A Cross-Sectional Study of the American Thrombosis and Hemostasis Network Dataset for Outcomes of Dental Extractions in People with Hemophilia
Authors: Messenger Heather , He Chunla , Recht Michael , Kulkarni Roshni 
Published: November 2021

Abstract
BACKGROUND: Dental extraction (DE) is one of the most common procedures in people with hemophilia A or hemophilia B (PWH-A, PWH-B), yet little is known about impact of the type of hemophilia, hemostatic therapies, and bleeding outcomes. To date, there is no standard protocol for how to treat PWH undergoing DE. Similar overall bleeding rates occur with pre- and postoperative factor replacement (FRP) therapy and single dose preoperative FRP (11.9% and 11.4%, respectively) (DE. Bajkin et al. Haemophilia 2020).
METHODS: We analyzed the American Thrombosis and Hemostasis Network dataset (ATHNdataset) to assess trends in prophylactic factor use and its impact on bleeding outcomes following dental extraction in PWH-A and PWH-B ≥2 years of age. A DE bleeding episode was defined as any oral or mouth bleeding occurring during or within one week following a DE procedure. Treated bleeds were defined as any oral or mouth bleeds treated with hemostatic medications during or within one week post-DE. Hospitalization and emergency department (ED) visit events were defined as any that occurred during or one day after a DE. Data on sociodemographic, clinical characteristics, and outcomes were collected prospectively between 2013 and 2019 at annual clinical visits to 134 ATHN-affiliated sites. Categorical variables were summarized using frequency and percentage. Logistic regression was used to evaluate associations between DE and sociodemographic and clinical variables. Simple logistic regression models were applied to identify factors potentially associated with dental bleeding episodes among PWH.
RESULTS: Sociodemographic and clinical characteristics revealed that of the 19,048 PWH in the ATHNdataset, 1,157 subjects underwent 1,301 episodes of DE; a majority (74.9%) were diagnosed hemophilia A and 94.4% were male. The odds of a DE were approximately 148% higher among male PWH compared to female PWH (OR: 2.48; 95%CI: 1.93-3.20). PWH with severe disease were less likely to undertake DE than those with mild hemophilia (OR: 0.83; 95%CI: 0.72-0.95). Compared to PWH-B, PWH-A tended to have DEs at a younger age (&lt;30 years). The chance of a DE did not differ by race, hemophilia type, and currently having or having a history of inhibitor. No significant associations were found between dental extraction, education or employment among PWH ages &gt;18 years.
Dental extraction clinical outcomes and related treatments indicated approximately 34% of PWH used prophylaxis versus on-demand therapy (18%) 292for dental/mouth bleeding. Approximately 5% of PWH who underwent DE reported oral/mouth bleeds within one week of the procedure. Of those bleeding episodes, 28.0% of hemophilia A patients and 12.5% of hemophilia B patients reported two or more oral/mouth bleeds during, and one-week post-DE. Rates of hospitalizations and ED visits were 7.4% and 1.3% respectively for PWH-A and 8.8% and 0.9% respectively for PWH-B. Among oral/mouth bleeds related to dental extraction, 34.0% and 50.0% patients with hemophilia A and B respectively received hemostatic therapies such as DDAVP, factor concentrates, or antifibrinolytics.
Factors associated with DE bleeding were as follows: Dental extractions performed with prophylactic regimen were found to experience insignificantly fewer dental bleeding episodes (P&gt;0.05). Similarly, no statistically significant difference in bleeding rate after DE was found in those using extended half-life factor (EHL) compared to standard half-life products (SHL). Prophylaxis was more prevalent among PWH-A compared to PWH-B (37.3% vs. 25.2% respectively). SHL products were more commonly used than EHL products for on-demand therapy (8.3% vs. 0.5% respectively) as well as prophylaxis (19.8% vs. 8.1%). PWH who have ever developed an inhibitor significantly increased the odds of dental bleeding (OR:2.09, 95%CI: 1.21-3.63). However, no significant relationship was found between inhibitor and DE bleedings among PWH who have been exposed to emicizumab (P=0.168).
DISCUSSION: This is the largest study of DE outcomes in PWH. DE tends to be performed more in those with mild hemophilia and at an earlier age. The use of hemostatic therapies and factor prophylaxis is associated with insignificantly less bleeding. The ATHNdataset allowed studies of outcomes in a large cohort of PWH. This project was part of the ATHN CARE Award.

Disclosures
He: ATHN: Ended employment in the past 24 months. Recht: Foundation for Women and Girls with Blood Disorders, Partners in Bleeding Disorders: Speakers Bureau; uniQure: Consultancy; Takeda: Consultancy; Sanofi: Consultancy; Pfizer: Consultancy; Octapharma: Consultancy; Novo Nordisk: Consultancy; Kedrion: Consultancy; Hema Biologics: Consultancy; Genentech: Consultancy; CSL Behring: Consultancy; Catalyst Biosciences: Consultancy; American Thrombosis and Hemostasis Network: Current Employment; Oregon Health & Science University: Current Employment. Kulkarni: Bayer: Consultancy, Research Funding; CSL Behring: Consultancy; Genentech/Roche: Consultancy, Research Funding; NovoNordisk: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Catalyst Bioscience: Research Funding; Foundation for Women and Girls with Blood Disorders: Membership on an entity's Board of Directors or advisory committees.