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Thrombotic microangiopathy transplant

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https://www.readbyqxmd.com/read/28801959/outcomes-of-patients-with-atypical-hemolytic-uremic-syndrome-with-native-and-transplanted-kidneys-treated-with-eculizumab-a-pooled-post-hoc-analysis
#1
Christophe M Legendre, Josep M Campistol, Thorsten Feldkamp, Giuseppe Remuzzi, John F Kincaid, Åsa Lommelé, Jimmy Wang, Laurent E Weekers, Neil S Sheerin
Atypical hemolytic uremic syndrome (aHUS) often leads to end-stage renal disease (ESRD) and kidney transplantation; graft loss rates are high due to disease recurrence. A post hoc analysis of four prospective clinical trials in aHUS was performed to evaluate eculizumab, a terminal complement inhibitor, in patients with native or transplanted kidneys. The trials included 26-week treatment and extension periods. Dialysis, transplant, and graft loss were evaluated. Study endpoints included complete thrombotic microangiopathy (TMA) response, TMA event-free status, hematologic and renal parameters, and adverse events...
August 12, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28801815/plasma-levels-of-complement-activation-fragments-c3b-and-sc5b-9-significantly-increased-in-patients-with-thrombotic-microangiopathy-after-allogeneic-stem-cell-transplantation
#2
Jiaqian Qi, Jie Wang, Jia Chen, Jian Su, Yaqiong Tang, Xiaojin Wu, Xiao Ma, Feng Chen, Changgeng Ruan, X Long Zheng, Depei Wu, Yue Han
Transplantation-associated thrombotic microangiopathy (TA-TMA) is an uncommon but severe complication in patients undergoing allogeneic stem cell transplantation (allo-SCT). However, the mechanism is unclear. From 2011 to 2014, 20 patients with TA-TMA, 20 patients without, and 54 patients with various other complications, including veno occlusive disease (VOD), graft-versus-host disease (GVHD), and infection, were recruited in the study. Plasma vWF antigen (vWFAg), vWF activity (vWFAc), and ADAMTS13 activity were determined in these patients by ELISAs and FRETS-vWF73 assay, respectively...
August 11, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28796639/development-and-validation-of-a-multivariable-prediction-rule-for-detecting-a-severe-acquired-adamts13-activity-deficiency-in-patients-with-thrombotic-microangiopathies
#3
Jorge M Nieto, Félix De La Fuente-Gonzalo, Fernando A González, Ana Villegas, Rafael Martínez, Manuel E Fuentes, Paloma Ropero
BACKGROUND: Thrombotic microangiopathies (TMAs) are a group of diseases that have different aetiologies and treatments, but a clinical differential diagnosis remains difficult. Among TMAs, thrombotic thrombocytopenic purpura (TTP) is characterised by a severe ADAMTS13 functional deficiency. However, assays exploring ADAMTS13 activity are limited to some specialised laboratories. Our objective was to develop and validate a diagnostic method for TTP in adult patients with TMA. METHODS: We generated a multivariable model (four predictors) on a cohort of 174 TMA patients in order to predict an ADAMTS13 activity deficiency (AUC of 0...
August 10, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28795840/a-complete-histologic-approach-to-gastrointestinal-biopsy-from-hematopoietic-stem-cell-transplant-patients-with-evidence-of-transplant-associated-gastrointestinal-thrombotic-microangiopathy
#4
Mikako Warren, Sonata Jodele, Christopher Dandoy, Kasiani C Myers, Gregory Wallace, Adam Nelson, Javier El-Bietar
CONTEXT: - Transplant-associated thrombotic microangiopathy is a serious complication of hematopoietic stem cell transplant that may progress to multi-organ dysfunction. Transplant-associated thrombotic microangiopathy may involve the intestinal vasculature (intestinal transplant-associated thrombotic microangiopathy [iTMA]), causing patients to experience debilitating symptoms of ischemic colitis, including disproportionately severe abdominal pain and gastrointestinal bleeding, requiring heavy narcotic use and frequent transfusion support...
August 10, 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/28736435/extracellular-vesicles-in-renal-disease
#5
REVIEW
Diana Karpman, Anne-Lie Ståhl, Ida Arvidsson
Extracellular vesicles, such as exosomes and microvesicles, are host cell-derived packages of information that allow cell-cell communication and enable cells to rid themselves of unwanted substances. The release and uptake of extracellular vesicles has important physiological functions and may also contribute to the development and propagation of inflammatory, vascular, malignant, infectious and neurodegenerative diseases. This Review describes the different types of extracellular vesicles, how they are detected and the mechanisms by which they communicate with cells and transfer information...
September 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28733186/easix-in-patients-with-acute-graft-versus-host-disease-a-retrospective-cohort-analysis
#6
Thomas Luft, Axel Benner, Sonata Jodele, Christopher E Dandoy, Rainer Storb, Ted Gooley, Brenda M Sandmaier, Natalia Becker, Aleksandar Radujkovic, Peter Dreger, Olaf Penack
BACKGROUND: Endothelial dysfunction links thrombotic microangiopathy to steroid-refractory graft-versus-host disease (GVHD) after allogeneic stem-cell transplantation. We aimed to assess if the simple formula-lactate dehydrogenase (U/L) × creatinine (mg/dL)/thrombocytes (10(9) cells per L)-termed the Endothelial Activation and Stress Index (EASIX), might be valuable for the prediction of death in patients with acute GVHD after allogeneic stem-cell transplantation. METHODS: For this retrospective analysis, we analysed a training cohort (in Germany) and three validation cohorts (in Germany and the USA) of patients with acute GVHD who had received consecutive allogeneic stem-cell transplantation...
July 18, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28705839/circulating-dsdna-endothelial-injury-and-complement-activation-in-thrombotic-microangiopathy-and-gvhd
#7
Nicholas J Gloude, Pooja Khandelwal, Nathan Luebbering, Dana T Lounder, Sonata Jodele, Matthew N Alder, Adam Lane, Alyss Wilkey, Kelly E Lake, Bridget Litts, Stella M Davies
TA-TMA is a common and poorly recognized complication of HSCT associated with excessive complement activation, likely triggered by endothelial injury. An important missing piece is the link between endothelial injury and complement activation. We hypothesized that neutrophil extracellular traps (NETs) mechanistically link endothelial damage with complement activation and subsequent TA-TMA. Neutrophil activation releases granule proteins together with double stranded DNA (dsDNA), to form extracellular fibers known as NETs...
July 13, 2017: Blood
https://www.readbyqxmd.com/read/28688917/real-world-economic-burden-associated-with-transplantation-related-complications
#8
Miguel-Angel Perales, Machaon Bonafede, Qian Cai, Phillip M Garfin, Donna McMorrow, Neil C Josephson, Akshara Richhariya
Approximately 20,000 hematopoietic cell transplantation (HCT) procedures are performed annually in the United States. Real-world data on the costs associated with post-transplantation complications are limited. Patients with hematologic malignancies aged ≥18 years undergoing autologous HCT (auto-HCT) or allogeneic HCT (allo-HCT) between January 1, 2011, and June 30, 2014, were identified in the Truven Health MarketScan Research Databases. Patients were required to have 12 months of continuous medical and pharmacy enrollment before and after HCT; patients who experience inpatient death within 12 months post-HCT were also included...
July 5, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28670985/-changes-in-diagnostic-criteria-of-thrombotic-microangiopathy-after-stem-cell-transplantation
#9
Orsolya Horváth, Zoltán Prohászka, Krisztián Kállay, Csaba Kassa, Anita Stréhn, Katalin Csordás, János Sinkó, Gergely Kriván
Hematopoietic stem cell transplantation associated thrombotic microangiopathy is a multifactorial complication, and has variable incidence in study populations due to different diagnostic criteria. The diversity of activity parameters, like elevated laktát-dehidrogenáz, hematological parameters and kidney function are not specific variables after stem cell transplantation. Dysregulation of the classical and alternative pathway can play an important role in the pathomechanism of thrombotic microangiopathy, but the understanding of the role of complement activation under transplantation conditions requires further investigation...
July 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/28651806/von-willebrand-factor-deposition-and-adamts-13-consumption-in-allograft-tissue-of-thrombotic-microangiopathy-like-disorder-after-living-donor-liver-transplantation-a-case-report
#10
S Nakanuma, T Miyashita, H Hayashi, Y Ohbatake, H Takamura, M Okazaki, T Yamaguchi, S Sakai, I Makino, K Oyama, H Tajima, I Ninomiya, S Fushida, T Ohta
BACKGROUND: Thrombotic microangiopathy (TMA) pathogenesis after living donor liver transplantation (LDLT) is thought to be caused by release of unusually large von Willebrand factor multimers (UL-vWFMs) resulting from sinusoidal endothelial cell damage and induction of platelet adhesion and aggregation. A decrease in a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs-13 (ADAMTS-13) that cleave UL-vWFMs might cause excessive UL-vWFMs activity and result in platelet thrombus formation...
June 23, 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28650448/transplant-associated-thrombotic-microangiopathy-is-an-endothelial-complication-associated-with-refractoriness-of-acute-gvhd
#11
M Zeisbrich, N Becker, A Benner, A Radujkovic, K Schmitt, J Beimler, A D Ho, M Zeier, P Dreger, T Luft
There is increasing evidence that endothelial dysfunction is involved in refractoriness of acute GvHD (aGvHD). Here we investigated the hypothesis that another endothelial complication, transplant-associated thrombotic microangiopathy (TMA), contributes to the pathogenesis of aGvHD refractoriness. TMA was retrospectively assessed in 771 patients after allogeneic stem cell transplantation (alloSCT). Incidences of TMA and refractory aGvHD were correlated with biomarkers of endothelial damage obtained before alloSCT for patients receiving or not receiving statin-based endothelial prophylaxis (SEP)...
June 26, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28611987/complement-in-kidney-transplantation
#12
REVIEW
Marek Cernoch, Ondrej Viklicky
The complement system is considered to be an important part of innate immune system with a significant role in inflammation processes. The activation can occur through classical, alternative, or lectin pathway, resulting in the creation of anaphylatoxins C3a and C5a, possessing a vast spectrum of immune functions, and the assembly of terminal complement cascade, capable of direct cell lysis. The activation processes are tightly regulated; inappropriate activation of the complement cascade plays a significant role in many renal diseases including organ transplantation...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28596415/hemolytic-uremic-syndrome-in-pregnancy-and-postpartum
#13
Alexandra Bruel, David Kavanagh, Marina Noris, Yahsou Delmas, Edwin K S Wong, Elena Bresin, François Provôt, Vicky Brocklebank, Caterina Mele, Giuseppe Remuzzi, Chantal Loirat, Véronique Frémeaux-Bacchi, Fadi Fakhouri
BACKGROUND: Pregnancy is associated with various forms of thrombotic microangiopathy, including hemolytic uremic syndrome. A previous small French study suggested that pregnancy-associated hemolytic uremic syndrome was to be included in the spectrum of atypical hemolytic uremic syndrome linked to complement alternative pathway dysregulation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We sought to retrospectively analyze the presentation, outcome, and frequency of complement alternative pathway gene variants in a larger international (France, United Kingdom, Italy) cohort of patients with pregnancy-associated hemolytic uremic syndrome...
June 8, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28592769/thrombotic-complications-after-hematopoietic-stem-cell-transplantation
#14
Shosaku Nomura
Hematopoietic stem cell transplantation (HSCT) involves some serious transplant-associated complications (TACs) or vascular disorders, such as veno-occlusive disease (VOD), thrombotic microangiopathy (TMA), and graft-versus-host disease (GVHD). VOD is related to a clinical syndrome characterized by tender hepatomegaly, jaundice, fluid retention, and unexplained weight gain. When TMA is described in patients who have undergone HSCT, it is often implied that the clinical diagnosis of TMA is similar to that of thrombotic thrombocytopenic purpura...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28575423/purtscher-like-retinopathy-and-transplant-associated-thrombotic-microangiopathy
#15
Satoko Tominaga, Shinji Makino
No abstract text is available yet for this article.
May 29, 2017: QJM: Monthly Journal of the Association of Physicians
https://www.readbyqxmd.com/read/28522344/acquired-complement-regulatory-gene-mutations-and-hematopoietic-stem-cell-transplant-related-thrombotic-microangiopathy
#16
Gianluigi Ardissino, Stefania Salardi, Silvia Berra, Giacomo Colussi, Massimo Cugno, Marco Zecca, Fabio Giglio, Jacopo Peccatori, Elisa Diral, Francesca Tel, Alberto Clivio, Silvana Tedeschi
Hematopoietic stem cell transplant-related thrombotic microangiopathy (HSCT-TMA) is a severe complication whose pathophysiology is unknown. We describe 6 patients in which the disease was associated with complement regulatory gene abnormalities received from their respective donors. It is suggested that mutated and transplanted monocyte-derived cells are responsible for production of abnormal proteins, complement dysregulation, and, ultimately, for the disease. This observation might have important drawbacks as far as HSCT-TMA pathophysiology and treatment are concerned...
May 15, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28509120/complex-glomerular-pathology-of-thrombotic-microangiopathy-and-focal-segmental-glomerulosclerosis-forms-tumor-like-mass-in-a-renal-transplant-donor-with-severe-renovascular-hypertension
#17
Michio Nagata, Yutaka Yamaguchi, Daisuke Toki, Izumi Yamamoto, Hiroaki Shinmura, Hiroshi Kawaguchi
The pathogenesis of glomerular hypertension-mediated FSGS and its histological variations in humans remains unknown. A 47-year-old man developed nephrotic syndrome, renal dysfunction, and malignant hypertension 2 years after donating a kidney to his son. The donor's remnant kidney developed renal mass at an upper pole which was fed by an aberrant artery that branched from the root of the renal artery. Furthermore, the main non-aberrant renal artery demonstrated severe stenosis that caused renovascular hypertension, resulting in malignant hypertension...
May 2017: CEN Case Reports
https://www.readbyqxmd.com/read/28485097/hematopoietic-stem-cell-transplantation-and-acute-kidney-injury-in-children-a-comprehensive-review
#18
REVIEW
Rupesh Raina, Nicholas Herrera, Vinod Krishnappa, Sidharth Kumar Sethi, Akash Deep, Wei-Ming Kao, Timothy Bunchman, Rolla Abu-Arja
AKI in the setting of HSCT is commonly investigated among adult patients. In the same way, malignancies requiring treatment with HSCT are not limited to the adult patient population, AKI following HSCT is frequently encountered within pediatric patient populations. However, inadequate information regarding epidemiology and pathophysiology specific to pediatric patients prevents development of appropriate and successful therapeutic strategies for those afflicted. Addressing AKI in the context of sinusoidal obstruction syndrome, chemotherapy, thrombotic microangiopathy and hypertension post chemotherapy, glomerulonephritis, and graft versus host disease provides greater insight into renal impairment associated with these HSCT-related ailments...
June 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28485072/therapeutic-plasma-exchange-in-children-one-center-s-experience
#19
Gerard Cortina, Violeta Ojinaga, Thomas Giner, Magdalena Riedl, Siegfried Waldegger, Alejandra Rosales, Raphaela Trojer, Johannes Hofer
BACKGROUND: Therapeutic plasma exchange (TPE) has evolved to an accepted therapy for selected indications. However, it is technically challenging in children. Moreover, data on safety and efficacy are mainly derived from adult series. The aim of this study was to review the procedure in the context of clinical indications, effectiveness, and safety. STUDY DESIGN AND METHODS: All TPE procedures performed at a tertiary care hospital during a 12-year period (2005-2016) were retrospectively evaluated...
May 9, 2017: Journal of Clinical Apheresis
https://www.readbyqxmd.com/read/28460546/an-update-on-chemical-pharmacotherapy-options-for-the-prevention-of-kidney-transplant-rejection-with-a-focus-on-costimulation-blockade
#20
Florian Kälble, Matthias Schaier, Sebastian Schäfer, Caner Süsal, Martin Zeier, Claudia Sommerer, Christian Morath
The introduction of calcineurin inhibitors (CNI) has greatly improved graft survival in the past three decades. However, long-term graft survival is still limited due to chronic allograft injury and side-effects of immunosuppressive medication. Areas covered: The present overview gives an update on pharmacotherapeutic strategies after kidney transplantation. The main focus is on CNI-sparing regimens using co-stimulatory blockade and on new substances on the horizone. Expert opinion: CNI sparing regimens are well-established...
June 2017: Expert Opinion on Pharmacotherapy
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