Prevalence and management of iron deficiency in patients with bleeding disorders: A single-center, retrospective cohort study Free

Background:

Iron deficiency (ID) is the most common micronutrient deficiency in the world. Yet, it is frequently undiagnosed and untreated. Patients with an underlying bleeding disorder are particularly at risk of developing ID, though the prevalence is largely unknown. Data evaluating the success rate of iron repletion and the strategies used in this susceptible group remains limited. In this study, we evaluate the prevalence and management of ID across various bleeding disorders, with particular attention to bleeding severity and treatment patterns.

Methods:

We conducted a retrospective, single-center cohort study of 156 adult patients (≥18 years) with bleeding disorders treated at the Hemophilia Center of Western Pennsylvania. Patients were included if they had a documented ferritin level ≤50 ng/mL between January 1, 2022, and March 17, 2025. Electronic medical records were assessed for demographic information, ID treatment strategy, and post-treatment iron testing. Bleeding disorder severity was assessed using documented Bleeding Assessment Tool (BAT) scores and disease-specific coagulation testing.

Results:

Of the 1,140 adult patients (both with and without bleeding disorders) evaluated, ferritin was measured in 591 (51.8%) patients with 335 patients having a ferritin ≤50 ng/mL. This observation corresponds to an iron deficiency prevalence of 29.3%. Of the 156 patients meeting our inclusion criteria, 139 were female (89.1%) with 131 of total participants being white females (84%). Thirteen patients (8.3%) identified as Amish. Von Willebrand disease (VWD) was the most common bleeding disorder (n=77; 49.4%) with type 1 VWD being the most common subtype (n=68, 88.3%). Other subtypes included 2A (n=1), 2B (n=3), 2M (n=2), 2N (n=1), and type 3 (n=2). Additional diagnoses included carrier hemophilia B (n=19, 12.2%), carrier hemophilia A (n=16, 10.3%), platelet functional defect (n=11, 7.1%), bleeding disorder of unknown cause (n=10, 6.4%), and hemophilia A (n=10, 6.4%).

Among the 77 patients with VWD, 49 had a documented BAT score; 28 (57.1%) had a BAT ≥ 6 with a total average BAT score of 6.4. In contrast, of 79 non-VWD patients, 37 had a documented BAT score; 13 (35.1%) had a BAT ≥ 6 with a total average score of 4.9 (p = 0.06). Among type 1 VWD, von Willebrand antigen levels did not correlate with increased BAT scores (R = 0.0001) or lower ferritin levels (R = 0.0005). Across all bleeding disorder subtypes, no significant differences were observed in initial ferritin levels (p=0.84) or BAT scores (p=0.06).

Of 156 patients included in the study, 81 (51.9%) received intravenous (IV) iron, 29 (18.6%) received oral iron, and 46 (29.5%) received no therapy. Post-treatment iron studies were available for 32 patients (29.1%), predominantly within the IV therapy group (n=31). Among those who received IV iron, ferritin increased significantly from 15.4 ng/mL (95% CI 11.8-19.0) to 126.9 ng/mL (95% CI 96.3-157.4) (p <0.05). Iron response did not differ significantly by bleeding severity; patients with BAT scores < 6 (n=6) had a mean ferritin increase of 132.5 ng/mL (95% CI 53.1-211.9) compared to 86.5 ng/mL (95% CI 28.3-144.8) in those with BAT scores ≥ 6 (n=11; p=0.28).

Conclusions:

Iron deficiency is common but remains under-treated among patients with bleeding disorders. The prevalence in this cohort exceeds prior adult estimates using the same ferritin cutoff. Many patients were untested or lacked an underlying bleeding disorder, suggesting the true prevalence of ID could be even higher. Nearly 30% of patients received no iron therapy, highlighting a treatment gap in a particularly high-risk population. Furthermore, follow-up testing was uncommon particularly within the oral iron group, demonstrating a lack of care continuity and outcome monitoring. IV iron was the predominant and most effective treatment modality with significant ferritin improvement post-treatment.Among patients with type 1 VWD, no correlation was found between VWF antigen levels and BAT scores or initial ferritin levels, reinforcing the idea that clinical phenotype not just laboratory severity should drive management decisions. The impact of iron repletion on bleeding events in the bleeding disorder population remains unknown. These findings underscore the importance of ongoing investigation regarding iron's impact on the clinical bleeding phenotype in the bleeding disorder population.