PB1172 - Impact of inhibitors on the procoagulant efficacy of bypass agents or hemostatic factors in combination with emicizumab

Tuesday, July 12, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Elena García Arias-Salgado, PhD

Senior researcher
La Paz University Hospital
Madrid, Madrid, Spain

Co-Author(s)

AD

Abel Dos Santos Ortas

Specialist in Hematology
La Paz University Hospital
Madrid, Madrid, Spain
EM

Elena Monzón Manzano

Research Associate
La Paz University Hospital
Madrid, Madrid, Spain
PA

Paula Acuña Butta

Bsc
La Paz University Hospital
Madrid, Madrid, Spain
María Teresa Alvarez-Román, MD, PhD

Head of the Thrombosis and Haemostasis Unit
La Paz University Hospital, Madrid, Spain
Madrid, Madrid, Spain
MM

Mónica Martín Salces

Specialist in Hematology
La Paz University Hospital
Madrid, Madrid, Spain
MR

Maria Isabel Rivas Pollmar

Specialist in Hematology
La Paz University Hospital
Madrid, Madrid, Spain
SG

Sara García Barcenilla, RN

Nurse
Hospital Universitario La Paz-IdiPAZ
Madrid, Madrid, Spain
NB

Nora V V. Butta Coll

Head of Hemostasis laboratory
La Paz University Hospital
Madrid, Madrid, Spain
Víctor Jiménez Yuste, MD PhD

Head of Hematology
La Paz University Hospital
Madrid, Madrid, Spain

Background: Hemophilia A patients (PwHA) treated with Emicizumab, exhibit mild-moderate bleeding phenotypes, thus FVIII or bypassing agents (BPAs) are required to control breakthrough/perioperative bleeds. Increments of FIX levels also induce emicizumab procoagulant effects similarly to FVIII or BPAs.

Aims: To elucidate the impact of FVIII inhibitors in the efficacy of this hemostatic response, we compared in vitro procoagulant effects of BPAs and FIX products in samples from emicizumab-treated patients with or without inhibitors.

Methods: Blood from 21 emicizumab-treated patients, 8 with inhibitor, was collected in CTI.
Therapeutic doses of rFVIII (100IU/dl octacog-alfa), BPAs (1µg/ml rFVIIa, 5IU/dl aPCC) or 100IU/dl of plasma-derived FIX (pFIX), two standard-half-life-rFIX (Nonacog-alfa and Nonacog-gamma), and extended-half-life-rFIX (albutrepenonacog-alfa) were tested.
Clotting time (CT) was evaluated by Rotational Thromboelastometry (ROTEM) and Thrombin Peak by thrombin generation test (TGT) using low tissue factor concentration.

Results: Emizicumab-treated samples showed prolonged CT (Fig-1A) and lower thrombin peak values (Fig-1B) than healthy controls and no significant differences were observed between samples with and without inhibitors.
Addition of 100IU/dl of all FIX products normalized the CT values similarly to the same dose of rFVIII. Nonacog-alfa was more efficient producing similar effects than the addition of 1μg/ml rFVIIa. aPCC response was stronger. Reduction of CT was similar in samples from PwHA without or with inhibitors in all assayed conditions (Fig-1A).
Higher thrombin peak values were obtained by the addition of all FVIII/FIX factors or BPAs tested by TGT but the procoagulant effect of all the recombinant FIX was significantly higher in samples with inhibitors (Fig-1B).

Conclusion(s): Procoagulant effect of BPAs with emicizumab was similar with or without inhibitors whereas thrombin generation induced by rFIX was enhanced in the presence of inhibitors.These results provide a rationale for investigating the concomitant use of rFIX and emicizumab in PwHA with inhibitor in breakthrough bleeding and surgery.

Funding: ISCIII-FEDER(PI19/00631); CSL Behring; Cátedra UAM-Roche.