Asthma and coagulation: A (seemingly) strange couple and its pathophysiological and clinical implications

Asthma is a heterogeneous disease characterized by chronic inflammation and variable airway remodeling, determining a range of clinical presentations defined by respiratory symptoms and airway involvement. Inflammation, driven by both adaptive and innate immune responses, plays a key role in the pathophysiology of asthma. Other crucial biological pathways, including the coagulation cascade, are closely and two-way entwined with inflammatory processes. Such interconnections represent the molecular bases explaining the asthma-related alterations of haemostatic balance, which are usually shifted to procoagulant states, leading to pathophysiological and clinical implications. Many different chronic inflammatory conditions have also been associated with prothrombotic diathesis and an increased risk of venous thromboembolism, but in asthma, these bidirectional interconnections appear particularly evident. A growing number of studies in the last decades have addressed the bidirectional relationship between asthma pathways and coagulation mechanisms. This narrative review summarises the molecular/biological proofs and clinical/epidemiological evidence linking asthma and coagulation. This relationship is not limited to the inflammatory-driven processes leading to procoagulant states and, therefore, to an increased risk of thrombosis in patients with asthma but it is also related to the extra-haemostatic effects of coagulation factors, which may modulate asthma pathways and even influence the development of respiratory manifestations. Consistent with the former issue, several epidemiological studies demonstrated a compelling association between asthma and an increased risk of venous thromboembolism, independent of potential confounding factors. Regarding the latter issue, it appears biologically suggestive and therapeutically intriguing that, at least in animal models, many anticoagulant drugs have been shown to reduce airway hyperresponsiveness/remodeling and improve respiratory performance in the setting of asthma. Certainly, such therapeutic approaches, whose effectiveness has yet to be fully demonstrated in humans and whose bleeding-related side effects represent a major concern about their use, remain only speculative in clinical practice and we are still very far from their hypothetical application. Anyway, a more thorough understanding of molecular mechanisms connecting asthma, allergic inflammation, coagulation, and thrombosis may allow a better knowledge of asthma pathophysiology, potentially paving the way towards innovative therapeutic approaches and leading to better strategies in the overall management of patients with asthma.