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BLOOD COMPONENT THERAPY

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  1. BLOOD COMPONENT THERAPY 2002 EVAN G. PIVALIZZA, FFA Department of Anesthesiology University of Texas at Houston

  2. A. BLOOD PRODUCTS • 22 x 106 components p.a. • 50-70 % peri-operatively • 18-57% inappropriate (NIH reviews in 80’s)

  3. Blood preservation and storage • 75 % RBC’s in circulation @ 24 hrs • Within 4 hrs, WB separated • WB: 63 ml preservative (HCT 36-40%) • CPD- A (citrate, phosphate, dextrose, adenine) shelf-life 35 days @ 1-60 C • PRBC: (HCT 60%) • CPD-A • ADSOL (adenine, dextrose, saline, mannitol) shelf-life 42 days

  4. Deglycerolized blood • Frozen with glycerol for storage, washed before transfusion (years) • Leucocyte depleted blood (see later) • Washed (IgA deficiency)

  5. DO2 / VO2 • DO2 = CO x [(Hb x SaO2 x 1.34) + PaO2 x 0.003] • Flow  pressure, 1/R4, viscosity • Balance hematocrit/ viscosity + 30%

  6. Compensations chronic anemia •  viscosity =  flow, venous return, SV •  O2 extraction except cardiac and cerebral circulation • O2 DC shifted to right • DO2 adequate to Hct 18-25%

  7. Indications for PRBC transfusion • ONLY: Increase O2 carrying capacity • Use of single ‘trigger’ transfusion inappropriate • TRICC: ? more conservative trigger in ICU (7-9 vs 10-12) • NOT apply to > 55, bleeding, cardiac surgery • Determination transfusion based patient risks for complication of inadequate DO2 • 10 ml/kg  Hct 10 %

  8. Indications for FFP transfusion • 2 million units p.a. • 200-260 ml: procoagulants (1U/ml) and fibrinogen (3-4 mg/ml) • Urgent reversal of coumadin therapy (5-8 ml/ kg) • Correction of known coagulation factor deficiencies (no concentrates available) to + 30% (10-15 ml/ kg) • Microvascular bleeding with PT/ PTT > 1.5 normal

  9. Massive BT with microvascular bleeding • >1 BV/ 24 hours • > 50 % BV within 3 hrs • > 150 ml/min • Plasmapheresis for TTP • AT-III deficiency • Succinylcholine apnea

  10. S.D plasma • Pooled plasma, Rx solvent and detergent • Virus inactivated,  bacteria, WBCs • Consistent coagulation factors (1 U  2-3%) BUT: • Cost • ? Transmission unknown particles

  11. Indications for cryoprecipitate transfusion • 10 ml: fibrinogen (150-250 mg), VIII (80-145 U), fibronectin, XIII • 1U/ 10kg  fibrinogen 50 mg/dL (usually a 6- pack)

  12. Hypofibrinogenemia (congenital or acquired) • Microvascular bleeding with massive BT (fibrinogen < 80-100mg/dL) • 2 BVs = < 100 mg/dL • Bleeding patients with vWD (or unresponsive to DDAVP)

  13. Indications for platelet transfusion • 7 million units p.a. • 50 ml: 0.5- 0.6 x 10 9 platelets (some RBC’s and WBC’s) • Single donor apheresis OR • Random donor (x 6)

  14. Decreased production • Prophylactic for surgical patient with platelets < 50,000 • Microvascular bleeding in surgical patient with platelets < 50,000 • Neuro/ ocular surgery > 75,000

  15. Massive transfusion with microvascular bleeding with platelets < 100,000 • 2 BVs = 50,000 • Qualitative dysfunction with microvascular bleeding (may be > 100,000) • Assessment of platelet function (TEG, Sonoclot) in O.R.

  16. B. TRANSFUSION REACTIONS • RBC’s • Nonhemolytic • 1-5 % transfusions: fever, chills, urticaria • Slow transfusion, diphenhydramine • Hemolytic • Immediate: ABO incompatibility (1/ 12-33,000) with fatality (1/ 500-800,000) • Majority are group O patients receiving type A, B or AB blood

  17. Anesthesiologist major trauma hospital: • Transmit HIV once / 1,000 years • Hep C 200 • Hep B 100 • Administer incorrect blood 30 • UK: 1996-99 – 97 life-threatening ABO incompatible transfusions

  18. Complement activation, RBC lysis, free Hb (+ direct Coombs Ab test) • Anesthesia: hypotension, urticaria, abnormal bleeding • Stop infusion, blood and urine to blood bank, coagulation screen (urine/plasma Hb, haptoglobin) • Fluid therapy and osmotic diuresis • Alkalinization of urine (increase solubility of Hb degradation products)

  19. Delayed: (extravascular immune) • 1/ 5-10,000 • Hemolysis 1-2 weeks after transfusion (reappearance of Ab against donor Ag from previous exposure) • Fever, anemia, jaundice • Alloimmunization • Recipient produces Ab’s against RBC membrane Ag • Related to future delayed hemolytic reactions and difficulty crossmatching

  20. WBC’s • Europe: All products leukodepleted • USA: Initial FDA recommendation now reversed pending objective data (NOT  length of stay for  expense) • Febrile reactions • Recipient Ab reacts with donor Ag, stimulates pyrogens (1-2 % transfusions) • 20 - 30% of platelet transfusions • Slow transfusion, antipyretic, meperidine for shivering

  21. TRALI (Transfusion related acute lung injury) • Donor Ab reacts with recipient Ag (1/ 10,000 but causes 15 % of mortality due to BT) • Noncardiogenic pulmonary edema • Supportive therapy • ? relation to multiparous donors (> 4 pregnancies)

  22. GVHD • Rare: immunocompromised patients • Suggestion that more common with designated donors • BMT, LBW neonates, Hodgkin's disease, exchange Tx in neonates

  23. Platelets Alloimmunization • 50 % of repeated platelet transfusions • Ab-dependent elimination of platelets with lack of response • Use single donor apheresis • Post-transfusion purpura • Recipient Ab leads to sudden destruction of platelets 1-2 weeks after transfusion (sudden onset)

  24. Immunomodulatory effects of transfusion • Wound infection: circumstantial evidence (? leukocyte filters for immunocompromised) • Beneficial effects on renal graft survival (now < NB with CyA) • 97: 9% graft survival advantage after 5 years • Nonspecific overload of RES •  lymphocytes, APCs • Modification T helper/suppressor ratio • Allogeneic lymphocytes may circulate for years after transfusion

  25. Cancer recurrence (mostly retrospective) • Colon: 90 % studies suggest increased recurrence • Breast: 70 % studies • Head and neck: 75 % studies • “Allogeneic blood products increase cancer recurrence after potentially curative surgical resection” - Landers • Evidence circumstantial NOT causal

  26. However, 2 recent prospective, randomized studies: no effect on tumor related morbidity/mortality, but poorer outcomes • Conservative trigger (< 3 units) • Clinical judgment to weigh risk-benefit ratio

  27. C. INFECTIOUS COMPLICATIONS I. Viral (Hepatitis 88% of per unit viral risk) • Hepatitis B • Risk 1/ 200,000 due to HBsAg, antiHBc screening (7-17 % of PTH) • Per unit risk 1/63-66,000 • 0.002% residual HBV remains in ‘negative’ donors (window 2-16 weeks) • Anti-HBc testing retained as surrogate marker for HIV

  28. NANB and Hepatitis C • Risk now 1/ 103,000 (NEJM 96) with 2nd/ 1/ 125,000 with 3rd generation HCV Ab/ HVC RNA tests • Window 4 weeks • 70 % patients become chronic carriers, 10-20 % develop cirrhosis

  29. HIV • 29 cases -transfusion recipients  93 • 7,800 by 12/ 95 • Current risk 1/ 450- 660,000 (95) • With current screening (Abs to HIV I, II and p24 Ag), window 6-8 weeks (third generation ELISA tests in Europe) •  sero -ve window to < 16 days

  30. HTLV I, II • Only in cellular components (not FFP, cryo) • Risk 1/ 641,000 (window period unknown) • Screening for antibody I may not pick up II

  31. CMV • Cellular components only • Problem in immunocompromised, although 80 % adults have serum Ab • WBC filtration decreases risk of transmission • CMV -ve blood: • CMV -ve pregnant patients, LBW neonates, CMV -ve transplant recipient, • CMV-ve/ HIV +ve

  32. CJD (and variant CJD) • BB implementing donor deferrals • 1980-96: • > 3 months UK • TF in UK • > 5 years in France

  33. II. Bacterial • Contamination unlikely in products stored for > 72 hours at 1-6 0 C (10 cases Yersinia) • Platelets stored at room temperature for 5 days, with infection rate of 0.25% • III. Protozoal • Trypanosoma cruzi (Chaga’s disease)

  34. D. METABOLIC COMPLICATIONS • Citrate toxicity • Citrate (3G/ unit WB) binds Ca2+ /Mg+ • Metabolized liver, mobilization bone stores • Hypocalcemia ONLY if > 1 unit/ 5 min or hepatic dysfunction • Hypotension more likely due to  cardiac output/ perfusion than  calcium (except neonates) • Worse with hypothermia/ hepatic dysfunction

  35. Hyperkalemia • After 3 weeks, K+ is 25- 30 mmol/l • Only 8- 15 mmol per unit PRBC/ WB • Concern with > 1 unit/5 min @ infants

  36. Acidosis • Acid load after after 3 weeks 30-40 mmol/l (pH 6.6 - 6.9) • Metabolic acidosis more likely due to decreased perfusion, hepatic impairment, hypothermia • NaHCO3 or THAM if base deficit > 7-10 mEq/l

  37. 2, 3 DPG • Depleted within 96 hours of storage • O2 Hb DC to left • Restored within 8- 24 hours of transfusion

  38. E. REFERENCES • Practice Guidelines for Blood Component Therapy (ASA Task Force). Anesthesiology 1996; 84: 732-47. • Safety of the Blood Supply. JAMA 1995; 274:1368--73. • Infectious Disease Testing for Blood Transfusions (NIH Consensus Conference). JAMA 1995; 274: 1374-9.

  39. Blood Transfusion- Induced Immunomodulation. Anesth Analg 1996; 82: 187-204 • ASA Questions and Answers about Transfusion Practices (3rd ed., 1997) • Immunomodulatory aspects of transfusion. Anesthesiology 1999; 91: 861-5.

  40. “Blood is still the best possible thing to have in our veins” - Woody Allen • “Blood transfusion is a lot like marriage. It should not be entered upon lightly, unadvisedly or wantonly, or more often than is absolutely necessary” - Beal