Thromboelastometry

Thromboelastometry (TEM), previously named rotational thromboelastography (ROTEG) or rotational thromboelastometry (ROTEM), is an established viscoelastic method for hemostasis testing in whole blood. It is a modification of traditional thromboelastography (TEG). TEM investigates the interaction of coagulation factors, their inhibitors, anticoagulant drugs, blood cells, specifically platelets, during clotting and subsequent fibrinolysis. The rheological conditions mimic the sluggish flow of blood in veins. TEM is performed with the ROTEM whole blood analyzer (Tem Innovations GmbH, Munich) and is an enhancement of thrombelastography, originally described by H. Hartert in 1948. Thromboelastometry (TEM), previously named rotational thromboelastography (ROTEG) or rotational thromboelastometry (ROTEM), is an established viscoelastic method for hemostasis testing in whole blood. It is a modification of traditional thromboelastography (TEG). TEM investigates the interaction of coagulation factors, their inhibitors, anticoagulant drugs, blood cells, specifically platelets, during clotting and subsequent fibrinolysis. The rheological conditions mimic the sluggish flow of blood in veins. TEM is performed with the ROTEM whole blood analyzer (Tem Innovations GmbH, Munich) and is an enhancement of thrombelastography, originally described by H. Hartert in 1948. While traditional thromboelastography is a global assay for blood clotting disorders and drug effects, TEM is primarily used in combination with appropriate differential assays. They allow testing in the presence of therapeutic heparin concentrations and provide differential diagnostic information to support decisions in therapy. In numerous publications the validity of the method is shown. Application of TEM at the point of care (POC) or in emergency laboratories is getting more and more popular. TEM detects both hypo- and hyperfunctional stages of the clotting process and is probably the only reliable rapid test for the diagnosis of hyperfibrinolysis. In contrast to standard clotting tests, the fibrin stabilizing effect of factor XIII contributes to the result. The rapid availability of results helps to discriminate surgical bleeding from a true haemostasis disorder and improves the therapy with blood products, factor concentrates, anticoagulants and protamine, hemostyptic and antifibrinolytic drugs. Several reports confirm that application of TEM is cost effective by reducing the consumption of blood products. Blood (300 µl, anticoagulated with citrate) is placed into the disposable cuvette using an electronic pipette. A disposable pin is attached to a shaft which is connected with a thin spring (the equivalent to Hartert’s torsion wire in thrombelastography) and slowly oscillates back and forth. The signal of the pin suspended in the blood sample is transmitted via an optical detector system. The test is started by adding appropriate reagents. The instrument measures and graphically displays the changes in elasticity at all stages of the developing and resolving clot. The typical test temperature is 37 °C, but different temperatures can be selected, e.g. for patients with hypothermia. In contrast to thrombelastography with its pendulum-like principle, the design of the TEM viscoelastic detection system (figure 1) makes it quite robust and insensitive against mechanical shocks or vibrations. The primary result of TEM is a reaction curve which shows the elasticity over time when the clot forms or dissolves. This curve is also called a TEMogram. Four key parameters describe the clotting curve for clinical routine. More than 10 additional calculated parameters, including derivative curves which are useful in specific research applications, e.g. in hemophilia or thrombophilia or for the effects of recombinant FVIIa are available for research purposes. CT (Clotting time):The CT is the latency time from adding the start reagent to blood until the clot starts to form. Prolongation of CT may be a result of coagulation deficiencies, primarily coagulation factors, or heparin (dependent on the test used). A potential contribution of heparin can be detected by comparing INTEM- with HEPTEM CT data (see “reagents” below). A shortening of CT indicates hypercoagulability. CFT (Clot formation time) and alpha-angle: The alpha angle is the angle of tangent between 0 mm and the curve when the clot firmness is 20 mm, while CFT is the time from CT until a clot firmness of 20 mm point has been reached. These parameters denote the speed at which a solid clot forms and are primarily influenced by platelet function, but to a certain extent especially fibrinogen and coagulation factors contribute. A prolonged CFT (or a lower alpha-angle) is usually caused by poor platelet function, low platelet count, fibrin polymerization disorders or fibrinogen deficiency. Apparently also FXIII seems to be involved already in this phase. Higher concentrations of heparin can also prolong CFT in the INTEM assay, but not in HEPTEM, EXTEM, FIBTEM or APTEM (see under “reagents”). A shortening of CFT (or a high alpha-angle) indicate hypercoagulability. MCF (Maximum clot firmness):MCF is the greatest vertical amplitude of the trace. It reflects the absolute strength of the fibrin and platelet clot. A low MCF is indicative of decreased platelet number or function, decreased fibrinogen level or fibrin polymerization disorders, or low activity of factor XIII. A mechanically weak clot represents a severe bleeding risk and should initiate immediate therapeutic steps. High doses of heparin can lower MCF in the INTEM assay, but not in HEPTEM, EXTEM, FIBTEM or APTEM (see under “reagents”). A5, A 10, A15 or A20 valueThese values describe the clot firmness (or amplitude) obtained after 10, 15 or 20 minutes (beginning from CFT) and provide a forecast on the expected MCF value at an earlier stage already. A recent investigation has validated this approach for the A15 value in more than 800 cases during liver transplantation. The advantage of the A15-values is obvious: It allows for a more rapid decision about therapeutic interventions. LI 30 (Lysis Index after 30 minutes) and ML (Maximum Lysis)The LI30 value is the percentage of remaining clot stability in relation to the MCF value at 30 min after CT. A similar value can also be calculated at other time points (45 or 60 min). The ML parameter describes the percentage of lost clot stability (relative to MCF, in %) viewed at any selected time point or when the test has been stopped. A low LI (X) value or a high ML value indicates hyperfibrinolysis. While in normal blood fibrinolysis activity is quite low, in clinical samples a more rapid loss of clot stability by hyperfibrinolysis may lead to bleeding complications which can be treated by the administration of antifibrinolytic drugs.