Impaired fibrinolysis and lower levels of plasma alpha(2)-macroglobulin are associated with an increased risk of severe asthma exacerbations

Stanislawa Bazan-Socha, Lucyna Mastalerz, Agnieszka Cybulska, Lech Zareba, Romy Kremers, Michal Zabczyk, Grazyna Pulka, Teresa Iwaniec, Jan G. Bazan, Coenraad Hemker, Anetta Undas*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Recently we have reported that asthma is associated with enhanced plasma thrombin formation, impaired fibrinolysis and platelet activation. In the present study we investigated whether described prothrombotic blood alterations might predispose to thromboembolic events or asthma exacerbations. In 164 adult asthmatics we assessed clinical events during 3-year follow-up and analyzed their associations with measured at baseline prothrombotic blood parameters. Data were obtained from 157 (95.7%) of the asthma patients. We documented 198 severe asthma exacerbations (64/ year), which occurred in 53 subjects (34%). These patients were older (p = 0.004), had worse asthma control (p = 0.02) and lower spirometry values (p = 0.01), at baseline. Interestingly, this subgroup had longer clot lysis time (CLT), as well as lower a2-macroglobulin (p = 0.038 and p = 0.04, respectively, after adjustment for potential confounders). Increased CLT and lower a2-macroglobulin were demonstrated as independent predictors of asthma exacerbation in multiple regression model. Moreover, we documented two episodes of deep vein thrombosis (1.3%), and eight acute coronary syndromes (5.1%). Patients who experienced thromboembolic events (n = 10, 6.4%, 2.1%/ year) had lower alpha(2)-macroglobulin (p = 0.04), without differences in efficiency of fibrinolysis and thrombin generation. Impaired fibrinolysis and lower levels of alpha(2)-macroglobulin might predispose to a higher rate of asthma exacerbations, suggesting new links between disturbed hemostasis and asthma.

Original languageEnglish
Article number11014
Number of pages10
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - 8 Sep 2017

Keywords

  • THROMBIN GENERATION
  • PROTHROMBOTIC STATE
  • STROKE
  • COAGULATION
  • ARTERIAL
  • DISEASES
  • SYSTEM
  • ALPHA

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