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

2. A. BLOOD PRODUCTS l 22 x 10 6 components p.a. l 50-70 % peri-operatively l 18-57% inappropriate (NIH reviews in 80’s)

3. Blood preservation and storage l 75 % RBC’s in circulation @ 24 hrs l Within 4 hrs, WB separated l WB: 63 ml preservative (HCT 36-40%) –CPD- A (citrate, phosphate, dextrose, adenine) shelf-life 35 days @ 1-6 0 C l PRBC: (HCT 60%) –CPD-A –ADSOL (adenine, dextrose, saline, mannitol) shelf-life 42 days

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

5. DO 2 / VO 2 l DO 2 = CO x [(Hb x SaO 2 x 1.34) + PaO 2 x 0.003] l Flow  pressure, 1/R 4, viscosity l Balance hematocrit/ viscosity + 30%

6. l Compensations chronic anemia –  viscosity =  flow, venous return, SV –  O 2 extraction except cardiac and cerebral circulation –O 2 DC shifted to right –DO 2 adequate to Hct 18-25%

7. Indications for PRBC transfusion l ONLY: Increase O 2 carrying capacity l Use of single ‘trigger’ transfusion inappropriate l TRICC: ? more conservative trigger in ICU (7-9 vs 10-12) –NOT apply to > 55, bleeding, cardiac surgery l Determination transfusion based patient risks for complication of inadequate DO 2 l 10 ml/kg  Hct 10 %

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

9. l Massive BT with microvascular bleeding –>1 BV/ 24 hours –> 50 % BV within 3 hrs –> 150 ml/min l Plasmapheresis for TTP l AT-III deficiency l 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 l 10 ml: fibrinogen (150-250 mg), VIII (80- 145 U), fibronectin, XIII l 1U/ 10kg  fibrinogen 50 mg/dL (usually a 6- pack)

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

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

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

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

16. B. TRANSFUSION REACTIONS l RBC’s l Nonhemolytic –1-5 % transfusions: fever, chills, urticaria –Slow transfusion, diphenhydramine l 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. l Anesthesiologist major trauma hospital: l Transmit HIV once / 1,000 years l Hep C 200 l Hep B 100 l Administer incorrect blood 30 –UK: 1996-99 – 97 life-threatening ABO incompatible transfusions

18. l 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. l WBC’s l Europe: All products leukodepleted l USA: Initial FDA recommendation now reversed pending objective data (NOT  length of stay for  expense) l 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. l 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. l GVHD –Rare: immunocompromised patients –Suggestion that more common with designated donors –BMT, LBW neonates, Hodgkin's disease, exchange Tx in neonates

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

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

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

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

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

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

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

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

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

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

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

34. D. METABOLIC COMPLICATIONS l Citrate toxicity l Citrate (3G/ unit WB) binds Ca 2+ / Mg + l Metabolized liver, mobilization bone stores l Hypocalcemia ONLY if > 1 unit/ 5 min or hepatic dysfunction l Hypotension more likely due to  cardiac output/ perfusion than  calcium (except neonates) l Worse with hypothermia/ hepatic dysfunction

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

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

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

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

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

40. l “Blood is still the best possible thing to have in our veins” - Woody Allen l “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