Coagulopathy in trauma patients

of 66 /66

Embed Size (px)

Transcript of Coagulopathy in trauma patients

  • Coagulopathy in

    Servicio de Medicina Intensiva Grupo de Inves3gacin 49.IdiPAZ

    Hospital Universitario La Paz-Carlos III. Madrid.


    Dr. M. Quintana

  • 3

    Charlas, estudios investigacin y ayudas a congresos XXXX XXXX XXXX

    Pertenencia a Sociedades Cientficas Miembro de la Comisin de Transfusiones del HULP Miembro del Documento de Sevilla Alternativas a la Transfusin Miembro del Documento Hemomas Miembro de GIEMSA/ AWGE/NATA Socio ESCIM/SEMICYUC/SETS/SEMES/SOMIUCAM

    Hospital Universitario La Paz. Madrid

    Facultad de Medicina. Universidad Autnoma de Madrid

    | Declaracin de conflicto de intereses. 2017

  • Agradecimientos

    Dra MJ Colomina/ BCN Dr F. Ariza/Cali

    Dr N. Suarez/ Madrid SEMICYUC Group of TyATSA

    CASTYM Group

  • The white rabbit wore his eyeglasses Where do I start, your majesty? Start from the biggining replied the king. Follow un3l you get to the end. Then stop.

    Alice's Adventures in Wonderland. Lewis Carroll. 1865

  • What we know

  • trauma = bleeding

  • In 2020 it will be the second cause of dead in all group of ages. Most of the patients do not get transfusions (91%) only a few

    need massive transfusion (3%). These received more than 71% of the RBC (18% not crossed) Bleeding could be the in hospital cause of death even up to 1/3 of

    the patients who died, specially in the first 24h of admission Mortality from 39% to 57%

    Patients who recieve more than 10 RBC during their stay at the ICU ( 2.6% of all trauma patients) have a 39% mortality

    Mortality of those who recieve more than 50 RBC whitin the first 24h (0.6% of all trauma patients) have a 57% mortality

    Survival of the bleeding patients depends on the right tranfusion treatment

    Just 1 patient can consume all the blood bank of a hospital

  • and what we learn about that

  • Mortality from major trauma con2nues to be a worldwide problem, and massive haemorrhage remains a major cause of poten3ally preventable deaths. Development of coagulopathy further increases mortality considerably, and coagulopathy is a key target in the phase of bleeding. The concepts of damage control surgery (DCS) and damage control resuscita3on (DCR) have been developed during the past 10 years to ensure early control of bleeding and coagulopathy in order to reduce morbidity and mortality in trauma haemorrhage.


    Norton R, Kobusingye O. Injuries. N Engl J Med 2013; 368:17231730. Johansson PI, Stensballe J, Oliveri R, et al. How I treat pa3ents with massive hemorrhage. Blood 2014; 124:30523058. Holcomb JB, Jenkins D, Rhee P, et al. Damage control resuscita3on: directly addressing the early coagulopathy of trauma. J Trauma 2007; 62:307310. Shapiro MB, Jenkins DH, Schwab CW, et al. Damage control: collec3ve review. J Trauma 2000; 49:969978.

  • damage control hemostatic time!!!

  • Clinical issues

    Bleeding is the first cause of death in severe trauma 1

    Trauma associated coagulopathy at admission is related with trauma severity and its mortality 2

    The right haemostatic treatment is fundamental in prognosis, just below a right ventilation3

    1Sauaia A et al. J trauma 1995; 38:185-193 2Brohi K et al. J Trauma 2003; 54:1127-1130

    3MacLeod JB et al. J Trauma 2003; 55:39-44

  • Clinical issues Primary causes: mechanic injury

    Mechanic organs injury Mechanic vessels injury

    Secondary causes: coagulopathy

    Bleeding associated coagulopathy Trauma associated coagulopathy

    Lynn M Bloodline Reviews 2001

  • baseline Coagulopathy

    associated Coagulopathy

    deriva1ve Coagulopathy

    added Coagulopathy

    Coagulopathy pathophysiology

  • Defects in clot strenght due to fibrinogen and platelet deficiency

    Defects in clot stability due to hyperfibrinolisis and FXIII deficiency

    Delay in clot forma3on due to factors deficiency secondary to its consume

    Bleeding associated coagulopathy pathophysiology

    *Kozek-Langenecker S. Yearbook of Intensive care and Emergency Medicine 2007

  • Whats new

  • Coagulopathy appears early after injury, before fluid infusion at the scene.

    Coagulation factors and fibrinolysis are activated precociously Coagulopathy (more than bleeding) incidence is high Severity is related to injury and not to hypoperfusion


    Severe Trauma

    Coagulopathy (Secondary)

    Coagulopathy (Primary)

    Consume (IDC) Deple3on

    Acidosis and hypoperfusion Hypothermia Cristaloid infusion Insufficient blood products infusion




    Arch surg/vol 143 (no. 8), Aug 2008

  • Trauma associated coagulopathy is.. early, primary, acute and related to traumatic shock worsen by fluid therapy, acidosis, hypocalcemia, hypothermia...

    no concept uniformity no animals model validity developed by now. retrospective, no controls All of them include classical mortality trauma factors, but they dont study coagulation factors, fibrinolysis,..

  • 22

  • Classically, coagulopathy had a late origin due to factors deficiency lost by bleeding added to dilu3on of the exis3ng ones by fluids


    Current studies report that coagulopathy appears very early and even a third of the pa3ents already have it by admission,

    even before fluid infusion

  • 24

  • 26

  • Coagulopathy

    This group vary according to laboratory criteria used to its diagnosis, showing to be less sensitive but more specific the APTT than PT

    (4) McLeod JB, Lynn M, McKenedy MG, Cohn SM, Murtha. Early coagulopathy predicts mortality in trauma. J Trauma.2003;55: 39-44.

  • 28

  • Coagulation monitoring how?

    Experiences with quick thromboelastography could lead us to a more efficient therapy with blood products and

    haemostatic related pharmacology Kashuk JL, Moore EE, Wohlauer M, Johnson JL, Pezold M, Lawrence J,et al. Initial experiences with point-of-care rapid thrombelastography for management of life-threatening postinjury coagulopathy. Transfusion. 2011. Jul 25. doi: 10.1111/j.1537-2995.2011.03264.x. [Epub ahead of print]

  • 31

  • MJ Colomina. Valencia 28 Abril 2007

    Everybody talks about it, nobody understands it

    JH Levy, 2000

  • 34

  • 35

    The pathophysiology of coagulopathy in trauma can be stra2fied into three dis3nct types that oRen exist in varying degrees, as single en22es in the less sick pa2ent but coexist with the poten2al to amplify in the bleeding trauma pa2ent: acute trauma3c coagulopathy (ATC), coagulopathy associated with the lethal (pentad?) triad consump3ve coagulopathy

  • 36



  • 37

    Acute coagulopathy of trauma (ATC) and shock (ACoTS), is observed in 2535% of trauma pa3ents at hospital arrival, associated with significant 2ssue injury, shock and increased mortality. ATC is a hypocoagulable condi3on evidenced by increased prothrombin 2me and by prolonged cloVng 2me as evaluated by viscoelas2c haemosta2c assays (VHA). An important cause of this coagulopathy is the endogenous an3coagula3on that develops to balance the increasingly more procoagulant vasculature, represented by the systemically injured endothelium .

    MacLeod JB, Lynn M, McKenney MG, et al. Early coagulopathy predicts mortality in trauma. J Trauma 2003; 55:3944. Brohi K, Singh J, Heron M, et al. Acute trauma2c coagulopathy. J Trauma 2003; 54:11271130. Co_on BA, Faz G, Hatch QM, et al. Rapid thrombelastography delivers real2me results that predict transfusion within 1 h of admission. J Trauma 2011; 71:407417. Davenport R, Manson J, Death H, et al. Func2onal defini2on and characteriza2on of acute trauma2c coagulopathy. Crit Care Med 2011; 39:26522658. Ostrowski SR, Sorensen AM, Larsen CF, et al. Thrombelastography and biomarker profiles in acute coagulopathy of trauma: a prospec2ve study. Scand J Trauma Resusc Emerg Med 2011; 19:64. Johansson PI, Stensballe J, Rasmussen LS, et al. A high admission syndecan- 1 level, a marker of endothelial glycocalyx degrada2on, is associated with inflamma2on, protein C deple2on, fibrinolysis, and increased mortality in trauma pa2ents. Ann Surg 2011; 254:194200. Johansson PI, Henriksen HH, Stensballe J, et al. Trauma2c endotheliopathy: a prospec2ve observa2onal study of 424 severely injured pa2ents. Ann Surg 2016. [Epub ahead of print]

  • 38

    Causes contribu3ng to endogenous an3coagula3on auto-hepariniza2on protein C ac2va2on hyperfibrinolysis

    these are all related to and driven by the state of the endothelium

  • 39

    the endothelial glycocalyx, consis2ng of a thick layer of proteoglycans and glycosaminoglycans, becomes shedded secondary to the endothelial damage, resul2ng in release of heparan sulphate and similar cons3tuents with heparin-like ac3vity to the circula3ng blood (auto-hepariniza3on)

    Reduced levels of protein C, a_ributed to increased produc2on of ac2vated protein C, contribu3ng to the hypocoagulablity observed.

    Increased fibrinolysis, the most potent endogenous an2coagula2on, is observed in pa2ents with extensive and widespread endothelial ac2va2on and damage secondary to trauma, leading to enhanced release of 2ssue-type plasminogen ac2vator (tPA) from the Weibel-Palade bodies of the endothelial cells, inducing premature resolu2on of the formed clot.

    endogenous anticoagulation

    Kashuk JL, Moore EE, Sawyer M, et al. Primary fibrinolysis is integral in the pathogenesisoRheacutecoagulopathyoRrauma.AnnSurg2010;252:434442. Co_on BA, Harvin JA, Kostousouv V. Hyperfibrinolysis at admission is an uncommon but highly lethal event associated with shock and prehospital fluid administra2on. J Trauma Acute Care Surg 2012; 73:365370

  • 40

    Hyperfibrinolysis is an important cause of severe haemorrhage and occurs in severely injured pa3ents

    correla3ng with poor outcome

  • 41


  • 42

  • Hipotermia

    Hipocalcemia Acidosis


    Hipoperfusin/Acidosis Hipocalcemia

    Hiperglicemia Hipoxia


    Cortesia Dr JN Carreo

  • 44

  • 45

    The lethal triad is frequently observed in pa3ents with massive haemorrhage and encompasses

    acidosis, hypothermia and coagulopathy associated with high mortality.

  • 46

    Hypothermia-induced coagulopathy is atributed to platelet dysfunc3on, reduced coagula3on factor ac3vity and, in the most extreme, induc3on of fibrinolysis.

    Acidosis is oRen induced by hypoperfusion and to some extent excess administra3on of ionic chloride, that is NaCl, during resuscita2on.

    Acidosis impairs almost all essen2al parts of the haemosta2c process resul2ng in, for example, a change in platelet structure and shape and reduced ac2vity of coagula2on factor complexes on the cell surface, ul2mately resul3ng in impaired thrombin genera3on.

    Duchesne JC, McSwain NE Jr, Co_on BA, et al. Damage control resuscita2on: the new face of damage control. J Trauma 2010; 69:976990. DjaldeV M, Fishman P, Bessler H, et al. pH-induced platelet ultrastructural altera2ons. A possible mechanism for impaired platelet aggrega2on. Arch Surg 1979; 114:707710. Mar2ni WZ, Dubick MA, Pusateri AE, et al. Does bicarbonate correct coagula2on func2on impaired by acidosis in swine? J Trauma 2006; 61:99106. Mar2ni WZ, Holcomb JB. Acidosis and coagulopathy: the differen2al effects on fibrinogen synthesis and breakdown in pigs. Ann Surg 2007; 246:831835.

  • 47

    Both hypothermia and acidosis impair fibrinogen availability as hypothermia inhibits fibrinogen synthesis and acidosis accelerates fibrinogen degrada3on, leading to hypofibrinogenemia.

  • 48


  • 49

    Tissue injury induces an immediate ac3va3on of the coagula3on system through exposure of 2ssue factor and other 2ssue or intracellular components, which promotes excessive thrombin genera3on. To protect the organism against intravascular thrombin by excess fibrin forma2on, the ini3al coagula3on ac3va3on is followed by enhanced plasminogen ac3va3on and fibrinoly3c ac3vity, and to prevent rebleeding by fibrinolysis, the plasminogen ac2vator inhibitor (PAI)-1 level increases progressively in the hours and days hereaRer.

    Drake TA, Cheng J, Chang A, et al. Expression of 3ssue factor, thrombomodulin, and E-selec3n in baboons with lethal Escherichia coli sepsis. Am J Pathol 1993; 142:14581470.

  • 50

    Importantly, extensive 3ssue injury and accompanying shock induces widespread endothelial injury, resul3ng in a prothrombo3c state of the microvasculature that further promotes coagula2on factor and platelet consump2on, ul3mately leading to coagulopathy and further risk of haemorrhage Occasionally, the normal an2coagulant and fibrinoly2c control mechanisms fail to restrict the haemosta3c ac3vity to the area of 3ssue damage resul3ng in disseminated intravascular coagula3on (DIC). Drake TA, Cheng J, Chang A, et al. Expression of 3ssue factor, thrombomodulin, and E-selec3n in baboons with lethal Escherichia coli sepsis. Am J Pathol 1993; 142:14581470.

  • 51

    Another important driver of consump3ve coagulopathy is the accompanying inflammatory response, which by inducing 2ssue factor expression on various cells supports a viscous cycle of reciprocal ac3va3on of the coagula3on system.

    A cri3cal driver of consump3ve coagulopathy is sympathoadrenal overac3va3on.

    Gando S, Sawamura A, Hayakawa M. Trauma, shock, and disseminated intravascular coagula3on: lessons from the classical literature. Ann Surg 2011; 254:1019. Levi M, van der PT. Inflamma3on and coagula3on. Crit Care Med 2010; 38:S26S34.

  • 52

    This occurs in response to excessive 3ssue injury and shock/hypoxia, leading to release of catecholamines in concentra2ons that are directly toxic for the endothelium, ul2mately resul2ng in further endothelial damage and downstream coagulopathy.

    Catecholamines are potent ac3vators of platelets and promote coagula3on factor release and ac3va3on

    Makhmudov RM, Mamedov Y, Dolgov VV, et al. Catecholamine-mediated injury to endothelium in rabbit perfused aorta: a quan3ta3ve analysis by scanning electron microscopy. Cor Vasa 1985; 27:456463. Cannon WB. A considera3on of possible toxic and nervous factors in the produc3on of trauma3c shock. Ann Surg 1934; 100:704713.

  • and whats about dilution

  • 54

    Coagulopathy secondary to dilu3on of coagula3on factors and platelets is also an important part of the lethal triad and dilu2onal coagulopathy is further aggravated when synthe3c colloids are administered. Hydroxyethyl starch (HES) causes an efflux of plasma proteins from the blood to the inters22al space, reduces the plasma concentra2on of coagula2on factor VIII and von Willebrand factor, inhibits platelet func2on and interferes with the interac2on between ac2vated FXIII and fibrin polymers ->This may contribute to the increased bleeding and mortality of HES administra3on in bleeding trauma Be careful with the quan1ty and the moment of administra3on!!!!

  • 55

    Administra3on of blood products also contributes significantly to coagulopathy in massive bleeding and the best haemosta2c capacity possible to accomplish with administra2on of balanced RBCs, plasma and platelets (1 : 1 : 1) results in a haematocrit around 30%, a coagula2on factor concentra2on 60% and a platelet count of 80 109 /l,

    which is far below normal concentra3ons

  • We know the problm but whats about the solution?

  • Bleeding Management

    First: STOP THE BLEEDING Second: Transfusion

    Third: Coagulophaty Treatment

  • 59

  • Defects in clot strenght due to fibrinogen and platelet deficiency

    Defects in clot stability due to hyperfibrinolisis and FXIII deficiency

    Delay in clot forma3on due to factors deficiency secondary to its consume

    Bleeding associated coagulopathy pathophysiology

    *Kozek-Langenecker S. Yearbook of Intensive care and Emergency Medicine 2007

  • Coagulophaty Treatment physiopathological objec3ves

    Trombin (genera2on) (Func2onal) fibrinogen (Func2onal) Platelets (Modula2on of ) fibrinolysis


  • What do you need to take


  • DCR: main components

    Haemosta3c resuscita3on early use of blood products to avoid further coagulopathy in respect to fluids and dilu2on.

    Permissive hypotensive resuscita3on to decrease bleeding and support bleeding control.

    Regaining homeostasis and avoid further coagulopathy related to hypothermia, acidosis and electrolyte disturbances (hypocalcemia,hyperkaliemia); hypoxia and hyperglicemia 63

  • Key points

    Coagulopathy is a key target for diagnosis and aggressive treatment in the bleeding phase.

    Haemosta3c resuscita3on aims to control coagulopathy early and consistently in bleeding trauma pa3ents.


  • 65

    trauma pa3ents present with an inherent risk of coagulopathy

    concurrent with the rapidity of changes in the haemosta3c system during massive bleeding

    the importance of rapid diagnosis and therapy cannot be stressed enough

    think in lethal pentad use prohemosta3c with head

  • Thank you for your attention


    [email protected]