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Many problems with transfusions are related to infection. In 1985, the chance for hepatitis was 10% and HIV 0.5%

Many problems with transfusions are related to infection. In 1985, the chance for hepatitis was 10% and HIV 0.5%. 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 8-10 HBV 1/200,000 59.

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Many problems with transfusions are related to infection. In 1985, the chance for hepatitis was 10% and HIV 0.5%

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  1. Many problems with transfusions are related to infection. In 1985, the chance for hepatitis was 10% and HIV 0.5%

  2. RISKWINDOW PERIOD (DAYS) HIV 1/800,000 22 11 HTLV I & II 1/641,000 51 Cytomegalovirus < 1.0% rapidly HCV 1/600,000 82 8-10 HBV 1/200,000 59 TABLE 47-11Percentage Risk of Transfusion-Transmitted InfectionWith a Unit of Screened Blood in the United States HIV human immunodeficiency virus type 1: HTLV human T-cell lymphotropic virus: HCV hepatitis C virus: HBV hepatitis B virus

  3. Discontinue serum alanine aminotransferase testing Hepatitis C antibody testing Antibody to hepatitis B core antigen HIV-1 HIV-2 HIV Ag (p24 antigen) HTLV I/II Serologic test for syphilis) TABLE 47-12Infectious Disease Testing For Blood Transfusions (1998) From JAMA 1995;274:1374 HIV, human immunodeficiency virus:HTLV, human T-cell lymphotropic virus

  4. IMPROVE TESTING • Molecular testing • Viral inactivation

  5. VIRUSRNA MINPOOLANTIBODY 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 TABLE 47-13Tests Used For Detecting Infectious Agents In All Units Of Blood (2004) HIV human immunodeficiency virus type 1: HTLV human T-cell lymphotropic virus: HCV hepatitis C virus: HBV hepatitis B virus

  6. HBV Hepatitis A Parvovirus 19 West Nile Virus NUCLEIC ACID TECHNOLOGY (NAT) TESTING WILL BE USED ON:

  7. DISEASERISK 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 TABLE 47-14INFECTIOUS DISEASES (2004) - NO TEST

  8. 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% *DONATED BLOOD WILL BE BANNEDFROM DONORS WHO: * American Red Cross

  9. 2 to 3 cases/year for 40 years Since 1982, all cases were from emigrants or residents from endemic areas MALARIA

  10. 4,000 cases of which 21 are transmitted by transfusion* In 2002, 23 cases** 43% were immunocompromised 8% were > 70 years WEST NILE VIRUS Science 2003; 299:1824 ** N Engl J Med 2003; 349:1236

  11. 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 TABLE 47-8TRANSFUSION FATALITIES (2001-2002) IN THE UNITED STATES*

  12. 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

  13. 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 PLATELET INDUCED SEPSIS

  14. RULE If a patient has a fever within 6 hours after receiving platelets, then it is platelet induced sepsis until proven otherwise.

  15. Prior to culture, risk was: RBC 1/300,000 Platelets 1/25,000 BACTERIAL CULTURE

  16. Hemolytic transfusion reaction ++ Sepsis ++ Anaphylaxis TRALI +/- Isolated WHAT IS THE DIFFERENTIAL DIAGNOSIS WHEN HYPOTENSION OCCURS DURING BLOOD ADMINSTRATION? ++ = Body temperature

  17. Should all blood (packed red cells) have the white blood cells removed?

  18. Definitive: Nonhemolytic febrile transfusion reactions Transmission of leukocyte-associated viruses Cytomegalovirus (CMV), Epstein-Barr virus (EBV), HTLV-1 Alloimmunization Table 1A: Adverse Effects Associated with Donor Leukocytes (4)

  19. Probable: Immunomodulatory effects Cancer recurrence Postoperative infections Table 1B: Adverse Effects Associated with Donor Leukocytes (4)

  20. Leukoreduction of all red cells and platelet products Europe uses it Canada - only platelets for cost Should eliminate CMV WHAT’S NEW?

  21. 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

  22. 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

  23. The incidence of post-CPB blindness from optic neuropathy is decreased. SHOULD POSTOPEATIVE HEMOGLOBIN BE MORE THAN 8.5gms/%? (Mayo Clinic)

  24. Allosteric modification of oxygen - Hbg 10 mm Hg shift by RSP 13 Can The Oxygen Dissociation Curve Be Shifted To The Right In Patients? * * Wahr et al: Anesth Analg 2001; 92:615-20

  25. Human erythrocytes >300 antigenic determinants Only ABO and Rh important in the majority of blood transfusions Most severe transfusion reactions due to ABO incompatibility BLOOD GROUPS- A REVIEW Alicia Gruber-Kalamas, MD, University of California San Francisco

  26. ABO INCOMPATIBILITY Alicia Gruber-Kalamas, MD, University of California San Francisco

  27. 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) THE Rh SYSTEM Alicia Gruber-Kalamas, MD, University of California San Francisco

  28. 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 Rh ANTIBODIES Alicia Gruber-Kalamas, MD, University of California San Francisco

  29. 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 Rh AND THE PREGNANT WOMAN Alicia Gruber-Kalamas, MD, University of California San Francisco

  30. 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 Rh PROPHYLAXIS- Rhlg Alicia Gruber-Kalamas, MD, University of California San Francisco

  31. 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 PREVENTION OF POST-TRANSFUSION Rh-ALLOIMMUNIZATION Alicia Gruber-Kalamas, MD, University of California San Francisco

  32. 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 Succesful Prevention of Post-Transfusion Rh Alloimmunization by IV WinRho Alicia Gruber-Kalamas, MD, University of California San Francisco

  33. Werch et al Transfusion 1993; 33:530 22 y/o Rh-negative woman received 10 units Rh-positive PRBC’s RBC exchange with Rh-negative cells 12 hours post-exposure in addition to RhIG 11 months later delivered healthy, Rh-negative child; no evidence of Anti-D RBC Exchange with Rh-negative Cells: An Alternative Approach Alicia Gruber-Kalamas, MD, University of California San Francisco

  34. 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 FOLLOW-UP Alicia Gruber-Kalamas, MD, University of California San Francisco

  35. 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 PROCEDURE AT SFGH Alicia Gruber-Kalamas, MD, University of California San Francisco

  36. 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 IN SUMMARY Alicia Gruber-Kalamas, MD, University of California San Francisco

  37. WHAT IS CORRECT BLOOD TYPE? FFP Type O Type A Type B Type AB Type O OK NoNoNo Type A OK OK NoNo Type B OK No OK No Type AB OK OK OK OK

  38. TABLE 47.5 An Algorithm for Massive Transfusion* From blood sample: • CBC including platelets • PT, PTT • Fibrinogen Blood to lab 4 units PRBC (0+) in ED (0-) women Indication for immediate transfusion No Crystalloids + re-evaluate Indications for type O blood: • BP < 70 mm Hg • PT, PTT • get fibrinogen Yes Crystalloids + blood by lab values No Give 2 units PRBC Indications for transfusion protocol: • BP < 90 mmHg after 2 PRBC • Blood loss = circulating blood volume Yes Review labs Coagulopathy present? Yes Give 4 units of FFP and 6 packs of platelets No Monitoring protocol: • Hct, PT, PTT, fibrinogen and platelets • Create flow sheet • EBV70-90 ml/kg Hct < 30 percent? Yes Give whole blood (preferred) or packed cells to HCT 30 No PT > transfusion threshold Transfusions thresholds • HCT, PT, PTT • INR > 2.0 usually • INR > eye, brain, airway, 1.7 bleeding • platelets < 75,000 usually • fibrinogen < 100 mg/dl No Give platelets, 6 packs to PC 25-50, 000 PC < transfusion threshold? Yes No Anticipated ongoing blood loss Transfuse to maintain thresholds: • Hct < 30 percent • FFP with PC ratio of 1:1 • Platelets with PC in ratio of 1:1 No De-activate massive transfusion protocol

  39. Platelet Count Total No. No. of Patients > 100,000 21 0 75,000 - 100,000 14 3 50,000 - 75,000 11 7 < 50,000 5 5 TABLE 47-6CORRELATION BETWEEN PLATELET COUNTAND INCIDENCE OF BLEEDING (Cells/mm3) of Patients With Bleeding 58 Data from Miller et al

  40. Recombinant activated coagulation Factor VII (r FVIIa) (NovoNordisk) Rx coagulopathic intraoperatively Expensive Should be viewed as “rescue” therapy until FDA is more evident A New Treatment For Transfusion Induced Coagulopathy

  41. Transmission of infectious diseases Dependent on volunteer donors (shortage?) Need for typing and cross-matching Short shelf-life LIMITATIONS OF BLOOD TRANSFUSIONS

  42. A genetically engineered recombinant human hemoglobin which can be used as red blood cell substitute RECOMBINANT HEMOGLOBIN (rHb)

  43. OLD HISTORIC PROBLEMS • Kidney failure • Oxygen dissociation curve

  44. WHAT ABOUT THE OXYGEN AFFINITY?

  45. 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 ADVANTAGES OF rHb

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