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. 2024 Jun 11;8(11):2901-2907.
doi: 10.1182/bloodadvances.2023012285.

Predictive parameters for spontaneous joint bleeding during emicizumab prophylaxis

Sara Arcudi  1 , Roberta Gualtierotti  1   2 , Erica Scalambrino  1 , Marigrazia Clerici  1 , Shermarke Hassan  1   3 , Valentina Begnozzi  1 , Elena Anna Boccalandro  1 , Cristina Novembrino  1 , Carla Valsecchi  1 , Roberta Palla  2 , Flora Peyvandi  1   2
Affiliations

Predictive parameters for spontaneous joint bleeding during emicizumab prophylaxis

Sara Arcudi et al. Blood Adv. .

Abstract

Emicizumab is approved for prophylaxis of patients with hemophilia A (HA). Despite its efficacy in reducing bleeding, some patients on emicizumab still experience hemarthrosis, but no tool is yet available to identify those at a higher risk of spontaneous joint bleeding. This study aimed to evaluate whether laboratory measurements (global coagulation assays and emicizumab concentration) and/or arthropathy scores can distinguish patients at higher risk of spontaneous joint bleeding while on emicizumab prophylaxis. A thrombin generation assay was performed upon the addition of tissue factor and synthetic phospholipids. Nonactivated thromboelastography was performed on citrated whole blood. Emicizumab concentrations were measured using a modified 1-stage factor VIII assay. The degree of hemophilic arthropathy was assessed using the Hemophilia Joint Health Score and Hemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) score. A Cox proportional hazards model was used to evaluate the association between variables and bleeding. The predictive power of these variables was investigated using receiver operating characteristic (ROC) analysis. Forty patients with severe HA, with or without inhibitors, on emicizumab prophylaxis were enrolled in an observational cohort study. Ten of 40 developed spontaneous joint bleeding. None of the laboratory parameters were able to distinguish patients with a higher risk of spontaneous joint bleeding. ROC analysis showed that during emicizumab prophylaxis, only the presence of synovitis and a higher HEAD-US score were associated with spontaneous joint bleeding (area under the curve, 0.84). A greater degree of arthropathy and the presence of synovitis could help predict the risk of spontaneous joint bleeding in patients with HA on emicizumab prophylaxis.

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Conflict of interest statement

Conflict-of-interest disclosure: F.P. received honoraria for participating in advisory boards organized by CSL Behring, BioMarin, Roche, Sanofi, and Sobi. R.G. received honoraria for participating as a speaker on advisory boards and seminars organized by Pfizer, Roche, Novo Nordisk, and Takeda, outside the present work. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Study flowchart.
Figure 2.
Figure 2.
Receiver operating characteristic analysis. HEAD-US total score and total synovitis score in the prediction model (AUC = 0.84).
See this image and copyright information in PMC

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