REVIEW URRENT C OPINION
Viscoelastic guidance of resuscitation Jakob Stensballe a,b, Sisse R. Ostrowski b, and Pa¨r I. Johansson b,c
Purpose of review Bleeding in trauma carries a high mortality and is increased in case of coagulopathy. Our understanding of hemostasis and coagulopathy has improved, leading to a change in the protocols for hemostatic monitoring. This review describes the current state of evidence supporting the use of viscoelastic hemostatic assays to guide trauma resuscitation. Recent findings Viscoelastic hemostatic assays such as thrombelastography and rotational thrombelastometry have shown to reduce bleeding, transfusion of fresh frozen plasma and platelets, and possibly mortality in different surgical populations. In trauma care, viscoelastic hemostatic assays allows for rapid and timely identification of coagulopathy and individualized, goal-directed transfusion therapy. As part of the resuscitation concept, viscoelastic hemostatic assays seem to improve outcome also in trauma; however, there is a need for randomized clinical trials to confirm this. Summary We are moving toward avoiding coagulopathy by individualized, goal-directed transfusion therapy, using viscoelastic hemostatic assays to guide ongoing resuscitation of actively bleeding patients in a goaldirected manner. Keywords coagulopathy, resuscitation, trauma, viscoelastic hemostatic monitoring
INTRODUCTION Bleeding is a leading cause of mortality in trauma. Our understanding of hemostasis during the last 10 years has emphasized that its monitoring should be performed in accordance with the cellbased model [1], evaluating all the elements of whole blood simultaneously. Disturbed clotting, denominated as coagulopathy, is associated with increased mortality, bleeding and transfusion needs in trauma [2,3], but coagulopathy is potentially reversible. Trauma-induced coagulopathy (TIC) is observed in 25–35% of trauma patients on hospital arrival. It has been described as a unique entity developing early in the postinjury phase, but in parallel with and independent of other causes of coagulopathy such as dilution and consumption of coagulation factors and platelets, hypothermia and acidosis [3]. The classical literature describes TIC as induced by shock and hypoperfusion, leading to the activation of the anticoagulant and fibrinolytic pathways mediated via the protein C-pathway, but several explanatory models currently exist [4], and our group recently found that increased activated protein C was associated with the degree of tissue injury [5,6 ,7]. &
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Hemostasis according to the cell-based model is described in the phases of initiation, amplification and propagation, from clot formation to clot lysis, with participation of all circulating plasmatic and cellular components [1]. Thrombin generation is central for clot development and strength. It primarily occurs on the surface of activated platelets and, hence, platelets and thrombin generation are closely related to the development of coagulopathy [8,9]. Clotting can be assessed by plasma-based coagulation tests (PBCTs) such as activated partial thromboplastin time (APTT), prothrombin a Department of Anesthesia, Centre of Head and Orthopedics, Copenhagen University Hospital, Rigshospitalet, bSection for Transfusion Medicine, Capital Region Blood Bank, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark and cDivision of Acute Care Surgery, Department of Surgery, Centre for Translational Injury Research (CeTIR), University of Texas Medical School at Houston, Houston, Texas, USA
Correspondence to Jakob Stensballe, MD, PhD, Section for Transfusion Medicine, Capital Region Blood Bank, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. Tel: +45 27538687; e-mail: [email protected] Curr Opin Anesthesiol 2014, 27:212–218 DOI:10.1097/ACO.0000000000000051 Volume 27 Number 2 April 2014
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Viscoelastic guidance of resuscitation Stensballe et al.
THE VISCOELASTICAL HEMOSTATIC ASSAYS TECHNOLOGY OF THROMBELASTOGRAPHY AND ROTATIONAL THROMBELASTOMETRY
KEY POINTS Routine coagulation tests only reflect the plasmatic activity of hemostasis and consequently cannot be used to monitor coagulopathy.
The VHA technology results in a visual profile, or trace, and variables with reference values (Fig. 1, Table 1). Briefly, the collected whole-blood sample is placed in a special designed cup. Inside the cup is suspended a pin connected to a detector system (a torsion wire in TEG, an optical detector in ROTEM), and the cup and pin are oscillated relative to each other with movement initiated from either the cup (TEG) or the pin (ROTEM). As fibrin strings form between the cup and pin, the transmitted rotation from the cup to pin (TEG) or the impedance of the rotation of the pin (ROTEM) are detected at the pin and a trace is generated as seen in Fig. 1. The standard assays are with kaolin activation in TEG, kaolin and tissue factor in RapidTEG and tissue factor or kaolin activation, respectively, in the ExTEM and InTEM assays in ROTEM, and several other dedicated assays are available from both technologies. The presence of heparins can be evaluated by adding heparinase to the cups in the heparinase assay in TEG and RapidTEG, and the HepTEM assay in ROTEM. The contribution of fibrinogen to clot strength can be evaluated in the functional fibrinogen assay in TEG and the FibTEM assay in ROTEM, and this is achieved by adding platelet inhibition agents to the cups in order to evaluate the fibrinogen and fibrin contribution to clot strength and thereby the functional level of fibrinogen [16]. Several algorithms on VHA-guided therapy are currently available and adapted to local resources and different patient populations [17,18]. However, the mainstay in the algorithms
Viscoelastic hemostatic assays such as TEG or ROTEM measures the clot formation and breakdown in whole blood, enabling us to rapidly and timely identify coagulopathy and act upon. As part of the resuscitation concept, viscoelastic hemostatic assays seem to improve outcome in trauma.
time (PT) and international normalized ratio (INR), and by functional whole-blood test such as the viscoelastical hemostatic assays (VHA), thrombelastography (TEG) (Haemonetic Corp, Niles, Illinois, USA) and rotational thrombelastometry (ROTEM) (Tem International, Munich, Germany) [10]. PBCT solely evaluates plasmatic activation without the cellular components of whole blood, and they do not reflect the physiology of cellbased thrombin generation [11 ]. In the VHA tests, a close association exists between thrombin generation and the profile of amplification and propagation, providing evidence that VHA are able to detect coagulopathies secondary to impaired thrombin generation [8,9,12 ,13 ]. Furthermore, VHA can differentiate between low fibrinogen level and function vs. reduced platelet function as the cause of impaired clot strength, and VHA is the only readily available clinical hemostatic test that provides an assessment of systemic fibrinolysis as seen in severe trauma [14,15]. &
&
&
Clot Clot Clot initiation kinetics strength Fibrinolysis Angle A10
R CT
MA MCF
TEG ROTEM
Ly30 Li30
A10 Angle
MA/MCF
R/CT
5
10
Ly30/Li30
15
Time (min)
FIGURE 1. TEG and ROTEM parameters in the different phases of clot initiation, amplification, propagation and degradation. TEG: R, reaction time; Angle; MA, maximum amplitude; Ly30, hyperfibrinolysis after 30 min; ROTEM: CT, clotting time; A10, amplitude after 10 min; Li30, hyperfibrinolysis after 30 min; MCF, maximum clot firmness. ROTEM, rotational thrombelastometry; TEG, thrombelastography. 0952-7907 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
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213
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Trauma and transfusion Table 1. TEG and ROTEM treatment algorithm for bleeding patients as used in Copenhagen, and adopted across Denmark according to the Danish Society of Blood Banking/Clinical Immunology TEG
ROTEM
Coagulopathy
Treatment options
R 10–14 min
ExTEM CT 80–100 s
Coagulation factors #
FFP 20 ml/kg
Coagulation factors ##
FFP 30 ml/kg
InTEM CT 200–240 s R >14 min
ExTEM CT >100 s InTEM CT >240 s
FFMA 7–14 mm
FibTEM MCF 6–9 mm
Fibrinogen #
FFP 20 ml/kg or cryoprecipitate 3 ml/kg or fibrinogen concentrate 20 mg/kg
FFMA 0–7 mm
FibTEM MCF 0–6 mm
Fibrinogen ##
FFP 30 ml/kg or cryoprecipitate 5 ml/kg or fibrinogen concentrate 30 mg/kg
MA 45–49 mm and FFMA >14 mm
ExTEM A10 35–42 mm and FibTEM 10 mm
Platelets #
Platelets 5 ml/kg
ExTEM A10 8%
ExTEM Li30 2 min
InTEM CT/HepTEM CT >1.25
Heparinazation
Protamine 50–100 mg or FFP 10–20 ml/kg
ExTEM MCF
Viscoelastic guidance of resuscitation Jakob Stensballe a,b, Sisse R. Ostrowski b, and Pa¨r I. Johansson b,c
Purpose of review Bleeding in trauma carries a high mortality and is increased in case of coagulopathy. Our understanding of hemostasis and coagulopathy has improved, leading to a change in the protocols for hemostatic monitoring. This review describes the current state of evidence supporting the use of viscoelastic hemostatic assays to guide trauma resuscitation. Recent findings Viscoelastic hemostatic assays such as thrombelastography and rotational thrombelastometry have shown to reduce bleeding, transfusion of fresh frozen plasma and platelets, and possibly mortality in different surgical populations. In trauma care, viscoelastic hemostatic assays allows for rapid and timely identification of coagulopathy and individualized, goal-directed transfusion therapy. As part of the resuscitation concept, viscoelastic hemostatic assays seem to improve outcome also in trauma; however, there is a need for randomized clinical trials to confirm this. Summary We are moving toward avoiding coagulopathy by individualized, goal-directed transfusion therapy, using viscoelastic hemostatic assays to guide ongoing resuscitation of actively bleeding patients in a goaldirected manner. Keywords coagulopathy, resuscitation, trauma, viscoelastic hemostatic monitoring
INTRODUCTION Bleeding is a leading cause of mortality in trauma. Our understanding of hemostasis during the last 10 years has emphasized that its monitoring should be performed in accordance with the cellbased model [1], evaluating all the elements of whole blood simultaneously. Disturbed clotting, denominated as coagulopathy, is associated with increased mortality, bleeding and transfusion needs in trauma [2,3], but coagulopathy is potentially reversible. Trauma-induced coagulopathy (TIC) is observed in 25–35% of trauma patients on hospital arrival. It has been described as a unique entity developing early in the postinjury phase, but in parallel with and independent of other causes of coagulopathy such as dilution and consumption of coagulation factors and platelets, hypothermia and acidosis [3]. The classical literature describes TIC as induced by shock and hypoperfusion, leading to the activation of the anticoagulant and fibrinolytic pathways mediated via the protein C-pathway, but several explanatory models currently exist [4], and our group recently found that increased activated protein C was associated with the degree of tissue injury [5,6 ,7]. &
www.co-anesthesiology.com
Hemostasis according to the cell-based model is described in the phases of initiation, amplification and propagation, from clot formation to clot lysis, with participation of all circulating plasmatic and cellular components [1]. Thrombin generation is central for clot development and strength. It primarily occurs on the surface of activated platelets and, hence, platelets and thrombin generation are closely related to the development of coagulopathy [8,9]. Clotting can be assessed by plasma-based coagulation tests (PBCTs) such as activated partial thromboplastin time (APTT), prothrombin a Department of Anesthesia, Centre of Head and Orthopedics, Copenhagen University Hospital, Rigshospitalet, bSection for Transfusion Medicine, Capital Region Blood Bank, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark and cDivision of Acute Care Surgery, Department of Surgery, Centre for Translational Injury Research (CeTIR), University of Texas Medical School at Houston, Houston, Texas, USA
Correspondence to Jakob Stensballe, MD, PhD, Section for Transfusion Medicine, Capital Region Blood Bank, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. Tel: +45 27538687; e-mail: [email protected] Curr Opin Anesthesiol 2014, 27:212–218 DOI:10.1097/ACO.0000000000000051 Volume 27 Number 2 April 2014
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Viscoelastic guidance of resuscitation Stensballe et al.
THE VISCOELASTICAL HEMOSTATIC ASSAYS TECHNOLOGY OF THROMBELASTOGRAPHY AND ROTATIONAL THROMBELASTOMETRY
KEY POINTS Routine coagulation tests only reflect the plasmatic activity of hemostasis and consequently cannot be used to monitor coagulopathy.
The VHA technology results in a visual profile, or trace, and variables with reference values (Fig. 1, Table 1). Briefly, the collected whole-blood sample is placed in a special designed cup. Inside the cup is suspended a pin connected to a detector system (a torsion wire in TEG, an optical detector in ROTEM), and the cup and pin are oscillated relative to each other with movement initiated from either the cup (TEG) or the pin (ROTEM). As fibrin strings form between the cup and pin, the transmitted rotation from the cup to pin (TEG) or the impedance of the rotation of the pin (ROTEM) are detected at the pin and a trace is generated as seen in Fig. 1. The standard assays are with kaolin activation in TEG, kaolin and tissue factor in RapidTEG and tissue factor or kaolin activation, respectively, in the ExTEM and InTEM assays in ROTEM, and several other dedicated assays are available from both technologies. The presence of heparins can be evaluated by adding heparinase to the cups in the heparinase assay in TEG and RapidTEG, and the HepTEM assay in ROTEM. The contribution of fibrinogen to clot strength can be evaluated in the functional fibrinogen assay in TEG and the FibTEM assay in ROTEM, and this is achieved by adding platelet inhibition agents to the cups in order to evaluate the fibrinogen and fibrin contribution to clot strength and thereby the functional level of fibrinogen [16]. Several algorithms on VHA-guided therapy are currently available and adapted to local resources and different patient populations [17,18]. However, the mainstay in the algorithms
Viscoelastic hemostatic assays such as TEG or ROTEM measures the clot formation and breakdown in whole blood, enabling us to rapidly and timely identify coagulopathy and act upon. As part of the resuscitation concept, viscoelastic hemostatic assays seem to improve outcome in trauma.
time (PT) and international normalized ratio (INR), and by functional whole-blood test such as the viscoelastical hemostatic assays (VHA), thrombelastography (TEG) (Haemonetic Corp, Niles, Illinois, USA) and rotational thrombelastometry (ROTEM) (Tem International, Munich, Germany) [10]. PBCT solely evaluates plasmatic activation without the cellular components of whole blood, and they do not reflect the physiology of cellbased thrombin generation [11 ]. In the VHA tests, a close association exists between thrombin generation and the profile of amplification and propagation, providing evidence that VHA are able to detect coagulopathies secondary to impaired thrombin generation [8,9,12 ,13 ]. Furthermore, VHA can differentiate between low fibrinogen level and function vs. reduced platelet function as the cause of impaired clot strength, and VHA is the only readily available clinical hemostatic test that provides an assessment of systemic fibrinolysis as seen in severe trauma [14,15]. &
&
&
Clot Clot Clot initiation kinetics strength Fibrinolysis Angle A10
R CT
MA MCF
TEG ROTEM
Ly30 Li30
A10 Angle
MA/MCF
R/CT
5
10
Ly30/Li30
15
Time (min)
FIGURE 1. TEG and ROTEM parameters in the different phases of clot initiation, amplification, propagation and degradation. TEG: R, reaction time; Angle; MA, maximum amplitude; Ly30, hyperfibrinolysis after 30 min; ROTEM: CT, clotting time; A10, amplitude after 10 min; Li30, hyperfibrinolysis after 30 min; MCF, maximum clot firmness. ROTEM, rotational thrombelastometry; TEG, thrombelastography. 0952-7907 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
www.co-anesthesiology.com
213
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Trauma and transfusion Table 1. TEG and ROTEM treatment algorithm for bleeding patients as used in Copenhagen, and adopted across Denmark according to the Danish Society of Blood Banking/Clinical Immunology TEG
ROTEM
Coagulopathy
Treatment options
R 10–14 min
ExTEM CT 80–100 s
Coagulation factors #
FFP 20 ml/kg
Coagulation factors ##
FFP 30 ml/kg
InTEM CT 200–240 s R >14 min
ExTEM CT >100 s InTEM CT >240 s
FFMA 7–14 mm
FibTEM MCF 6–9 mm
Fibrinogen #
FFP 20 ml/kg or cryoprecipitate 3 ml/kg or fibrinogen concentrate 20 mg/kg
FFMA 0–7 mm
FibTEM MCF 0–6 mm
Fibrinogen ##
FFP 30 ml/kg or cryoprecipitate 5 ml/kg or fibrinogen concentrate 30 mg/kg
MA 45–49 mm and FFMA >14 mm
ExTEM A10 35–42 mm and FibTEM 10 mm
Platelets #
Platelets 5 ml/kg
ExTEM A10 8%
ExTEM Li30 2 min
InTEM CT/HepTEM CT >1.25
Heparinazation
Protamine 50–100 mg or FFP 10–20 ml/kg
ExTEM MCF
