Advances and challenges in hemophilic arthropathy

Abstract

Hemophilic arthropathy is a form of joint disease that develops in secondary to joint bleeding and presents with synovial hypertrophy, cartilage and bony destruction. The arthropathy can develop despite clotting factor replacement and is especially disabling in the aging population. Pathobiological tissue changes are triggered by release of hemoglobin and iron deposition in the joint, but the sequence of events and the molecular mechanisms resulting in joint deterioration are incompletely understood. Treatment options other than clotting factor replacement are limited. Improvements in the treatment of hemophilia necessitate a better understanding of the processes that lead to this disabling condition and better diagnostic tools. Towards that end, studies of the molecular mechanisms leading to the arthropathy, as well as the development of sensitive imaging techniques and biomarkers are needed. These will pave the way to identify the cause of acute pain such as joint bleeding or synovitis, detect early, potentially reversible structural changes, and predict progression of disease. This review describes current imaging techniques and the development of high resolution musculoskeletal ultrasound with power Doppler to afford point-of-care diagnosis and management, the potential utility of diagnostic biomarkers, and summarizes our current knowledge of the pathobiology of hemophilic arthropathy.

Mechanisms of vascular permeability and remodeling associated with hemarthrosis in factor VIII‐deficient mice

“…Hemarthrosis remains a prominent clinical feature in patients with hemophilia A (Factor VIII [FVIII] deficiency) and cannot be prevented in many adult patients despite clotting factor prophylaxis . A single joint bleed can trigger a vicious cycle of rebleeding leading to development of “target joints” and HA . Pathological changes include synovial inflammation/hypertrophy and cartilage destruction .…”

“…A single joint bleed can trigger a vicious cycle of rebleeding leading to development of “target joints” and HA . Pathological changes include synovial inflammation/hypertrophy and cartilage destruction . Recent studies have identified profound vascular changes associated with joint bleeding that may destabilize vessels, thereby contributing to bleeding tendencies and HA progression .…”

The hypertension of hemophilia is associated with vascular remodeling in the joint

“…Hemophilia is an X‐linked bleeding disorder that is characterized by Factor VIII or Factor IX deficiency and occurs with a frequency of one in 5000 to one in 30 000 male live births depending on the type and severity of hemophilia. Starting in early childhood, PWH suffer from frequent spontaneous joint bleeding that causes hemophilic arthropathy, clinically characterized by joint deformities, synovial hypertrophy, and destruction of cartilage and bone. While the progression of hemophilic arthropathy can be mitigated by clotting factor replacement therapy, it cannot be entirely abrogated.…”

“…Starting in early childhood, PWH suffer from frequent spontaneous joint bleeding that causes hemophilic arthropathy, clinically characterized by joint deformities, synovial hypertrophy, and destruction of cartilage and bone. While the progression of hemophilic arthropathy can be mitigated by clotting factor replacement therapy, it cannot be entirely abrogated. A marked feature of hemophilia is the higher prevalence of hypertension and higher blood pressures than the general population.…”

Development and Reliability of the Joint Tissue Activity and Damage Examination for Quantitation of Structural Abnormalities by Musculoskeletal Ultrasound in Hemophilic Joints

“…Hemophilia is an X chromosome–linked bleeding disorder manifested by repetitive hemarthroses leading to debilitating joint arthropathy, characterized by soft tissue hypertrophy and inflammation, as well as osteochondral deformities and destruction . The extent to which these changes are reversible is unclear.…”