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Transfusion Practices with Combat Wounded. Francis (Frank) M. Chiricosta, LTC, MC Transfusion Medicine Consultant, US Army. Overview. Massive Transfusion / Coagulopathy Resuscitation change in practices Traditional Guidelines / Practices Use of plasma Use of Fresh Whole Blood Factor VIIa

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Transfusion Practices with Combat Wounded

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Transfusion Practices with Combat Wounded

Francis (Frank) M. Chiricosta, LTC, MC

Transfusion Medicine Consultant, US Army

www.milblood.mil


Overview

  • Massive Transfusion / Coagulopathy

  • Resuscitation change in practices

  • Traditional Guidelines / Practices

  • Use of plasma

  • Use of Fresh Whole Blood

  • Factor VIIa

  • Age of blood

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Hemorrhagic Mortality

  • While bleeding is the #2 cause of mortality, hemorrhage is the #1 reversible cause for mortality

  • Bleeding to death is an acute problem

  • Almost all mortality from hemorrhage occurs within 1st 24 hours

  • Early control of hemorrhage can save lives

Data adapted from: Acosta, et al. J Am Coll Surg 1998 & Sauaia, et al. J Trauma 1995

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Slide courtesy JG Perkins


Massive transfusion

  • One body volume in 24 hours

  • “Dilutional” coagulopathy

    • depleted coagulation factors

    • thrombocytopenia

    • hypoperfusion

    • confounding conditions: DIC, sepsis

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N=450 combat casualties in the Vietnam War on Admission

Hematocrit %

20 40

Heart Rate (BPM)

70 90 110 130 150

Lactate mg/100 mL

20 40 60 80 100

Base Deficit mEq/L

0 2 4 6 8 10

Pathophysiology of Trauma

  • With decreased blood pressure

    • Base deficit increased

    • Lactate Increased

    • Hematocrit Modestly Decreased

    • Heart Rate Increased

Adapted from:

Collins JA, Simmons RL, James PM, Bredenberg CE, Anderson RW, Heisterkamp CA 3rd.The acid-base status of seriously wounded combat casualties. I. Before treatment. Ann Surg. 1970 Apr;171(4):595-608.

Slide courtesy JG Perkins


Pathophysiology of Trauma

Acidosis

Coagulopathy

Hypothermia


Traditional resucitation

  • Replace lost volume first with crystalloid

  • May be able to restore normal BP

  • Blood transfusion comes later

  • Potential complications of aggressive fluid resuscitation

    • “Pop the clot”

    • Hemodilution

    • Coagulopathy

    • Hypothermia

    • Acidosis

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Damage Control Resucitation

  • Do not replace volume quickly

  • Hypovolemia / hypotension is tolerated

  • Stop bleeding

  • Correct abnormal physiology later

  • “... inaccessible or uncontrolled sources of blood loss should not be treated with intravenous fluids until the time of surgical control.” --Cannon WB, FaserJ, CollewEM: The preventive treatment of wound shock. JAMA, 47:618, 1918

1918! Not a totally new idea

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Coagulopathy of Trauma

  • Hemodilution due to resucitation… and

  • Coagulopathy that is due to the trauma itself

  • Evidence that coagulopathy starts before fluid resuscitation; not a dilutional coagulopathy

  • Molecular mechanism: thrombomodulin, protein C (Brohi, K)

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Massive Transfusion,Transfusion considerations

  • assessment: clinical and lab together

    • microvascular bleeding

    • PT/PTT > 1.5 nl, plt < 50 – 100

    • Warm patient

  • one 6-pk platelets roughly same coag. factors as U FFP

  • Plt, CRYO, FFP short/difficult supply

  • Fresh whole blood

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Massive Transfusion,Problematic transfusion management

  • Transfused plasma is foreign to recipient; has anti-A, -B; A substance, B substance

  • ABO incompatible plasma (e.g. type O rbc/WB/Plt to type A patient) may be associated with adverse outcome (Blumberg, N)

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Massive Transfusion,complications

  • Citrate toxicity

    • Hypocalcemia, prolonged QT

    • With normal liver, not generally a problem

    • Rapid infusion centrally can be a problem

    • Alkalosis with metabolism

  • Hyperkalemia?

    • Usually the opposite: with metabolic derangement, K+ goes low

    • Theoretic problem in renal failure

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Massive Transfusion,complications

  • Hypothermia (use of blood warmer)

    • PT/PTT elevation

    • Platelet dysfunction

  • Dilutional coagulopathy

  • Old blood is bad blood?

  • Transfusion reactions

    • More error prone

    • Less likely to recognize

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Packed Red Blood Cellspurpose of the transfusion

  • To increase oxygen carrying capacity in an anemic patient when it is needed

  • Need is based on clinical assessment of risk of complications of low oxygen delivery (e.g.. when cardiac oxygen demand increases to increase cardiac output)

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Traditional Guidelines

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Existing Guidelines

  • Red cell transfusion

    • Purpose: oxygen carrying

    • loss of 30%+ of blood volume

    • normovolemic, P>100, SBP<100, ssx

  • Diluent: normal saline only

  • Assessment: clinical; H/H may not be valid

  • Golden Hour

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Red Cell Indicationsclinical studies

  • Hébert, et al. 1999

    • randomized, controlled clinical trial, 838 critically ill patients

      • liberal group: Hb tx. trigger 10g/dl

      • restrictive group: trigger 7 g/dl

    • findings:

      • overall 30-day mortality similar (p=0.11)

      • lower rates for restrictive group for less acutely ill and age<55 (p=0.02, 0.03)

      • in-hospital mortality rate lower in restrictive group (p=0.05)

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Red Cell Indicationsclinical studies

  • Hébert, et al. 1999

    • findings:

      • liberal group had significantly higher rates for:

        • MI (p=0.02)

        • pulmonary edema (p<0.01)

      • no significant difference in other complications

      • trend toward lower 30-day mortality in restrictive group

      • decreased blood exposure in restrictive group

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Red Cell Indicationsclinical studies

  • Carson, 1998

    • almost 9000 patients 60 years and older getting hip fracture repair

    • at pre-transfusion Hb (“trigger”) of 8 to 10 g/dl, no difference in 30- and 90-day mortality between transfused and not transfused

  • Weiskopf, 1998

    • experiment in isovolemic hemodilution in 23 healthy adults

    • Hb as low as 5g/dl tolerated at rest

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Treating Bleeding Related to Coagulation AbnormalitiesPlatelets, FFP, and CRYO

  • General rule: If bleeding greater than expected and is of a microvascular nature and lab values meet threshold (or not available in time or dysfunction of hemostasis is known or suspected)

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Microvascular Bleeding

  • surgical: wetness/oozing from all or most exposed tissue, no visible vessel to mechanically stop

  • non-surgical:

    • ecchymosis at sites other than surgical wound

    • oozing around catheters; from mucosal surfaces

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PlateletsIndications, Guidelines and Practice Parameters

  • American Society of Anesthesiology

    • Prophylactic transfusion is rarely indicated if thrombocytopenia is due to increased destruction

    • With surgery,

      • usually not indicated >100,000

      • usually indicated <50,000

      • between 50 and 100,000: base on risk of bleeding

    • With microvascular bleeding,

      • same guidelines as for surgery

      • known platelet dysfunction

    • Procedures associated with insignificant blood loss may be done <50,000

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Fresh Frozen PlasmaIndications, Guidelines and Practice Parameters

  • American Society of Anesthesiology, 1996

    • urgent reversal of warfarin effect

    • correction of known factor deficiency

    • for correction of microvascular bleeding in the presence of elevated (>1.5 x nl.) PT or PTT

    • for correction of microvascular bleeding in a patient who has received >1 blood volume

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Fresh Frozen PlasmaIndications, Guidelines and Practice Parameters

  • College of American Pathologists, 1994

    • with active bleeding or procedure and

      • PT* 1.5 x midpoint of normal (18s) or

      • PTT* 1.5 x top of normal (51s)

    • in massive transfusion with microvascular bleeding and coagulation abnormality

*fibrinogen must be normal, >100mg/dl; patient not on heparin

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Fresh Frozen PlasmaInappropriate Use

  • Volume expander, Source of albumin, When heparin is cause of lab abnormality, When a specific therapy is available (VIII, IX, ATIII, Vitamin K, DDAVP)

  • On a routine schedule with red cell transfusion (prophylactically in massive transfusion)

British JH 2004

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Evidence against Routine Schedule of Plamsa in Massive Transfusion

Mannucci et al. Vox Sang 42(3):113-23 (1982)

“Standard schemas involving the administration of platelet concentrates and/or fresh-frozen plasma without evaluation of hemostasis … failed to decrease the requirements for … packed red cells. Therefore, indiscriminate administration in the massively transfused postoperative patient of blood components based on preestablished schemes appears to be unjustified.”

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Current Practice with Plasma

  • More aggressive? earlier

  • Agrees with traditional guidelines:

    • Apply aggressive strategy for patients that present with coagulopathy

    • Is treating bleeding assoc with abnl lab

  • Apparent conflict with guidelines (ratio, routine schedule), but not if there is evidence of coagulopathy

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Evidence Supporting use of1:1 Ratio RBC:plasma

  • Borgman, MA. J Trauma 2007

  • Retrospective study

  • Stratified patients by ratio of plasma:rbc

  • Improved outcome with higher plasma proportion

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Mortality %

RBC:FFP ratio

Recent Evidence, Plasma

(Borgman, MA. J Trauma 2007)

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Slide courtesy JG Perkins


Evidence Supporting use of Apheresis Platelets

  • Retrospective study pts at Ibn Sina

  • Received 10 or more rbcs/FWB

  • Compare groups:

    • Did not get platelets or FWB

    • Received platelets and not FWB

    • Received FWB

  • Findings:

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Study Profile - Retrospective

8,618 Trauma Patients Arrived at CSH

2,024 (23%) Received Blood Transfusions

708 (8.2%) Received ≥ 10 u Blood (RBC + FWB) in 24 hours

12 MT occurred during hospital course, not on admission

89 treated at forward surgical teams/hospitals prior to transfer to CSH

434 charts reviewed for analysis

285 Platelets – either as FWB or aPLT

149 No FWB or aPLT

23 Both FWB and aPLT

78 FWB

184 aPLT

Time Period: January 2004 – December 2006

CSH = Combat Support Hospital, RBC = red blood cell, FWB = fresh whole blood, aPLT = apheresis platelets, MT = massive transfusion


P<0.001

p=0.04

Log Rank p=0.003

48 Hour and 30 Day Survival by Platelet versus No Platelet Groups

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p=0.72

p=0.87

Log Rank p=0.96

48 Hour and 30 Day Survival by Fresh Whole Blood versus Apheresis Platelet Subgroups

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Factor VII Use

  • rFVIIa (NovoSeven)

    • Hemophiliac with anti-VIII (approved for)

    • Coumadin reversal

    • Stroke

    • Massive transfusion

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Factor VII Use and Outcome in OIF1 of 2

  • Jan04 – Oct05, records for 61 of 117 patients who rec’d FVIIa

  • Groups:

    • Early (FVIIa before 8 units blood)

    • Late (after 8 units)

  • Groups similar for severity of injuries

- Perkins, JG. J Trauma, 2007 May;62(5):1095-9

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Factor VII Use and Outcome in OIF 2 of 2

  • Early group rec’d fewer units of blood (20.6 vs. 25.7, p=0.048) and pRBC (16.7 vs. 21.7, p=0.049)

  • Similar outcomes

    • Mortality (33.3% vs. 34.2%, p=NS)

    • ARDS (5.9 vs. 6.8%, p=NS)

    • Infection (5.9% vs. 9.1%, p=NS)

    • Thrombotic events (0% vs. 2.3%, p=NS)

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Conclusions Regarding Blood Therapy in Massive Transfusion

For select patients with coagulopathy (7-8%)

  • Use of either FWB or aPLT is associated with improved survival at 48 hrs and 30 days

  • FWB and aPLT appear equivalent with regards to survival

  • FFP:RBC ratios 1:2 to 1:1 are associated with improved survival at 48 hours, though this survival benefit is not apparent at 30 days.

  • FVIIa use might reduce red cell with no appreciable excess adverse outcome

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Is Old Blood Bad Blood?

  • “Age:” duration of storage

  • Storage lesion

    • Decreased pH

    • Increased K+

    • Decreased 2,3-DPG

    • Decreased deformability

  • Clinical outcomes worse? (or not)

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Age of Blood: the Evidence

  • Retrospective

  • Inconsistent definition of age

  • Different preservatives, modifications

  • Inconsistent findings

  • Uniform or near uniform findings/conclusions:

    • Number of units is associated with worse outcome

    • Findings are insufficient to recommend routine use of “young” units

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Age of Blood: the Evidence

Basran Anesth Analg 2006;103:15–20

  • Retrospective, 321 re-do CABG pts

  • Measures of age: mean; oldest unit

  • Findings: correlates with longer LOS, mortality

  • Conclusions: should be studied with RCT before informing practice

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Age of Blood: the Evidence

Vamvakas Transfusion 1999;39:701-710

  • Retrospective, 269 cardiac surgery pts

  • Measures of age: mean;

  • Findings: age correlates with pneumonia, not with wound infection

  • Conclusions: should be studied with RCT before guiding transfusion policy

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Age of Blood: the Evidence

Vamvakas Transfusion 2000;40:101-109

  • Retrospective, 268 cardiac surgery pts

  • Measures of age: mean; oldest; 2 oldest

  • Findings: age does not correlate with LOS, time on ventilator

  • Conclusions: future studies of transfusion should consider age

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Age of Blood: the Evidence

Keller J Trauma 2002;53:1023–1025

  • Retrospective registry 18 hospitals, 86 trauma pts who rec’d 1-4 units

  • Measures of age: mean; oldest; 2 oldest; number >7d; >14d; >21d; >28d

  • Findings: only number of units >14d correlated with total LOS, not with ICU stay or vent

  • Conclusions: further study needed

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Age of Blood: the Evidence

Leal-Noval Anesthesiology 2003;98:815-22

  • Prospective cohort, 585 cardiac surgery pts

  • Measures of age: mean; oldest; youngest

  • Findings:

    • age does not correlate with LOS, time on ventilator, MI

    • Oldest unit and youngest unit correlates with pneumonia

  • Conclusions: age does not increase morbity except maybe pneumonia (number of units)

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Age of Blood: the Evidence

Van de Watering Transfusion2006;46:1712-1718

  • Retrospective, 2732 cardiac surgery pts

  • Measures of age: mean; oldest; youngest; comparisons for patients with all units < 18d vs all units > 18d

  • Findings: age correlates with number; no correlation with outcome

  • Conclusions: there is no justification for limitation of storage time

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Age of Blood: the Evidence

Walsh Crit Care Med 2004; 32(2):364 –371

  • Randomized ControlledTrial, 22 critical pts

  • Comparison: ≤5d vs ≥20d

  • Findings: age has no adverse effect on gastric function or measures of global oxygenation

  • Conclusions: no support for the use of fresh red cells in critically ill patients

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Summary

  • Current resucitation emphasizes early control of bleeding, later correction of injury

  • Aggressive plasma transfusion is probably best practice for coagulopathic bleeding patient

  • Component therapy better than FWB

  • FWB as good when component therapy not available

  • rFVII may be helpful in reducing red cell use

  • We will do our patients more good (or at least less harm) by reducing number of units compared with reducing age of units

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