title: Chronic thromboembolic pulmonary hypertension-associated dysfibrinogenemias exhibit disorganized fibrin structure.
abstract: BACKGROUND
  Mechanisms contributing to the pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) are poorly understood. This disorder is characterized by incomplete resolution of pulmonary perfusion defects resulting from acute venous thromboembolism. We previously identified several dysfibrinogenemias in some patients with CTEPH. The purpose of this study was to determine whether fibrin clot architecture might be implicated in the thrombolytic resistance in patients with these CTEPH-associated dysfibrinogenemias.
  
  
  METHODS
  Purified fibrinogen from patients and healthy controls was clotted with thrombin in the presence of calcium. Clot turbidity, porosity, and susceptibility to fibrinolysis were evaluated by spectrophotometric and permeation analyses. Fibrin network structure was assessed by laser-scanning confocal microscopy.
  
  
  RESULTS
  Compared to normal fibrinogen, CTEPH-associated dysfibrinogenemias exhibited low clot turbidity, decreased porosity, and fibrinolytic resistance. In addition, the dysfibrinogenemias exhibited a more disorganized fibrin network structure characterized by thinner fibers, greater network dispersal and more extensive fiber branching.
  
  
  CONCLUSIONS
  Abnormal clot architecture and fibrinolytic resistance may contribute to incomplete clot resolution following acute venous thromboembolism in patients with CTEPH-associated dyfibrinogenemia.
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California, San Diego, CA, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Marsh
authors.forename: Peter G
authors.initials: PG
authors.lastname: Chiles
authors.forename: Ni-Cheng
authors.initials: NC
authors.lastname: Liang
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Morris
mesh_terms: D000347:Afibrinogenemia / Q000097:blood / Q000209:etiology* / Q000473:pathology; D016022:Case-Control Studies; D015331:Cohort Studies; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000737:chemistry / Q000378:metabolism; D005342:Fibrinolysis; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000150:complications* / Q000473:pathology; D018613:Microscopy, Confocal; D008958:Models, Molecular; D011487:Protein Conformation; D013927:Thrombosis / Q000097:blood / Q000150:complications* / Q000473:pathology
chemical_list: D005337:Fibrin; D005340:Fibrinogen
keywords: CTEPH; CTVD; Confocal microscopy; Fibrinogen; Fibrinolysis; Pulmonary embolism; Thrombosis; chronic thromboembolic pulmonary hypertension; chronic thrombotic venous disease