BLOOD COMPONENT BLOOD COMPONENT THERAPYTHERAPY

2002

EVAN G. PIVALIZZA, FFA

Department of Anesthesiology

University of Texas at Houston

A. BLOOD PRODUCTSA. BLOOD PRODUCTS

22 x 106 components p.a.

50-70 % peri-operatively

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

Blood preservation and Blood preservation and storagestorage

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)

DODO22 / VO / VO22

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 Indications for PRBC transfusiontransfusion

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 transfusionIndications 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 Indications for cryoprecipitate transfusiontransfusion

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 Indications for platelet transfusiontransfusion

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 B. TRANSFUSION REACTIONSREACTIONS

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 C. INFECTIOUS COMPLICATIONSCOMPLICATIONS

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 UKTF 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 D. METABOLIC COMPLICATIONSCOMPLICATIONS

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. REFERENCESE. 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