New insights into sinusoidal obstruction syndrome

Piccin, Andrea; Sartori, Maria Teresa; Bisogno, Gianni; Schilfgaarde, Muriel van; Saggiorato, Graziella; Pierro, Angela Maria Di; Corvetta, Daisy; Marcheselli, Luigi; Andrea, Mega; Gastl, Günther; Cesaro, Simone

doi:10.1111/imj.13550

Cited by 26 publications

(21 citation statements)

References 35 publications

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“…Diverse biomarkers for potential prediction and early detection of VOD/SOS have been proposed, which may prove useful, although they are not yet widely accepted (Table 6) [64]. Of these, increased plasminogen activator inhibitor-1 antigen level is perhaps the most well studied and supported [13,[65][66][67]. However, the identified biomarkers encompass a wide array of pathogenic pathways, each with a sound rationale for investigation (Table 6) [64].…”

Section: Biomarkersmentioning

confidence: 99%

“…has received honoraria and research funding from Jazz Pharmaceuticals. Broad-spectrum/multiple mechanism Panel of changes in tumorogenicity-2, angiopoieten-2, L-ficolin, hyaluronic acid, and VCAM-1 [68] # L-ficolin plasma level [83] Genetic polymorphisms MTHFR C677T/A1298C [84] Heparanase single nucleotide polymorphisms [85] Hematologic and endothelial # Protein C levels [86][87][88] # Antithrombin III levels [13,87] # Type III procollagen and tPA [88] " PAI-1 antigen levels [13,[65][66][67] " Extra-cellular endothelial vesicles CD144 + [13] " vWF, thrombomodulin, soluble IAM-1* [89] Hepatic/splenic " Maximum total serum bilirubin/bilirubin increase at any point in time [90] " Total bilirubin, D-dimer [67] " Hepatocyte growth factors/with/without IL-6 [91] " APRI [70] " Splenic volume [71] " Panel of liver fibrosis indices: API, APRI, PSR, FIB-4 y [69] Inflammatory/immune response " IL-6, IL-10, TNF-a plasma levels z [92] " IL-6 plasma level at + day 7 post-HSCT [93] # IGF and IGFBP-3 plasma levels [94] API indicates age-platelet index; APRI, aspartate aminotransferase-to-platelet ratio; FIB-4, fibrosis-4; IAM, intercellular adhesion molecule; IGF, insulin-like growth factor; IGFBP, insulin-like growth factor binding protein; PAI, plasminogen [84] activator inhibitor; PSR, platelet-to-spleen ratio; tPA, tissue plasminogen activator; vWF, von Willebrand factor; VCAM, vascular cell adhesion molecule. * In patients receiving sirolimus.…”

Section: Acknowledgmentsmentioning

confidence: 99%

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Risk Factors for Development of and Progression of Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome

Corbacioglu

Jabbour

Mohty

2019

Biology of Blood and Marrow Transplantation

120

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A B S T R A C T Veno-occlusive disease, also known as sinusoidal obstruction syndrome (VOD/SOS), is a potentially life-threatening complication of allogeneic or autologous hematopoietic stem cell transplantation (HSCT) most commonly associated with high-intensity chemotherapies. The development of VOD/SOS may be rapid and unpredictable, and the importance of identifying risk factors to facilitate prompt diagnosis and timely treatment has become increasingly recognized. The reporting of new retrospective study data for adults and children and the emergence of novel anticancer therapies that may increase the risk of VOD/SOD also necessitate updates on risk factors, as provided in this review. The latest studies reporting VOD/SOS risk factors support previously published data, although the importance of patient-related factors, such as acute kidney injury, increased international normalized ratio, female sex (in children), and platelet refractoriness, is given greater emphasis in the recent data. Nontransplantation-related chemotherapies associated with increased risk for VOD/SOS include oxaliplatin and 5-fluorouracil chemotherapies. The novel antibody drug conjugates gemtuzumab ozogamicin and inotuzumab ozogamicin are now reported in product labeling to pose risks for VOD/SOS based on clinical trial data; an expert consensus panel has issued recommendations for risk reduction measures with inotuzumab ozogamicin treatment, including VOD/SOS prophylaxis and limitation to 2 inotuzumab ozogamicin treatment cycles. A wide range of biomarkers, including genetic, hematologic, hepatic, and inflammatory factors, as well as novel diagnostic techniques such as thromboelastography and measures of liver stiffness, may further enhance future risk calculation for VOD/SOS, although none has been widely adopted. Continual monitoring for and recognition of VOD/SOS risk factors are essential for optimal management of this complication.

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Section: Biomarkersmentioning

confidence: 99%

Section: Acknowledgmentsmentioning

confidence: 99%

Risk Factors for Development of and Progression of Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome

Corbacioglu

Jabbour

Mohty

2019

Biology of Blood and Marrow Transplantation

120

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“…Analysis of EVs may have applications in therapy, prognosis, and biomarker development in various fields. The hope is that, using EV analysis, clinicians will be able to detect the presence of disease as well as to classify its progression using noninvasive methods such as liquid biopsy (Boukouris & Mathivanan, 2015;Piccin, 2014;Piccin et al, 2017a;Piccin et al, 2017b;Piccin, Van Schilfgaarde & Smith, 2015).…”

Section: Introductionmentioning

confidence: 99%

Characterization and function of medium and large extracellular vesicles from plasma and urine by surface antigens and Annexin V

Igami

Uchiumi

Ueda

et al. 2020

PeerJ Analytical Chemistry

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Background Extracellular vesicles (EVs) are released by most cell types and are involved in multiple basic biological processes. Medium/large EVs (m/lEVs), which are of a different size from exosomes, play an important role in the coagulation in blood, and are secreted from cancer cells, etc., suggesting functions related to malignant transformation. The m/lEVs levels in blood or urine may help unravel pathophysiological findings in many diseases. However, it remains unclear how many naturally-occurring m/lEV subtypes exist as well as how their characteristics and functions differ from one another. Methods We used the blood and urinal sample from each 10 healthy donors for analysis. Using a flow cytometer, we focus on characterization of EVs with large sizes (>200 nm) that are different from exosomes. We also searched for a membrane protein for characterization with a flow cytometer using shotgun proteomics. We then identified m/lEVs pelleted from plasma and urine samples by differential centrifugation and characterized by flow cytometry. Results Using proteomic profiling, we identified several proteins involved in m/lEV biogenesis including adhesion molecules, peptidases and exocytosis regulatory proteins. In healthy human plasma, we could distinguish m/lEVs derived from platelets, erythrocytes, monocytes/macrophages, T and B cells, and vascular endothelial cells with more than two positive surface antigens. The ratio of phosphatidylserine appearing on the membrane surface differed depending on the cell-derived m/lEVs. In urine, 50% of m/lEVs were Annexin V negative but contained various membrane peptidases derived from renal tubular villi. Urinary m/lEVs, but not plasma m/lEVs, showed peptidase activity. The knowledge of the new characteristics is considered to be useful as a diagnostic material and the newly developed method suggests the possibility of clinical application.

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“…Furthermore, PS may be expelled as microvesicles. The involvement of these particles in the pathogenesis of SCA and other conditions has been widely postulated (Piccin et al , 2007, 2015a, 2017; Nebor et al , 2014). …”

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confidence: 99%

Oxidative stress and phosphatidylserine exposure in red cells from patients with sickle cell anaemia

et al. 2018

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SummaryPhosphatidylserine (PS) exposure increases as red cells age, and is an important signal for the removal of senescent cells from the circulation. PS exposure is elevated in red cells from sickle cell anaemia (SCA) patients and is thought to enhance haemolysis and vaso‐occlusion. Although precise conditions leading to its externalisation are unclear, high intracellular Ca2+ has been implicated. Red cells from SCA patients are also exposed to an increased oxidative challenge, and we postulated that this stimulates PS exposure, through increased Ca2+ levels. We tested four different ways of generating oxidative stress: hypoxanthine and xanthine oxidase, phenazine methosulphate, nitrite and tert‐butyl hydroperoxide, together with thiol modification with N‐ethylmaleimide (NEM), dithiothreitol and hypochlorous acid (HOCl), in red cells permeabilised to Ca2+ using bromo‐A23187. Unexpectedly, our findings showed that the four oxidants significantly reduced Ca2+‐induced PS exposure (by 40–60%) with no appreciable effect on Ca2+ affinity. By contrast, NEM markedly increased PS exposure (by about 400%) and slightly but significantly increased the affinity for Ca2+. Dithiothreitol modestly reduced PS exposure (by 25%) and HOCl had no effect. These findings emphasise the importance of thiol modification for PS exposure in sickle cells but suggest that increased oxidant stress alone is not important.

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New insights into sinusoidal obstruction syndrome

Abstract: This study demonstrates the existence of an ongoing procoagulant and hypofibrinolytic status in SOS, indicating a possible role for anticoagulant therapy. Moreover, these findings suggest a role for EV CD 144+, either alone or in combination with PAI-1, as a new biomarker for SOS.

Cited by 26 publications

References 35 publications

Risk Factors for Development of and Progression of Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome

Risk Factors for Development of and Progression of Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome

Characterization and function of medium and large extracellular vesicles from plasma and urine by surface antigens and Annexin V

Oxidative stress and phosphatidylserine exposure in red cells from patients with sickle cell anaemia

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