PB1432 - Tissue Factor mRNA (TF mRNA) and Activated FVII-Antithrombin Complex (FVIIa/AT) As Potential Markers of Thrombo-Hemorrhagic Events (THE) in APL Patients

Tuesday, June 25, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Co-Author(s)

LR

Laura Russo

MSc
Division of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
Bergamo, Lombardia, Italy
Marina Marchetti

MSc, PhD
Division of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII,Bergamo
Bergamo, Lombardia, Italy
FS

Francesca Schieppati

MD
Division of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
Bergamo, Lombardia, Italy
CT

Carmen J. Tartari

MSc,PhD
Division of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
Bergamo, Lombardia, Italy
TB

TIziano Barbui

MD, Prof
Research Foundation, Hospital Papa Giovanni XXIII, Bergamo, Italy
Bergamo, Lombardia, Italy
ED

Eros Di Bona

MD
Division of Hematology, Ospedale S. Bortolo, Vicenza, Italy
Vicenza, Lombardia, Italy

Presenting Author(s)

Anna Falanga, MD PhD

MD, PhD, Prof
University of Milano Bicocca, School of Medicine, Monza, Italy
Bergamo, Lombardia, Italy

Background: APL-associated coagulopathy still represents a limiting factor to the cure of APL, despite the great efficacy of modern protocols and beneficial effects of ATRA on the hemostastic derangement, due in part to its capacity to downregulate cellular TF expression. Therefore, characterizing the coagulopathy and identifying predictive markers remain critical issues.

Aims: In newly diagnosed APL patients, we prospectively recorded THE occurrence in the first month after diagnosis, and monitored cellular TF expression in relation to hypercoagulability.

Methods: 65 consecutive APL patients receiving ATRA+Idarubicin (n=60, GIMEMA AIDA2000) or ATRA+ATO (n=5, GIMEMA APL0406) for remission induction were enrolled in 2 Italian centers from 2005 to 2015. Blood samples were obtained from 35 patients at diagnosis before therapy (D0), and during induction on days (D)7, 14 and 28, and tested for TF mRNA expression by peripheral mononuclear cells and for plasma levels of FVIIa-AT, a parameter of TF activity, together with markers of thrombin generation (TAT) and fibrinolysis (D-dimer).

Results: At D0, 12 patients presented with THE: 8 major bleeding (3 fatal intracranial), and 4 thrombosis (1 fatal). Within 3 days of ATRA, 2 additional fatal intracranial bleeding occurred, accounting for total 9% early deaths. In the next 20 days, 3 non-fatal major bleeding and 2 non-fatal thrombosis developed. Laboratory study showed, at D0, APL TF mRNA significantly higher than controls, which progressively decreased by 68%, 70%, and 90%, at D7, D14 and D28, respectively. TAT and D-dimer levels, initially elevated, significantly decreased at D7, and were lowest at D28, while FVIIa-AT dropped significantly only at D28. Significant correlations existed between the decreases in TF mRNA and FVIIa-AT levels.

Conclusion(s): Our study confirms a relevant rate of early fatal THE in APL. Laboratory data demonstrate the TF mRNA downregulation under ATRA, which parallels hypercoagulation markers decrease. Persistent high TF-dependent clotting activation might explain post-ATRA THE.