An in vitro evaluation of standard rotational thromboelastography in monitoring of effects of recombinant factor VIIa on coagulopathy induced by hydroxy ethyl starch

Abstract

BACKGROUND: Rotational thromboelastography (ROTEG) has been proposed as a monitoring tool that can be used to monitor treatment of hemophilia with recombinant factor VIIa (rFVIIa). In these studies special non-standard reagents were used as activators of the coagulation. The aim of this study was to evaluate if standard ROTEG analysis could be used for monitoring of effects of recombinant factor VIIa (rFVIIa) on Hydroxy Ethyl Starch-induced dilutional coagulopathy. METHODS: The study was performed in vitro on healthy volunteers. Prothrombin time (PT) and ROTEG analysis were performed after dilution with 33% hydroxy ethyl starch and also after addition of rFVIIa to the diluted blood. RESULTS: PT was impaired with INR changing from 0.9 before dilution to 1.2 after dilution while addition of rFVIIa to diluted blood lead to an overcorrection of the PT to an International Normalized Ratio (INR) value of 0.6 (p = 0.01). ROTEG activated with the contact activator ellagic acid was impaired by hemodilution (p = 0.01) while addition of rFVIIa had no further effects. ROTEG activated with tissue factor (TF) was also impaired by hemodilution (p = 0.01) while addition of rFVIIa lead to further impairment of the coagulation (p = 0.01). CONCLUSIONS: The parameters affected in the ROTEG analysis were Clot Formation Time and Amplitude after 15 minutes while the Clotting Time was unaffected. We believe these effects to be due to methodological problems when using standard activators of the coagulation in the ROTEG analysis in combination with rFVIIa.

Figure 1

The figure shows the 3 representative tracings of the EXTEG analysis from one of the participants in the study. Above the normal tracing with a short CT and CFT is shown. It can be seen that the clot strength is rapidly increasing after initiation of the clotting. In the middle the tracing after hemodilution with HES is found. It can be seen that the CFT is prolonged and that the strength of the clot is increasing slower. Below the tracing after hemodilution and addition of rFVIIa is found. The clotting is then severely impaired, the clot strength is increasing slower and the maximum strength is also severely impaired.

Figure 2

The figure shows the result of a ROTEG analysis. Time is represented on the X axis and clot strength on the Y axis. The clot strength is arbitrarily measured in mm where maximum clot strength is 100 mm. The Clotting Time (CT) is the time from initiation of the analysis until the clot strength is 2 mm. The Clot Formation Time (CFT) is the time from clot strength 2 mm until clot strength 20 mm. A15 is the clot strength at 15 minutes.