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Blood Components and Indications for Their Use Christopher J. Gresens, M.D. VP & Medical Director, Clinical Services BloodSource 1665 — 1st Documented Animal-to-Animal Transfusion Dog-to-dog transfusion by Richard Lower. From Petz and Swisher’s Clinical Practice of Transfusion Medicine, 2nd ed., 1989. 1667—1st Documented Animal-to-Human Transfusion Jean Baptiste Denis infuses 15year-old boy with lamb’s blood. From Zmijewski’s Immunohematology. 1818—1st Documented Human-to-Human Transfusion Following a 150-year transfusion hiatus, James Blundell transfuses patient with blood from a human donor. From Petz and Swisher’s Clinical Practice of Transfusion Medicine, 2nd ed., 1989. 1800’s—All Manner of Blood Collection Devices Utilized (You think present-day donor centers sometimes face challenges in recruiting repeat blood donors?) From Petz and Swisher’s Clinical Practice of Transfusion Medicine, 2nd ed., 1989. 1900— ABH Blood Group System ID’d From Transfusion, Vol. 1, p. 2 (1961) Karl Landsteiner discovers ABH system when he types individuals as (what we now call) group A, group B, and group O. In 1902, his proteges identify a group AB individual for the first time. The Discovery of Many Other Red Cell Antigens Followed • • • • • • • Rh (C, c, D, E, e, …) Kell (K, k, …) Kidd (Jka, Jkb, …) Duffy (Fya, Fyb, …) MNSs, … Lewis (Lea, Leb) … … … Early 1900’s—Getting Blood from Point A to Point B From Petz and Swisher’s Clinical Practice of Transfusion Medicine, 2nd ed., 1989. Direct, donor-topatient anastamosis performed by American surgeon, George Crile. 1914— Modern Anticoagulation is Born Citrate first used for blood anticoagulatio n purposes. From Petz and Swisher’s Clinical Practice of Transfusion Medicine, 2nd ed., 1989. 1939/40—Rh and Cause of HDFN Discovered Levine, Wiener, and colleagues combined their efforts in making these seminal discoveries From Netter Monograph Series But, the importance of ABO supersedes all … From Petz and Swisher’s Clinical Practice of Transfusion Medicine, 2nd ed., 1989. Outline Blood Collection and Component Preparation • • • • • Blood Collection Whole Blood Separation into Components Apheresis Blood Bag Solutions Donor Testing Outline Major Types of Blood Components/Derivatives • • • • Whole Blood Red Blood Cells (RBCs) Platelets Fresh Frozen Plasma (FFP) ·Cryoprecipitate Granulocytes · Derivatives · Outline Specialized Types of Blood Components & Transfusions • Irradiated Blood • CMV-seronegative Blood • Leukoreduced Blood Blood Collection & Component Preparation Blood Collection 1. Via Whole Blood Donation: Whole blood is collected from healthy blood donors into sterile blood bags that contain anticoagulant/preservative. 2. Via Hemapheresis: Machines with internal centrifuges separate a donor’s blood into individual components. The desired components are retained, while the remainder is returned to the donor. Four-Bag Collection System for Whole Blood + “Light” Spin = … + “Heavy” Spin = … FFP vs. … ? … Cryoprecipitate Apheresis-Assisted Donor Collection Trima/Trima Accel • Used for donor procedures, only (singleor double-RBC units; single-triple plateletpheresis, and/or plasma) From Gambro BCT website The Principles of Hemapheresis Blood Bag Solutions • Purpose of Anticoagulant-Preservatives – To prevent clotting – To provide nutrients for continued metabolism and stabilization of cells • Basic Needs of Stored Blood Cells – Adequate glucose (dextrose) – Adequate ATP levels – Appropriate pH Blood Bag Solutions • The Storage Lesion: These are the metabolic changes that occur to stored blood over time. Following is an example for CPDA-1 RBCs. Parameter 0 Days 35 Days % Viable Cells 100 71 pH 7.55 6.71 [K+] (mmol/L) 5.1 78.5 [Plasma Hgb] (mg/L) 78 658 [2,3-DPG] (% of initial) 100 < 10 AABB Technical Manual, 14th ed. Testing • • • • ABO Rh Antibody Screen Infectious Diseases – – – – Syphilis HBsAg Anti-HIV-1/2 Anti-HBc Testing • Infectious Disease Testing (cont.) – – – – – – – – Anti-HTLV-I/II Anti-HCV HIV Nucleic acid testing (NAT) HCV NAT HBV NAT WNV NAT Anti-T. cruzi (On some units) Anti-CMV Currently Accepted Risks of Transfusion • Acute immune-mediated hemolytic transfusion reactions: 1 in 19,000 risk for ABO mismatched transfusion; 1 in 33,000 for major ABO mismatch; 1 in 600,000 for death (Linden et al. Transfusion 1992; 32: 601-606) • TRALI: 1: 300 to 1:5,000 (Kao S, et al. Transfusion 2003; 43: 185191) • Septic transfusion reactions: < 1: 777 plateletpheresis units; 1: 38,565 RBC units (Infectious Risks of Blood Transfusion. Blood Bulletin (America’s Blood Centers), December, 2001) • Anaphylactic transfusion reactions: 1: 20,000 to 1:47,000 (Salama A, et al. Transfusion 2004; 44: 509-511) Transfusion Risks (Continued) • • • • • Circulatory overload Allergic transfusion reactions Febrile nonhemolytic transfusion reactions Delayed hemolytic transfusion reactions Transfusion-related graft-versus-host disease • Post-transfusion purpura Transfusion Risks (Continued) • • • • • HIV: 1 in 2,135,000 units HBV: 1 in 205,000-to-488,000 units HCV: 1 in 1,935,000 units HTLV-I/II: 1 in 514,000-2,993,000 units CMV: << 1: 100 (when leukoreduced or CMVnegative blood used) • WNV: ? (region-specific; very low) • vCJD: ? (risk very, very low—even in U.K.) “Infectious Risks of Blood Transfusion.” Blood Bulletin (America’s Blood Centers). December 2001. Top-10 Reasons for Giving Blood 10. 9. 8. 7. 6. It makes me feel good about myself. How else can I instantly lose one pound? To put up my feet and relax without guilt. All my friends & family do it, so I do, too. It’s a nice way to meet people with similar philosophies. Top-10 Reasons for Giving Blood 5. 4. 3. 2. The good-looking nurses (and doctors). Because, even though I have few material possessions to give, I always (God willing) will have enough blood to share. Because I know that, whatever they take from me, I can replace. How else can I experience so much satisfaction with my clothes on? …and the Number 1 Reason for Giving Blood 1. To help save the lives of others. Whole Blood • Clinical Indications: Provides both O2 delivery and volume in patients with hypovolemic shock. • Contraindications – Thrombocytopenia (unless unit is VERY fresh) – Factor VIII or V deficiencies – Normovolemic chronic anemia Whole Blood • Transfusion Criteria – Must be ABO-identical – Should be crossmatch compatible • Dosage: One unit should raise a 70 kg patient’s Hct by approximately 3% (in the absence of ongoing bleeding or hemolysis). “Shotgun” Approach vs. . . . Component Therapy Recommended Target Hematocrits for RBC Transfusions (To be Revisited) • Clinical Indications: To restore O2-carrying capacity in clinically significant (acute or chronic) anemias. – Asymptomatic anemia: Typically, in stable patients, Hgb thresholds of 7-to-8 g/dL should be crossed before transfusion would be considered. – Bleeding/acute blood loss: Transfuse at the discretion of physician. – Occasional exceptions, such as the need to transfuse pre-renal transplant patients, regardless of their Hcts (i.e., to induce immune tolerance), exist. Recommended Target Hematocrits for RBC Transfusions (Revisited) • Lower limit (or “transfusion trigger”) for general medical and surgical patients remains at Hgb (Hct) levels of 7.0 g/dL (21%). • Some patient groups (e.g., elderly with acute MI’s) seem to have better outcomes when Hct is in 30-33% range. “Current data suggest restraining transfusions favors positive patient outcomes—except when significant underlying cardiac disease is present.” “The Transfusion Trigger Updated: Current Indications for Red Cell Therapy.” Blood Bulletin, Vol. 6; July, 2003. RBC Transfusions • Contraindications – Pharmacologically treatable anemias – Most coagulation deficiencies • Transfusion Criteria – Must be ABO-compatible (group O is “universal”); – Should be crossmatch-compatible; • Dosage: One unit generally will raise the Hct (Hgb) of a 70-kg, non-bleeding/hemolyzing patient by 3% (1 g/dL). Clinical Indications for Platelets • Overview: Platelet transfusions are used for the treatment and/or prevention of bleeding in patients with thrombocytopenia or (less often) platelet function defects Clinical Indications for Platelets 1910: Duke demonstrated that platelets from transfused whole blood decrease bleeding time and control bleeding.1 1962: Gaydos, et al. first documented relationship between platelet count and spontaneous bleeding in leukemia patients (hemorrhage not seen until platelet count fell to < 50,000/uL).2 1. Duke WW. JAMA 1910; 55: 1185-92. 2. Gaydos, et al. NEJM 1962; 266: 905-9. Clinical Indications for Platelets 1978: Slichter & Harker showed that blood loss in stable aplastic patients accelerated only when platelet count < 10,000/uL (moreover, bleeding increased substantially with platelet count of < 5,000/uL).1 1986: NIH-Sponsored Consensus Conference …2 Plt ct > 50,000: Bleeding probably not due to low plt ct Plt ct < 5,000: Severe bleeding risk Plt ct 5-10K: risk of spontaneous bleeding Plt ct 10-50K: risk of bleeding during hemostatic challenge 1. Slichter & Harker. Clin Hemat 1978; 7: 523-39. 2. Consensus Conference on Platelet Transfusion Therapy. JAMA 1987; 257: 1777-80. Clinical Indications for Platelets A. Guidelines for Prophylactic Platelet Transfusions 1. No Clinical Factors—Maintain platelet count > 10,000/uL 2. Significant Clinical Factors (e.g., sepsis, DIC, VOD, GVHD)—Maintain platelet count > 20,000/uL B. If Patient is Bleeding or Pre-Surgery, maintain platelet count > 50,000/uL C. Exceptions … (To be discussed) Dosing Platelets A. For Infants/Children: 5-10 mL platelets/kg B. For Adults (> 40 kg): 1 plateletpheresis unit (rarely 2) C. Formula for Calculating Dose: Platelet Dose = Desired Increment x BV 0.67 D. Expectations: Ideally, an appropriate dose of platelets should raise the platelet count by 30,000-60,000/uL (more discussion to come …) F. Important: Obtain a platelet count within 24 hours of transfusion (ideally, within 1 hours—especially if refractoriness suspected) Special Platelet Topics A. Platelet Selection Criteria 1. ABO Matching a. 1st Choice: ABO identical (e.g., A to A) b. 2nd Choice: Plasma compatible (AB to A) c. 3rd Choice: Plasma incompatible (A to AB) 2. Rh Matching: It sometimes is necessary to give Rh- positive platelets to an Rh-negative patient. If the patient is a female of child-bearing potential, consider the use of RhIg. Special Platelet Topics B. Contraindications to Platelet Transfusions 1. TTP/HUS (unless bleeding) 2. ITP and HIT (unless bleeding) 3. DIC (unless bleeding) 4. (Controversial) Chronic aplastic anemia or MDS (unless bleeding)1 5. Plasma coagulation defects unrelated to platelets 1. Consensus Conf, Platelet Transfusion Therapy. JAMA 1987; 257: 1777-80. Special Platelet Topics C. Platelet-Associated Transfusion Reactions 1. List includes most of the usual reactions (e.g., TRALI, anaphylactic, circulatory overload, etc.), but most notably … 2. Septic transfusion reactions 3. Acute hemolytic transfusion reactions (from incompatible donor plasma) 4. Alloimmunization to class I HLA and other antigens FFP Transfusions • Clinical Indications – Coagulopathy (with active bleeding) documented by (at least one of): INR > 1.5, PTT > 1.5 x upper limit; coag factor assay of < 25% activity; – Emergent reversal of warfarin effect; – Documented acquired or congenital coagulation factor deficiency (when specific factor concentrate is unavailable); – Plasma exchange for TTP/HUS. FFP Transfusions • Contraindications: Should not be used as a: – volume expander in absence of factor deficiency; – nutritional source; – substitute for a readily available factor concentrate; • Transfusion Criteria: Must be ABO-compatible with patient (with only the rarest of exceptions); • Dosage: Determined by clinical situation and body size; generally, 15 mL/kg for loading dose and 10 mL/kg to maintain hemostasis. Cryoprecipitate Transfusions • Clinical Indications – Correction of factor VIII deficiency or von Willebrand’s disease when a specific factor concentrate isn’t available; – Factor XIII deficiency – Hypofibrinogenemia (e.g., in DIC) – Source of fibrin glue Cryoprecipitate Transfusions • Contraindications: Always first consider safer, more effective therapies, e.g., – DDAVP for vWD; – Factor VIII concentrate (if available) for hemoph. A; – Tisseel™ for fibrin sealant; • Transfusion Criteria: ABO generally is not very important, unless a lot is transfused quickly (e.g., on the order of > 30 units over 72 hours). Cryoprecipitate Transfusions • Dosage Total Bags Needed = [Total Factor Required] [Units of Factor per Bag] Total Factor Required = [Pt’s Plasma Volume] x [Desired - Initial Level] Plasma Volume Of Ave. Adult = [kg body wt.] x [70 mL/kg] x [1 - Hct] Granulocyte Transfusions • Clinical Indications – Generally Accepted Indication • Documented severe bacterial infections unresponsive to 24-48 hours of appropriate antibiotics in a patient with severe neutropenia/neutrophil dysfunction – Less Clear “Indication” • Documented severe fungal infection unresponsive to appropriate antifungal therapy in a patient with severe neutropenia Granulocyte Transfusions • Contraindications – Fever in absence of documented infection – Prophylactic transfusions • Transfusion Criteria: Must be ABOcompatible (red cell crossmatch is performed with each concentrate). • Dosage: Generally transfused daily (1-2 units/day) until infection clears or neutrophil count exceeds 500/uL. Plasma Derivatives • • • • • • Albumin (5% or 25%) Plasma Protein Fraction Factor VIII Factor IX Immune Globulins (e.g., IVIG, RhIG, HBIG, . . . ) Etc. Intravenous Immune Globulin • Clinical Indications – Replacement Therapy--e.g., • Primary hypogammaglobulinemia • S/p progenitor cell transplant • Pediatric HIV sepsis – Immunomodulant Therapy--e.g., • ITP • Acute Guillain-Barre syndrome • Chronic inflammatory demyelinating polyneuropathy • Dosage: Varies. Specialized Blood Components • CMV-seronegative • Irradiated • Leukoreduced Indications for CMV-Seronegative Blood • Pre-/post-hematopoietic stem cell transplant (if pt. is CMV-neg) • Low birth weight (< 1,200 g) neonate (if mom is CMV-neg) • Intrauterine fetal transfusion (regardless of mom’s CMV serology) • Pregnancy (if mom is CMV-neg) • Congenital immunodeficiency (if pt. is CMV-neg) • Pre-/post-solid organ transplant (if pt. is CMV-neg) • HIV infection/AIDS(if pt. is CMV-neg) • Other possible indications: hematologic/solid malignancy; neonatal exchange (if pt. is CMV-neg) Indications for Irradiated Blood • • • • • • • Pre-/post-hematopoietic stem cell transplant Hodgkin’s disease Low birth weight neonate (< 1,200 g) Neonatal exchange transfusion Intrauterine fetal transfusion Related donor HLA-matched donor or crossmatch-compatible platelet donor • Treatment with either fludarabine or 2-CDA Summary • Blood Collection and Component Preparation • Major Types of Blood Components and Plasma Derivatives • Specialized Blood Components – CMV-seronegative – Irradiated, etc. Top 10 Bogus Reasons for Transfusing a Patient 10. My patient could use some extra calories. 9. For wound healing purposes. 8. My patient is specifically requesting it, and who am I to say no? 7. (For autologous blood) It’s the patient’s blood anyway, so what harm could come of it? 6. Since it’s been out of storage for > 30 minutes, and the blood bank won’t take it back. Top 10 Bogus Reasons for Transfusing a Patient 5. Because I’m “only” a resident, and my attending ordered it. 4. (For FFP) The patient requires volume support. 3. (For platelets) My non-bleeding patient has ITP with a platelet count of < 5,000/uL. 2. Because the Tour de France is coming up. And the Number 1 Bogus Reason for Transfusing a Patient… 1. Hey! It’s only blood. What’s the big deal? Please donate blood ... … You never know whose life you might save. Action Comics # 403 (1970)