transfusion medicine in emergency medicine scott koepsell m.d., ph.d. march 7, 2015 i have no...

Transfusion Medicine in Emergency MedicineScott Koepsell M.D., Ph.D.

March 7, 2015

I have no conflicts of interest to disclose

Agenda

• Transfusion history/components

• Trauma/hemorrhage versus anemic patients

• Evidence based recommendations

• Questions/Discussion

Blood Bank History

• 1936 Chicago’s Cook County Hospital

• 1941 Irwin Memorial Blood Bank, SF

• WWII – Returning surgeons demanded blood– Initially whole blood in glass bottles, but also

lyophilized plasma as well

• 1970s – component blood products

Blood Components

Plasma can be manufactured into cryo

Blood Components: RBCs

• Uncrossmatched RBCs, Group O– 0.4% chance of acute hemolytic reaction– 2.6% chance of delayed hemolytic reaction

• O-positive for males and woman >50 usually ok

AJCP 2010;134:202-206

Blood Components

• Plasma – AB or A– Group A plasma usually has low anti-B– Only about 10% of population is Group B or AB– Group A plasma is likely safe for all adult

patients

• Platelets or cryoprecipitate – Any typeJ Trauma Acute Care Surg 2012; 74:69-75

Blood Components

• What product to give to which patients?

– Trauma with bleeding– Non-trauma with bleeding– Anemia

Severely Injured or Trauma Patients

• Warm Fresh Whole Blood (WFWB) has been shown to increase survival with combat-related injuries

• Not really available in USA, but early administration of plasma in trauma likely lowers mortality

J Trauma 2009:6(S4):S69-76

Reviewed in Hematology 2013: 656-659

Severely Injured or Trauma Patients

• Many hospitals have adopted a massive transfusion policy that includes plasma and platelets– Subject to logistics and cost

• PROPPR trial showed 1:1:1 resuscitation or 1:1:2 had equivalent mortality at 24 hours and at 30 days

JAMA 2015: 313(5):471-482

Non-trauma bleeding patient

• 48 yo male presents to ED with coffee-ground emesis– PMH: EtOH abuse, cirrhosis– Vitals: T 37.5 P 105 R 18 BP 110/70– PE: spider angiomata, ascites– Lab: INR 1.7, Na 130, Hgb 7.5


• NG tube placed: blood-tinged fluid returned (~20 mL)

• GI consulted and on their way

• Would you transfuse this patient (Hgb 7.5 g/dL)?

Evidence Based Transfusion Medicine

• Prospective, randomized trial of 921 patients with severe acute upper GI bleeding– 461 Restrictive (<7 g/dL)– 460 Liberal (<9 g/dL)

NEJM 2013; 368: 11-21


NEJM 2013; 368: 11-21


NEJM 2013; 368: 11-21

• Major complication in the liberally transfused was further bleeding– 45/444 vs 71/445, p=0.01

• Hepatic hemodynamic studies showed an increased portal pressure in the transfused group


• Not a lot of data exists, and clinical judgment that integrates laboratory and physical exam findings is key

• In some cases (stable upper GI bleeding), transfusion may be harmful

• Questions or comments?

Non-trauma patients

• In 1942 Dr. John Lundy • “When the concentration of hemoglobin is less

than 8 to 10 grams per 100 cubic centimeters of whole blood, it is wise to give a blood transfusion…”

• No data given for basis of recommendation

Blood transfusion dogma

• If < 10 g/dL then give 2 units– 2 Unit dose of RBCs

• Based off hospital utilization guidelines in the mid-20th century

• Donating 1 units seems benign, so how could 1 unit transfusion help?

• If you are going to transfuse, then transfuse!!

– Perpetuated in medical education for years– Empiric

Anemia, Case 1

• 68 year-old male presents to ED for SOB– PMH: COPD, HTN, DM, CKD, EtOH abuse

– Vitals: T 38.1 P 98 BP 150/80 R 20 O2 89% NC

– PE: In mild distress, decreased R breath sounds & wheezing, clubbing, dry mucous membranes

– Labs: WBC 13K, Hgb 9.0 g/dL, Cr 1.6

– Imaging: RLL consolidation

Case 1

• While waiting for the patient to be admitted, would you transfuse this patient with RBCs at this point (Hgb 9.0 g/dL)?

• Would you transfuse this patient with RBCs if the Hgb 7.9 g/dL?

• Would you transfuse this patient with RBCs if the Hgb 7.0 g/dL?


• Prospectively randomized 838 ICU patients– Restrictive transfusion: <7.0 g/dL

• Average Hgb 8.5 +/- 0.7 g/dL• 2.6 +/- 4.1 RBC units transfused

– Liberal transfusion: <10.0 g/dL• Average Hgb 10.7 +/- 0.7 g/dL• 5.6 +/- 5.3 RBC units transfused

NEJM: TRICC Trial


• Cochrane Reviews (2012)– 19 trials involving 6264 patients

• Restrictive transfusion (7-8 g/dL)– Reduces risk of blood transfusion 39%– Reduces in hospital mortality (RR 0.77)– No impact on adverse events (mortality, cardiac events,

myocardial infarction, stroke, pneumonia, thromboembolism)


• 18 randomized trials involving 7593 patients– Restrictive transfusion (7-8 g/dL)

• Reduces risk of health care-associated infections (RR 0.82) with NNT 38

– Restrictive transfusion (<7 g/dL)• Reduces risk of health care-associated infections (RR 0.80)

with NNT: 20

– Most pronounced in patients presenting with sepsis

JAMA 2014; 311:1317-1326

Anemia, Case 1


Anemia, Case 2• 72 yo female presents to ED for SOB, fatigue,

weight gain– PMH: CHF, CAD, HTN, CKD, anemia of chronic

disease– Vitals: T 37.1 P 80 R 18 BP 135/75 O2 94%– PE: S3, pitting edema, crackles– Labs: Heart failure peptide 800 pg/mL, Hgb 7.2– Imaging: CXR: Cardiomegaly, Kerley lines in lungs

Anemia, Case 2

• While waiting for admission for diuresis/treatment of CHF would you transfuse for Hgb of 7.2 g/dL?


• CCM 2001; 29: 227-234

TRICC subset analysis of patients with pre-existing heart disease


• AABB– Adhere to a restrictive transfusion strategy (7-

8 g/dL) for hospitalized, stable patients– For stable patients with pre-existing

cardiovascular disease, 8 g/dL

– Transfuse slowly in patients with fluid overload

Ann Intern Med 2012;157:49-58

Anemia, Case 2


Anemia, Case 3

• 61 yo male presents to ED with chest pain– PMH: HTN, CKD, DM, anemia of chronic

disease– Vitals: T 37.5 P 95 R 18 BP 110/70– PE: diaphoretic– Lab: elevated troponin, Cr 2.9, Hgb 8.2– ECG: no ST-segment elevation noted

Anemia, Case 3

• 61 yo male with acute MI

– Would you transfuse this patient (Hgb 8.2)?

– If so, 1 or 2 units?


JAMA 2013;173(2):132-139

• Meta analysis of 10 studies– “blood transfusion was associated with a

higher risk for mortality independent of baseline hemoglobin level, nadir hemoglobin level, and change in hemoglobin level during the hospital stay. Blood transfusion was also significantly associated with a higher risk for subsequent myocardial infarction (risk ratio, 2.04; 95% CI, 1.06-3.93; P=.03)”


Am J Cardiol 2011; 108:1108-1111

• CRIT Trial– 45 patients with acute MI and hemoglobin <10

g/dL on admission prospectively randomized• Transfuse at hgb <10 (liberal)• Transfuse at hgb <8 (restrictive)

Am J Cardiol 2011; 108:1108-1111

Anemia, Case 3

• No definite guidelines exist in the setting of ACS

• Volume status is likely an important variable


Risk versus Benefit of RBC transfusion

• Blood transfusions carry more risk than previously appreciated– Not transfusion-transmitted infections

• i.e. risk of TT-Hepatitis B is 1:282,000 transfusions

– Not well understood• Why more end-organ failure and in hospital mortality

with increasing transfusions?• Why more infections?

• Storage lesion of RBCs in bag may be the reason– 42-day shelf life means increases in:

• Free iron (supports microbial growth)• Free hemoglobin (vasoconstricts)• Lipid microparticles (thrombogenic)• No 2,3-DPG (requires 24 hours for equilibration)• Damaged RBCs (overwhelms reticuloendothelial

system)• Less deformable RBCs (cannot flow through

microvasculature)

Transfusion Threshold

• 7 – 8 grams/dL represents a balance– Benefit: increased oxygen carrying capacity

for tissues– Risk: increased complications (infection, fluid

overload, etc)

Risk versus Benefit of RBC transfusion• Bottom line

– Restrictive transfusion thresholds (7-8 g/dL) improve non-trauma patient outcomes (even ICU patients, or upper GI bleed, or CAD)

– Many hospitals have implemented restrictive transfusion policies for years without deleterious effects

– Any transfusion for a hemoglobin > 8 g/dL ought to have evidence-based rationalization documented in the medical chart The appropriate dose is almost always 1 unit unless bleeding

Change is coming…

Discussion?

Ebola virus disease

• Categories of patients– Patient with febrile illness

• Patients under investigation for EVD• Unknown or unsuspected EVD

– Patient without illness but high level risk– Patient with confirmed EVD

• In all cases, history (travel/contact) is important in risk stratification

Ebola virus disease

• Healthcare works encounter highly-infectious fluids (blood, urine etc) from patients with EVD– Remain highly infectious for weeks

• J Appl Microbiol. 109(5): 1531-9

– Viral loads reported to be up to 108 per ml– Infectious dose as few as 1 to 10 virions

• JAMA 1997: 278,(5),399-411

Ebola virus disease

• CDC guidance on PPE (recently updated to increase protection)

• Treatment largely remains supportive (electrolyte replacement, IV hydration)– Experimental therapies

• Convalescent plasma• Antivirals• ZMapp

Ebola virus disease - CP

Ebola virus disease - CP

• Currently, Phase I safety trial of passive immune therapy during acute EVD– Clinicaltrials.gov NCT02295501

• Online Ebola information (PPE, education etc)• http://www.nebraskamed.com/biocontainment-

unit/ebola

transfusion medicine in emergency medicine scott koepsell m.d., ph.d. march 7, 2015 i have no...

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