Heterotopic Ossification in Hemophilia: A Multi-Center Case Series

BACKGROUND: Heterotopic Ossification (HO), or Myositis Ossificans Traumatica, is the post-traumatic formation of unwanted abnormal benign lamellar ectopic bone within extra skeletal tissue locations. HO can form in varying sizes and sites in the body and can significantly impair muscle performance, range of motion (ROM), and function. Since the recent adoption of diagnostic musculoskeletal ultrasound (MSKUS) in hemophilia care, providers and physical therapists have deepened their understanding of hemarthropathic and hemarthrosis progression. MSKUS has also aided in detecting soft tissue injuries, muscle hematoma, and resultant HO formation. Despite advances in therapies for hemophilia, HO is emerging as an unforeseen complication of contusion and injury-related muscle bleeding in hemophilia. Its detection is important as delayed or inappropriate rehabilitation may prolong recovery and disability time. This multicenter retrospective case series sought to verify and confirm HO detection and investigate whether specific types and severities of hemophilia are at increased risk of HO.

METHODS: Deidentified data and MSKUS images from 29 cases were collected from 9 Hemophilia Treatment Centers from the USA, the Netherlands, and Canada from 2016 to June 2023. The case series was declared exempt from IRB approval. Diagnostic and evaluative data was compiled in Redcap. Images were reviewed and diagnostically confirmed by an RMSK-certified Doctor of Physical Therapy and a Radiologist. A single clinic subset was compared to the national hemophilia incidence taken from the ATHN dataset 2022.

RESULTS: We detected HO formation in 29 patients across 9 HTCs. Trauma-induced HO was observed in all bleeding disorder types and severities. (See Table 1). The patients' ages at the time of the inciting injury ranged from 7-56 years, with a mean age of 22.3 and a median of 16. The study's highest incidence of HO cases occurred in patients with type A hemophilia totaling 22/29 subjects or 74.8% of all cases. Except for one severe A, one severe B and a moderate B, the patients were not on prophylactic hemostatic management at the time of injury. The majority of HO (n=24, 82.8%) occurred in the anterior and lateral compartments of the thigh and hip. There were 5 incidents in the upper extremity (4 in the upper anterior arm, 1 in the hand). 24 cases were due to blunt trauma except for 4 in the psoas at the level of the anterior hip and 1 in the elbow flexors of the upper arm. HO formation was mostly associated with deep muscle bleeds next to the bony cortex (n=24). HO was detected on average at 22.97 days after injury (median 21, range 11 to 60), with most detected with MSKUS (n=24) by the physical therapist (n=22) and physician (n=2) in clinic. At the Washington Center for Bleeding Disorders (WACBD), where strict MSKUS follow-up was possible in 7 patients, HO induction was confirmed at day 23, 26, 18, 11, 14, 20, and 22 for a mean of 19.14 days (SD = 5.24).

DISCUSSION: Our study shows that HO occurs regularly in Hemophilia despite its omission in the recently revised 2020 World Federation of Hemophilia guidelines. Notably, the severity or type did not appear to be the sole determinant of HO formation, as the combined total of mild and moderate hemophilia genotypes was 21 (72.4%). Conversely, though limited by the study's small sample size, 74.8% of the HO incidence was reported in type A hemophilia, which appears to be an overrepresentation when compared to the ATHN dataset 2022 report, which indicates an overall 45.59% type A hemophilia incidence. The increased detection of HO in hemophilia may be explained by the growing use of MSKUS by HTC physicians and physical therapists. MSKUS has the advantages of safety and earlier HO detection than radiography. As shown in Fig. 1, HO bears the sonographic signature of hyperechoic contours and deeper acoustic shadowing. The WACBD conducted a review yielding an HO incidence of 23.68% (9 of 38 contusion events) compared to 9-17% in the non-hemophilia population. Though the single-center report is of limited significance, the suggestion of increased HO risk to hemophilia patients merits further study.

CONCLUSION: This case series acknowledges HO as a complication of deep contusions in people with bleeding disorders, especially those not on hemostatic prophylaxis. Further study is needed to determine HO's incidence and risk in Hemophilia. Hemophilia treatment guidelines must be revised to include this complication.