Transcript Hemostasis for the Anesthesiologist

Hemostasis for the Anesthesiologist:
Treatment Practices
Richard P. Dutton, MD, MBA
Associate Professor of Anesthesiology
University of Maryland School of Medicine
Director of Trauma Anesthesiology
R Adams Cowley Shock Trauma Center
Baltimore, Maryland
“Keeping on Center”: Moving Toward
Normal Hemostasis
Topical Hemostatics
Purified Factors, FFP, Cryo, PLTs
Procoagulant
Activity
Bleeding
Clotting
Aminocaproic acid,
Tranexamic acid, Aprotinin
Antifibrinolytic
Activity
Normal
Hemostasis
Fibrinolytic
Activity
t-PA, SK, UPA
FFP=fresh frozen plasma; Cryo=cryoprecipitate; PLTs=platelets; SK=streptokinase;
UPA=urinary-type plasminogen activator; LMWH=low-molecular-weight heparin.
Adapted from Lawson JH, et al. Semin Hematol. 2004;41(suppl):55-64.
Anticoagulant
Activity
Heparin, Warfarin
LMWH, Argatroban
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Challenges to Normal Hemostasis
• Patient medications
• Anatomic disruption by surgeons
• Inflammatory by-products of surgery
(eg, embolized bone marrow)
• Hypothermia
• Acidosis
• Loss and dilution of clotting factors
Levy JH. Transfusion. 2006;46:919-933.
Dutton RP, et al. J Trauma. 2004;57:709-719.
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The Cycle of Coagulopathy
Tissue injury
Hemorrhage
Inflammation
Loss, consumption, dilution
Coagulopathy
Acidosis
Dysfunction
Dysfunction
Anticoagulants
Genetics
Hypothermia
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The Basic Clinical Concept . . .
Keeping Up
(maintaining normal hemostasis)
vs
Catching Up
(rescuing the coagulopathic patient)
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Avoiding Coagulopathy: Basics
• Stop all anticoagulant medications before surgery1,2:
 Heparins: 12 hours
 Aspirin: 5-7 days
 Clopidogrel: 5-7 days
 Warfarin: 5-6 days
 Herbal medications: 2 weeks3
• Plan the anesthetic to reduce estimated
blood loss (EBL)
 Regional anesthesia if possible
 Deliberate hypotension
1. Pass SE, et al. Am J Health Syst Pharm. 2004;61:899-912; 2. Jaffer AK, et al.
Cleve Clin J Med. 2006;73(suppl 1):S100-S105; 3. Ang-Lee MK, et al. JAMA.
2001;286:208-216.
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Avoiding Coagulopathy: Basics (cont)
• Conserve native blood
 Careful surgical technique
 Limit blood draws
 Cell salvage
• Keep patient warm and well perfused
• Have blood products ready
• Have a plan to manage the actively bleeding patient
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If Active Bleeding Occurs . . .
• Expedite control of hemorrhage
• Limit crystalloid infusion
• Maintain anesthesia and paralysis
• Keep BP low (80-100 systolic)
• Resuscitate with blood: 1:1:1 RBC/plasma
• Follow labs closely—especially calcium and pH
Dutton RP. Pharmacotherapy. 2007;27(9 pt 2):85S–92S.
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Resuscitation
Vigorous fluid
resuscitation
Hemodilution
increased bleeding
Recurrent
hypotension
Dutton RP. Pharmacotherapy. 2007;27(9 pt 2):85S–92S.
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Dilution Is Inevitable When Giving
Blood Components
Whole blood 500 mL
(Hct 38%–50%; PLTs 150K–400K; Plasma
coagulation activity 100%)
150 mL anticoagulant added; centrifuged
1 U PRBC
(335 mL, Hct 55%)
1 U Plasma
(275 mL, coagulation activity 80%)
1 U PLTs
(50 mL, 5.5 x 1010 PLTs
Patient Receives 650 mL fluid:
Hct 29%, PLTs 88K, 65% coagulation activity
Adapted from Dutton RP. Pharmacotherapy. 2007;27(9 pt 2):85S–92S.
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Effect of FFP:RBC Ratio on Overall Mortality in
252 Massively Transfused Trauma Patients
(long-term outcomes)
70
Chi Square
RB: P=.006
RG: P<.001
BG: P=.034
65%
60
Mortality %
50
40
34%
30
20%
20
10
n=31
n=56
n=165
1:3.9 - 1:2.1
1:2 - 1:0.59
0
0:22 - 1:4
FFP:RBC Ratio
Borgman MA, et al. J Trauma. 2007;63:805-813.
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Guiding Principle
Any fluid that does not clot or carry
oxygen should be suspect.
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“Citrate Intoxication”
• Occurs in any patient receiving a rapid transfusion
(>2 U/hr)
• Caused by citrate in the transfused blood chelating
circulating calcium
•  serum ionized calcium leads to coagulopathy,
 cardiac performance
• Treated with calcium administration
Dutton RP. Anesthesiology Clin. 2007;25:23-24.
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The Basic Clinical Concept . . .
Keeping Up
(maintaining normal hemostasis)
vs
Catching Up
(rescuing the coagulopathic patient)
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“Jump-starting” Coagulation
• Active bleeding in the coagulopathic patient
• Concentrated clotting factors:
 Cryoprecipitate (fibrinogen)
 Platelets
 Recombinant factor VIIa (rVIIa)
• Bicarbonate/THAM?
THAM=tris-hydroxymethyl aminomethane.
Dutton RP. Pharmacotherapy. 2007;27(9 pt 2):85S–92S.
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The Ideal Hemostatic Agent
• Will clot inappropriate hemorrhage
• Will not clot working vessels
• Will not have side effects
• Will be easy to store and use
• Will be free
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Recombinant Factor VIIa
• Recombinant human product1
• Facilitates cell-based coagulation, triggering
thrombin burst on platelet surface2
• In large doses, requires only factor I (fibrinogen),
II (thrombin), and platelets to produce clotting1,2
• Licensed only for use in hemophiliacs with
inhibitors to factor VIII or IX1
1. Mannucci PM, et al. N Engl J Med. 2007;356:2301-2311.
2. Dutton RP, et al. J Trauma. 2004;57:709-719.
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Recombinant Factor VIIa: Packaging
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Recombinant Factor VIIa: Mechanism of Action
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Recombinant Factor VIIa: Procedure for Use, STC
• “Off-label” use requested by attending physician
• Gatekeeper approval required
 Life-threatening hemorrhage
 Coagulopathy
 Failure of conventional therapy
 Non-futile
• Periodic data analysis approved by the IRB
STC=R Adams Cowley Shock Trauma Center.
Dutton RP, et al. J Trauma. 2004;57:709-719.
Thomas GO, et al. J Trauma. 2007;62:564-569.
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400 Patients to Date
• Acute hemorrhagic shock
• Traumatic brain injury
• Warfarin, clopidogrel
• Sepsis, ICU coagulopathy
• Cirrhosis
• FVII deficiency
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Dosing of Recombinant Factor VIIa
• 100 mcg/kg1
 Shock
 Rapid bleeding
• 1.2 mg (smallest possible dose)2
 No shock
 Slow or no bleeding
1. Dutton RP, et al. J Trauma. 2004;57:709-719.
2. Dutton RP. Pharmacotherapy. 2007;27(9 pt 2):85S–92S.
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Hemostasis
• 10% no response (futile)
 Massive hemorrhage
 Profound shock
• 90% response rate
Dutton RP. Pharmacotherapy. 2007;27(9 pt 2):85S–92S.
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Survival
• Overall survival about 65%
• Causes of death:
 Overwhelming shock
 Severe brain injury
 Multisystem failure
Dutton RP. Pharmacotherapy. 2007;27(9 pt 2):85S–92S.
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Change in Prothrombin Time
Prothrombin Time (sec)
28
24
20
16
12
8
Pre PT
Dutton RP, et al. J Trauma. 2004;57:709-719.
Post PT
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Thromboelastogram Before and After
Recombinant Factor VIIa
Reprinted with permission from Dutton RP, et al. J Trauma. 2004;57:709-719.
©2004 Lippincott Williams & Wilkins http://lww.com
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Safety of Recombinant Factor VIIa
• 9% thromboembolic complications
 Mostly arterial
 Occur in the region of surgery/trauma
• 3% highly associated with rVIIa
• 1% highly associated with rVIIa and lethal
Thomas GO, et al. J Trauma. 2007;62:564-569.
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Thromboembolic Complications
• rVIIa is a potent procoagulant
• Thrombotic complications will be highly
patient-dependent
 Unstable atherosclerotic disease
 Blunt vascular injury (carotid,
mesenteric arteries)
 Extracorporeal circulation
 Other procoagulants?
• Probably not dose-dependent
Thomas GO, et al. J Trauma. 2007;62:564-569.
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Summary
• The anesthesiologist can contribute
substantially to hemostasis
• Planning should begin pre-op; the best
approach is to prevent coagulopathy from
ever occurring
• If the patient does become coagulopathic,
catching up is difficult, but not impossible
• rVIIa may be a useful option
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