**4.4 Viscoelastic testing**

*Advances in Extracorporeal Membrane Oxygenation - Volume 3*

heparin [2, 18].

anti-factor Xa [21].

patient variability [19].

**4.3 Anti-factor Xa assay**

**4.2 Activated partial thromboplastin time**

**4.1 Activated clotting time**

found to be superior to monitor heparin during ECMO. ECMO centers worldwide vary in their practices on the type of test or combination of tests used to monitor

The activated clotting time (ACT) is a whole blood test used at the bedside that provides immediate results [3, 6]. The ACT measures the time in seconds to form a fibrin clot after the addition of specific coagulation activators, thus it does not solely measure the effect of unfractionated heparin. It is a relatively inexpensive test that has been widely used to monitor heparin during cardiopulmonary bypass, but coagulation factor deficiencies, hemodilution, platelet function, and hypofibrinogenemia may affect the value [3, 19]. Due to these limitations in ACT, Baird and colleagues retrospectively reviewed 600 pediatric ECMO patients and found only a modest correlation between ACT and UFH dose suggesting that ACT may not be an accurate tool for monitoring UFH anticoagulation [20]. Bembea and colleagues found similar results to Baird with only a 42% correlation between target ACTs and

Activated partial thromboplastin time (aPTT) is a plasma-based test, instead of a whole blood test, which only measures the initial 5% of thrombin generated and without incorporating platelet function or assessing clot strength. The aPTT measures the time from FXII activation to fibrin formation after addition of the PTT reagent and calcium [3, 19]. The therapeutic range for aPTT in adults has been shown to correlate to 1.5–2.5× the patient's baseline aPTT [22]. However, this range has not been validated in pediatric patients and can vary significantly compared to adults. For example, an aPTT that correlates to anti-factor Xa between 0.35 IU/ml and 0.7 IU/ml in a patient less than 1 year old is between 58 and 105 seconds, but in a patient 6–10 years old the anti-factor Xa correlates to an aPTT between 45 and 251 seconds [23]. The results of aPTT can be affected by fibrinogen level, presence of acute phase reactants, and increased levels of FVIII. These variables are often skewed in critically ill patients, which can lead to a high degree of intra- and inter-

The anti-Xa assay is a plasma-based test that measures the ability of UFH to catalyze antithrombin's inhibition of factor Xa. Anti-Xa assay differs from ACT and aPTT as it measures the heparin concentration in the patient's blood [24]. Since the anti-Xa assay only measures one specific action of heparin, the value is used as a surrogate to approximate overall function [19]. The anti-Xa value may be affected in patients with elevated plasma-free hemoglobin, hyperbilirubinemia, hypertriglyceridemia, and antithrombin (depending on test reagants). A point of care anti-Xa test is available, but it is currently not widely used. Anti-factor Xa has been shown to have improved correlation to heparin activity as compared to aPTT and ACT [25]. In addition, a retrospective review of 62 pediatric ECMO patients with a mean anti-factor Xa level >0.2 IU/ml was associated with decreased circuit change [26]. Published literature supports the correlation between anti-factor Xa values and UFH dose. Unfortunately, many studies have shown a poor correlation between anti-factor Xa and ACT and/or aPTT. Multiple cardiac studies evaluating patients

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Viscoelastic testing such as thromboelastography (TEG) and rotational thromboelastometry (ROTEM) are whole blood tests that measure the interaction of clotting factors, fibrinogen, and platelets as well as fibrinolysis (**Figure 2**). By measuring more than clotting factors, viscoelastic tests can give a more global picture of the coagulation system and allow for tailored transfusion management [3, 19]. **Figure 2** shows the standard TEG measurements including reaction time (R), kinetics (K), and maximum amplitude (MA). The R value is the time necessary for the initial clot formation. This value can be affected by the presence of anticoagulants, factor deficiencies, and hypercoagulable states. The K value measures the time for the clot to strengthen and can be affected by platelet count, fibrinogen, and coagulation factors. The maximum amplitude quantifies the final strength of the clot. Overall clot strength can be affected by the amount and function of fibrinogen and platelets [3]. In general, viscoelastic tests can be limited by static flow conditions [19]. While there is limited evidence in trauma, obstetrics, liver transplantation, and hemophilia using viscoelastic testing to help define coagulopathy and decrease overall blood product transfusions, studies are needed to confirm these results in ECMO patients [34]. Furthermore, prospective studies should examine the use of TEG and ROTEM in conjunction with aPTT and/or anti-factor Xa.

#### **Figure 2.**

*Thromboelastography (TEG). R, reaction time; K, kinetics; MA, maximum amplitude; LY30, amplitude at 30 minutes.*
