Hematologic malignancies, including plasma cell dyscrasias, are associated with an increased risk of thrombosis. Despite therapeutic responsiveness, patients often succumb to thrombotic events, such as stroke and myocardial infarction.
Among plasma cell dyscrasias, immunoglobulin light chain (AL) amyloidosis, a treatable but presently incurable plasma cell disorder, is understudied yet carries a high risk for both arterial thrombosis (AT) and venous thromboembolism (VTE). Even in cases of AL cardiac amyloidosis (AL-CA), intracardiac thrombosis persists despite atrial arrhythmia management and left atrial appendage ligation.
Recent research suggests that platelet dysfunction may cause thrombosis in systemic diseases, like cancer and AL-CA. Platelets, anucleate cells essential for hemostasis, become dysregulated in inflammatory states and conditions of blood stasis, both common in AL-CA due to cardiac remodeling and abnormal blood flow. Whether altered platelet function directly contributes to thrombotic risk in AL-CA patients remains unclear.
Investigating this could lead to improved patient management by identifying platelet-targeted antithrombotic therapies. This study aims to test the hypothesis that a dysregulated platelet phenotype in AL-CA contributes to thrombosis. Two specific aims will leverage a collection of AL-CA patient samples and enhance collaboration with various experts.
Aim 1 will compare platelet phenotypes in AL-CA and transthyretin cardiac amyloidosis (ATTR-CA) to assess differences in thrombotic mechanisms. Aim 2 will analyze thromboembolic outcomes in AL-CA patients, evaluating the effects of antithrombotic therapy in a propensity-matched cohort. The findings could directly inform clinical practice and guide future research into amyloidosis-associated thrombosis.
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