The role of Viscoelastic Hemostatic Assays in critically ill patients

Transcription

1 The role of Viscoelastic Hemostatic Assays in critically ill patients Mauro Panigada, MD Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Milano 7 Aprile UK NEQAS USERS MEETING

2 Thromboelastography/metry Dynamic tests based on the visco-elastic properties of blood during the coagulation process

3 1958 thrombotic postoperative risk Fibrinolysis in OLTX 1990 Computerized

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8 Vantaggi della tromboelastografia Distinzione tra sanguinamento chirurgico e non Eseguibile su sangue intero senza la necessità di utilizzare provette con trisodio citrato (entro 4 minuti dal prelievo) Valutazione globale e dinamica del profilo emostatico Valutazione rapida della fibrinolisi Velocità di esecuzione: Metodica P-O-C Tempo di esecuzione del test 20 minuti Test dell emostasi alla temperatura corporea del paziente

9 Acquired postoperative coagulopathy Limitations of routine coagulation tests to guide coagulation management in bleeding: Delay in test reports They cannot differentiate the predominant mechanism i.e. prolonged aptt: intrinsic coagulation factor deficiency requiring specific substitution fibrinogen deficiency requiring fibrinogen substitution hypothermia requiring rewarming heparinization requiring protamin reversal hyperfibrinolysis requiring antifibrinolytic drugs Kozek-Langenecker SA et al. Curr Opin Crit Care 2014, Aug;20(4):460-6.

10 TEG EFFECTIVE IN REDUCING TRANSFUSION REQUIREMENTS Shore-Lesserson L et al. Anesth Analg 1999, Mar;88(2):312-9.

11 Functional fibrinogen assay Harr JN et al. Shock 2013, Jan;39(1):45-9.

12 Fibrinogen and Trauma VHA better than global tests Park MS et al. J Trauma. 2009; 67(2): Martini W et al. J Trauma. 2008; 65(3): Counts RB et al. Ann Surg. 1979; 190(1):91-99 Lucas CE et al. Am Surg. 1981; 47(3): Spahn DR et al. Crit Care 2013;17(2):R76 Cell-based model (Hoffman) European trauma centers (Fibrinogen) vs American (Platelets)

13 Algorithm for bleeding patients (Danish Society of Blood Banking/Clinical Immunology) Stensballe J et al. Curr Opin Anaesthesiol 2014, Apr;27(2):212-8.

14 Kang YG et al. Anesth Analg 1985, Sep 1;64(9):

15 Rebalanced hemostasis Lisman T. Blood 2010, Aug 12;116(6):878-85

16 A procoagulant state is preserved in cirrhosis Thrombin generation is indistinguishable in patients with stable cirrhosis from healthy volunteers Provided the addition to the test mixture of thrombomodulin, a physiological endothelial activator of protein C Provided that the platelet count is > 60000/L Tripodi A et al. Hepatology 2005; 41: Tripodi A et al. Hepatology 2006; 44: Tripodi A et al. J Hepatol 2013; 59:

17 Invasive procedures in cirrhosis 30 pts TEG guided transfusion strategy, 30 pts SOC guided TEG group receive FFP if the reaction time (r native) > 40mm and/or PLT if maximum amplitude (MA) <30mm. SOC received FFP 10 ml/ with INR > 1.8 and/or received PLT if platelet < 50x109/L Endpoints blood product use and bleeding complications All SOC received blood products compared to only 5 TEG Only one bleeding in SOC group De Pietri L et al. Hepatology 2015, Sep 4.

18 Perioperative measurement of anticoagulation 24 pts scheduled for ortho surgery Enoxaparin at postoperative timepoints Klein SM et al. Anesth Analg 2000, Nov;91(5):

19 48 pregnant thrombophilic patients Delta R to measure enoxaparin coaugulation Able to differentiate thrombophilic from normal

20 Typical TEG tracings during heparin therapy No effect of heparin Moderate effect of heparin Excessive effect of heparin

21 Retrospective analysis of 32 patients in ECMO for severe respiratory failure (12/2011 8/2013) Frequency distribution of R times without heparinase (316 paired k kh TEG) flat-line in 46% of the samples aptt = 1.67 [ ] ratio ACT = 173 [ ] sec R-KH TEG = 9 [7 11] min Heparin = 16 [12 20] IU/Kg/die Panigada M, et al. ASAIO J 2015, Dec 30.

22 Prospective Randomized Study Of Anticoagulation Monitoring With Thromboelastography Versus aptt During Extracorporeal Membrane Oxygenation In Adults Feasibility: Aim: to compare to standardized protocol for anticoagulation management during ECMO: 1. TEG: study group 2. aptt: control group N. tests in range N. of heparin dose changes N. of protocol violation Safety: N. hemorrhagic/thrombotic events Blood transfusion Artificial lung failure/changes (score)

23 The whole blood viscoelastic assay TEG R displayed linearity towards fixed concentrations of dabigatran and correlated strongly to the current goldstandard tests Hemoclot and ECT, for assessing dabigatran

24 High mortality rate with elevated PAI-1 90 pts. severe sepsis or septic shock randomized to tight glycemic control or conventional glycemic control Fibrinolysis was inhibited in only about 40% of the patients Mortality at 90 days was doubled in group with inhibited fibrinolysis 32

25 Fibrinolysis PAI-1 TEG High costs Long turnaround time Relatively low costs Point of Care 33

26 Sepsis-induced impairment of fibrinolysis detected at UK- TEG was associated with increased markers of cellular damage, morbidity and mortality Panigada M et al. PLoS One 2015;10(8):e

27 Confirmed previous findings The lysis time was strongly associated with the time to MCF (r = 0.73, p<0.001) Coexistence of impaired fibrinolysis with defective fibrin formation

28 Limiti della tromboelastografia Metodica originariamente qualitativa, solo recentemente divenuta quantitativa grazie allo sviluppo del tromboelastografo e di software dedicati Necessità di una standardizzazione Preparazione del campione operatore dipendente: Corretta esecuzione del prelievo Maneggiare con cura il campione per evitare l attivazione della coagulazione Pipettatura corretta Avviare il test entro 4 minuti dal prelievo Limiti operatore indipendenti: Vibrazioni o shocks interferiscono con la formazione del coagulo e con la funzione piastrinica

29 Inter/intra-operator variability CV is the ratio between SD/mean = standardized measure of dispersion CVs significantly lower for ROTEM compared with TEG ROTEM may be better suited for use in a multiuser environment

30 Effect of different activators on TEG No significant difference between any of the TEG clot forming variables was found when WB was activated by kaolin or TF (1:17,000) Only the initiation phase is accelerated not the coagulation process not influencing the amplification or propagation phase The CV% varied between 4 and 14 In the two-way ANOVA with day as a fixed effect and person as a random effect, the effect of day was only significant in 2 of the 36 combinations of variable and assay. Johansson PI et al. Transfusion 2008, Nov;48(11):

31 TEG on native blood yields the most reliable results TEG blood coagulation parameters in recalcified citrated blood differ from those in native blood and change signifcantly during 30 ± 60 min of storage but remain stable between 1 and 8 h Camenzind V et al. Anesthesiology 2000, May;92(5):

32 Effect of blood sample storage in citrate R time was significantly affected (12%) when samples rested for 0 and 30 minutes TEG analysis in a laboratory setting may be performed by kaolin activation of citrated WB Johansson PI et al. Transfusion 2008, Nov;48(11):

33 Unmet needs for the clinician Involvement of central lab? Routine quality control? Calibration verification normal values? Reagents? Involvement of coagulation specialist? (Usually unaware of POC techniques)

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