title: Unfavorably Altered Fibrin Clot Properties in Patients with Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome): Association with Thrombin Generation and Eosinophilia.
abstract: OBJECTIVE
  Given reports on the increased prevalence of thromboembolic incidents in patients with eosinophilic granulomatosis with polyangiitis (EGPA; Churg-Strauss syndrome), we investigated whether fibrin clot properties are unfavorably altered in EGPA.
  
  
  METHODS
  Ex vivo plasma fibrin clot characteristics, including clot permeability, turbidimetry and efficiency of fibrinolysis using two assays, were investigated in 34 consecutive patients with remission in EGPA according to the Birmingham Vasculitis Activity Score version 3 (23 female, 11 male), aged 48 (range, 21-80) years. The control group comprised 34 age- and sex- matched volunteers.
  
  
  RESULTS
  Compared with controls, patients with EGPA were characterized by denser fiber clots (estimated pore size, Ks, 7.30±0.93 vs 10.14±1.07 10-9 cm2), faster fibrin polymerization (lag phase in a turbidimetric curve, 41.8±3.6 vs 47.4±2.9 s), thicker fibrin fibers (maximum absorbance, ΔAbs, 0.87±0.09 vs 0.72±0.07), higher maximum levels of D-dimer released from clots (DDmax 4.10±0.46 vs 3.54±0.35 mg/L), and prolonged clot lysis time (t50%; 9.50±1.45 vs 7.56±0.87 min); all p<0.0001. Scanning electron microscopy images confirmed denser plasma fibrin networks composed of thinner fibers formed in EGPA. Antineutrophil cytoplasmic antibody status and C-reactive protein did not affect clot variables. Multivariate analysis adjusted for fibrinogen showed that Ks was predicted by eosinophil count, peak thrombin generation, factor VIII, and soluble CD40 ligand, whereas eosinophil count, peak thrombin generation and antiplasmin predicted t50%.
  
  
  CONCLUSIONS
  This study is the first to show that EGPA is associated with prothrombotic plasma fibrin clot phenotype, which may contribute to thromboembolic manifestations reported in this disease.
authors.affiliation: 2nd Department of Medicine, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Lucyna
authors.initials: L
authors.lastname: Mastalerz
authors.affiliation: 2nd Department of Medicine, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Celińska-Lӧwenhoff
authors.affiliation: Department of Rheumatology, Dietl Hospital, Kraków, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Krawiec
authors.affiliation: Department of Rheumatology, Dietl Hospital, Kraków, Poland.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Batko
authors.affiliation: Department of Internal Diseases and Rheumatology, Military Institute of the Health Services, Central Clinical Hospital of the Department of National Defense, Warszawa, Poland.
authors.forename: Witold
authors.initials: W
authors.lastname: Tłustochowicz
authors.affiliation: Institute of Cardiology, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Anetta
authors.initials: A
authors.lastname: Undas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001777:Blood Coagulation / Q000502:physiology*; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D015267:Churg-Strauss Syndrome / Q000378:metabolism*; D004802:Eosinophilia / Q000378:metabolism*; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D063285:Fibrin Clot Lysis Time / Q000379:methods; D005340:Fibrinogen / Q000378:metabolism; D005342:Fibrinolysis / Q000502:physiology; D014890:Granulomatosis with Polyangiitis / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013917:Thrombin / Q000378:metabolism*; D013927:Thrombosis / Q000378:metabolism; D055815:Young Adult
chemical_list: D005337:Fibrin; D005340:Fibrinogen; D002097:C-Reactive Protein; D013917:Thrombin