PB0667 - Results of thromboelastography and thrombin generation assays for pediatric severe hemophilia A patients are highly variable and not predictive of clinical phenotypes

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Co-Author(s)

NM

Natalie Mathews

Hemostasis/Thrombosis Fellow
Hospital for Sick Children
Hamilton, Ontario, Canada
FP

Fred G. Pluthero

Laboratory Manager
Hospital for Sick Children
Toronto, Ontario, Canada
MR

Margaret L. Rand

Professor
Hospital for Sick Children/University of Toronto
Toronto, Ontario, Canada
AS

Ann Marie Stain

Hemophilia Nurse Coordinator (Retired)
Hospital for Sick Children
Toronto, Ontario, Canada
Manuel Carcao, MD, FRCPC

Director, Haemophilia Clinic and Haemostasis Program
Hospital for Sick Children, Toronto, Canada
Toronto, Ontario, Canada
VB

Victor S. Blanchette

Staff Hematologist, Professor
Hospital for Sick Children/University of Toronto
Toronto, Ontario, Canada

Presenting Author(s)

WK

Walter H.A. Kahr

Staff Hematologist, Professor
Hospital for Sick Children/University of Toronto
Toronto, Ontario, Canada

Background: Severe hemophilia A (SHA) patients vary in clinical traits including severity of bleeding, arthropathy and requirements for replacement factor VIII (FVIII). Hemostasis can be assessed in vitro via thromboelastography (TEG) using blood, and calibrated automated thrombography (CAT) using platelet-rich (PRP) or platelet-poor (PPP) plasma.

Aims: Use CAT and TEG to assess baseline hemostatic activity in a cohort of thirty pediatric SHA patients with factor requirements varying from on demand to 3 doses/week, for whom clinical data were available, and examine: 1) variability within the cohort of assay results using different tissue factor concentrations; 2) correlations among assay results and between them and clinical parameters.

Methods: Key clinical parameter was FVIII dosing regimen; others included Von Willebrand factor level (VWF:Ag) and Pettersson arthropathy score. Blood samples were obtained after factor washout (treated with corn trypsin inhibitor), subjected to TEG and used to prepare PRP and PPP for CAT assays. Varying concentrations of tissue factor (TF) were used. Statistical analysis examined relationships between assay results, and between them and clinical parameters.

Results: TEG data and CAT results with PPP and PRP all indicated weak hemostatic function in samples at low TF levels, and many but not all samples approached normal assay results at high TF concentrations (Figure 1). A significant positive correlation was observed between TEG and CAT-PRP results. Correlations were not detected between assay results and clinical parameters (Figure 2).

Conclusion(s): In vitro hemostatic assay results indicated considerable heterogeneity among patients at all TF concentrations used. Correlation was observed among some assay results, but not between those results and FVIII requirements or other clinical parameters. We conclude that patient heterogeneity is likely influenced by factors other than baseline hemostatic activity.