PPA News



Posted by: Brandy Zeller on Nov 30, 2015

Authors:
Steve Martin, PharmD
Wyn Wheeler, PharmD, FCCM


Background

Maintenance of hemostasis is an important part of care of the critically ill child. Various laboratory tests can be used to monitor clot formation and dissolution and are often integrated into the care of patients receiving complex medical treatments, including those on extracorporeal membrane oxygenation (ECMO) and external ventricular assist devices. Historically, many of these tests are isolated measures of clotting including platelet count, activated partial thromboplastin time, fibrinogen level, D-Dimer level, etc.

Thromboelastography (TEG®)

In 1948, Dr. Hellmut Hartert first developed thromboelastography as a method to measure the viscoelastic properties of a clot developing in whole blood1. The clot forming process requires both enzymatic (clotting cascade) processes and platelet aggregation. While most conventional monitoring assays only demonstrate the effects on one process, TEG provides insight on all phases of clot formation from thrombin formation to clot strength to clot fibrinolysis. This provides a more comprehensive assessment of general hemostasis and assists in monitoring patients with challenging anticoagulation needs.

Non-anticoagulated blood is added to a cup placed on the TEG machine which is in constant oscillating motion at a slight angle. The result is a mechanical shear modulus between the sample and the cup. A pin attached to a torsion wire is lowered into the sample and begins to rotate as the blood sample begins to clot. The time until the wire begins to turn and the degree of wire rotation demonstrates the mechanical properties of the clot and clotting process, which is translated into an electrical signal to the electromagnetic transducer 2.

One of the challenges with using TEG monitoring is the breadth of information it provides. Knowing how to interpret the data to effectively impact anticoagulation management is key. Many acronyms are used which are provided below in a comprehensive but simplistic table.

Table 1. Interpretation of TEG parameters with management guidance for values outside normal range

 

 

 

 

 

 

 

 

 

FFP, fresh frozen plasma; tPA, tissue plasminogen activator

 

Figure 1. Representative example of thromboelastograph with measured parameters depicted schematically. CI, coagulation index; EPL, estimated percent lysis; G, clot strength; MA, maximum amplitude; SP, split point.4

 

 

 

 

 

 

 

 

 

 

Many patient populations benefit from TEG monitoring. Examples include patients with a Berlin Heart Excor® external biventricular device and patients on ECMO. The Edmonton anticoagulation guidelines associated with the Berlin Heart Excor® rely heavily on TEG monitoring to maintain adequate anticoagulation. In a 2013 study published in Pediatric Critical Care Medicine, Bembea and colleagues reported 43% of respondents reported TEG use in monitoring patients on ECMO3. Literature continues to emerge in additional areas including perioperative treatment of hemophilia, trauma, and patients with mechanical valves. Conventional anticoagulation monitoring is generally sufficient in many patients but, occasionally, the monitoring data does not match the clinical picture. TEG monitoring might provide insight into a more broad coagulation picture, helping guide targeted therapy to provide the best outcomes possible.

An additional benefit of TEG is the ability to assess platelet function in addition to overall hemostasis. Antiplatelet therapy can inhibit either the aggregation or activation of platelets. As depicted in Figure 2, antiplatelet therapy generally affects the arachidonic acid (AA) conversion to thromboxane A2 (TXA2), prostaglandin inhibition, adenosine diphosphate (ADP) blocking, and/or glycoprotein (GP) IIb-IIIa receptors. As such, platelet mapping with TEG can determine the amount of platelet inhibition via the AA (mechanism of aspirin) or ADP (mechanism of dipyridamole/clopidogrel) pathways as seen below. Assessment of platelet mapping is generally reported as percent inhibition or clot strength (net G). As platelet inhibition increases, the AA or ADP tracing narrows approaching the activated graph.

Figure 2. Platelet mapping tracing example. AA, arachidonic acid; ADP, adenosine diphosphate5

 

 

 

 

 

 

 

 

 

Conclusion

There is much more to come in the area of TEG and its application in various areas of pediatric critical care. Pharmacists are positioned well to serve as experts, not only in the pharmacology of the individual medication used to modulate the coagulation cascade, but also in interpreting TEG monitoring and serving an important role in the multidisciplinary team caring for these challenging patients. Although TEG monitoring provides a more complete assessment of the anticoagulation status, it does not replace clinical assessment of the patient.

References:

1. Thakur M, Ahmed AB. A review of thromboelastography. International Journal of Perioperative Ultrasound and Applied Technologies. Jan-Apr 2012;1(1):25-29.

2. Stammers AH, Willett L, Fristoe L, et al. Coagulation monitoring during extracorporeal membrane oxygenation: the role of thrombelastography. Journal of Extra-Corporeal Technology. Sep 1995;27(3):137-145.

3. Bembea MM, Annich G, Rycus P, Oldenburg G, Berkowitz I, Pronovost P. Variability in anticoagulation management of patients on extracorporeal membrane oxygenation: an international survey. PCCM Feb 2013;14(2):e77.

4. Forman K. Effect of temperature on thromboelastography and implications for clinical use in newborns undergoing therapeutic hypothermia. Pediatric RESEARCH. 2014; 75(5):663-669

5. Bliden KP, DiChiara J, et al. Increased risk in patients with high platelet aggregation receiving chronic clopidogrel therapy undergoing percutaneous coronary intervention. Journal of the American College of Cardiology. February 2007;49(6):657-666