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


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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10%

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100%

Prehospital First 24 hours After 24 hours

Per

cent

age

of d

eath

s

Hemorrhage CNS Other

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

Slide courtesy JG Perkins


Massive transfusion

• One body volume in 24 hours

• “Dilutional” coagulopathy– depleted coagulation factors– thrombocytopenia– hypoperfusion– confounding conditions: DIC, sepsis

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.

Base Deficit Lactate Hematocrit Heart Rate

Unobtainable ≤ 90 mm Hg > 90 mm Hg

B

ase

Def

icit

mE

q/L

0

2

4

6

8

1

0

Lact

ate

mg/

100

mL

20

40

6

0

80

100

Hem

atoc

rit %

20

40

Hea

rt R

ate

(BP

M)

70

90

11

0 1

30 1

50 N=450 combat casualties in the Vietnam War on Admission


Pathophysiology of Trauma

Coagulopathy

Acidosis

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


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


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)


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


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)


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


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


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)


Traditional Guidelines


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


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)



• 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



• 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


Treating Bleeding Related to Coagulation Abnormalities

Platelets, 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)


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


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


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


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


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


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.”


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


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


Recent Evidence, PlasmaRBC:FFP effect on mortality in massive transfusion

0

10

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30

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70

>5:1-4:1 4:1-3:1 3:1-2:1 2:1-1:1 <1:1

Mor

talit

y %

RBC:FFP ratio

(Borgman, MA. J Trauma 2007)



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:

Time Period: January 2004 – December 2006

Study Profile - Retrospective

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

8,618 Trauma Patients Arrived at CSH

2,024 (23%) Received Blood Transfusions

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

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

285 Platelets – either as FWB or aPLT 149 No FWB or aPLT

23 Both FWB and aPLT 78 FWB 184 aPLT


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

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48hr 30day

Platelets

No Platelets

Log Rank p=0.003

P<0.001

p=0.04

1 Compared using Chi-square and Mantel-Cox Log Rank

2 Forty-Eight Hour Survival: Platelet Group (218/266, 82 ± 2%), No platelet Group (90/137, 66 ± 3%) p <0.001

3 Thirty Day Survival: Platelet Group 121/196 (62 ± 4%), No Platelet Group (53/107) (50 ± 5%) p-=0.04


48 Hour and 30 Day Survival by Fresh Whole Blood versus

Apheresis Platelet Subgroups

0%

20%

40%

60%

80%

100%

48 hour Survival 30 Day Survival

Fresh Whole Blood

Apheresis Plateletsp=0.72

p=0.87

Log Rank p=0.96

1 Compared using Chi-square and Mantel-Cox Log Rank

2 Forty-Eight Hour Survival: Fresh Whole Blood Group (56/70, 80 ± 5%), Apheresis Platelet Group (143/174, 82 ± 3%) p = NS

3 Thirty Day Survival: Fresh Whole Blood Group (36/60, 60 ± 6%), Apheresis Platelet Group (72/117, 62 ± 5%) p = NS


1

TIME = 0 Initial Labs Type&Cross Immediate 4 donors to “prime” pump

then: > provide blood runners > provide extra nursing for screening

Additional Donors

Called from phone List ~8 at a time Any gaps in 30 MINUTES Donors Filled with Additional donors 60 MINUTES 90 MINUTES 120 MINUTES

4 pRBC 4 FFP

Blood Bank Nursing Supervisor

Surgeon

Notify Command

Suspend routine duties Get help

Whole Blood Drive

Massive Transfusion Pack: 4 pRBC 4 FFP 10 cryoppt

4 pRBC 4 FFP 1 6pk platelets (when available)

4 Fresh Whole Blood

4 pRBC 4 FFP

4 Fresh Whole Blood

“Walking Blood Bank”

Emergency Release pRBCs

PROTOCOL TERMINATED WHEN NO LONGER NEEDED

Figure 1: Whole-Blood-Based Massive Transfusion Protocol


Factor VII Use

• rFVIIa (NovoSeven)– Hemophiliac with anti-VIII (approved for)– Coumadin reversal– Stroke– Massive transfusion


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


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)


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


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)


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



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



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



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



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


Age of Blood: the EvidenceLeal-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)



Van de Watering Transfusion 2006;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


Age of Blood: the EvidenceWalsh 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


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

transfusion practices with combat wounded

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