Thromboelastography and thrombin generation assessments for pediatric severe hemophilia A patients are highly variable and not predictive of clinical phenotypes

Abstract

Background: Severe hemophilia A (SHA) patients vary in severity of bleeding, arthropathy, and requirements for replacement factor VIII (FVIII). Baseline hemostatic activity assays using calibrated automated thrombography (CAT) and thromboelastography (TEG) may offer insights into the physiological basis of clinical heterogeneity.Objectives: Use CAT and TEG to measure baseline hemostatic activity in a cohort of 30 pediatric SHA patients with available clinical data. Determine effect of contact activation inhibition with corn trypsin inhibitor (CTI). Assess heterogeneity among patients for baseline hemostatic activity and examine correlations between assay results and clinical parameters including FVIII dosing regimen, von Willebrand factor level, and Pettersson arthropathy score.Methods: SHA blood after FVIII washout was subjected to TEG, and platelet-rich (PRP) and platelet-poor plasma was used for CAT assays. Varying concentrations of tissue factor (TF) were used. Statistical analysis examined relationships between assay results, and clinical parameters.Results: CTI treatment was required to obtain TEG and CAT results representative of baseline hemostatic activity. Weak activity was observed in assays with low TF concentrations (0.5-2 pM), and most but not all samples approached normal activity levels at high TF concentrations (10-20 pM). A significant positive correlation was observed between results of TEG and CAT-PRP assays. Correlations were not detected between hemostatic assay results and clinical parameters. Conclusions:In vitro hemostatic assay results of samples containing platelets showed concordance. Assay results were not predictive of FVIII requirements or correlated with other clinical parameters. SHA patient heterogeneity is influenced by factors other than baseline hemostatic activity.

Constitutive hypercoagulability in pediatric sickle cell disease patients with hemoglobin SS genotype

“…The potential complexity of hypercoagulability in SCD patients has prompted the application of global assays of hemostasis, such as thromboelastography (TEG), which allows ex vivo monitoring of coagulation in whole blood [ 14 , 15 ]. As with CAT, a variety of clinical and laboratory variables can influence TEG results [ 16 ], and in several studies employing these assays, we have minimized these factors by having tests performed by a single operator under consistent conditions [ [17] , [18] , [19] , [20] , [21] , [22] ]. TEG has been employed (along with CAT) to assess chronic hypercoagulability in adult SCD patients of HbSS and HbSB°–thalassemia genotypes, where TEG results were consistent with hypercoagulability relative to normal healthy controls (NC) [ 14 ].…”