Is Complement Alternative Pathway Disregulation Involved in Veno-Occlusive Disease of the Liver?

Bucalossi, Alessandro; Toraldo, Francesca; Tozzi, Monica; Lenoci, Mariapia; Castagnini, Cinzia; Artuso, Rosangela; Renieri, Alessandra; Marotta, Giuseppe

doi:10.1016/j.bbmt.2010.09.002

Cited by 4 publications

(4 citation statements)

References 5 publications

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“…Bucalossi et al studied seven patients who underwent alloHSCT (three with SOS/VOD) and detected two CFH variants in patients with SOS/VOD [76]. The methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C genotype has been found as a possible risk factor for the development of SOS/VOD [77].…”

Section: Sos/vod and Genetic Susceptibilitymentioning

confidence: 99%

Genetic Susceptibility in Endothelial Injury Syndromes after Hematopoietic Cell Transplantation and Other Cellular Therapies: Climbing a Steep Hill

Evangelidis,

Kalmoukos

et al. 2024

CIMB

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Hematopoietic stem cell transplantation (HSCT) remains a cornerstone in the management of patients with hematological malignancies. Endothelial injury syndromes, such as HSCT-associated thrombotic microangiopathy (HSCT-TMA), veno-occlusive disease/sinusoidal obstruction syndrome (SOS/VOD), and capillary leak syndrome (CLS), constitute complications after HSCT. Moreover, endothelial damage is prevalent after immunotherapy with chimeric antigen receptor-T (CAR-T) and can be manifested with cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS). Our literature review aims to investigate the genetic susceptibility in endothelial injury syndromes after HSCT and CAR-T cell therapy. Variations in complement pathway- and endothelial function-related genes have been associated with the development of HSCT-TMA. In these genes, CFHR5, CFHR1, CFHR3, CFI, ADAMTS13, CFB, C3, C4, C5, and MASP1 are included. Thus, patients with these variations might have a predisposition to complement activation, which is also exaggerated by other factors (such as acute graft-versus-host disease, infections, and calcineurin inhibitors). Few studies have examined the genetic susceptibility to SOS/VOD syndrome, and the implicated genes include CFH, methylenetetrahydrofolate reductase, and heparinase. Finally, specific mutations have been associated with the onset of CRS (PFKFB4, CX3CR1) and ICANS (PPM1D, DNMT3A, TE2, ASXL1). More research is essential in this field to achieve better outcomes for our patients.

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Section: Sos/vod and Genetic Susceptibilitymentioning

confidence: 99%

Genetic Susceptibility in Endothelial Injury Syndromes after Hematopoietic Cell Transplantation and Other Cellular Therapies: Climbing a Steep Hill

Evangelidis,

Kalmoukos

et al. 2024

CIMB

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“…In line with these data, a former case report documented increased complement activation in a SOS/VOD patient who was efficiently treated with the complement inhibitor C1 esterase inhibitor (C1-INH-C) [ 64 ]. Concerning genetic studies, two complement factor H (CFH) variants were detected in three SOS/VOD patients by Bucalossi et al No other complement-related genes have been studied except for complement factor I (CFI) [ 65 ]. Given the scarcity of available data, we aim to prospectively study the genetic susceptibility of complement dysregulation in patients with SOS/VOD and associate data from genetic and functional complement assays with clinical characteristics and outcomes.…”

Section: Complement Activation In Sos/vodmentioning

confidence: 99%

Molecular Advances in Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease

Mavrikou

Chatzidimitriou

Skoura

et al. 2023

IJMS

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Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) detected in the liver has been considered a severe complication of hematopoietic stem cell transplantation (HSCT). SOS/VOD is characterized by hepatomegaly, right upper quadrant pain, jaundice, and ascites. The severe forms of the disease may result in multi-organ dysfunction (MOD) with a high mortality rate (>80%). The development of SOS/VOD can be rapid and unpredictable. Therefore, early identification and severity assessment is crucial in facilitating prompt diagnosis and timely treatment. Effective treatment and potential prophylaxis with defibrotide highlight the need for characterizing a sub-group of patients at high risk for SOS/VOD. Moreover, antibodies that are conjugated with calicheamicin, gemtuzumab, and inotuzumab ozogamicin, have led to renewed interest in this syndrome. Evaluation and management of serious adverse events associated with gemtuzumab and inotuzumab ozogamicin are recommended. We review hepatic-, transplant- and patient-related risk factors, criteria for diagnosis and grading classification, and SOS/VOD potential biomarkers. Furthermore, we examine pathogenesis, clinical presentation, diagnostic criteria, risk factors, prophylaxis, and treatment of SOS/VOD occurring post HSCT. Moreover, we aim to provide an up-to-date summary of molecular advances in the diagnosis and management of SOS/VOD. We performed a comprehensive review of the literature and examined the recently available data, mostly using the PubMed and Medline search engines for original articles published over the last decade. In the era of precision medicine, our review provides up-to-date knowledge of genetic or sera markers for SOS/VOD with the goal of identifying a subset of high-risk patients.

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“…However, others [22] disagree since TA-TMA, with its mixed endothelial/immune origin is included [21]. Furthermore, immunological involvement in the pathogenesis of SOS is also very likely since injured ECs release cytokines and mitogens and these are capable of complement cascade activation and disruption [23]. These can also activate the coagulation cascade via the intrinsic pathway further increasing thrombin production.…”

Section: Sinusoidal Obstruction Syndrome and Transplant Associated Th...mentioning

confidence: 99%

Danaparoid Sodium: A Review of Its Use in Hepatic Thrombotic Disorders

Magnani¹

2022

Anticoagulation - Current Perspectives

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Danaparoid sodium is an antithrombotic isolated from porcine mucosa. Its main constituent is a mixture of heparan sulphates that inhibits thrombin generation and also possesses anti-inflammatory and immune-modulatory activity. It has shown safety and efficacy in its main indications of deep venous thrombosis prophylaxis, heparin-induced thrombocytopenia treatment and disseminated intravascular thrombosis treatment. In addition, there are reports of its off-label use for the treatment of portal vein thrombosis in adults and for prevention of the hepatic thrombotic microangiopathies haematogenous that complicate recovery after stem cell transplantation in adults and children. The results of these studies provide further support for its safety and efficacy even in subjects with cirrhosis and/or severe hepatic dysfunction. In this chapter the rationale for danaparoid use is presented and the collated results of comparative studies and case reports are compared with those of other pharmaceutical options for managing these hepatic thrombotic disorders.

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Is Complement Alternative Pathway Disregulation Involved in Veno-Occlusive Disease of the Liver?

Cited by 4 publications

References 5 publications

Genetic Susceptibility in Endothelial Injury Syndromes after Hematopoietic Cell Transplantation and Other Cellular Therapies: Climbing a Steep Hill

Genetic Susceptibility in Endothelial Injury Syndromes after Hematopoietic Cell Transplantation and Other Cellular Therapies: Climbing a Steep Hill

Molecular Advances in Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease

Danaparoid Sodium: A Review of Its Use in Hepatic Thrombotic Disorders

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