Thromboelastography for Monitoring of Hemostatic Changes Following Factor Administration
Authors: Chitlur Meera B. , Rao Latha B. , Callaghan Michael , Rajpurkar Madhvi , Lusher Jeanne M. 
Published: October 2019

Abstract
Abstract 3373

Introduction:
Monitoring therapy in children with hemophilia receiving factor replacement products is a major challenge. Measurement of factor levels following treatment is time consuming and not available in time to make changes to the treatment regimen. This study evaluates the use of thromboelastography (TEG), in monitoring the treatment with factor replacement products in children with severe hemophilia without inhibitors. Because of limitations of standard coagulation assays that test specific isolated end points of coagulation, thromboelastography has been used to assess hemostasis as a global process and can assess thrombin/fibrin generation potential of the whole blood.

Materials and Methods:
This is an ongoing study that has been approved by our University IRB. The aim of this study is to evaluate the haemostatic changes as demonstrated by TEG, following the administration of a single dose of replacement factor in pediatric patients with severe hemophilia A (SHA) or B (SHB) without inhibitors.
Patients on prophylaxis or on-demand therapy, who had not received any replacement factor for a minimum of 72 hours were included on study. A baseline TEG and FVIII/IX activity was obtained in the non-bleeding state at the time of enrollment and subsequent samples were obtained at 15mins, 1, 4, 8, 24 and 48 hours post factor replacement.

Results:
24 patients with SHA (n=21) or SHB (n=3) have been enrolled to date. 1 patient had to be eliminated from the study as he was noted to have an inhibitor on the day of study enrolment. The mean age of our patients on study was 12.2 years with the range of 2–24 years. The mean factor activity at the time of enrollment was 1.2%. 3 patients who had FVIII or IX levels >2% at the time of enrollment were excluded from the analysis; 2 with SHB on prophylaxis 2–3 times per week (FIX activity= 2.44% and 5.12%); 1 with SHA on twice weekly prophylaxis (FVIII=13.9). This may be related to FIX having a longer half life, or non-compliance with 72 hour washout period.
The mean Factor level prior to factor administration, after elimination of these subjects was 0.42%. The mean Factor level and R time at each time point of the study are presented in Table 1. The calculated half life of FVIII (t1/2) ranged from 5.89 to 14.52 hours. There was no significant difference in factor t1/2 for children below or above 10 years of age. The rate of rise in the R time at 8 hours and 48 hours correlated with the drop in factor activity following infusion of a single dose of factor and was statistically significant (p=0.05, shown in table 1). This indicates that a prolonged R time at 8 or 48 hours is associated with a significantly shorter t1/2.

Conclusion:
Thromboelastography has been used for monitoring the factor therapy in children with hemophilia. Our study indicates that this may be a potentially useful tool to predict the half life of Factor with a single blood draw at 8 hours. This is extremely important given the variability in half life seen from patient to patient in everyday practice and the difficulty in conducting a PK analysis at several time points especially in children. The TEG is a quick (less than 3 hours) and easy method to monitor and make necessary changes to ongoing therapy. Larger multicenter studies may help define the use of TEG parameters for this purpose more accurately. The small sample size was a major limitation of our study, and hence we were unable to make clinical correlations to bleeding rates.

Disclosures:
No relevant conflicts of interest to declare.