fibrin and Eosinophilia

Topics: Blood Coagulation; Down-Regulation; Edema; Eosinophilia; Fibrin; Humans; Inflammation; Nasal Polyps; Tissue Plasminogen Activator

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

A 33-year-old woman presented with abdominal pain and distention, diarrhoea and marked eosinophilia in blood and ascites. As other causes could be excluded, the subserosal type of eosinophilic gastroenteropathy was diagnosed. The low plasma fibrinogen level (less than 100 mg/100 ml) found in this patient is an as yet undescribed feature. During prednisolone therapy it increased concurrently with the fall of blood eosinophils and the relief of clinical symptoms. Interest was further directed to the ascitic fluid where not only the presence of eosinophils (74%) enveloped in fibrin yarn and of basophils (2%) but also of 24% T lymphocytes (among them 75% CD4+, 24% CD8+, 4% CD25+, less than 1% CD19+, less than 1% natural killer cells) could be demonstrated. These lymphocytes are likely to be the source for lymphokine production chemoattracting eosinophils into the intestine. In addition they seem to be involved in IgE hyperproduction, which after adequate therapy and complete resolution of the clinical symptoms, tended to decrease slowly.

Topics: Adult; Afibrinogenemia; Eosinophilia; Female; Fibrin; Gastrointestinal Diseases; Humans; Prednisolone; T-Lymphocytes

Patients with the hypereosinophilic syndrome (HES) are at increased risk of thrombosis and have signs of fibrin deposition in the myocardial cavity; the pathogenesis of these complications is still unknown. We have studied a 51-year-old man affected by HES with heart, lung, skin, and gastrointestinal involvement. Routine laboratory parameters of the hemostatic system were normal with the exception of blood fibrinolytic activity. The latter was evaluated by both diluted blood clot lysis time and euglobulin lytic activity on fibrin plates before and after 10 min venous occlusion. The fibrinolytic activity measured on four occasions during a 3-month period, was impaired both in basal conditions and following venous occlusion. Platelet studies on two different occasions before and during therapy showed spontaneous platelet aggregation, lowered threshold concentrations of various aggregating agents, reduced platelet regeneration time and increased plasma beta-thromboglobulin concentration. The patient's polymorphonuclear cells (more than 75% eosinophils) were devoid of any procoagulant activity (PCA). Instead, patient's mononuclear cells studied before therapy generated significantly higher PCA on stimulation by endotoxin than cells from control subjects. The procoagulant response to endotoxin decreased markedly during therapy. The observed abnormalities could, at least partially, contribute to fibrin deposition in HES.

Topics: beta-Thromboglobulin; Blood Coagulation Factors; Blood Coagulation Tests; Eosinophilia; Fibrin; Fibrinolysis; Heart Failure; Humans; Male; Middle Aged; Platelet Aggregation; Syndrome

Topics: Blood Coagulation; Eosinophilia; Fibrin; Humans; Male; Middle Aged; Monocytes; Syndrome

Guinea pigs primed for cutaneous basophil hypersensitivity (CBH) with several soluble proteins or with sheep erythrocytes developed a systemic, delayed-onset, maculopapular rash when challenged parenterally with specific antigen. The rash was most readily induced 5 to 7 days after immunization, at a time when local CBH skin test reactivity was also optimal. Miscroscopically, the rash resembled local CBH skin test reactions, being comprised of a papillary dermal infiltrate of basophils and lymphocytes and a striking dilatation and compaction of superficial venules. In addition to the systemic rash, animals expressing systemic CBH (SCBH) exhibited a striking eosinophilia at 24 hr which gave way to basophilia at 48 hr. Focal collections of eosinophils, and of smaller numbers of basophils, were found in the lungs and spleen; both eosinophils and basophils infiltrated the medulla of the thymus. Thus, basophil-rich infiltrations are favored in the skin even after systemic challenge with antigen and occur only to a much smaller extent in other organs where eosinophils may predominate. These differences in the response of various organs to challenge with parenteral antigen suggest that as yet unidentified local factors play a determinative role in regulating the inflammatory response. The pathogenesis of SCBH is not yet established, but it shares many of the properties of local CBH: histology, carrier specificity, development early after sensitization in the absence of detectable antibodies. Passive transfer has not been accomplished with serum alone but has been achieved irregularly with cells plus serum. SCBH may serve as a useful model for several disease states in man characterized by a systemic rash and eosinophilia, including certain types of drug reaction.

Topics: Animals; Antigens; Basophils; Dermatitis, Contact; Eosinophilia; Epitopes; Erythrocytes; Female; Fibrin; Fibrinogen; Guinea Pigs; Hypersensitivity, Delayed; Immunity, Cellular; Immunization, Passive; Lymphokines; Male; Mitogens; Skin; Time Factors

Topics: Bone Marrow Cells; Cytoplasmic Granules; Eosinophilia; Eosinophils; Fibrin; Humans; Infant; Leukocyte Count; Male; Microscopy, Electron