Reduced clot retraction rate and altered platelet energy production in patients with asthma

Abstract

Objective: Asthma enhances the risk of pulmonary embolism. The mechanism of this phenomenon is unclear. Methods: We evaluated the kinetics of clot formation, clot retraction rate (CRR), clot volume at 40 min, the rate of lactate production (a marker of aerobic glycolysis in platelets in contracting clots), blood eosinophil count (EOS), nitric oxide in exhaled breath (FE_NO), and spirometry (FEV₁) in 50 healthy controls and in 81 allergic asthmatics (41 subjects with steroid-naïve asthma and 40 with steroid-treated asthma). Results: Thromboelastometry revealed that only steroid-treated asthmatics had slightly activated coagulation. Compared with healthy controls, whole asthmatics demonstrated (p < 0.05) reduced CRR, higher clot volume at 40 minutes, higher FE_NO, decreased FEV₁, elevated EOS, and augmented lactate production in retracting clots. Reduced CRR was observed also in the absence of native plasma. In whole study population (asthmatics and healthy controls), CRR positively correlated with spirometry (r_S = 0.668, p = <0.001) and negatively with FE_NO (r_S = −0.543; p < 0.001), EOS (r_S = −0.367, p < 0.002), and lactate production (r_S = −0.791; p < 0.001). However, in steroid-treated asthmatics, the CRR did not correlate with FE_NO and EOS. In all study patients lactate production negatively correlated with FEV₁ and positively with FE_NO. Conclusion: Collectively, this data is consistent with the hypothesis that, in asthmatics, reactive nitrogen species produced in the lungs may reduce platelet contractility (and CRR) through the diminution of platelet energy production. CRR inhibition would predispose asthmatics to pulmonary embolism.

Keywords:

• Asthma
• clot retraction
• glycolysis
• inflammation
• mitochondria
• nitric oxide