Thromboembolic and Bleeding Events in Transthyretin Amyloidosis and Coagulation System Abnormalities: A Review

Abstract

Transthyretin amyloidosis (ATTR) is a group of diseases caused by the deposition of insoluble fibrils derived from misfolded transthyretin, which compromises the structure and function of various organs, including the heart. Thromboembolic events and increased bleeding risk are among the most important complications of ATTR, though the underlying mechanisms are not yet fully understood. Transthyretin plays a complex role in the coagulation cascade, contributing to the activation and regulation of the coagulation and fibrinolytic systems. The prevalence of atrial fibrillation, cardiac mechanical dysfunction, and atrial myopathy in patients with ATTR may contribute to thrombosis, though such events may also occur in patients with a normal sinus rhythm and rarely in properly anticoagulated patients. Haemorrhagic events are modest and mainly linked to perivascular amyloid deposits with consequent capillary fragility and coagulation anomalies, such as labile international-normalised ratio during anticoagulant therapy. Therefore, it is paramount to carefully stratify the thrombotic and haemorrhagic risks, especially when initiating anticoagulant therapy. Our review aims to ascertain the prevalence of thromboembolic and haemorrhagic events in ATTR and identify potential risk factors and predictors and their impact on antithrombotic therapy.

Cryptogenic ischemic stroke in cardiac transthyretin amyloidosis and sinus rhythm: a case report

“…Thrombotic events are among the most severe complications of amyloidosis, particularly in ATTR and mainly as it pertains to intracardiac thrombi and cerebrovascular events. In a recently published review ( 19 ), we endeavored to identify studies that investigated the incidence of and the risk factors associated with thromboembolism in patients with ATTR — there were few and comprising small cohorts. The study by Bukari S et al ( 20 ) confirmed a high thromboembolic risk in patients with ATTRwt-CA and AF, considering the latter was present on average in 88% of patients.…”

Editorial: Case reports in thrombosis: 2023

“…Transthyretin amyloidosis is known to be associated with a significant increase in thrombotic risk, though the underlying mechanisms are still largely unknown ( 5 ). It is therefore critical to study the coagulation profile of these patients using non-traditional methods, such as thromboelastometry, thrombin generation, and/or microparticle measurement, in order to better understand the mechanisms of hypercoagulability and identify patients at higher prothrombotic risk.…”