1. Managing the Coagulopathy of Trauma: Use of Transfusion Protocols and Prohemostatic Agents

2. Faculty Bryan A. Cotton, MD, MPH
The University of Texas Health Science Center Houston, Texas
Richard P. Dutton, MD, MBA
University of Maryland School of Medicine
R Adams Cowley Shock Trauma Center
Baltimore, Maryland
Martin A. Schreiber, MD, FACS
Oregon Health & Science University
Portland, Oregon

3. Hemorrhage Leading cause of death in first hour of arrival1
Responsible for more than 80% of OR deaths2
Accounts for nearly 50% of deaths in first 24 h2
1. Acosta JA, et al. J Am Coll Surg. 1998;186: ; 2. Kauvar DS, et al. J Trauma. 2006;60:S3-S11.

4. How Acute and How Lethal Is the Coagulopathy?
38% (+) coagulopathic on arrival; mortality (+) coagulopathic 24% (vs 4%)1
24% arrive (+) coagulopathic; these patients have higher mortality (46% vs 11%)2
MT patients, 70% coagulopathic on arrival; mortality in coagulopathic patients 67% (vs 42%) 3
MT=massive transfusion.
1. Niles SE, et al. J Trauma. 2008;64: ; 2. Brohi K, et al. J Trauma. 2003;54: ; 3. Cotton BA, et al. J Trauma. 2008;64:

5. What to Replace? PT: 0.87 BV lost Fibrinogen: 1.14 BV lost
Platelets: 1.83 BV lost
PT subhemostatic once patient has received only 3.6 U RBCs
Preparedness is essential
BV=blood volumes.
Hirshberg A, et al. J Trauma. 2003;54:

6. Why Implement a Protocol?
Many patients arrive with coagulopathy present
An organized protocol to address exsanguinating hemorrhage in the most severely injured patients minimizes delays
Delays in access to appropriate blood products
Delays of sufficient quantities and ratios

7. Exsanguination Protocol
Surgeon activates trauma exsanguination protocol
(TEP)
Blood bank prepares first round of products
10 U RBC
6 U plasma
2 apheresis platelets
Blood bank begins preparation of next round of
products
6 U RBC
4 U plasma
Cotton BA, et al. J Trauma. 2008;64:

8. Exsanguination Protocol
Unless specified, blood bank releases second box and ceases preparation of future boxes
Surgeon notifies blood bank and stops TEP if
Hemostasis achieved
Case completed
Patient expires
Cotton BA, et al. J Trauma. 2008;64:

9. Damage Control Resuscitation
Damage control hematology: the impact of a trauma exsanguination protocol on survival and blood product utilization
(Cotton et al. Journal of Trauma, 2008)
Three components
Hematologic
Limited crystalloid
Permissive hypotension
Cotton BA, et al. J Trauma. 2008;64:

10. Improved Survival 74% reduction in the odds of mortality
Increase in unexpected survivors
Decrease in unexpected deaths
Less intraoperative crystalloid; fewer postoperative blood products
Cotton BA, et al. J Trauma. 2008;64:

11. Higher Ratios
Mortality reduction attributed to empiric delivery of higher, predefined ratios of plasma and platelets1
Higher fibrinogen (plasma):RBC ratio independently associated with improved survival2
Higher plasma and platelet ratios improved survival in MT patients1
1. Gunter OL Jr, et al. J Trauma. 2008;65: ; 2. Stinger HK, et al. J Trauma. 2008;64(2 suppl):S74-S85.

12. Predefined MT Protocols
Predefined massive transfusion protocols are
associated with a reduction in organ failure and postinjury complications
(Cotton et al. Journal of Trauma, 2009)
MT historically associated with higher rates
of organ failure and postinjury complications
Risk reduced with early delivery of blood
products through predefined protocol
MT=massive transfusion.
Cotton BA, et al. J Trauma. 2009;66:41-49.

13. Predefined MT Protocols
Implementation of protocol results in
Reduction in MOF
Fewer pulmonary issues
Reduced incidence of open abdomens in
compartment syndrome
MOF=multiorgan failure.
Cotton BA, et al. J Trauma. 2009;66:41-49.

14. MLR Analysis for 30-Day Survival
P value
95% CI
ED protocol activation
2.79
.042
Plasma:RBC ratio of 2:3
12.28
<.001
Platelet:RBC ratio of 1:5
3.72
.009
Trauma Attending activation
0.895
.922
ED type and screen sent
0.195
.130
Age in years
0.98
.354
Male gender
0.75
.599
Injury Severity Score
0.96
.190

15. Recombinant Factor VIIa (rVIIa)
rVIIa: Adjuvant for treatment of coagulopathy in patients with severe torso hemorrhage
rVIIa: Binds tissue factor at site of endothelial injury, triggering local coagulation process
rVIIa: Reduces incidence/severity of coagulopathy in severely injured patients with ongoing transfusions
Martinowitz U, et al. J Trauma. 2001;51: ; Rizoli SB, et al. Crit Care. 2006;10:1-11; Stein DM, et al J Trauma. 2008;64:

16. Recombinant Factor VIIa (rVIIa)
Several OIF/OEF studies showed improved outcomes1,2
Phase II trauma study of rVIIa demonstrated a reduction in RBC use, trend toward less MOF3
Potentially limited with acidosis and thrombocytopenia4,5
Reports of thromboembolic adverse events6
1. Perkins JG, et al. J Trauma. 2007;62: ; 2. Spinella PC, et al. J Trauma. 2008;64: ; 3. Boffard KD, et al. J Trauma. 2005;59:8-15; 4. Martini WZ, et al. Ann Surg. 2007;246: ; 5. Stein DM, et al. J Trauma. 2005;59: ; 6. O’Connell KA, et al. JAMA. 2006;295:

17. Recent Studies: rVIIa Stein et al. Injury (2008)
Objective: Examine safety and efficacy of rVIIa
for reversing mild to moderate coagulopathy
Retrospective review,
Results: Decreased utilization of PRBCs and
FFP; lower vol fluid administration; rapid
reversal of coagulopathy
Stein DM, et al. Injury. 2008;39:

18. Recent Studies: rVIIa Horton et al. Am Surg (2008)
Objective: Examine frequency and patterns of
rVIIa use since Jan 2005
Survey of 156 US trauma centers, level I and II
Horton JD, et al. Am Surg. 2008;74:

19. Prothrombin Complex Concentrate (PCC)
PCC: Clotting factors (II, VII, IX, and X) that can be used to reverse coagulopathy
PCC: Effects are fast and long acting
PCC: Use in trauma patients appears safe and beneficial in critically injured population
Associated with thrombogenicity
Kalina M, et al. Am Surg. 2008;74: ; Köhler M. Thromb Res. 1999;95(4 suppl):S13-S17; Riess HB, et al. Thromb Res. 2007;121:9-16.

20. Recent Studies: PCC Dickneite et al. Br J Anaesth (2009)
Objective: Compare effects of PCC and FFP
on hemorrhage after injury and impact of both agents on coagulation function in vivo
Porcine trauma model: 47 castrated male pigs
Results: PCC, not FFP, reversed hemodilution effects
Dickneite G, et al. Br J Anaesth

21. Recent Studies: PCC Riess et al. Thromb Res (2007)
Objective: Examine efficacy of PCC for
reversing anticoagulant effects
60 patients with bleeding complications
or undergoing invasive procedures
Result: Rapid and safe reversal of
anticoagulation with PCC
Riess HB, et al. Thromb Res. 2007;121:9-16.

22. Question-and-Answer Session

23. Bryan A. Cotton, MD, MPH
Associate Professor of Surgery
The University of Texas
Health Science Center and
Center for Translational Injury Research
Houston, Texas

24. What are your thoughts concerning recombinant factor VIIa data, including studies indicating that the agent may reduce transfusion requirement but have no effect on ultimate outcome?

25. Availability of recombinant factor VIIa when unable to get surgical control
Medivac helicopters
Fluid replacement to avoid hemodilution
Smaller-volume trauma centers
No in-house trauma surgeon
Delivered with the second box of product

26. Timing of use
Protracted wait = poor outcome
Have agent ready early enough but not
too early

27. Martin A. Schreiber, MD, FACS
Oregon Health & Science University
Portland, Oregon

28. From your perspective, how has recombinant factor VIIa evolved as an off-label drug to treat the coagulopathy of trauma?

29. Evolution of rVIIa use
Previously misused based on improper patient care
Crystalloid and blood products
Used as rescue drug to counter cycle of coagulopathy
Current recognition of coagulopathy on admission
Need for resuscitation with high ratios of plasma to platelets
Replacement Therapy
Fell behind
Still evolving

30. Richard P. Dutton, MD, MBA
Professor of Anesthesiology
University of Maryland School of Medicine
Attending Anesthesiologist
R Adams Cowley Shock Trauma Center
Baltimore, Maryland

31. Which of the treatment strategies that are just beginning to be recognized for the coagulopathy of trauma do you believe will be routinely performed 5 years from now?

32. Better testing of coagulation early
Individual factor therapy
Combinations of factor therapy
Fibrinolytic mechanism
Use of deep anesthesia

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