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BLOOD COMPONENT THERAPY 2002 EVAN G. PIVALIZZA, FFA Department of Anesthesiology University of Texas at Houston A. BLOOD PRODUCTS 22 x 10 6 components p.a. 50-70 % peri-operatively 18-57% inappropriate (NIH reviews in 80’s) Blood preservation and storage

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BLOOD COMPONENT THERAPY

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BLOOD COMPONENT THERAPY

2002

EVAN G. PIVALIZZA, FFA

Department of Anesthesiology

University of Texas at Houston


A. BLOOD PRODUCTS

  • 22 x 106 components p.a.

  • 50-70 % peri-operatively

  • 18-57% inappropriate (NIH reviews in 80’s)


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


  • Deglycerolized blood

    • Frozen with glycerol for storage, washed before transfusion (years)

  • Leucocyte depleted blood (see later)

  • Washed (IgA deficiency)


DO2 / VO2

  • DO2 = CO x [(Hb x SaO2 x 1.34) + PaO2 x 0.003]

  • Flow  pressure, 1/R4, viscosity

  • Balance hematocrit/ viscosity + 30%


  • 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%


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 %


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


  • 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


  • 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


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)


  • 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)


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)


  • Decreased production

  • Prophylactic for surgical patient with platelets < 50,000

  • Microvascular bleeding in surgical patient with platelets < 50,000

  • Neuro/ ocular surgery > 75,000


  • 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.


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


  • 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


  • 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)


  • 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


  • 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


  • 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)


  • GVHD

    • Rare: immunocompromised patients

    • Suggestion that more common with designated donors

    • BMT, LBW neonates, Hodgkin's disease, exchange Tx in neonates


  • 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)


  • 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


  • 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


  • 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


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


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


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


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


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


CJD (and variant CJD)

  • BB implementing donor deferrals

    • 1980-96:

      • > 3 months UK

      • TF in UK

      • > 5 years in France


  • 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)


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


  • 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


  • 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


  • 2, 3 DPG

  • Depleted within 96 hours of storage

  • O2 Hb DC to left

  • Restored within 8- 24 hours of transfusion


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.


  • 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.


  • “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


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