Dr. Susan Louw Haematopathologist NHLS / WITS / SASTH

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1 Dr. Susan Louw Haematopathologist NHLS / WITS / SASTH

2 Since 1948 Initially a research tool Utility in management of bleeding and thrombosis Guide clotting factor replacement, platelet / blood transfusions and fibrinolysis treatment

3 Kaolin activated blood (citrate or native) at 37 C Cuvette oscillating at 4 wt frequency of 0.1 Hrtz Stationary pin suspended in cup by torsion wire wire acts as a torque transducer 1 mm gap between cup and pin

4 Liquid blood: no impact on pin As blood clots: fibrin strands links pin and cup changes in viscoelasticity of blood transmitted to pin and then to wire Resulting torque generates an electrical signal: Magnitude plotted over time to produce a TEG trace As blood clots: progressive increase in signal amplitude

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6 Information re speed and strength of clot formation Normal haemostasis: controlled activation of clot formation balanced by clot lysis TEG measures both using visco-elasticity of clotting blood Assessment is dependent on cellular and plasma components activity and concentration components procoagulant and fibrinolytic activity

7 Provide continuous real time information on viscoelastic properties of evolving clot: time of initial fibrin formation through platelet aggregation. fibrin cross linkage and clot strengthening to clot lysis Analysis can determine the speed of clot generation its strength and stability

8 Clotting is a dynamic process Conventional tests e.g. aptt and platelet aggregometry assess isolated components of haemostatic system unable to predict role of components in the context of haemostasis as a whole Advantage of TEG: incorporates the interaction of all of the components of coagulation (platelets, clotting factors and thrombin) as well as providing information about the quality of the clot and fibrinolysis

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10 TEG trace: TEG parameters: R: time to detection of clot: Clotting factor and inhibitor activity K: time from end of R until clot reaches 20mm Speed of clot formation Rapidity of fibrin cross linking α angle: tangent of curve made as K is reached similar information as K Maximum Amplitude (MA): reflection of clot strength activity of platelets and fibrin LY30: % of clot lysed after 30 minutes

11 Coagulaion Index (CI): A calculation incorporating R-, K-value, α angle and MA Area under TEG curve Overall assessment of coagulability G-value: log-derivation of MA Represent clot strength in dynes/sec Elevation possibly indicates hypercoagulability Estimated percent lysis (EPL): Estimated percentage of clot which has lysed after 30 minutes Fibrinolysis parameters are possibly related to risk of haemorrhage

12 Reagent: Citrate Heparin Heparinase GP IIb / IIIa inhibitor Anti-fibrinolytic (e.g. Tranexamic acid) Platelet agonists (e.g. Arachidonic acid or ADP) Rationale: Prolongs storage of sample Inhibits thrombin allowing assessment of contribution by platelets to clot formation Reverses the effect of Heparin Inhibits platelets allowing assessment of contribution of fibrin to clot formation Assessment of fibrinolysis inhibition Assess therapeutic effect of anti-platelet agents Activator FM (e.g. FXIII activator) Activates fibrin without activation of platelets

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15 Native whole blood: speed! Analysis within 4 minutes of venipuncture Possible advantage in post injury haemostasis assessment However: native whole blood clots! Test ASAP and before clotting begins: may not be suitable. BUT: Differences in results between citrated and non-citrated whole blood due to incomplete inhibition of coagulation during the time between sampling and testing Reportedly overcome by leaving the sample to equilibrate for 30 minutes post collection After 2 hours of storage: B-thromboglobulin levels increase Optimal testing of a citrated whole blood sample is between 30 minutes and 2 hours of venipuncture

16 Blood is often drawn from indwelling lines Undesirable heparin contamination Minimum discard volume of 4 ml of blood from indwelling catheters (5 times catheter dead space) to remove effect of heparin Increasing volumes between 1 and 4 ml resulted in a decrease in R-value, α-angle and MA Discard volumes >4 ml showed no such relationship

17 Alternative to discarding blood: addition of heparinase to TEG cup to neutralise heparin A comparison of heparinase vs. untreated blood: used to eliminate heparin effect from background haemostatic potential in patients on heparin treatment Often used in haemostatic assessment of patients on cardiopulmonary bypass

18 Number of percutaneous coronary interventions has exploded: Major complication: acute vessel or stent occlusion Need to inhibit platelet aggregation/activation Resistance to anti-platelets do occur with risk of occlusive complications TEG has clinical use in the monitoring of anti-platelet Rx Platelet mapping: Platelet component of TEG enhanced by specific platelet agonists added to reaction mixture: Adenosine diphosphate (ADP) as a platelet activator: can detect resistance to ADP receptor inhibiting drugs e.g. clopidogrel Arachidonic acid (AA) as a platelet activator: can detect resistance to aspirin

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22 Advantages: Disadvantages: Improve quality of care: immediate results Possible cost reduction Less labour intensive Patients not lost to follow-up Non-laboratorians have difficulty with quality control, documentation etc. essential for reliable testing Usually higher unit cost per test vs. central laboratory Additional tests needed: multiple collections Adding to workload of personnel with existing responsibilities: errors caused by multitasking Ongoing training and competency assessment needed

23 Haemostasis: wide range of normal values due to variability in components of the haemostatic system (platelet count and function, GPIIb/IIIa receptor number and fibrinogen concentration): Difficult to determine normal reference range. Ideally: each patient should have baseline TEG before treatment or procedure internal, individualised reference for change Difficulties with validation and standardisation therefore: computer software to analyse the TEG disposable cups and pins temperature control kaolin for initiation of clotting process

24 External Quality Assurance (EQA): Improves reliability and performance of laboratory testing Accuracy and precision are determined Quality variables can be audited Requirement in modern laboratory for accreditation by external bodies; BUT: No widely used scheme whereby whole blood samples can be tested in an EQA setting

25 IQC: Commercial controls are available for both normal and abnormal samples and provide the means whereby quality can be assessed on a daily basis Operator can assess aspects of the assay including machine function, operator competency and interpretation of results

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