and inhibitors
  4. Indications
    1. Coagulopathy due to congenital or acquired factor deficiency with active bleeding
    2. PT and/or PTT >1.4X control with relatively normal fibrinogen levels
    3. Coagulation factor assay of <25% normal activity
    4. Massive blood transfusion (>5L)
    5. Reversal of warfarin effect (usually with active bleeding)
    6. Deficiency of antithrombin (AT III)
    7. Plasma exchange (see below)
  5. Use of recombinant coagulation proteins strongly reduces risk of infectious agents [26]
  6. Cryoprecipitate for treatment of vWF deficiency has been replaced with plasma-derived factor VIII (pdFVIII)

L. Plasma Exchange [17]navigator

  1. Goal is removal of plasma proteins with or without replacement of missing factors
    1. Blood is removed from the patient
    2. Cellular components are separated from plasma
    3. Cells are washed and then reinfused with new plasma
  2. Indications
    1. Thrombotic Thrombocytopenia Purpura (TTP) [5]
    2. Myasthenia Gravis - IVIg therapy is as effective
    3. Chronic Inflammatory Demyelinating Polyneuropathy
    4. Waldenstrom's Macroglobulinemia
    5. Guillain-Barre Syndrome - IVIg is as effective, easier to administer
  3. Ineffective
    1. Rheumatoid Arthritis
    2. Systemic Lupus Erythematosus
    3. Multiple Sclerosis

M. Cryoprecipitatenavigator

  1. Cold precipitable protein fraction from FFP (thawed to 1-6°C)
  2. Usually resuspended in residual volume of plasma (~15mL)
  3. Only FDA approved blood component with concentrated fibrinogen level
  4. Indications
    1. Hypofibrinogenemia - usually with consumptive coagulopathy, such as DIC
    2. Von Willebrand's Disease - usually Factor VIII concentrate is preferred [13]
  5. Note that this material is quite pro-thrombotic

References navigator

  1. Goodnough LT, Brecher ME, Kanter MH, AuBuchon JP. 1999. NEJM. 340(6):438 abstract
  2. Goodnough LT, Brecher ME, Kanter MH, AuBuchon JP 1999. NEJM. 340(7):525 abstract
  3. Edgren G, Hjalgrim H, Reilly M, et al. 2007. Lancet. 369(9574):1724 abstract
  4. Gregori L, Gurgel PV, Lthrop JT, et al. 2006. Lancet. 368(9554):2226 abstract
  5. George JN. 2006. NEJM. 354(18):1927 abstract
  6. Klein HG, Spahn DR, Carson JL. 2007. Lancet. 370(9585):415 abstract
  7. Stroncek DF and Rebulla P. 2007. Lancet. 370(9585):417
  8. Jensen LS, Kissmeyer-Nielsen P, Wolff B, Qvist N. 1996. Lancet. 348:841 abstract
  9. Trial to Reduce Alloimmunization to Platelets Study Group. 1997. NEJM. 337(26):1861 abstract
  10. Rebulla P, Finazzi G, Marangoni F, et al. 1997. NEJM. 337(26):1870 abstract
  11. Weiskopf RB, Viele MK, Feiner J, et al. 1998. JAMA. 279(3):217 abstract
  12. Vaughan JI, Manning M, Warwick RM, et al. 1998. NEJM. 338(12):798 abstract
  13. Stroncek DF and Rebulla P. 2007. Lancet. 370(9585):427 abstract
  14. Pealer LN, Marfin AA, Petersen LR, et al. 2003. NEJM. 349(13):1236 abstract
  15. Hebert PC, Fergusson D, Blajchman MA, et al. 2003. JAMA. 289(15):1941 abstract
  16. Hebert PC, Wells G, Blajchman MA, et al. 1999. NEJM. 340(6):409 abstract
  17. Clark WF, Rock GA, Buskard N, et al. 1999. Ann Intern Med. 131(6):453 abstract
  18. Weatherall DJ and Provan AB. 2000. Lancet. 355(9120):1169
  19. Mullon J, Giacoppe G, Clagett C, et al. 2000. NEJM. 342(22):1638 abstract
  20. Feagan BG, Wong CJ, Kirkley A, et al. 2000. Ann Intern Med. 133(11):845 abstract
  21. Phipps RP, Kaufman J, Blumberg N. 2001. Lancet. 357(9273):2023 abstract
  22. Rigas B, Hasan I, Rehman R, et al. 2001. Lancet. 958(9297):1961
  23. Kopko PM, Marshall CS, MacKenzie MR, et al. 2002. JAMA. 287(15):1968 abstract
  24. Stramer SL, Fang CT, Foster GA, et al. 2005. NEJM. 353(5):451 abstract
  25. Busch MP, Caglioti S, Robertson EF, et al. 2005. NEJM. 353(5):460 abstract
  26. Ludlam CA, Powderly WG, Bozzette S, et al. 2006. Lancet. 367(9506):252 abstract
  27. Wine SJ, Pal S, Siddique D, et al. 2006. Lancet. 368(9552):2061 abstract
  28. Collinge J. 1999. Lancet. 354(9175):317 abstract
  29. Koch CG, Li L, Sessler DI, et al. 2008. NEJM. 358(12):1229 abstract
  30. Natanson C, Kern SJ, Lurie P, et al. 2008. JAMA. 299(19):2304 abstract