Platelet Function and Fibrinolytic Activity in Patients with Bronchial Asthma

Abstract

Platelets have the capacity to release mediators with potent inflammatory or anaphylactic properties. Platelet factor-4 (PF4) and beta-thromboglobulin (BTG) are two of these mediators. On the other hand, plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA) are two important mediators of fibrinolysis. Both mediators are secreted mainly by vascular endothelium. Plasma levels of PF4, BTG, PAI-1, and tPA may show changes in chronic inflammatory diseases such as asthma. This study examined the role of thrombocytes and the function of the endothelium in asthmatic patients during an attack and during a stable phase. Eighteen patients with known allergic asthma who came to our emergency department with an asthma attack and 14 control subjects were included in the study. Blood samples were taken after starting therapy with salbutamol inhalation. Lung function tests were performed after receiving the first emergency therapy for asthma. Plasma levels of PF4, BTG, PAI-1, tPA were determined before starting steroid therapy and after receiving 1 week of steroid therapy. Plasma levels of PF4 among patients with an asthma attack were significantly higher than those of controls (150.5+/-8.92 IU/mL vs. 92.5+/-7.63 IU/mL, p<0.001). A further increase in plasma PF4 levels was detected after steroid therapy (163.5+/-9.16 IU/mL). Plasma BTG levels of patients on admission were not statistically different from those in the control group (140.4+/-6.34 IU/mL vs. 152.2+/-8.71 IU/mL). An increase was detected after therapy (171.6+/-7.27 IU/mL) and post-treatment plasma levels were statistically meaningful versus the controls. Plasma levels of tPA and PAI were statistically higher than those in controls in asthmatic patients on admission (6.01+/-2.72 vs. 5.4+/-2.3 ng/mL for tPA and 75.2+/-27.2 ng/mL vs. 32.7+/-14.3 ng/mL for PAI-1). Further increases were detected in two parameters after 1 week of therapy with steroids (tPA levels were 6.85+/-2.96 ng/mL and PAI-1 levels were 83.5+/-29.6 ng/mL). There seems to be an increased activity of platelets during an asthma attack. Elevated PAI-1 and tPA levels may also indicate the activated endothelium in asthma. Increases of plasma levels of PAI-1 and tPA after steroid therapy need further investigation because elevated PAI-1 levels enhance airway remodeling.

The role of platelets in the pathophysiology of asthma

“…Similar observations were made in individuals having experienced an acute asthma attack [74] and in patients with nocturnal asthma [68]. In the latter study, the peak of platelet activation occurred concomitantly with the maximum increase in BHR, thus suggesting that platelets are partly responsible for the hyperresponsiveness or, at least, playing a role in the ensuing bronchoconstriction.…”

Defining a role for platelets in allergic inflammation

“…Indeed, the chronicity of platelet activation has been highlighted in studies where platelet activation has been shown to persist some time after the late asthmatic response has occurred in asthmatic patients [16], even though documented increases in platelet-leucocyte interactions within the circulation have returned to basal levels at 24 h post-allergen exposure [8], implicating platelets in chronic inflammatory events and airway remodelling [14,42]. Platelets may release a number of mitogens and enzymes that may contribute to airway remodelling directly, affecting bronchial smooth muscle growth, myofibroblast proliferation, subepithelial fibrosis, as well as altering the composition of the extracellular matrix after increased thrombopoiesis [42]. This response to injury is perhaps through the release of chemotactic factors for circulating structural cells [43].…”

Time for a paradigm shift in asthma treatment: From relieving bronchospasm to controlling systemic inflammation

“…31 Systemic increases in platelet activation are seen in patients with allergic asthma when challenged with allergen 32 and when experiencing an acute asthma exacerbation. 33 In women asthma has been shown to be associated with an increased prevalence of carotid atherosclerosis, 34 and recent data from the United Kingdom show that patients with asthma, as well as those with chronic obstructive pulmonary disease, have increased cardiovascular comorbidity. 31 Although cardiovascular complications in asthmatic patients have mostly been attributed to asthma treatment, 35,36 it cannot be excluded that systemic inflammatory mechanisms might make some contribution to the observed increase in risk.…”