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Haemostasis and TEG® Technology

www.haemoscope.comCopyright © 2001 Haemoscope Corporation

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Hemostasis Issues Facing Clinicians

• Before surgery– Is there a coagulopathy present and how should it be treated– Prophylactic treatment / Autologous platelet plasmapheresis

• During surgery– What coagulopathy is developing

• After surgery– If the patient is bleeding, is it due to

• Surgical• Excess of heparin• Coagulopathy and how it should be treated

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Normal Hemostasis…

… is controlled activation of clot formation and clot lysis that stops hemorrhage without permitting inappropriate clotting (thrombosis).

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Hemostasis Components

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The Procoagulant

Cascade

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The Hemostasis

Process

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The Clot

• The only end result of the activated coagulation protein is the fibrin strand which, together with activated platelets, forms fibrin-platelet bonding to produce the final clot.

• The strength and stability of the clot, that is its physical properties, determine its ability to do the work of hemostasis, which is to mechanically impede hemorrhage.

• The clot is in essence a damage control device, a temporary stopper, which gradually dissolves during vascular recovery.

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TEG® Technology

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Clot Kinetics

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TEG Data Related to Pathways

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Formal Definition of TEG® Parameters

R R is the time of latency from the time that the blood was placed in the TEG® analyzer until the intial fibrin formation.

The value measures the rapidity (kinetics) of fibrin build-up and cross-linking, that is, the speed of clot strengthening.

K K time is a measure of the rapidity to reach a certain level of clot strength

MA MA, or Maximum Amplitude, is a direct function of the maximum dynamic properties of fibrin and platelet bonding via GPIIb/IIIa and represents the ultimate strength of the fibrin clot.

LY30 LY30 measures the rate of amplitude reduction 30 minutes after MA. This measurement gives an indication of the stability of the clot.

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Pattern Recognitio

n

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AMI – before treatment

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AMI – immediately post treatment

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AMI – during recovery

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Monitoring Hirudin with TEG® Analysis

0

1

2

3

4

0 2 4

Hirudin (ug/ml)

R (

min

)

y= 0.78x + 0.56

r-square = 0.99

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Monitoring Anti-Xa with TEG® Analysis

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TEG® Tracing

Schematic

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Sampling Protocol (Cardiovascular)

Sampling Protocol — All samples are Kaolin activated

Sample #

When Cup type

1 On induction Heparinase bonded (blue) cup and pin

2 At rewarming (approx 36°C) on CPB Heparinase bonded (blue) cup and pin

3 & 4 10 min post protamine Split sample:Heparinase bonded (blue) cup and pinPlain (clear) cup and pin

5 & 6 Post op Split sample:Heparinase bonded (blue) cup and pinPlain (clear) cup and pin

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Suggested Treatment

Treatment protocol

TEG® value Clinical cause Suggested Treatment

R between 7 - 10 min ↓ clotting factors x 1 FFP or 4 ml/kg

R between 11-14 min ↓↓ clotting factors x 2 FFP or 8 ml/kg

R greater than 14 min ↓↓↓clotting factors x 4 FFP or 16 ml/kg

MA between 49 -54 mm ↓platelet function .03g/kg DDAVP

MA between 41 -48 mm ↓↓ platelet function x5 platelet units

MA at 40 mm or less ↓↓↓ platelet function x10 platelet units

less than 45° ↓↓ fibrinogen level .06 u/kg cryo

LY30 at 7.5% or greater, C.I. less than 3.0 Primary fibrinolysis antifibrinolytic of choice

LY30 at 7.5% or greater, C.I. greater than 3.0 Secondary fibrinolysis anticoagulant of choice

LY30 less than 7.5%, C.I. greater than 3.0 Prothrombotic state anticoagulant of choice

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Predictive Value of Blood Clotting Tests in Cardiac Surgical Patients

• A study using 897 consecutive cardiac surgical patients over 18 months in which “(t)he tests included activated clotting time, activated partial thromboplastin time, prothrombin time, thrombin time, fibrinogen, fibrin/fibrinogen degradation products, platelet count, and Duke’s earlobe bleeding time.”

• “The best multivariate model constructed could explain only 12% of the observed variation in postoperative blood loss.”

(Ann Thorac Surg 1994; 58:216-21)

Glenn P. Gravlee et alGlenn P. Gravlee et al

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Thrombelastography as an Indicator of Post-

Cardiopulmonary Bypass Coagulopathies

Bruce D Spiess et al

“Thrombelastography was a significantly better predictor (87%) accuracy) of postoperative hemorrhage and need for reoperation than was the activated clotting time (30%) or coagulation profile (51%).”

(J Clin Mon, Vol 3 No 1 January 1987)

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Baseline

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Platelet Dysfunction

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Baseline & Pump

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Post Protamine

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After Platelet Transfusion

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Before and After Platelet Transfusion

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Standard Protocol for Cardiovascular

Applications

• Baseline tracing on induction– 1 sample with kaolin and heparinase (heparinase in case of

heparin presence or contamination)

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Standard Protocol for Cardiovascular

Applications

• Baseline tracing on induction– 1 sample with kaolin and heparinase (heparinase in case of

heparin presence or contamination)• At rewarming (approx 36°) on CPB

– 1 sample with kaolin and heparinase

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Standard Protocol for Cardiovascular

Applications

• Baseline tracing on induction– 1 sample with kaolin and heparinase (heparinase in case of

heparin presence or contamination)• At rewarming (approx 36°) on CPB

– 1 sample with kaolin and heparinase • *10 min post protamine, 2 TEG® columns needed

– 1 sample with kaolin and heparinase– 1 sample with kaolin only

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* Post Protamine

• Looking at only the R parameter, if the samples with and without heparinase are the same, the patient has received enough protamine to reverse heparin.

• If both tracings are normal and the patient is bleeding, the reason is surgical.

• If the R without heparinase is elongated and the heparinase tracing is normal and the patient is bleeding, the bleeding is due to excess of heparin.

• If the tracing with heparinase shows a coagulopathy, the patient is treated accordingly. Most likely coagulopathies will be consistent with those observed during monitoring while the patient is on the pump.

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Reduced Hemostatic Factor Transfusion Using Heparinase-modified Thrombelastography

During Cardiopulmonary Bypass (CPB)

Stephen von Kier and David Royston

GroupActual Predicted

C(n=30)

DT(n=30)

C(TEG®)

DT(lab)

Pts transfused 10 5 2 12

Platelets 16 5 1 22

FFP 9 1 1 8

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Thrombelastography Decreases Transfusion Requirement After

Cardiac Surgery

Linda Shore-Lesserson MD et al

RBCintra

RBCpost

Non-RBCintra

Non-RBCpost

CTD(ml)

TEG 17/53 10/53 5/53 3/53 577 ± 412

Control 23/52 12/52 8/52 13/52** 659 ± 429

** p < 0.006 TEG vs control

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Mayo Clinic Study: Blood Product Transfusion Therapy after Liver

Transplantation(LT): Comparison of the Thrombelastogram (TEG®) and

Conventional Coagulation Studies (CCS)

D. J. Plevak et al

TEG® CCS TEG® reduction in %

RBC 1.47 3.06 52

FFP .11 .78 86

Platelet .95 2.67 64

Cryoprecipitate 0.00 1.67 100

N of donors 2.53 8.17 69

Cost 149.60 282.00 47

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Cardiopulmonary Bypass Coagulation Management, Education and Transfusion

Practice at the University of Washington*

* ASA Scientific Exhibit, 1991, Dr. Gilles, BSA, et al, Seattle WA** p<.01

Incidence of Reoperation

Monitoring with:Standard lab (units) TEG® (units)

Total 28/4885.7%

9/5911.5%**

CABG 16/3554.5%

6/4431.4%**

Open Ventricle

12/1339.0%

03/1482.0%**

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Residual Heparin

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Before Protamine

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After Protamine

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TEG® Applications

• Liver transplantation• Cardiovascular surgery• Heart assist device• Percutaneous Transluminal Coronary Angioplasty

(PTCA)• Trauma• Obstetrics• ICU• Orthopedics

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TEG® Analyzer

5000 Series

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Baseline Hypercoagulability

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With Heparinase

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Post Protamine

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Haemostasis in the New Millennium

www.haemoscope.comCopyright © 2001 Haemoscope Corporation

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Major Role of Platelets

• Are activated by and attached to negatively charged surfaces of the subendothelium collagen

• Provide the phospholipid surfaces to enable the hemostasis protein’s enzymatic reaction to take place

• Localize the clotting process at the site of injury• Protect the enzyme complexes from inhibitors that circulate to protect against

propagation of the clotting activation downstream• Fibrin bonding via platelet GPIIb/IIIa receptor to form the clot• Stabilize the three-dimensional fibrin structure by its position in the fibrin

network cross point• Provide contractility forces to the clot enabling it to resist the deforming shear

forces of the circulating blood

Introduction

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The Hemostasis Process

Introduction

• Interactive process– Multiple interactions between factors that include coagulation

and fibrinolytic proteins, platelets, activators, and inhibitors• Dynamic and complex

– Not static– Does not occur in isolation

• All enzymatic reactions take place on platelet phospholipid surfaces

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Haemostasis in the Old vs the New Millennium

• Old: Cause and treatment of hemorrhagic state

• New: Cause and treatment of prothrombotic state

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Coagulation in the New MilleniumTreatment and identification of the source

of the prothrombotic state

• Identification of the source of the prothrombotic state1. Platelets2. Enzymatic3. Differential treatment

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Treating the Prothrombotic State — Platelets

AMI

Acute myocardial infarction (AMI)• High incidence of AMI is the leading cause of death under age 75

in Western World and projected to increase, becoming leading cause of death worldwide by 2020.

• Despite treatment with thrombolytic agents, only 40-60% of cases result in normal coronary flow, and 7-10% mortality rates occur.– Due to patent coronary artery reocclusion caused by residual thrombus– GPIIb/IIIa inhibitor should minimize reformation of thrombus

• Future: Combination therapy of GPIIb/IIIa inhibitors with thrombolytics will replace monotherapy in AMI patients.

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Treating the Prothrombotic State — Enzymatic

D.I.C.

• Disseminated Intravascular Coagulation (D.I.C.) is commonly initiated through activation of the extrinsic pathway. The D.I.C. process can be divided into three stages:– Stage I — Prothrombotic phase– Stage II — Secondary fibrinolytic phase– State III — Consumptive hemorrhagic phase

• Future: Treat prothrombotic phase

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Treating the Prothrombotic State — Enzymatic

Placental Infarct

Placental Infarct (miscarriage)• The prothrombotic state of pregnant women is attributed

to high levels of fibrinogen. • Prothrombotic state exacerbated by pregnancy can lead

to deposit of thrombin in the placenta, resulting in placental infarct.

• Future: treat the prothrombotic state

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New Millennium Monitoring of Hemostasis

Including Prothrombotic State

• Has been proven clinically to reduce use of blood products and predict thrombotic events

• All phases of hemostasis measured with whole blood sample• Measures the net product between clot formation and clot lysis• Measures patient risk of either hemorrhagic or prothrombotic

states• Differentiates between surgical and physiological bleeding• Provides results in less than 15 minutes• Has a high level of reproducibility and low coefficient of variation

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• Software that interfaces with the hospital network to allow viewing of hemostasis information anywhere

• Software that interfaces with the hospital information system to merge hemostasis information with clinical variables

• Software that can interpret the hemostasis results and advise therapy

• Software that can check the instrument’s electronics and detect faulty user procedures

New Millennium Monitoring of Hemostasis Including

Prothrombotic State