Clinical and prognostic significance of serum levels of von Willebrand factor and ADAMTS-13 antigens in AL amyloidosis

Kastritis, Efstathios; Papassotiriou, Ioannis; Terpos, Evangelos; Ρούσσου, Μαρία; Gavriatopoulou, Maria; Komitopoulou, Anna; Skevaki, Chrysanthi; Eleutherakis‐Papaiakovou, Evangelos; Pamboucas, Constantinos; Psimenou, Erasmia; Manios, Efstathios; Giannouli, Stavroula; Politou, Marianna; Gakiopoulou, Harikleia; Papadopoulou, Elektra; Stamatelopoulos, Kimon; Tasidou, Anna

doi:10.1182/blood-2016-02-702696

Cited by 43 publications

(26 citation statements)

References 38 publications

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“…Activation of fibrinolysis may also lead to D‐dimer elevation, as the fibrinolytic pathway is known to be active in AL amyloidosis and could be the mechanism by which many patients have an increased bleeding risk . Additionally, the elevation in D‐dimer may be related to the underlying endothelial dysfunction and abnormal vascular morphology found in AL amyloidosis . Vascular abnormalities are known to be independent of overt cardiac involvement, and may contribute to the adverse prognosis seen in patients with an elevated D‐dimer.…”

Section: Discussionsupporting

confidence: 67%

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

et al. 2019

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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.

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Section: Discussionsupporting

confidence: 67%

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

et al. 2019

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“…Kastritis et al. [14] investigated GDF-15 levels in the peripheral blood in two independent cohorts at two different centres (Pavia and Athens). Independently of cardiac biomarkers and renal involvement, elevated GDF-15 levels >7575 pg/ml were associated with early death, shorter survival times and faster progression to dialysis.…”

Section: Introductionmentioning

confidence: 99%

“…Kastritis et al. presented the first prospective randomised phase III trial of melphalan and dexamethasone (MDex) versus bortezomib, melphalan and dexamethasone (BMDex) for newly diagnosed patients [16]. Alahwal et al.…”

Section: Introductionmentioning

confidence: 99%

News in AL Amyloidosis ASH 2016

Agis

2017

memo

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SummaryAmyloidosis is a rare but life-threatening protein misfolding disease. The early diagnosis and enrollment of patients into multicentre trials is of great importance, as is the need for intensive collaboration between multiple medical departments and experienced specialists. In the following review, the most interesting abstracts from the annual American Society of Hematology (ASH) meeting in 2016 are presented. The topics include the limitations of established biomarkers in risk assessment and response evaluation, the introduction of a new biomarker, the comparison of different treatment sequences and the efficacy of a multiple drug regimen in light-chain (AL) amyloidosis.

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“…A number of new and interesting biomarkers reported over the past few years also show promise in determining prognosis in AL amyloidosis. These include: osteoprotegerin (mechanism unclear), 6 von Willebrand factor (probably a marker of endothelial toxicity), 7 soluble ST2 (a marker of myocardial remodelling and fibrosis), 8 an abnormal Hevylite ratio, and percentage of normal vs abnormal plasma cells in the bone marrow by multiparameter flow cytometry (probably markers of the aggressiveness of the clone). 9 None, however, has made it to the main stream.…”

mentioning

confidence: 99%

Biomarkers in AL amyloidosis: is the summit in sight?

Wechalekar

2018

Blood

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Clinical and prognostic significance of serum levels of von Willebrand factor and ADAMTS-13 antigens in AL amyloidosis

Abstract: Key Points Serum levels of VWF antigen are elevated in AL amyloidosis, reflecting endothelial dysfunction. High VWF levels predict for poor outcome in patients with cardiac involvement and discriminate high-risk patients even within stage IIIB.

Cited by 43 publications

References 38 publications

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

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

News in AL Amyloidosis ASH 2016

Biomarkers in AL amyloidosis: is the summit in sight?

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