Scientific associate Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Greece, Attiki, Greece
Introduction: Hemostatic abnormalities and deregulated coagulation are among the less well studied complications in AL amyloidosis linked to significant mortality and morbidity for patients with the disease. We describe thrombotic and hemorrhagic events in AL patients treated in the recent era to better understand the causes of deregulated coagulation.
Methods: We analyzed the records of 450 patients treated in a single center to identify clinically relevant episodes of venous (VTE), arterial embolic events (AEE) and bleeding events.
Results: Median age was 65 years (39-95) and 54% were male. The median follow-up was 55.3 months (95% CI 49.3-63.0). In 26 (5.8%) patients at least one VTE was recorded; deep vein thrombosis in 2.3%, pulmonary embolism in 2.4%, other in 1.1%. Eighteen patients were on anti-clonal treatment at the time of the event; 11 were on IMiDs-agent based therapy. Among patients with VTE, 36% were on antiplatelets and 52% on antithrombotic prophylaxis. AEE was reported in 22 (5%) of patients; stroke 2.9%, acute myocardial infarction 1.6%, other in 0.5%. Median time from diagnosis to VTE was 9.5 months (0.1 – 107 months) and to AEE 14 months (0.62-114 months). Lower albumin levels (p=0.040), lower eGFR (p=0.010), extensive bone marrow infiltration (0.010), soft tissue involvement (p=0.029), IMiD-based therapy (p=0.001) and history of prior thrombosis (≤0.001) were associated with VTE. A prior VTE history remained the only prognostic variable in the multivariate model (HR 9.3, p=0.001, 95% CI 2.36-36.6). Coronary arterial disease (p=0.045), prior AEE (p=0.041), higher 24hour urine protein (p=0.008) and higher platelet count at diagnosis (p=0.020) were associated with AEE risk. Cardiac involvement and Mayo stage were not risk factors for thrombotic events. Significant bleeding events were reported in 41 patients (9%) and were the cause of death in 8 (mortality 19%); CNS in 1.3%, GI in 4.6%, other in 3.1%. Median time from diagnosis to bleeding events was 1.7 months (0.1 to 166 months). Bleeding risk was higher in patients on antiplatelets (15% vs 7.4%, p=0.05) but not on antithrombotic therapy. Higher serum creatinine (p=0.040) and higher baseline vWFAg (p=0.001, n=112) were linked to bleeding. Using competing risk analysis (death due to any cause as competing event), the cumulative probability of thrombosis and bleeding at 6 months was 4.1% and 4.6% vs 14.5% for death, at 1 year 6% and 5.6% vs 23% for death, at 2 years 7% and 6.8% vs 29% for death, and at 5 years 10.8%, 9.8% and 41% respectively.
Conclusions: Hemostatic complications associated with AL amyloidosis are common. Increased thrombotic risk and hemorrhagic diathesis or both, increase morbidity and mortality and make optimal management highly complex. Most events occur early but a constant risk remains present throughout the disease course. To optimize anticoagulation clinical risk factors need to be coupled to clotting parameter abnormalities in future studies.
