OC 26.5 - Predisposing conditions and drugs to caplacizumab-related bleeding episodes in patients with acute immune-mediated TTP: real-world data from the Milan Center

Sunday, June 23, 2024

15:45 – 16:00 ICT

Room: 111 A-C

Presenting Author(s)

Pasquale Agosti, MD, PhD

Assistant Professor Clinician
Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milan, Italy; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy.
Milan, Lombardia, Italy

Co-Author(s)

MR

Matilde Reichenbach

Medical Doctor
Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milan, Italy
Milan, Lombardia, Italy
IM

Ilaria Mancini

Biologist
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
Milan, Lombardia, Italy
PD

Pasqualina De Leo

Biologist
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
Milano, Lombardia, Italy
GL

Giulia Maria Giorgia Lo Piano

BSc in biology
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy.
Milan, Lombardia, Italy
Addolorata Truma, MD

Research fellow
Università degli studi di Milano, Department of Pathophysiology and Transplantation, Milan, Italy.
milano, Lombardia, Italy
Juri Alessandro Giannotta, Medical Doctor

MD
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
Milano, Lombardia, Italy
BF

Barbara Ferrari

MD
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
Milan, Lombardia, Italy
Andrea Artoni

MD
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
Milan, Lombardia, Italy
Flora Peyvandi, MD, PhD

Full Professor
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Università degli Studi di Milano, Department of Pathophysiology and Transplantation
Milan, Lombardia, Italy

Background: The humanized bivalent nanobody caplacizumab has changed the therapeutic paradigm in acute immune-mediated thrombotic thrombocytopenic purpura (iTTP). However, real-world data on its safety are still limited, especially in patients with concomitant bleeding risk factors.

Aims: To estimate the incidence of caplacizumab-related bleeding episodes and identify the main risk factors associated with these episodes.

Methods: In this cross-sectional study, we included outpatients followed at the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center (Milan, Italy) who received caplacizumab for an acute iTTP episode occurred between September 2018 and October 2023. Data on bleeding episodes occurred during caplacizumab treatment were retrospectively collected, alongside patient- and episode-related features, clinical conditions and drugs that increase bleeding risk.

Results: Out of 61 acute iTTP episodes, 8/61 (13%) were complicated with caplacizumab-related bleeds, including 4 major bleeds, 2 clinically-relevant non major bleeds (1 trauma-related), and 2 minor bleeds. Predominantly, these bleeding events occurred in patients with predisposing bleeding conditions (Table 1).
Patients with caplacizumab-related bleeding chronically used a significantly higher median number of drugs (p=0.03), with increased daily use of antiplatelet and anticoagulant drugs [OR: 5.6 (1.4-21.8, p=0.04)]. No difference in the severity of TTP episodes was found between the two groups (Table 2). Notably, bleeding events occurred 3 to 27 days after caplacizumab start, generally after platelet count normalization (Table 1).

Conclusion(s): Although further studies with larger sample size are needed, our findings suggest that the risk of bleeding related to caplacizumab is mostly secondary to the concomitant use of antiplatelet agents and anticoagulants. A careful revision of the therapeutic indications of these concomitant drugs and the related risk-benefit balance is recommended during caplacizumab treatment.