Asthma is associated with enhanced thrombin formation and impaired fibrinolysis

Bazan-Socha, Stanisława; Mastalerz, Lucyna; Cybulska, Agnieszka; Zaręba, Lech; Kremers, Romy; Ząbczyk, Michał; Pulka, Grażyna; Iwaniec, Teresa; Hemker, H.C.; Undas, Anetta

doi:10.1111/cea.12734

Cited by 45 publications

(84 citation statements)

References 36 publications

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“…Inclusion and exclusion criteria were described previously [8]. Briefly, diagnosis of asthma was established based on a history of recurrent respiratory symptoms, including wheezing, shortness of breath, chest tightness, and cough, together with the documented post-bronchodilator increase in forced expiratory volume in 1 s (FEV 1 ) of at least 12% and 200 ml from the baseline.…”

Section: Methodsmentioning

confidence: 99%

“…Fibrinogen, high-sensitivity (hs) CRP, and immunoglobulin E (IgE) were measured as previously described [8]. Blood samples were drawn into tubes containing 0.109 mol/l sodium citrate (vol/vol, 9:1) and serum separation tubes, centrifuged 2000× g for 20 min at room temperature, within 2 h from sampling.…”

Section: Methodsmentioning

confidence: 99%

“…A hemostatic imbalance in asthma has been postulated after a rising number of reports on the increased risk of thromboembolic events in asthmatics [4–7]. Recently, we have investigated parameters of blood coagulation, platelet activation, and fibrinolysis in a large cohort of asthmatics and demonstrated that this disease is characterized by enhanced plasma thrombin formation, associated with impaired clot lysis and blood platelet activation [8]. Prothrombotic state in asthmatics has also been documented by Sneeboer et al [9], who showed increased thrombin generation, together with higher levels of plasminogen activator inhibitor-1 (PAI-1), D-dimer, von Willebrand factor, and plasmin-α 2 -antiplasmin complexes in this disease.…”

Section: Introductionmentioning

confidence: 99%

“…Prothrombotic state in asthmatics has also been documented by Sneeboer et al [9], who showed increased thrombin generation, together with higher levels of plasminogen activator inhibitor-1 (PAI-1), D-dimer, von Willebrand factor, and plasmin-α 2 -antiplasmin complexes in this disease. In our study, the hypercoagulable state in asthma was potently and independently determined by increased blood C-reactive protein (CRP) concentrations [8]. Based on this finding, we hypothesized that a hypercoagulable state in asthma is related to the systemic inflammatory response largely mediated by interleukin (IL)-6, which is the most important inducer of the synthesis of acute phase proteins, including CRP [10].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, we speculated that Th2-driven inflammation, reflected by periostin concentrations, is involved in the prothrombotic state in this disease. Therefore, we investigated the associations between the previously analyzed parameters of a prothrombotic state in asthma [8] and concentrations of IL-6 and TNFα and periostin in peripheral venous blood.…”

Section: Introductionmentioning

confidence: 99%

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Prothrombotic State in Asthma Is Related to Increased Levels of Inflammatory Cytokines, IL-6 and TNFα, in Peripheral Blood

et al. 2017

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Recently, we have reported that asthma is associated with enhanced plasma thrombin formation and impaired fibrinolysis. The mechanisms underlying the prothrombotic state in this disease are unknown. Our aim was to investigate whether prothrombotic alterations in asthmatics are associated with inflammation. We studied 164 adult, white, stable asthmatics and 72 controls matched for age, sex, body mass index (BMI), and smoking. Plasma tumor necrosis factor α (TNFα), interleukin (IL)-6, and serum periostin were evaluated using ELISAs, and their associations with thrombin generation, fibrinolytic capacity, expressed as clot lysis time (CLT), and platelet markers were later analyzed. Asthma was characterized by 62% higher plasma IL-6 and 35% higher TNFα (both, p < 0.0001). Inflammatory cytokines were higher in sporadic and persistent asthmatics compared to controls, also after adjustment for potential confounders. IL-6 was inversely related to the forced expiratory volume in 1 s/vital capacity (FEV1/VC) spirometry index after correction for age, sex, and BMI. IL-6 and TNFα were associated with C-reactive protein in asthmatics (β = 0.6 [95% CI, 0.54–0.67] and β = 0.33 [95% CI, 0.25–0.41], respectively) and controls (β = 0.43 [95% CI, 0.29–0.57] and β = 0.33 [95% CI, 0.18–0.48], respectively). In asthma, IL-6 and TNFα positively correlated with the endogenous thrombin potential (β = 0.35 [95% CI, 0.28–0.42] and β = 0.15 [95% CI, 0.07–0.23], respectively) but not with CLT or platelet markers. However, TNFα predicted CLT in a multiple linear regression model. Periostin was not associated with any hemostatic parameters. Enhanced thrombin generation is driven in asthma by a systemic inflammatory state mediated by IL-6 and to a lesser extent TNFα, however, not periostin. TNFα might contribute to impaired fibrinolysis.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%