Effect of a 10-day oral corticosteroid course on hemostasis and inflammation in patients with stable asthma

Abstract

Background: Patients with asthma have an increased risk of pulmonary embolism, which may be associated with asthma severity, oral corticosteroid use or its combination. Aim: To determine whether a 10-day oral corticosteroid course promotes hemostasis and inflammation in patients with asthma. Methods: 60 patients with stable mild-moderate and severe asthma were randomly assigned to receive either prednisolone 0.5mg/kg (n=30) or placebo (n=30) once daily for 10 days. Changes from baseline in plasma markers of coagulation (peak thrombin of the endogenous thrombin potential (ETP), thrombin-antithrombin complexes (TATc)), fibrinolysis (D-dimer, plasminogen activator inhibitor type-1(PAI-1), plasmin-alpha2-antiplasmin complexes (PAPc)), and endothelial activation (von Willebrand factor (vWF)) were compared between groups and related to changes in inflammatory cells and CRP. Results: Compared to placebo, prednisolone increased the fold change of peak ETP (1.11 (SD 0.13), p=0.01), vWF (1.22 (SD 0.19), p<0.01), PAI-1 (1.80 (IQR 0.75-2.07), p=0.04), and decreased PAPc (0.90 (SD 0.2), p=0.04). TATc and D-dimer did not change. Leuco-, mono-, lymphocytes, and neutrophils increased, while eosino-, basophils and CRP decreased (all p<0.01) The change in peak ETP correlated with neutrophils (R=0.42, p<0.01), and the change in PAI-1, PAPc, and D-dimer correlated with lymphocytes (R=0.30, -0.38, -0.31 resp.; all p<0.05). No correlations were found for eosinophils. Conclusion: Oral corticosteroids induce a hypercoagulable state and suppress fibrinolysis in patients with asthma. These results suggest that corticosteroids play a role in the increased risk of pulmonary embolism in patients with asthma.