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Many problems with transfusions are related to infection. In 1985, the chance for hepatitis was 10% and HIV 0.5% TABLE 47-11 Percentage Risk of Transfusion-Transmitted Infection With a Unit of Screened Blood in the United States RISK WINDOW PERIOD (DAYS) HIV 1/800,000 22 11 HTLV I & II 1/641,000 51 Cytomegalovirus < 1.0% rapidly HCV 1/600,000 82 HBV 1/200,000 59 8-10 HIV human immunodeficiency virus type 1: HTLV human T-cell lymphotropic virus: HCV hepatitis C virus: HBV hepatitis B virus TABLE 47-12 Infectious Disease Testing For Blood Transfusions (1998) 1. Discontinue serum alanine aminotransferase testing 2. Hepatitis C antibody testing 3. Antibody to hepatitis B core antigen 4. HIV-1 5. HIV-2 6. HIV Ag (p24 antigen) 7. HTLV I/II 8. Serologic test for syphilis) From JAMA 1995;274:1374 HIV, human immunodeficiency virus:HTLV, human T-cell lymphotropic virus IMPROVE TESTING • Molecular testing • Viral inactivation TABLE 47-13 Tests Used For Detecting Infectious Agents In All Units Of Blood (2004) VIRUS RNA MINPOOL ANTIBODY TO HIV NAT HIV, I, II & O HCV NAT HCV HBV HBC HTLV HTLV I & II WNV NAT NAT = nucleic acid technology WNV = West Nile Virus HIV human immunodeficiency virus type 1: HTLV human T-cell lymphotropic virus: HCV hepatitis C virus: HBV hepatitis B virus NUCLEIC ACID TECHNOLOGY (NAT) TESTING WILL BE USED ON: • HBV • Hepatitis A • Parvovirus 19 • West Nile Virus TABLE 47-14 INFECTIOUS DISEASES (2004) - NO TEST DISEASE RISK Malaria 2-3 cases per year in USA Chagas 0.1 -0.2% of units SARS ? VCJD ? V CJD = Variant Creutzfeldt-Jakob Disease SARS = Severe Acute Respiratory Syndrome *DONATED BLOOD WILL BE BANNED FROM DONORS WHO: • Lived in UK 3 months or longer since 1980 • Lived in Europe 6 months since 1980 • Anyone who has received blood in UK • Will decrease donors by 8-9% * American Red Cross MALARIA • 2 to 3 cases/year for 40 years • Since 1982, all cases were from emigrants or residents from endemic areas WEST NILE VIRUS • 4,000 cases of which 21 are transmitted by transfusion* • In 2002, 23 cases** • 43% were immunocompromised • 8% were > 70 years Science 2003; 299:1824 ** N Engl J Med 2003; 349:1236 TABLE 47-8 TRANSFUSION FATALITIES (2001-2002) IN THE UNITED STATES* • Bacterial contamination - 17 • TRALI - 16 • Mistransfusion - ABO mismatch - 14 *From the Federal Drug Administration (Oct. 1, 2001 to September, 30, 2002) TRALI = transfusion related acute lung injury PLATELET INDUCED SEPSIS • 33 year old male with chronic pancytopenia from failed allogeneic bone marrow Tx • Platelets caused hypotension refractory to pressor respiratory failure, acidosis, etc. • Klebsiella pneumonia PLATELET INDUCED SEPSIS • 57 year old post blood stem cell transplant for multiple myeloma • Post MI & CABG; deep vein thrombosis • Neutropenic fever • Gave platelets • 40°C, dyspnea, 85% SAT, AF • Culture positive for klebsiella pneumonia RULE If a patient has a fever within 6 hours after receiving platelets, then it is platelet induced sepsis until proven otherwise. BACTERIAL CULTURE Prior to culture, risk was: RBC 1/300,000 Platelets 1/25,000 WHAT IS THE DIFFERENTIAL DIAGNOSIS WHEN HYPOTENSION OCCURS DURING BLOOD ADMINSTRATION? Hemolytic transfusion reaction ++ Sepsis ++ Anaphylaxis TRALI +/Isolated ++ = Body temperature Should all blood (packed red cells) have the white blood cells removed? Table 1A: Adverse Effects Associated with Donor Leukocytes (4) Definitive: • Nonhemolytic febrile transfusion reactions • Transmission of leukocyte-associated viruses • Cytomegalovirus (CMV), Epstein-Barr virus (EBV), HTLV-1 • Alloimmunization Table 1B: Adverse Effects Associated with Donor Leukocytes (4) Probable: • Immunomodulatory effects • Cancer recurrence • Postoperative infections WHAT’S NEW? • Leukoreduction of all red cells and platelet products • Europe uses it • Canada - only platelets for cost • Should eliminate CMV INDICATIONS FOR BLOOD * • Should not be dictated by single hemoglobin • Should be based on patient’s risk of inadequate oxygenation • BUT, rarely indicated Hbg > 10 gm/dl and always indicated < 6 gm/dl • Abstract not written by committee * Anesthesiology 1996;84:732 TRANSFUSION TRIGGER 1998 * What are these patient risks that should increase transfusion trigger? • patients who have a rapid HR (cannot compensate) • patients who do not increase CO appropriately (cannot compensate) • presence of vital organ dysfunction • more blood loss * Weiskopf et al. JAMA 1998;279;217-221 SHOULD POSTOPEATIVE HEMOGLOBIN BE MORE THAN 8.5gms/%? (Mayo Clinic) The incidence of post-CPB blindness from optic neuropathy is decreased. Can The Oxygen Dissociation Curve Be Shifted To The Right In Patients? * • Allosteric modification of oxygen - Hbg • 10 mm Hg shift by RSP 13 * Wahr et al: Anesth Analg 2001; 92:615-20 BLOOD GROUPS- A REVIEW • Human erythrocytes >300 antigenic determinants • Only ABO and Rh important in the majority of blood transfusions • Most severe transfusion reactions due to ABO incompatibility Alicia Gruber-Kalamas, MD, University of California San Francisco ABO INCOMPATIBILITY Donor blood antigen + Recipient antibodies (IgM) Activates Complement Intravascular Hemolysis Hemoglobinemia Hemoglobinuria DIC Profuse Bleeding Acute Circulatory Collapse Anuria DEATH Alicia Gruber-Kalamas, MD, University of California San Francisco THE Rh SYSTEM • Rh gene 3 chromosomal loci with 6 alleles • D antigen is the most common and most immunogenic • Approximately 80-85% Caucasians have D antigen • Individuals lacking this allele are called “Rh-negative” • Only develop antibodies against the D antigen after exposure (transfusion/pregnancy) Alicia Gruber-Kalamas, MD, University of California San Francisco Rh ANTIBODIES • IgG class of immunoglobulins • Lack capacity to bind complement • Elimination of red cells primarily in the spleen • Clinical symptoms mild, generally limited to fever/chills Alicia Gruber-Kalamas, MD, University of California San Francisco Rh AND THE PREGNANT WOMAN • Transplacental passage of D-positive fetal RBC’s into D-negative mother produces anti-D (IgG) • Anti-D IgG traverses the placenta and coats fetal RBC’S leading to extravascular hemolysis • Clinically manifest as hemolytic disease of the fetus and newborn- anemia, hepatosplenomegaly, hydrops fetalis, and death Alicia Gruber-Kalamas, MD, University of California San Francisco Rh PROPHYLAXIS- Rhlg • 1968 RhIg first licensed for prophylactic administration via IM route (RhoGam) • IgG anti-D derived from human plasma • Exact mechanism unknown • 20 mcg purified RhIG provides protection against 1 ml Rh-positive blood • WinRho IV preparation Alicia Gruber-Kalamas, MD, University of California San Francisco PREVENTION OF POST-TRANSFUSION Rh-ALLOIMMUNIZATION The protective effect of RhIg is dose dependent RhIg can prevent Rh immunization if: 1) Sufficient dose is administered 2) RhIg is given within 72 hours of exposure Alicia Gruber-Kalamas, MD, University of California San Francisco Succesful Prevention of Post-Transfusion Rh Alloimmunization by IV WinRho Anderson, et al A. J. Hematology 1999; 60:245 Case Report • 10 mo old D-negative female • Received 40 ml D-positive PRBC’s • Administered 1200mcg IV WinRho • At 1 year follow-up, no evidence of Anti-D Alicia Gruber-Kalamas, MD, University of California San Francisco RBC Exchange with Rh-negative Cells: An Alternative Approach Werch et al Transfusion 1993; 33:530 • 22 y/o Rh-negative woman received 10 units Rhpositive PRBC’s • RBC exchange with Rh-negative cells 12 hours postexposure in addition to RhIG • 11 months later delivered healthy, Rh-negative child; no evidence of Anti-D Alicia Gruber-Kalamas, MD, University of California San Francisco FOLLOW-UP • Blood Bank informed of the error • Calculated dose was 27,000 IU WinRho • 3000 IU IV Q8hrs x 9 doses ($$$$$$) • Pt will require follow-up at 6 months to check for presence of anti-D antibodies Alicia Gruber-Kalamas, MD, University of California San Francisco PROCEDURE AT SFGH • Blood bank alerted to activation of “911” • If pt male, 2U O-positive sent to ED; if pt female, 2U O-negative sent to ED • 6U O-positive is kept in OR at all times • O-negative must be sent from Blood Bank Alicia Gruber-Kalamas, MD, University of California San Francisco IN SUMMARY • Rh D Antigen is of huge clinical significance for young females and women of child-bearing age • If a Rh-negative women inadvertently receives Rh-positive PRBC’s, whole blood, or platelets, the appropriate calculated dose of WinRho must be administered within 72 hours of exposure Alicia Gruber-Kalamas, MD, University of California San Francisco WHAT IS CORRECT BLOOD TYPE? FFP Type O Type A Type B Type AB Type O OK No No No Type A OK OK No No Type B OK No OK No Type AB OK OK OK OK TABLE 47.5 Blood to lab 4 units PRBC (0+) in ED (0-) women Indication for immediate transfusion Yes An Algorithm for Massive Transfusion* No No Give 2 units PRBC Crystalloids + re-evaluate Crystalloids + blood by lab values Yes Give 4 units of FFP and 6 packs of platelets No Hct < 30 percent? Yes Give whole blood (preferred) or packed cells to HCT 30 No PT > transfusion threshold No PC < transfusion threshold? No Anticipated ongoing blood loss No De-activate massive transfusion protocol Indications for type O blood: • BP < 70 mm Hg • PT, PTT • get fibrinogen Indications for transfusion protocol: • BP < 90 mmHg after 2 PRBC • Blood loss = circulating blood volume Yes Review labs Coagulopathy present? From blood sample: • CBC including platelets • PT, PTT • Fibrinogen Yes Give platelets, 6 packs to PC 25-50, 000 Monitoring protocol: • Hct, PT, PTT, fibrinogen and platelets • Create flow sheet • EBV70-90 ml/kg Transfusions thresholds • HCT, PT, PTT • INR > 2.0 usually • INR > eye, brain, airway, 1.7 bleeding • platelets < 75,000 usually • fibrinogen < 100 mg/dl Transfuse to maintain thresholds: • Hct < 30 percent • FFP with PC ratio of 1:1 • Platelets with PC in ratio of 1:1 TABLE 47-6 CORRELATION BETWEEN PLATELET COUNT AND INCIDENCE OF BLEEDING Platelet Count Total No. of Patients No. of Patients With Bleeding > 100,000 21 0 75,000 - 100,000 14 3 50,000 - 75,000 11 7 < 50,000 5 5 (Cells/mm3) Data from Miller et al 58 A New Treatment For Transfusion Induced Coagulopathy • Recombinant activated coagulation Factor VII (r FVIIa) (NovoNordisk) • Rx coagulopathic intraoperatively • Expensive • Should be viewed as “rescue” therapy until FDA is more evident LIMITATIONS OF BLOOD TRANSFUSIONS • Transmission of infectious diseases • Dependent on volunteer donors (shortage?) • Need for typing and cross-matching • Short shelf-life RECOMBINANT HEMOGLOBIN (rHb) A genetically engineered recombinant human hemoglobin which can be used as red blood cell substitute OLD HISTORIC PROBLEMS • Kidney failure • Oxygen dissociation curve WHAT ABOUT THE OXYGEN AFFINITY? ADVANTAGES OF rHb • No risk of blood-borne infection • No need to type and cross-match • Optimized oxygen delivery • No need for chemical modifications • Improved shelf-life • Economic scale-up, production, and supply UPDATE SYNTHETIC BLOOD Biopure produces a product named Hemopure. It is approved in South Africa and will be in the USA and Europe in a year. Stealth Red Cell. Polyglycol covering preventing antibodies from getting to it, but still needs ABO testing. Will lengthen halflife by many days. (or 30 days.) PREDICTION: In 15 years, human blood will not be used as a blood transfusion (at least for the purpose of delivering oxygen.)