Coagulation dysfunctions in severe traumaBleeding in trauma – epidemiology (1) Trauma leading...

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Coagulation dysfunctions in severe trauma D. Săndesc “V. Babes” University of Medicine and Pharmacy Timisoara, Romania 1
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Transcript of Coagulation dysfunctions in severe traumaBleeding in trauma – epidemiology (1) Trauma leading...

  • Coagulation dysfunctions in severe trauma

    D. Săndesc “V. Babes” University of Medicine and Pharmacy Timisoara, Romania

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  • საღამო მშვიდობისა! saghamo mshvidobisa! მადლობა ! Madloba !

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  • Prevention of upper gastrointestinal bleeding (UGIB) and gastric stress ulcers (GSU) in the critically ill and postop patients

    D. Săndesc “V. Babes” University of Medicine and Pharmacology Timisoara , Romania 4

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  • Coagulation dysfunctions in severe trauma

    Main topic: what is the acute coagulopathy of severe trauma:

    1.A primary phenomenon or a secondary one (dilution, hypotermia, acidosis)?

    2. A form of DIC(Disseminated Intravascular

    Coagulation) or a totally different syndrome?

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  • Coagulation dysfunctions in severe trauma

    Main topic : what is the acute coagulopathy in severe trauma ? •a form of DIC? •a different syndrome?

  • The crucifixion of Jesus: Review of hypothesized mechanisms of death and implications of shock and trauma-induced coagulopathy

    “Trauma-induced coagulopathy may have been a contributing factor, if not the primary factor, in Jesus’ death.

    It would explain how Jesus’ death could occur so rapidly, namely 6 hrs, rather than several days. It would also explain how blood could flow from Jesus’ corpse when his chest was impaled by the spear.”

    Joseph W. Bergeron MD. Available online 12 July 2011

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    http://media.photobucket.com/image/jesus on cross/cutiepie419_bucket/cross.jpg?o=65

  • Hess JR, Lawson JH. The Coagulopathy of Frida Kahlo Trauma J Trauma 2006; 60: S12-S19

    Acute coagulopathy of trauma – clinical definition

    “ … a syndrome of non-surgical bleeding from mucosal lesions, serosal surfaces, wounds and vascular access sites that continues after identifiable vascular bleeding has been controlled” *

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  • 1. CDC: Web-based Injury Statistics Query and Reporting System, 2002

    2. Acosta JA, Yang JC, Winchell RJ, et al. J Ann Coll Surg 1998; 186: 528-533

    Bleeding in trauma – epidemiology (1)

    Trauma leading cause of death 1-44 years leading cause of years of potential

    life lost1

    Coagulopathy affects at least 1 in 4 seriously

    injured trauma patients2 largest proportion of deaths in the

    first hour of trauma center over 80% of operating room deaths almost 50% of deaths in the first 24

    hours

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  • Bleeding in trauma – epidemiology (2)

    Journal of Trauma-Injury Infection & Critical Care. Early Massive Trauma Transfusion: Current State of the Art. 60(6) Supplement:S3-S11, June

    Journal of Trauma-Injury Infection &Critical Care.) Supplement:S3S11, June 2006 2006

    Frida Kahlo, “The broken column”

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  • Frida Kahlo

    Bleeding in trauma – epidemiology (3)

    Acute Traumatic Coagulopathy.. Journal of Trauma Injury Infection & Critical Care. 54(6):1127-1130, June 2003

    .

    Incidence of coagulopathy. ISS, Injury Severity Score.

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  • Bleeding in trauma – epidemiology (4)

    Journal of Trauma-InjuryInfection & Critical

    Care 54(6):1127-1130 June 2003

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  • Coagulation dysfunctions in severe trauma

    Main topic: what is the acute coagulopathy of severe trauma:

    A primary phenomenon or a secondary one (dilution, hypotermia, acidosis)?

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  • The classical paradigm:Acute coagulopathy of trauma –a secondary phenomenom

    Acidosis Hypothermia

    Hemodilution

    Coagulopathy

    Death

    Brohi, K, et al. J Trauma, 2003.

  • 1. Brazil EV, Coats TJ. Sonoclot coagulation analysis of in-vitro haemodilution with resuscitation solutions. J R Soc Med 2000; 93:507–510. 2. Brohi K, Singh J, Heron M, et al. Acute traumatic coagulopathy. J Trauma 2003; 54:1127–1130.

    Instigators of the coagulopathy in trauma: hemodilution Bleeding, volume therapy,

    transfusions German study:

    coagulopathy present in 50% of patients that received> 3 l in prehospital

    role of the type of solutions in coagulopathy(HES)1

    London study:2 simillar incidence of

    coagulopathy with german study minimal prehospital fluid

    administration (500 ml media) Hemodilution: contributor, not

    instigator factor

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  • 1. Cosgriff N, Moore EE, Sauaia A, Kenny-Moynihan M, Burch JM, Galloway B. Predicting life-threatening coagulopathy in the massively transfused trauma patient: Hypothermia and acidoses revisited. J Trauma. 1997;42:857–861. 2. Shafi S, Elliott AC, Gentilello L. Is hypothermia simply a marker of shock and injury severity or an independent risk factor for mortality in trauma patients? Analysis of a large national trauma registry. J Trauma 2005; 59:1081–1085.

    Instigators of the coagulopathy in trauma: hypotermia Influence on coagulation

    factor’s activity Influence on platelet’s

    function1

    Significant effects on coagulation: only at temperatures bellow 330C 2

    Severe hypotermia: only in 9% of trauma patients

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    http://www.arthistoryarchive.com/arthistory/surrealism/images/FridaKahlo-Girl-with-Death-Mask-1938.jpg

  • 1. Cosgriff N, Moore EE, Sauaia A, Kenny-Moynihan M. . J Trauma. 1997;42:857–861.

    Instigators of the coagulopathy in trauma: acidosis Considered “clasically”

    the most important instigator of the coagulopathy in trauma

    Hydrogen ions: interface with ionic interactions of coagulation factors and activated plateletes1

    But it is difficult to separate the effects of acidemia per se from the effects of shock

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  • A new paradigm: Acute coagulopathy of trauma- a primary phenomenon

    Main instigator of the acute coagulopathy of trauma : Shock/hypoperfusion

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  • Acute coagulopathy in trauma –new paradigm: Anticoagulation

    Acute coagulopathy of trauma:mechanism, identification and effect.Brohi, Karim; Cohen, Mitchell; Davenport, Ross Current Opinion in Critical Care. 13(6):680-685, December 2007.

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  • Acute coagulopathy of trauma: mechanism, identification and effect.Brohi, Karim; Cohen, Mitchell; Davenport, RossCurrent Opinion in Critical Care. 13(6):680-685, December 2007.

    Acute coagulopathy in trauma –new paradigm: Hyperfibrinolysis

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  • Endothelium as an organ

    Approximately 1013 endothelial cells 1 1kg, 4000-7000 m2 !(SIZE DOES MATTER…) HIGHLY ACTIVE, sensing and responding to alterations of

    local/general homeostasis (bacteriemia, trauma, ischemia etc.)

    Wide variety of functions2,3: Vasomotor tone Cellular and nutrient trafficking Inflammatory response Blood fluidity/coagulation Generation of new blood vessels Programmed cell death etc.

    1. Fisher CJJr, Agosti JM, Opal SM, et al. NEJM 1996. 2. Cines DB, Pollak ES, Buck CA, et al. Blood 1998; 91. 3. Gross PL, Aird WC. Semin thromb Hemost 2000;26.

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  • Shock / Tissue hypoperfusion

    A new paradigm: Acute coagulopathy of trauma-a primary phenomenon

    Endothelium (genotype?)

    Acidemia Dilution Hypotermia

    TM ↑

    TM / Thrombin complex

    Thrombin ↓

    Hypocoagulation

    PC

    aPC PAI-1-

    V- VIII- PAI-1 ↓

    tPA ↑

    Hyperfibrinolysis

    Subendothelial type III collagen

    Von Willebrand Platelets

    TF

    Coagulation cascade

    Consumption

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  • LATE HYPERCOAGULABILITY AND THROMBOSIS RISK Hypercoagulable

    state in severe trauma patients-in a few days

    A possible explanation:protein C depletion

    Risks of thrombosis

    Schreiber MA, Differding J,Thorborg P,et al. J Trauma 2005; 58:475- 480.

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  • Coagulation dysfunctions in severe trauma

    Main topic: what is the acute coagulopathy of severe trauma:

    1.A primary phenomenon or a secondary one (dilution, hypotermia, acidosis)?

    2. A form of DIC(Disseminated

    Intravascular Coagulation) or a totally different syndrome?

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  • * Hess J R, Brohi K, Dutton RP, et al. The Coagulopathy of Trauma: A Review of Mechanisms. The Journal of Trauma: Injury, Infection, and Critical Care 2008; 65(4):748-754.

    Coagulopathy in trauma: a form of DIC or not?

    The Educational Initiative on Critical Bleeding in Trauma

    (EICBT)

    “… although there are similarities, the initiators, underlying mechanisms and management are different, and apling the generic “DIC” to trauma coagulopathy is unhelpful and potentially counterproductive.”

    Terms proposed: “Acute Traumatic Coagulopathy”

    “Early Coagulopathy of Trauma” “Trauma – Induced Coagulopathy” “Acute Coagulopathy of Trauma – Shock” *

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  • Disseminated Intravascular Coagulation

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    Current Concepts: Disseminated Intravascular Coagulation. Levi, Marcel; ten Cate, Hugo New England Journal of Medicine. 341(8):586-592, August 19, 1999.

    products.

  • Shock / Tissue hypoperfusion

    A new paradigm: Acute coagulopathy of trauma-a primary phenomenon

    Endothelium (genotype?)

    Acidemia Dilution Hypotermia

    TM ↑

    TM / Thrombin complex

    Thrombin ↓

    Hypocoagulation

    PC

    aPC PAI-1-

    V- VIII- PAI-1 ↓

    tPA ↑

    Hyperfibrinolysis

    Subendothelial type III collagen

    Von Willebrand Platelets

    TF

    Coagulation cascade

    Consumption

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  • Coagulopathy in trauma: a form of DIC or not?

    Acute Coagulopathy of

    Trauma Shock and Coagulopathy of Trauma: A Rebuttal. You Are Going Down the Wrong Path. Gardo S. The Journal of Trauma: Injury, Infection and Critical Care 2009; 67(2): 381-383

    Aird: “I think it’s dangerous to start thinking up new terms . Call it what it is, call it DIC”. 37

  • Coagulation management in severe trauma: new evidences and challlenges

    “Damage Control Hemostatic Resuscitation”:Massive

    early transfusions protocols in a 1:1:1 ratio (red cells/ plasma/platelets)

    Whole Warm Blood

    Antifibrinolytics-Tranexamic acid

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    Massive early transfusions protocols in a 1:1:1 ratio(packed red blood cells/ fresh frozen plasma/platelets):

    DAMAGE CONTROL HEMOSTATIC RESUSCITATION

    Massive Transfusion: New Insights.Sihler, Kristen; MD, MS; Napolitano, Lena; MD, FCCP Chest. 136(6):1654-1667, December 2009.

  • . Coagulation management in massive bleeding.Griffee, Matthew; DeLoughery, Thomas; Thorborg, Per Current Opinion in Anaesthesiology. 23(2):263-268, April 2010

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    Massive early transfusions protocols in a 1:1:1 ratio (packed red blood cells/ fresh frozen plasma/platelets)

  • Warm Fresh Whole Blood

    Spinella, PC, Perkins, JG, et al “Association of Warm Fresh Whole Blood with Survival” J Trauma. 2009; 66;S69-S76

    Retrospective, 354 pts transfused ≥10 U of RBCs

    Compared patients transfused Fresh Whole Blood + (PRBC, FFP) Stored components (PRBC, FFP, aPLTs)

    Groups compared equal in: Age, severity of injury Admission vital signs and labs, RBC amount Average patient was in hemorrhagic shock Base deficit of 6 and INR of 1.4

  • Days30.0025.0020.0015.0010.005.000.00

    Surv

    ival

    1.0

    0.9

    0.8

    0.7

    0.6

    0.5

    Kaplan Meier Curve of 30 day survival

    WFWB group CT group

    Log rank test, p= 0.002

    Warm Fresh Whole Blood

    Blood Components Therapy

  • Variable WFWB (n=100) CT (n=254) p value

    Pulmonary Embolism

    7 (7%) 11 (4%) 0.3

    Myocardial Infarction

    1 (1%) 0 (0%) 0.28

    Cerebral Stroke 0 (0%) 5 (2%) 0.33 ARDS 7 (7%) 7 (3%) 0.08 Deep Vein Thrombosis

    15 (15%) 21 (8%) 0.06

    Renal Failure 8 (8%) 7 (3%) 0.04

    Comparison of adverse events between study groups

  • Potential mechanisms for WFWB association with improved survival Improved function of RBCs, plasma, platelets

    in WFWB Thoroughly documented - Increased storage time for

    all blood products leads to decreased function 1-4

    WFWB use minimizes use of old RBCs Old RBCs: hyperinflammatory, immunomodulatory,

    impair vasoregulation, poor O2 delivery

    Increased anti-coagulants and preservatives in stored components

    1 Spinella PC, Crit Care Med, 2007 2 Napolitano LM, Crit Care Clinics, 2004 3 Lavee J, J Thor Cardiov Surg, 1989 4 Mohr R, J Thor Cardiov Surg, 1988

  • Whole Fresh Warm Blood Studies-Limitations Retrospective Hypothesis generating not hypothesis testing

    WFWB group had mix of WFWB, RBC, plasma Not available in database Crystalloid and colloid amounts AIS scores Cause of death

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    age Control Hemostatic Resuscitation

  • “Damage Control Resuscitation represents the most important advance in trauma care for hospitalized civilian and military casualties from this war.”

    Cordts, Brosch and Holcomb, J Trauma, 2008

  • Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial

    274 hospitals; 40 countries; 20 211 adult patients within 8 h of injury:-tranexamic acid (loading dose 1

    g over 10 min then infusion of 1 g over 8 h) OR -placebo.

    All-cause mortality significantly reduced with

    tranexamic acid (p=0·0035).

    The risk of death due to bleeding was significantly reduced (p=0·0077).

    www.thelancet.com Published online June 15, 2010 DOI:10.1016/S0140-6736(10)60835-5

  • CRASH-2 TRIAL: Conclusions

    “Tranexamic acid safely reduced the risk of death in bleeding trauma patients

    …tranexamic acid should be considered for use in bleeding trauma patients.”

    www.thelancet.com Published online June 15, 2010

    DOI:10.1016/S0140-6736(10)60835-5

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    Thank you, bye !

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    Coagulation dysfunctions in�severe trauma�Slide Number 2Slide Number 3Prevention of upper gastrointestinal bleeding (UGIB) and gastric stress ulcers (GSU) in the critically ill and postop patients Slide Number 5Slide Number 6Slide Number 7Slide Number 8Slide Number 9Slide Number 10Slide Number 11Coagulation dysfunctions in�severe traumaCoagulation dysfunctions in�severe traumaSlide Number 14��������The crucifixion of Jesus: Review of �hypothesized mechanisms of death and implications of shock and trauma-induced coagulopathy �Acute coagulopathy of trauma –�clinical definitionSlide Number 17Bleeding in trauma – epidemiology (1)Bleeding in trauma – epidemiology (2)Bleeding in trauma – epidemiology (3)Bleeding in trauma – epidemiology (4)Coagulation dysfunctions in�severe traumaThe classical paradigm:Acute coagulopathy of trauma –a secondary phenomenom Instigators of the coagulopathy in trauma: hemodilutionInstigators of the coagulopathy in trauma: hypotermiaInstigators of the coagulopathy in trauma: acidosisA new paradigm: �Acute coagulopathy of trauma-�a primary phenomenonAcute coagulopathy in trauma –new paradigm: AnticoagulationAcute coagulopathy in trauma –new paradigm: HyperfibrinolysisEndothelium as an organA new paradigm: Acute coagulopathy of trauma-a primary phenomenonLATE HYPERCOAGULABILITY AND THROMBOSIS RISK�Coagulation dysfunctions in�severe traumaCoagulopathy in trauma: a form of DIC or not? Disseminated Intravascular Coagulation A new paradigm: Acute coagulopathy of trauma-a primary phenomenonCoagulopathy in trauma: a form of DIC or not? Slide Number 38Coagulation management in severe trauma: new evidences and challlengesSlide Number 40Massive early transfusions protocols in a 1:1:1 ratio (packed red blood cells/ fresh frozen plasma/platelets)Warm Fresh Whole BloodSlide Number 43Slide Number 44Potential mechanisms for WFWB association with improved survival�Whole Fresh Warm Blood Studies-LimitationsSlide Number 48Slide Number 49Slide Number 50CRASH-2 TRIAL: ConclusionsSlide Number 52Slide Number 53Slide Number 54Slide Number 55Slide Number 56Slide Number 57Slide Number 58