Prevalence and prognostic value of D‐dimer elevation in patients with AL amyloidosis

Abstract

Light chain (AL) amyloidosis is a protein folding disorder that can affect many different organ systems, in addition to the coagulation pathway. D-dimer, a measurement of fibrin degradation, is commonly elevated in hematologic malignancies, but the prevalence and significance of D-dimer elevation in AL amyloidosis is unknown. We conducted an analysis of 921 patients with AL amyloidosis that presented to the Boston University Amyloidosis Center. Baseline characteristics and laboratory data of the 897 patients included in the final cohort were analyzed. Four hundred twenty three patients (47%) had an elevated D-dimer (>0.5 μg/mL). Multivariate analysis demonstrated that a normal D-dimer level of ≤0.5 μg/mL, and a level of >0.5 μg/mL but <1 μg/mL, conferred a lower risk of mortality (HR 0.49 and 0.59, respectively) when compared to a D-dimer level ≥ 1 μg/mL. The increased risk of mortality in patients with a D-dimer level ≥ 1 μg/mL was present in all cardiac stages. The median overall survival based on D-dimer range of ≤0.5, >0.5 but <1, and ≥ 1 μg/mL was 5.86, 4.04, and 2.08 years, respectively (P < .001). This retrospective analysis demonstrates the high prevalence of D-dimer elevation in AL amyloidosis and confirms that this laboratory finding is independently associated with decreased survival.Median age at first visit, y (range)62 (27-90) Males/Females (%) 62/38 Organ involvementRenal, n (%) 661 (74) Cardiac, n (%) 547 (61) Gastrointestinal, n (%) 153 (17) Liver, n (%) 148 (17) Peripheral nervous system, n (%) 132 (15) Autonomic nervous system, n (%) 242 (27) Soft tissue, n (%) 173 (19) Median number of involved organs (range) 2 (1 -7) Cardiac biomarkers Median BNP, pg/mL (range), N = 803 204 (0 -6 026) Median troponin-I, ng/mL (range), N = 466 0.064 (<0.006 -8.915) Boston University Cardiac stage b Stage I, n (%) 77 (18) Stage II, n (%) 199 (47) Stage III, n (%) 75 (18) Stage IIIb, n (%) 69 (16) Renal assessment Median eGFR, mL/min/1.73m 2 (range) 67 (3 -319) Median creatinine, mg/dL (range) 1.1 (0.2 -15.5) Median proteinuria, mg/24 hours (range) 2 643.5 (0-153 613) Renal stage b Stage I, n (%) 423 (50) Stage II, n (%) 302 (36) Stage III, n (%) 115 (14) Hematological parameters Median dFLC, mg/L (range) 123 (0 -10 154) D-dimer, mcg/mL ≤0.5, n (%) 474 (53) >0.5-<1, n (%) 200 (22) ≥1, n (%) 223 (25) Confirmation of venous thrombosis a , n (%) 71 (8) Abbreviations: BNP, B-type Natriuretic Peptide; eGFR, estimated Glomerular Filtration Rate; sFLC, serum free light chain ratio; dFLC, difference between involved and uninvolved free light chains. a Cardiac staging data available for 420 patients and renal staging data available for 840 patients. b Not all patients were evaluated for venous thrombosis.

Biomarkers in AL Amyloidosis

“…The prognostic importance of VWF as a surrogate marker of endothelial dysfunction was assessed in 111 patients with newly diagnosed AL amyloidosis. VWF:Ag levels were significantly higher in patients with AL compared to that measured in healthy controls [87] and serum VWF:Ag ≥ 230 U/dL was associated with higher probability of early death and remained an independent predictor of death within 6 months even among patients with Mayo stage III, (1-year OS of 17% vs. 68% for patients with stage III disease and lower VWF levels, p < 0.001). Among patients with stage IIIb disease, high VWF levels could further discriminate them into two outcome groups (2 vs. 6 months, p = 0.006).…”

Search for AL amyloidosis risk factors using Mendelian randomization

“…38 Because increasing fibrinolysis with concomitant bleeding and clotting complications are known in AL amyloidosis, it is possible that the low fibrinogen levels reflect the cause and the consequence in the disease sequelae. 39 The borderline association with low hematocrit percentage may be related to bleeding complications in some patients.…”

Challenges in the management of patients with systemic light chain (AL) amyloidosis during the COVID‐19 pandemic

“…The American Society of Hematology (ASH) recommends that all hospitalised patients with COVID-19 should receive thromboprophylaxis with low-molecular-weight heparin (LMWH) or fondaparinux (suggested over unfractionated heparin to reduce contact), unless the patient is at increased bleeding risk. 6 However, in patients with AL amyloidosis the coagulation and fibrinolytic system may be already deregulated [61][62][63] , while small vessels may be dysfunctional due to amyloid deposition: 64 a bleeding and a thrombotic diathesis co-exist. Thus, use of thromboprophylaxis in patients with AL amyloidosis with COVID-19 should be cautious and closely monitored.…”