Silverstein and Hopper Chapter 187: Viscoelastic Monitoring

What do viscoelastic tests measure?

• Kinetics of clot formation (time needed for the clot to form)

• Mechanical properties of the clot (tensile strength)

• Time to dissolution of the clot (fibrinolysis)

How do TEG and ROTEM instruments work?

• Consist of a pin attached to a torsion wire that is introduced into a cup

• The blood sample is incubated with an activator and a specific temperature in a cup above which is an axis connected to an optical detection system

• Movement causes low shear conditions

• As long as the blood remains in a liquid state, the pin rotates freely

• Fibrin strands that are forming gradually limit the rotation of this pin

• The firmer the clot (increase in its viscoelastic properties), the more the resistance increases, and the more the pin's rotation is hampered

• Alternative rotary movement of the pin are detected by an optical system and their variations are translated into a tracing in which the amplitude of the wire oscillation is on the y-axis and the time is on the x-axis

• Amplitude is directly converted to physical units that represent the strength of the formed clot

Angle of Rotation in ROTEM

4.75 degrees

Angle of Rotation in TEG

4.45 degrees

What initiates the rotary movement in ROTEM?

The pin

What initiates the rotary movement in TEG?

The cup

PROVETS Recommendations

• Results from various analyzers are not directly comparable and extrapolation of the results from one machine to the other should be avoided

  • Recommended that each site create their own site specific reference values for each machine

• Jugular venipuncture recommended but samples from IVCs can be used if there is easy withdrawal of blood

• Evacuated blood tubes and 21 gauge needles or larger suggested

  • Collect blood samples in a tube with 3.2% buffered sodium citrate in a strict 1:9 ratio of citrate to blood and then held at room temperature for 30 minutes prior to analysis

• For clinical practice, conduct tests long enough to obtain all relevant values

• For research, conduct all tests long enough to obtain the values of the fibrinolysis parameters

• All four standard TEG and ROTEM variables should be universally reported and the reporting of shear elastic modulus (G) is encouraged

• Contemporary values for hematocrit, fibrinogen concentration, and platelet count should be reported in addition to the TEG/ROTEM results

What is the diagram produced by ROTEM called?

Thromboelastomer

What is the diagram produced by TEG called?

Thromboelastogram

Draw the TEG/ROTEM Diagram

Initiation Phase of TEG/ROTEM

Corresponds to the time between the beginning of the analysis and the formation of the first strands of fibrin; the end of this phase is characterized by the divergence of the plot into two curves

Stabilization Phase of TEG/ROTEM

Corresponds to the time between the end of initiation and the maximum separation of the two curves; represents the formation of the clot

Lysis Phase of TEG/ROTEM

Corresponds to the progressive convergence time of the two curves until the end of the test or the complete convergence of the two curves; describes fibrinolysis

Time from Activation of the Test to a Clot Firmness of 2 mm

CT (coagulation time) - ROTEM

R (reaction time) - TEG

What does CT/R correspond with in ROTEM/TEG?

Corresponds to the initiation phase of coagulation until the appearance of the first fibrin filaments and activated platelets

What are the factors that most contribute to CT/R in ROTEM/TEG?

Hematocrit and plasma concentrations of factors, V, VII, IX, and X

Time from End of CT or R until a Clot Firmness of 20 mm point has been reached

CFT (clot formation time) - ROTEM

K - TEG

What does CFT/K indicate in ROTEM/TEG?

The speed of appearance of fibrin and the connection of fibrin filaments within the clot

Represents the speed of clot formation

What are the most significant contributing factors to CFT/K in ROTEM/TEG?

Hematocrit, platelet count, and plasma fibrinogen and factor V concentrations

Alpha Angle (a Angle)

Expressed in degrees

The angle formed between the baseline and a tangential line to the ROTEM at CT or the TEG at R (2 mm amplitude)

What does the alpha angle describe?

The kinetics of clot formation

What are the factors that contribute most to the alpha angle?

Hematocrit, platelet count, and the plasma concentrations of fibrinogen, factor V, and factor IX

Maximum Amplitude of the Clot

Maximum clot firmness (MCF) - ROTEM

Maximum amplitude (MA) -TEG

What does MCF/MA measure in ROTEM/TEG?

The final strength of the clot and is the expression of its ultimate viscoelastic properties

What is MCF/MA primarily determined by in ROTEM/TEG?

Hematocrit, platelet count, and plasma fibrinogen concentration

What do amplitudes at 5, 10, 15, and 20 minutes (A5, A10, A15, A20) represent?

The firmness of the clot 5, 10, 15, and 20 minutes after the end of CT/R

What are A5, A10, A15, and A20 used to predict?

MCF/MA at an earlier stage

Seldom reported in veterinary medicine

Lysis Indices at 30, 45, and 60 Minutes

Li30, Li45, Li60 - ROTEM

Ly30, Ly45, Ly60 - TEG

Ratio between the value of the amplitude of the clot measure at 30, 45, and 60. minutes after the end of CT/R to that of the MCF/MA

What do the Li30, Li45, Li60/Ly30, Ly45, Ly60 describe?

The progression of fibrinolysis detected during the analysis

Maximum Lysis (ML)

Maximum fibrinolysis detected during the analysis

Defined as the ratio between the lowest amplitude after reaching the MCF/MA and the MCF/MA

Maximum Clot Elasticity (MCE) Formulas

ROTEM: (100 x MCF):(100-MCF)

TEG: (100 x MA): (100-MA)

Shear Elastic Modulus Strength (G) Equations

50 x MCE

ROTEM: (500 x MCF): (100- MCF)

TEG: (5000 x MA): (100-MA)

Thrombodynamic Potential Index (TPI) Equations

ROTEM: MCE:CFT

TEG: MCE:K

Coagulation Index (CI) Equations

TEG: 0.1227 x R + 0.0092 x CFT + 0.1655 X MA - 0.0241 x a - 5.0220

Clot Elasticity (CE) Equation

• CE = (100 x A):(100 -A)

  • A - amplitude of the clot

What does a CI greater than 4 suggest?

A hypercoagulable profile

What does a CI less than -4 suggest?

A hypocoagulable profile

What is the activator added to evaluate the extrinsic pathway with ROTEM/TEG?

Tissue factor (exTEM for ROTEM)

What is the activator added to evaluate the intrinsic pathway with ROTEM/TEG?

• Activator is ellagic acid (inTEM for ROTEM) and kaolin or ellagic acid (for TEG)

  • Characterized by an elongation of the CT or R compared with the assays evaluating the extrinsic pathway

Fibrinogen Function (fibTEM)

• Evaluates fibrinogen function by adding tissue factor and cytochalazine D, a powerful inhibitor of platelet aggregation

  • Characterized by lower amplitudes and MCF compared with the exTEM assay

Heparinase-Based TEM (hepTEM)

Evaluates hemostasis by initiating the intrinsic pathway (activation by ellagic acid) while inhibiting the activity of heparins by adding heparinase

Aprotinin-Based TEM (apTEM)

Evaluates fibinolysis (activation of hemostasis by tissue factor) by adding an antifibrinolytic, aprotinin

VCM-VET

• Uses fresh, nonanticoagulated blood that is tested immediately after sampling

• Relies on viscoelastic properties of whole blood

• Does not routinely utilize activators

• Test cartridges are preheated to 37*C on the heating plate

• Blood is placed in the cup associated with the cartridge and the cartridge is placed inside the machine

• Cartridge has two flexible arms, one of which is moved by the motor of the analyzer and the other is unattached, both have a built-in glass plate

• Blood flows in between the glass plates and as blood clots and fibrin forms the glass plates adhere to each other and the arms start moving together

• Info transmitted into a graphic form

• Values are the same as those of ROTEM

VCM-VET Clotting Time

Time from test initiation until amplitude of 1% is achieved

VCM-VET Clot Formation Time

Time between the 1% amplitude and 10% amplitude of the clotting signal

VCM-VET Alpha Angle

The angle between the middle axis and the tangent to the clotting curve through the 1% amplitude point

VCM-VET Maximum Clot Firmness

Maximum amplitude of the VCM graph

VCM-VET Lysis Index at 30 Min

Fibrinolysis 30 minutes after CT; measured as the relation of the amplitude to the maximum clot firmness (% remaining clot firmness)

What changes on ROTEM/TEG are consistent with hypercoagulability?

Shortened CT/R or CFT/K or increased a angle or MCF/MA

What changes on ROTEM/TEG are consistent with hypocoagulability?

Prolonged CT/R or CFT/K or decreased a angle or MCF/MA

Hypocoagulable TEG/ROTEM

Normal TEG/ROTEM

Hypercoagulable TEG/ROTEM

Hypercoagulable/Hypocoagulable Profile vs State

• Viscoelastic tests can only exhibit a hypercoagulable or hypocoagulable profile and not a hyper/hypocoagulable state

  • Hyper/hypocoagulable state = hypercoagulable/hypocoagulable profile associated with clinical and/or biological signs of thrombosis/hemorrhagic diathesis

What are some factors that can affect ROTEM and TEG Profiles?

• Anemia can cause artifactual hypercoagulable profile

• Increased hematocrit can cause TEG variables indicative of hypocoagulability

• Decreased fibrinogen and platelet count will caused decreased clot strength

Detection of Hyperfibrinolysis with TEG

Depending on the methodology, there may be an increase or decrease in lysis calculation

Detection of Hypofibrinolysis with TEG/ROTEM

Standard TEG/ROTEM assays may be unable to detect hypofibrinolysis in dogs and cats

Using ROTEM/TEG to Monitor Antithrombotic Therapy

• Gold standard for monitoring the effect of heparin on coagulability is anti-factor Xa activity but his isn't readily available

  • Can use viscoelastic tests for this purpose

• Use of unfractionated heparin was associated with hypocoagulability in healthy cats and dogs

• The use of LMWH was not associated with significant alterations of ROTEM and TEG parameters in healthy cats and healthy dogs unless supraphysiological doses were used in healthy dogs

Limitations of ROTEM/TEG

• Major limitation remains the interpretation of results

• Second limitation is price of systems

• Third, systems require long technical time and rigorous machine maintenance

• Fundamental difference in the use of viscoelastic tests between human and veterinary medicine

  • In human medicine, they appear to be an aid in the therapeutic management of critically ill patients due to publications

  • In veterinary medicine, they remain confined only to the observation of hemostatic changes present in a patient