title: Persistent Vascular Remodeling and Leakiness are Important Components of the Pathobiology of Re-bleeding in Hemophilic Joints: Two Informative Cases.
abstract: It is unclear if vascular remodeling in hemophilic joints perpetuates bleeding because it is difficult to gauge leakiness in the setting of low clotting factor levels. Two patients provided the unique opportunity to demonstrate that vascular changes directly contribute to joint bleeding.
  
  
  
  Two patients had severe hemophilic arthropathies; joint vascularity and bleeding were studied during periods of normalized plasma clotting factor activities with MSKUS and PD. One patient was "cured" of hemophilia with liver transplantation. Abnormal elbow vascularization persisted despite normalization of coagulation status and was associated with severe bleeding years after transplant. Dynamic vascular changes were detected prior to and during bleeding; angiography revealed enlarged, thickened vessels consistent with remodeling, and required arterial embolization. The second patient had continued knee bleeding and fluctuating vascular changes for months following knee replacement, unresponsive to intense daily factor treatment. Subsequently, new bleeds developed in other joints associated with similar vascular changes despite continued factor replacement.
  
  
  
  Vascular remodeling contributes to perpetuated hemophilic joint bleeding and therefore contributes to progressive arthropathy. Intra-articular or systemic administration of anti-angiogenic drugs, such as vascular endothelial growth factor antagonists, might be of benefit in such patients, but requires study.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of California San Diego, San Diego, California, USA.
authors.forename: Wesley
authors.initials: W
authors.lastname: Kidder
authors.affiliation: Radiology Service, VA San Diego Healthcare System, San Diego, California, USA.|Department of Radiology, University of California San Diego, San Diego, California, USA.
authors.forename: Eric Y
authors.initials: EY
authors.lastname: Chang
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of California San Diego, San Diego, California, USA.
authors.forename: Colleen
authors.initials: C
authors.lastname: M Moran
authors.affiliation: Department of Radiology, University of California San Diego, San Diego, California, USA.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Rose
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of California San Diego, San Diego, California, USA.|Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Annette
authors.initials: A
authors.lastname: von Drygalski
mesh_terms: D004551:Elbow Joint / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D006395:Hemarthrosis / Q000209:etiology*; D006467:Hemophilia A / Q000150:complications / Q000601:surgery; D006801:Humans; D007719:Knee Joint / Q000098:blood supply / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D042461:Vascular Endothelial Growth Factor A / Q000627:therapeutic use; D066253:Vascular Remodeling
chemical_list: D042461:Vascular Endothelial Growth Factor A
keywords: arthropathy; bleeding; hemarthrosis; hemophilia; hemostasis; joint disease; vascular remodeling