fibrin and Granulomatosis-with-Polyangiitis

Patients with granulomatosis with polyangiitis (GPA) show increased tendency toward thromboembolic phenomena in exacerbation of their disease.. The aim of the study was to evaluate thrombin generation potential and fibrinolytic plasma activity in patients with GPA, both in exacerbation and in remission.. We included 38 patients with GPA: 18 with exacerbated GPA and 20 in remission. The control group included 39 healthy participants matched for age and sex. Plasma thrombogenic potential was assessed using calibrated automated thrombography. Plasma fibrinolytic potential was assessed using clot lysis time (CLT). We also measured levels of inflammatory markers, thrombomodulin, and fibrinolysis proteins in all participants.. In the whole group of patients with GPA, endogenous thrombin potential was higher by about 25% (P <0.001), while CLT was lower by about 20% (P = 0.02) when compared with controls. The endogenous thrombin potential was higher, the CLT lower, and the levels of thrombomodulin and inflammation markers (C‑reactive protein, fibrinogen, factor VIII) higher both in patients with exacerbation and in remission than in the control group; no such differences were noted when comparing those with exacerbation and those in remission, however. The only parameter that differentiated patients with GPA exacerbation from those in remission was the D‑dimer level (median [interquartile range], 1151 [597.2-2468.7] ng/ml vs 340.4 [255.1-500.7] ng/ml; P <0.001), a marker of lysis of intravascularly formed fibrin.. Patients with GPA show an increased prothrombotic state, regardless of the disease phase. This is probably related to ongoing low-grade inflammation and endothelial injury. Large clinical studies are required to address the need for, and appropriate type of, antithrombotic prophylaxis during the course of GPA.

Topics: Fibrin; Fibrin Clot Lysis Time; Fibrinolysis; Granulomatosis with Polyangiitis; Humans; Thrombin

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.. 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.. 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%.. 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.

Topics: Adult; Aged; Aged, 80 and over; Blood Coagulation; C-Reactive Protein; Case-Control Studies; Churg-Strauss Syndrome; Eosinophilia; Female; Fibrin; Fibrin Clot Lysis Time; Fibrinogen; Fibrinolysis; Granulomatosis with Polyangiitis; Humans; Male; Middle Aged; Thrombin; Thrombosis; Young Adult

Topics: Adult; Biopsy; Conjunctivitis; Diagnosis, Differential; Fibrin; Gingival Hemorrhage; Gingival Hyperplasia; Granulomatosis with Polyangiitis; Humans; Hyalin; Male; Periodontitis; Plasminogen; Sarcoidosis; Skin Diseases, Genetic

Topics: Adult; Eosine Yellowish-(YS); Fibrin; Fluorescent Antibody Technique, Direct; Granulomatosis with Polyangiitis; Hematoxylin; Humans; Male; Skin; Staining and Labeling

Intravascular lysis of leucocytes was an early event in the process of tissue injury in a patient with limited Wegener's granulomatosis. This lysis, with consequent liberation of free organelles into the circulation, was followed by platelet aggregation and fibrin deposition in vessels with intact endothelial cells. Necrosis of endothelial cells also occurred early in the tissue injury. Complete obstruction of vessel lumina, with necrosis of their walls and of alveolar pneumocytes, followed. The alveolar spaces filled with fibrin and cell debris, and macrophages and fibroblasts migrated into these areas. The ultrastructural findings offer a rationale for current therapy. Cyclophosphamide therapy led to improvement in the clinical state, pulmonary function and histological changes.

Topics: Capillaries; Cyclophosphamide; Female; Fibrin; Granulomatosis with Polyangiitis; Humans; Leukocytes; Lung; Middle Aged; Platelet Aggregation

Topics: Amyloid; Arthritis, Rheumatoid; Basement Membrane; Biopsy; Blood Proteins; Complement System Proteins; Diagnosis, Differential; Fibrin; Glomerulonephritis; Glycoproteins; Granulomatosis with Polyangiitis; Histocytochemistry; Humans; Hypersensitivity; Immunoglobulins; Kidney Glomerulus; Methenamine; Methods; Proteins; Purpura; Silver; Staining and Labeling

Topics: Azathioprine; Biopsy; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Female; Fibrin; Granulomatosis with Polyangiitis; Heparin; Humans; Immunosuppressive Agents; Kidney; Kidney Failure, Chronic; Kidney Glomerulus; Prednisone; Pregnancy

Topics: Blood Vessels; Diphtheria; Fibrin; Granulomatosis with Polyangiitis; Humans; Hypertension, Malignant; Lupus Erythematosus, Systemic; Necrosis; Polyarteritis Nodosa; Pyelonephritis; Rheumatic Fever; Sepsis; Splenic Artery; Tuberculosis, Meningeal; Vascular Diseases