Transfusion Therapy:Optimal Use of Blood

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Jennifer Jou M.D.

September 2, 2011

Objectives

Review risks/benefits of RBC, platelet, and FFP transfusion

Re-examine our strategies to optimize transfusion for each of these components relative to patient population

Case

49 y.o., 5'4", 95kg female presents for Posterior Fusion of C5- C7. Her past medical history is significant for HTN and smoking (1/4ppd x 30 yrs). Her medications are Metoprolol, Percocet prn, and occasional Advil prn. Her vital signs are normal.

The patient is intubated and positioned uneventfully. During dissection, the Orthopedic surgeon states that the patient is oozy and bleeding and asks to have blood and platelets hung. What do you do?

Lab Values

H/H= 11/33Plts= 101kINR= 1.2Chemistry: Cr = 1.3 o/w WNLEKG: NSR with flipped T's in lateral leads

CXR: hyperinflation

State of Blood Utilization in the U.S. American Association of Blood Bankers 2009

Nationwide Blood collection and Utilization Survey Report Total number of transfusions unchanged Decreased autologous blood collection and

transfusion Increased allogeneic transfusion Increased use of leukocyte reduced blood by 20% Increase in cost of each unit of leukocyte

reduced blood (approx 5.5%, $223) mean age of RBC at time of transfusion 18.2 days

Variation in Transfusion PracticeDespite availability of guidelines, variation persists

Not explained by patient or surgical variables, rather by differences in provider and institutional preferences.

A “best practice” is yet to be identified

Surgenor et al. Determinants of red cell, platelet, plasma and cryoprecipitate transfusions during coronary artery bypass graft surgery: the Collaborative Hospital Transfusion Study. Transfusion 1996;36:521-32.

Guidelines Overview

National Institute of Health, American College of Physicians, Blood Management Practice Guidelines Conference, American Society of Anesthesiologists, Society of Cardiovascular Anesthesiologists...etc.

Old “10/30,” Adams and Lundy, 1942 Strict guidelines relatively ineffective in reducing unwarranted

transfusions One prescribed trigger is not appropriate for all patients and

clinical scenarios (ie: there is no consistent physiologic deterioration seen in all patients at a specific H/H level)

An overall understanding of benefits and risks of transfusion specific to the patient should be used to guide decision making.

Adams RC, Lundy JS. Anesthesia in cases of poor risk. Some suggestions for decreasing risk. Surg Gynecol Obstet 1942;74:1011-101

RBC Transfusions

1. Risks of Anemia

2. Benefits of RBC Transfusion

3. Risks of RBC Transfusion

Risks of Anemia

Mortality is related more to blood loss than low preoperative hematocrit.

Acute Normovolemic Hemodilutional Anemia in Healthy Patients has historically been well tolerated.

Hemodilutional Anemia during CPB is less tolerated

Carson JL et al. Severity of anemia and operative mortality and morbidity. Lancet 1988;1:727-729

Benefits of Transfusion

1. Critically Ill without active bleeding (with and without cardiovascular disease)

2. Patients with Acute Coronary Syndromes (AMI and unstable angina)

3. Patients with sepsis or septic shock

Benefits of Transfusion TRICC Trial: Transfusion in critically ill patients

without active bleeding11

Restrictive strategy (Hgb 7-9g/dL) vs Liberal strategy (10-12g/dL)

Population: Euvolemic patients not actively bleeding Exclusion: Chronic anemia following cardiac surgery,

significant CAD Endpoint: 30 day survival Result: Restrictive strategy at least as effective

and possible superior to liberal strategy. Improved 30 day survival in patients younger than 55 yrs old or those with APACHE II scores less than 20 managed with restrictive strategy.

Hebert PC et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med 1999;340:409-417

Benefits of Transfusion

TRICC subgroup: Patients with Cardiovascular Disease 357 pts with cardiovascular disease no difference in mortality rates comparing restrictive vs. liberal strategy

Decreased Survival in restrictive group in setting of ACS (AMI or unstable angina)

Studies specifically looking at ACS/AMI patients

Wu et al. Improved survival in patients with AMI and HCT<30 who received transfusion

Yang et al. Increased risk of death or reinfarction in ACS patients who received transfusion

Rao et al. Association of increased 30 day mortality and transfusion in patients with ACS (significant for nadir Hct as low as 25%)

All 3 studies were retrospective in nature. Need for prospective analysis.

Wu et al. Blood Transfusion in elderly patients with acute myocardial infarction. NEJM 2001; 345: 1230-6

Yang X et al. The implication of blood transfusions for patients with non-ST elevation acute coronary syndromes. JACC 2005; 46: 1490-5.

Rao SV et al. Relationship of Blood Transfusion and clinical Outcomes in Patients with Acute coronary Syndromes. JAMA 2004; 292:1555-62

Transfusion during Sepsis or Septic Shock Rivers et al.

randomized, standard resuscitation vs goal-directed protocol.

RBC transfusions performed in goal-directed protocol to maintain Central Venous Oxygen >70%.

Improved mortality with goal directed therapy in hospital, at day 28 and day 60.

**Multiple other interventions were used as part of the goal directed therapy so not possible to discern the true effect of transfusion on survival benefit.

Rivers et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. NEJM 2001; 345:1368-77

Risks of RBC Transfusion

Transmission of Infectious Disease

Negative effects on immune system

TRALI/ARDS

Risk of Transmission

Viral: Well known: HBV, HCV, HIV, HTLVEmerging: Chagas, West Nile, Malaria, Creutzfeldt-Jakob disease

Screening tests contribute to rising cost of transfusion

Immune System Effects

Postoperative Infection Taylor et al: 10% increase in nosocomial infection with each unit of transfused RBC19

Chemeler et al: similar results of increased nosocomial infection in patients undergoing CABG.

Taylor RW et al. Red blood cell transfusions and nosocomial infections in critically ill patients. Crit Care Med 2006; 34:2302-08

Chemeler SB et al. Association of bacterial infection and RBC transfusion after coronary bypass surgery. Ann Thor Surg 2002; 73: 138-42.

Immune System Effects

Immunomodulation Moore et al: dose response relationship between early

transfusion and development of multi organ failure in trauma patients

Fransen et al: Increased concentrations of inflammatory mediators after intra-op allogeneic blood transfusion Prospective Study LBP*, BPI*, IL-6

Moore FA et al. Blood transfusion: An independent risk factor for post-injury multiple organ failure. Arch Surg 1997; 132:620-25

Fransen E et al. Impact of blood transfusions on Inflammatory Mediator Release in patients undergoing cardiac surgery. Chest 1999;116:1233-1239.

Immune System Effects

Mechanism? Possible mediation by allogeneic white blood cells (donor leukocytes) directly impacting recipient’s immune function or causing release of mediators of immunomodulation into the stored RBC unit)

Vamvakas EC. White blood cell containing allogeneic blood transfusion and postoperative infection or mortality: an updated meta-analysis. Vox Sang 2007; 92:224-32

ARDS/TRALI

ARDS: Defined clinically as dyspnea, bilateral pulmonary infiltrates, hypoxemia, non-cardiogenic edema

TRALI: Non-specific constellation of dyspnea, hypotension, non-cardiogenic edema, and fever.

**Importance of differentiation: Low mortality in TRALI in contrast to ARDS

Donor anti-leukocyte antibodies react with WBCs of recipient

Curtis BR et al. Mechanisms of transfusion related acute lung injury; anti leukocyte antibodies. Crit Care Med 2006;34: s118-23.

Other Factors Influencing Risk/BenefitLeukocyte Reduction

Hypothesized to be capable of reducing the aforementioned morbidity/mortality

Both randomized controlled and meta-analyses have failed to justify a universal adoption of leukocyte reduced transfusion except perhaps for the cardiac surgery population.

Costly: $223 per unit

Gong MN et al. Clinical predictors of and mortality in acute respiratory distress syndrome; the potential role of red blood cell transfusion. Crit Care Med 2005; 33: 1191-8.

Other Factors Influencing Risk/Benefit

Storage Lesionpredictable changes to RBCs during storage

loss of biconcave shape renders the cells less deformable and more adherent to endothelium

depletion of ATP and 2,3-DPG

Platelet Transfusions

collection methodsTransmission of Bacterial InfectionTRALIFebrile ReactionsCirculatory OverloadPlatelet use in CABG Surgery PatientsLimited Data (majority relevant to chemotherapy induced thrombocytopenia)

Platelet Transfusion

Collection Room Temp and Constant Motion = Shorter Shelf Life (typically 5 days)

Semi Permeable Plastic

Platelet Transfusion

Bacterial Contamination1:2,000 to 1:3,000donor bacteremia, collection bag contamination, contamination during processing, room temperature storage

Schrezenneier et al. Bacterial contamination of platelet concentrates: results of a prospective multicenter study comparing pooled whole blood-derived platelets and apheresis platelets. Transfusion 2007;47:644-52

Platelet Transfusion

Other RisksTRALIFebrile ReactionsTransfusion Associated Circulatory Overload (dyspnea, orthopnea, peripheral edema, rapid increase in blood pressure)

Platelet Transfusion

CABG Patients (adjusted for patient and disease characteristics) Increased risk of

stroke inotrope requirement pulmonary dysfunction death

Spiess BD et al. Platelet transfusion during coronary artery bypass surgery are associated with serious adverse outcomes. Transfusion 2004; 44: 1143-8.

Platelet Transfusion

Looking at the data...Majority derived from management of non-critically ill heme-onc patients

thrombocytopenia 2/2 chemotherapydifficulty extrapolating this data to the OR and ICU

Ongjen G et al. Fresh frozen plasma and platelet transfusion for non-bleeding patients in the intensive care unit. Crit Care Med 2006; 34 [suppl]: 170-3.

FFP and Cryoprecitpitate

FFP: factors plus fibrinogen Cryo: made from FFP, higher conc. of fibrinogen,

vWF, Factor VIII Administered to patients with elevated Prothrombin

(PT) or Activated Partial Thromboplastin Time (PTT) Risks of use: infection, allergic reactions,

hemolysis, circulatory volume overload, ABO incompatibility, TRALI

Serious hazards of transfusion steering committee. Serious hazards of transfusion: annual report 2004.

FFP and Cryoprecipitate

Appropriate: abnormal coagulation studies prior to procedures

associated with bleeding risks during an episode of active hemorrhage

Inappropriate: Volume expansion Prevention of spontaneous bleeding

Chin-Lee I et al. Transfusion of red blood cells under shock conditions in the rat microvasculature. Blood 2004; 104:2713A

Gajic O. et al. Fresh frozen plasma and platelet transfusion for nonbleeding patients in the intensive car unit: benefit or harm? Crit care Med 2006; 34: S170-3.

Key Points

Pre-op Risk Factor Identification organ ischemia (cardiorespiratory disease) coagulopathy (inherent or iatrogenic)

Intra and Post-op close monitoring for blood loss and inadequate perfusion

generally, transfuse Hb<6, don’t transfuse Hb>106-10...JUSTIFY

Plt transfusion rarely indicated >100 x 109/L, Usually indicated <50 x 109/L in presence of excessive bleeding

FFP if bleeding and PT >1.5 x nl or INR >2, PTT > 2 x nl Cryo if fibrinogen < 80-100mg/dl with bleeding

A look back at the case...

What changes, if any would you make to your initial transfusion strategy?

THANKS!