In situ Pulmonary Artery Thrombosis: A Previously Overlooked Disease

Abstract

Pulmonary thromboembolism (PTE) is the third leading cause of death in cardiovascular diseases. PTE is believed to be caused by thrombi detached from deep veins of lower extremities. The thrombi travel with systemic circulation to the lung and block pulmonary arteries, leading to sudden disruption of hemodynamics and blood gas exchange. However, this concept has recently been challenged by accumulating evidence demonstrating that de novo thrombosis may be formed in pulmonary arteries without deep venous thrombosis. On the other hand, chronic thromboembolic pulmonary hypertension (CTEPH), a subtype of pulmonary hypertension, could have different pathogenesis than traditional PTE. Therefore, this article summarized and compared the risk factors, the common and specific pathogenic mechanisms underlying PTE, in situ pulmonary artery thrombosis, and CTEPH at molecular and cellular levels, and suggested the therapeutic strategies to these diseases, aiming to facilitate understanding of pathogenesis, differential diagnosis, and precision therapeutics of the three pulmonary artery thrombotic diseases.

Venous thromboembolism with JAK inhibitors and other immune-modulatory drugs: a Swedish comparative safety study among patients with rheumatoid arthritis

“…22 It has also been proposed that PE in the absence of DVT (or in situ pulmonary artery embolism) could be a separate entity triggered by local inflammation and ensuing imbalance in the coagulation system. 23 On the other hand, since our previous study on RA disease activity and the risk of VTE observed a somewhat stronger association between RA disease activity and PE risk, compared with DVT risk, confounding by indication cannot be ruled out as a partial explanation for our findings (but not for those from ORAL surveillance and other trials). 10 Whether, and how much, ongoing anticoagulant therapy alter the risk of VTE for patients with (or without) a history of VTE treated with any b/tsDMARD is an important clinical question; limited statistical precision precluded a detailed assessment of risks by history of VTE by anticoagulant use at treatment start and during the follow-up.…”

Recommendations from the ICM-VTE: General

“…Thrombosis can also arise directly within the pulmonary vasculature. Patients at risk of in-situ pulmonary artery thrombosis display a pronounced prothrombotic phenotype, with contributions from abnormal fibrinogen variants, family history, autoimmune disease, endocrine dysregulation, and active cancer 674,686,687 . Separate to both hematological pathophysiological pathways, increased intramedullary pressure during arthroplasty procedures has been shown to embolize prothrombotic fat, bone marrow and cement fragments through systemic veins into the pulmonary vascular system 682,688,689 .…”

Neutrophils Mediate Pulmonary Artery Thrombosis In Situ

“…For example, PA clots contain larger quantities of fibrin, leukocytes and microparticles compared to venous thrombi [ 2 ]. This suggests that both systemic and local conditions, such as vascular endothelial cell dysfunction, hypoxia, and inflammation, likely provoke thrombosis directly in the pulmonary circulation [ 17 ]. Such systemic conditions can be mediated by circulating blood cells.…”