ACT remains the standard of monitoring during heparin anticoagulation in ECMO. The ACT provides a bedside assessment of the intrinsic and common pathway integrity.
During ECMO, the ACT is usually maintained between 180 and 220 s [ 20 ].
However, it is well established that the correlation between heparin concentration and ACT is poor during CPB [ 37 , 38 ]. However, direct measurement of heparin con- centration is unpractical, and the optimal level of heparin concentration while on ECMO has not yet been established. Studies confronting heparin concentration with ACT values during ECMO reported variable heparin concentrations between 0.1 and 0.4 IU/mL, with correspondent ACT values ranging from 110 to 220 s [ 39 – 41 ].
7.5.2 Conventional Laboratory Tests
Activated partial thromboplastin time (APTT) explores the intrinsic and common pathways of coagulation and is the classical measure for heparin therapy [ 20 ].
APTT poorly correlates with ACT [ 42 ]; conversely, it has an acceptable degree of correlation with heparin concentration [ 43 ] and is therefore to be considered supe- rior to the ACT for heparin treatment monitoring during ECMO. An APTT of 1.5 times the baseline APTT (50–80 s) is considered the target value during ECMO and corresponds to a heparin concentration of 0.2–0.3 IU/mL [ 20 ].
Prothrombin time (PT) is a marker of the extrinsic and common coagulation pathways and should be performed in order to detect the level of coagulation factors and to guide their supplementation with fresh frozen plasma (FFP), prothrombin complex concentrates (PCC), or cryoprecipitates.
Platelet count, fi brinogen levels, and d -dimers assays should be performed daily, since they determine the need for platelet concentrates, FFP, fi brinogen, and antifi brinolytics.
7.5.3 Thromboelastography and Thromboelastometry
Thromboelastography (TEG) and thromboelastometry (TEM) are dynamic tests based on the viscoelastic properties of blood during the coagulation process. In both tests, the time to change the physical nature of blood from liquid to gel ( gel point ) is represented by a straight line and defi ned as r time (TEG) or coagulation time (TEM).
Once the gel point is reached, other parameters represent the kinetic of clot formation ( alpha angle ) and the retraction force of the clot ( maximum amplitude in TEG and maximum clot fi rmness in TEM). Finally, the decrease over time of the clot strength is an index of fi brinolysis ( clot lysis index in TEG and maximum lysis in TEM) (Fig. 7.1 ).
TEG and TEM have a number of advantages over the routine coagulation tests.
They provide a comprehensive and dynamic analysis of coagulation kinetic, can be done at point-of-care, provide data within about 30 min, and, fi nally, can be used for detecting hyperfi brinolysis. Therefore, their use for monitoring coagulation and anticoagulation gained wide popularity in recent years.
The r time and coagulation time are surrogates for thrombin generation and may guide the UFH infusion rate during ECMO. There is not a universally accepted value of r time for optimal UFH dose, but the majority of the authors report an optimal window between two and three times the upper normal limit (16–25 min) [ 20 , 21 ] (Fig. 7.2 ).
Both TEG and TEM offer an additional number of tests. Adding heparinase, it is possible to detect the “natural” underlying behavior of clot formation. This is par- ticularly useful when the r time is excessively prolonged, to distinguish a heparin overload from a coagulation factor defi ciency and for guiding the therapy with PCC, FFP, or cryoprecipitates. Specifi c tests ( functional fi brinogen in TEG and Fibtem in TEM) provide a measurement of fi brinogen concentration (Fig. 7.3 ). These last values may guide the therapy with FFP and fi brinogen.
R min 12.2 4–8
K min 2.7 0–4
Angle deg 54.0 47–74
MA mm 57.4 54–72
PMA 0.0
G d/sc 6.7K 6.0K–13.2K
EPL
% 1.2 0–15
A mm 48.7 Clot firmness
Fibrin + platelets
Clot lysis Thrombin generation
Coagulation factors
CI –5.7 –3–3
LY30
% 1.2 0–8
Fig. 7.1 Thromboelastographic tracing
R min 29.5 4–8
K min 7.8 1–4
Angle deg 24.1 47–74
MA mm 49.6 55–73
PMA 1.0
G d/sc 4.9K 6.0K–13.2K
EPL
% 0.0 0–15
A mm 52.2 ECMO
10 millimetri 2 Kaolin with heparinase
Campione: 16/11/2009 11.36.04 PM – 01.37.09 AM
CI –22.0
–3–3 LY30
% 0.0 0–8 Fig. 7.2 An adequate TEG during ECMO
CT : CFT :
2011–04–11
FIBTEM 14:55
A20 : 11 mm 11 mm
– MCF :
α : •
– s A10 : 10 mm
Fig. 7.3 ROTEM analysis 77s for fi brinogen concentration (FIBTEM)
7.5.4 Other Hemostasis and Coagulation Tests
Given the limitations of ACT, and the fact that APTT values may change depending on the laboratory method used, some authors [ 44 ] suggested the use of more spe- cifi c tests for the defi nition of the UFH infusion rate. The anti-Xa UFH assay mea- sures the anti-Xa activity of heparin in plasma. An optimal value, corresponding to an APTT 1.5–2 times the baseline, is between 0.3 and 0.7 IU/mL [ 43 ].
Platelet function analysis with point-of-care tests during ECMO is suggested by some authors [ 35 ]. At present, there is a gap in knowledge about platelet function and antiplatelet drugs use during ECMO. There is not a clearly defi ned cutoff value suggesting platelet concentrate transfusion, and many of the available tests may be biased by the usually low platelet count during ECMO.