title: Asthma is associated with enhanced thrombin formation and impaired fibrinolysis.
abstract: There is evidence that altered blood coagulation and fibrinolysis are involved in the pathogenesis of asthma. Increased thromboembolic risk has been reported in asthmatics.
  
  
  
  To investigate whether enhanced thrombin generation and impaired fibrinolysis occur in asthmatics.
  
  
  
  Plasma thrombin generation profile together with a computational assessment of thrombin dynamics and fibrinolytic capacity expressed as clot lysis time (CLT) were determined in 164 consecutive patients with stable asthma and 72 controls matched for age, gender, weight and smoking.
  
  
  
  Asthma patients had 20.2% increased endogenous thrombin potential (ETP), 41.4% higher peak thrombin concentration, 61% higher maximal prothrombin conversion rate, 15.5% faster rate of thrombin formation (all, P < 0.0001) and 10% lower thrombin decay capacity (P = 0.0004) compared with controls. Asthmatics had also 14.4% longer CLT (P = 0.001) associated with 21.3% higher plasminogen activator inhibitor-1 (PAI-1) (P < 0.0001), and 13% higher plasma α2 -macroglobulin (P = 0.0002). Using ETP and CLT above 75th percentile of the control values as the cut-off levels, we found increased risks of enhanced thrombin generation and hypofibrinolysis in asthmatics, also after correction for potential confounders. ETP and CLT were associated inversely with forced expiratory volume in 1 s/vital capacity (FEV1 /VC) index, after adjustment for age and body mass index. Non-allergic asthma (n = 70, 42.6%) was characterized by 17.5% longer CLT (P = 0.02), which positively associated with PAI-1. Thrombin generation profile was not affected by allergy.
  
  
  
  Asthma is associated with enhanced thrombin generation and impaired fibrinolysis, which might contribute to thromboembolic events in this disease.
authors.affiliation: Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: S
authors.initials: S
authors.lastname: Bazan-Socha
authors.affiliation: Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: L
authors.initials: L
authors.lastname: Mastalerz
authors.affiliation: Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Cybulska
authors.affiliation: Department of Differential Equations and Statistics, Faculty of Mathematics and Natural Sciences, University of Rzeszow, Rzeszow, Poland.
authors.forename: L
authors.initials: L
authors.lastname: Zareba
authors.affiliation: Synapse bv, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Kremers
authors.affiliation: Centre for Medical Research and Technologies, The John Paul II Hospital, Krakow, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Zabczyk
authors.affiliation: Allergy and Clinical Immunology Department, University Hospital, Krakow, Poland.
authors.forename: G
authors.initials: G
authors.lastname: Pulka
authors.affiliation: Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: T
authors.initials: T
authors.lastname: Iwaniec
authors.affiliation: Synapse bv, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Hemker
authors.affiliation: Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland.|Centre for Medical Research and Technologies, The John Paul II Hospital, Krakow, Poland.|Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Undas
mesh_terms: D001249:Asthma / Q000097:blood* / Q000175:diagnosis; D001777:Blood Coagulation; D001780:Blood Coagulation Tests; D016022:Case-Control Studies; D015897:Comorbidity; D003955:Diagnostic Tests, Routine; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012307:Risk Factors; D013917:Thrombin / Q000096:biosynthesis*
chemical_list: D013917:Thrombin
keywords: asthma; clot lysis time; thrombin generation; thrombosis