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Thrombotic microangiopathy transplant

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https://www.readbyqxmd.com/read/28303518/potentially-life-threatening-coagulopathy-associated-with-simultaneous-reduction-in-coagulation-and-fibrinolytic-function-in-pediatric-acute-leukemia-after-hematopoietic-stem-cell-transplantation
#1
Takashi Ishihara, Keiji Nogami, Tomoko Matsumoto, Akitaka Nomura, Yasufumi Takeshita, Satoshi Ochi, Midori Shima
The pathogenesis of sinusoidal obstruction syndrome (SOS) and thrombotic microangiopathy (TMA) after hematopoietic stem cell transplantation (HSCT) is poorly understood, and limited information is available on global hemostatic function in HSCT. We assessed changes in coagulation and fibrinolysis using a simultaneous thrombin and plasmin generation assay (T/P-GA) during HSCT. Measurements of endogenous thrombin potential (T-EP) and plasmin peak height (P-Peak) using T/P-GA in six pediatric acute leukemia patients treated with HSCT were compared to normal plasma...
March 16, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28287636/transplant-associated-thrombotic-microangiopathy-opening-pandora-s-box
#2
REVIEW
E Gavriilaki, I Sakellari, A Anagnostopoulos, R A Brodsky
Transplant-associated thrombotic microangiopathy (TA-TMA) is an early complication of hematopoietic cell transplantation (HCT). A high mortality rate is documented in patients who are refractory to calcineurin inhibitor cessation. Estimates of TA-TMA prevalence vary significantly and are higher in allogeneic compared with autologous HCT. Furthermore, our understanding of the pathophysiology that is strongly related to diagnosis and treatment options is limited. Recent evidence has linked TA-TMA with atypical hemolytic uremic syndrome, a disease of excessive activation of the alternative pathway of complement, opening the Pandora's box in treatment options...
March 13, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28271596/team-based-approach-to-identify-cardiac-toxicity-in-critically-ill-hematopoietic-stem-cell-transplant-recipients
#3
Christopher E Dandoy, Sonata Jodele, Zachary Paff, Russel Hirsch, Thomas D Ryan, John L Jefferies, Michelle Cash, Seth Rotz, Abigail Pate, Michael D Taylor, Javier El-Bietar, Kasiani C Myers, Gregory Wallace, Adam Nelson, Michael Grimley, Thomas Pfeiffer, Adam Lane, Stella M Davies, Ranjit S Chima
INTRODUCTION: We observed pulmonary hypertension (PH), pericardial effusions, and left ventricular systolic dysfunction (LVSD) in multiple critically ill hematopoietic stem cell transplant (HSCT) recipients. We implemented routine structured echocardiography screening for HSCT recipients admitted to the pediatric intensive care unit (PICU) using a standardized multidisciplinary process. METHODS: HSCT recipients admitted to the PICU with respiratory distress, hypoxia, shock, and complications related to transplant-associated thrombotic microangiopathy were screened on admission and every 1-2 weeks thereafter...
March 8, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28226413/thrombalexin-use-of-a-cytotopic-anticoagulant-to-reduce-thrombotic-microangiopathy-in-a-highly-sensitized-model-of-kidney-transplantation
#4
Miriam Manook, Jean Kwun, Christian Burghuber, Kannan Samy, Michael Mulvihill, Janghoon Yoon, He Xu, Andrea L MacDonald, Kyle Freischlag, Verna Curfman, Evelyn Branum, David Howell, Alton Brad Farris, Richard A Smith, Stephen Sacks, Anthony Dorling, Nizam Mamode, Stuart Knechtle
Early activation of coagulation is an important factor in the initiation of innate immunity, as characterized by thrombotic microangiopathy (TMA). In transplantation, systemic anti-coagulation is difficult due to bleeding. A novel 'cytotopic' agent, 'Thrombalexin', (TLN) combines a cell-membrane bound (mirystoyl tail) anti-thrombin (HLL peptide) which can be perfused directly to the donor organ or cells.. Thromboelastography (TEG) was used to measure time to clot formation (r-time) in both rhesus and human blood, comparing TLN vs...
February 22, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28207978/glomerular-c4d-deposits-can-mark-structural-capillary-wall-remodeling-in-thrombotic-microangiopathy-and-transplant-glomerulopathy-c4d-beyond-active-antibody-mediated-injury
#5
Adil H Gasim, Jamie S Chua, Ron Wolterbeek, John Schmitz, Eric Weimer, Harsharan K Singh, Volker Nickeleit
Peritubular capillary C4d (ptc-C4d) usually marks active antibody mediated rejection, while pseudolinear glomerular capillary C4d (GBM-C4d) is of undetermined diagnostic significance, especially when seen in isolation without concurrent ptc-C4d. We correlated GBM-C4d with structural GBM abnormalities and active antibody mediated rejection in 319 renal transplant and 35 control native kidney biopsies. In kidney transplants ptc-C4d was associated with GBM-C4d in 97% by immunofluorescence microscopy (IF) and 61% by immunohistochemistry (IHC; p<0...
February 16, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28187980/patients-with-hypertension-associated-thrombotic%C3%A2-microangiopathy-may-present-with%C3%A2-complement-abnormalities
#6
Sjoerd A M E G Timmermans, Myrurgia A Abdul-Hamid, Joris Vanderlocht, Jan G M C Damoiseaux, Chris P Reutelingsperger, Pieter van Paassen
Thrombotic microangiopathy (TMA) is a pattern of endothelial damage that can be found in association with diverse clinical conditions such as malignant hypertension. Although the pathophysiological mechanisms differ, accumulating evidence links complement dysregulation to various TMA syndromes and in particular the atypical hemolytic uremic syndrome. Here, we evaluated the role of complement in nine consecutive patients with biopsy-proven renal TMA attributed to severe hypertension. Profound hematologic symptoms of TMA were uncommon...
February 7, 2017: Kidney International
https://www.readbyqxmd.com/read/28176480/de-novo-thrombotic-microangiopathy-following-simultaneous-pancreas-and-kidney-transplantation-managed-with-eculizumab
#7
REVIEW
Lani Shochet, John Kanellis, Ian Simpson, Joseph Ta, William Mulley
Thrombotic microangiopathy (TMA) is a well-recognised complication following transplantation, often due to an underlying genetic predisposition, medications or rejection. The use of eculizumab in these settings has been previously described, but its role still remains to be clarified. A 45-year-old man, with a history of type 1 diabetes mellitus and subsequent end-stage kidney failure, presented for a simultaneous pancreas-kidney transplant. Immunologically, he was well matched with the donor, and he received standard induction immunosuppression including tacrolimus...
February 2017: Nephrology
https://www.readbyqxmd.com/read/28176476/recurrent-atypical-haemolytic-uraemic-syndrome-post-kidney-transplant-due-to-a-cd46-mutation-in-the-setting-of-smarcal1-mediated-inherited-kidney-disease
#8
REVIEW
Samuel Chan, Andrew J Mallett, Chirag Patel, Ross S Francis, David W Johnson, David W Mudge, Nicole M Isbel
Disorders in the regulation of the alternate complement pathway often result in complement-mediated damage to the microvascular endothelium and can be associated with both glomerulonephritis and atypical haemolytic uraemic syndrome. Inherited defects in complement regulatory genes or autoantibodies against complement regulatory proteins are predictive of the severity of the disease and the risk of recurrence post kidney transplantation. Heterozygous mutations in CD46, which codes for a transmembrane cofactor glycoprotein membrane cofactor protein, usually have a lower incidence of end-stage kidney disease and decreased risk of recurrent disease post transplant, as wild-type membrane cofactor protein is present in the transplanted kidney...
February 2017: Nephrology
https://www.readbyqxmd.com/read/28110970/-plasma-exchange-in-nephrology-indications-and-technique
#9
Christophe Ridel, Sébastien Kissling, Laurent Mesnard, Alexandre Hertig, Éric Rondeau
Plasma exchange is a non-selective apheresis technique that can be performed by filtration or centrifugation allowing rapid purification of high molecular weight pathogens. An immunosuppressive treatment is generally associated to reduce the rebound effect of the purified substance. Substitution solutes such as human albumin and macromolecules are needed to compensate for plasma extraction. Compensation by viro-attenuated plasma is reserved solely for the treatment of thrombotic microangiopathies or when there is a risk of bleeding, because this product is very allergenic and expensive...
January 16, 2017: Néphrologie & Thérapeutique
https://www.readbyqxmd.com/read/28104125/efficacy-of-eculizumab-therapy-for-atypical-hemolytic-uremic-syndrome-recurrence-and-antibody-mediated-rejection-progress-after-renal-transplantation-with-preformed-donor-specific-antibodies-case-report
#10
T Yamamoto, Y Watarai, K Futamura, M Okada, M Tsujita, T Hiramitsu, N Goto, S Narumi, A Takeda, T Kobayashi
Atypical hemolytic uremic syndrome (aHUS) develops as the result of unregulated complement progression and precipitates de novo thrombotic microangiopathy. Plasma therapy is used to control the progression of the complement cascade, but that therapy is not effective in all patients and is accompanied by risk of infection and/or allergy. Eculizumab has been reported as an efficient therapy for aHUS. We report the case of a 35-year old woman who underwent effective eculizumab therapy for aHUS recurrence and antibody-mediated rejection (AMR) progress after renal transplantation with preformed donor-specific antibodies (DSA)...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28092354/use-of-defibrotide-to-treat-transplant-associated-thrombotic-microangiopathy-a-retrospective-study-of-the-paediatric-diseases-and-inborn-errors-working-parties-of-the-european-society-of-blood-and-marrow-transplantation
#11
L Yeates, M A Slatter, S Bonanomi, F L W I Lim, S Y Ong, A Dalissier, W Barberi, A Shulz, M Duval, C Heilmann, A Willekens, W H Y Hwang, C Uderzo, P Bader, A R Gennery
No abstract text is available yet for this article.
January 16, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28089409/the-italian-registry-of-therapeutic-apheresis-2015
#12
REVIEW
Giustina De Silvestro
Data collection on apheresis activities in Italy throughout 2015 including techniques, clinical indications and adverse effects was performed by means of a SidEM model questionnaire (aggregate data). These data provided by 67 Apheresis Units from 17 Italian regions, albeit rough, are sufficiently informative, mainly in comparison with previous surveys on these statistics. PEx has been the most frequent technique for plasma removal/treatment (11787 procedures) followed by LDL-apheresis (927 procedures). ECP/photopheresis has been the most frequent cytapheresis procedure: 6,606 session, mainlyby using the off-line technique...
February 2017: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/28060108/diagnostic-utility-of-complement-immunohistochemical-studies-in-post-stem-cell-transplant-intestinal-thrombotic-microangiopathy-case-report
#13
Jenna E Rossoff, Jennifer Schneiderman, Sonali Chaudhury, Nicoleta C Arva
Thrombotic complications are a significant source of morbidity and mortality following hematopoietic stem cell transplants. Among them, transplant-associated thrombotic microangiopathy (TA-TMA) is a well-recognized syndrome that can affect various organ systems. Its etiology is related to endothelial injury accompanied by complement activation. As many of the signs and symptoms of the disease are also encountered in other complications following hematopoietic stem cell transplant, it can often be difficult to establish the diagnosis based on clinical data alone...
January 5, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/27998645/thrombotic-microangiopathy-associated-with-monoclonal-gammopathy
#14
Aishwarya Ravindran, Ronald S Go, Fernando C Fervenza, Sanjeev Sethi
Thrombotic microangiopathy (TMA) is a rare disease comprising of a diverse set of disorders linked by a common histologic finding of endothelial injury. Monoclonal immunoglobulins may act as a potential trigger in the pathogenesis of TMA. To determine the prevalence of monoclonal gammopathy and clinicopathological features of TMA associated with monoclonal immunoglobulin, we performed a retrospective study in adults (18 and older) with a clinical diagnosis of TMA. Of 146 patients with TMA, we detected monoclonal immunoglobulin in 20 patients (13...
December 17, 2016: Kidney International
https://www.readbyqxmd.com/read/27977428/breaking-down-the-complement-system-a-review-and-update-on-novel-therapies
#15
Yuvaram N V Reddy, Andrew M Siedlecki, Jean M Francis
PURPOSE OF REVIEW: The complement system represents one of the more primitive forms of innate immunity. It has increasingly been found to contribute to pathologies in the native and transplanted kidney. We provide a concise review of the physiology of the complement cascade, and discuss current and upcoming complement-based therapies. RECENT FINDINGS: Current agents in clinical use either bind to complement components directly or prevent complement from binding to antibodies affixed to the endothelial surface...
March 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/27974406/thrombotic-microangiopathy-in-inverted-formin-2-mediated-renal-disease
#16
Rachel C Challis, Troels Ring, Yaobo Xu, Edwin K S Wong, Oliver Flossmann, Ian S D Roberts, Saeed Ahmed, Michael Wetherall, Giedrius Salkus, Vicky Brocklebank, Julian Fester, Lisa Strain, Valerie Wilson, Katrina M Wood, Kevin J Marchbank, Mauro Santibanez-Koref, Timothy H J Goodship, David Kavanagh
The demonstration of impaired C regulation in the thrombotic microangiopathy (TMA) atypical hemolytic uremic syndrome (aHUS) resulted in the successful introduction of the C inhibitor eculizumab into clinical practice. C abnormalities account for approximately 50% of aHUS cases; however, mutations in the non-C gene diacylglycerol kinase-ε have been described recently in individuals not responsive to eculizumab. We report here a family in which the proposita presented with aHUS but did not respond to eculizumab...
December 14, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27956735/increased-incidence-of-thrombotic-microangiopathy-after-abo-incompatible-living-donor-liver-transplantation
#17
Norihiro Kishida, Masahiro Shinoda, Osamu Itano, Hideaki Obara, Minoru Kitago, Taizo Hibi, Hiroshi Yagi, Yuta Abe, Kentaro Matsubara, Masanori Odaira, Minoru Tanabe, Motohide Shimazu, Yuko Kitagawa
BACKGROUND Thrombotic microangiopathy (TMA) is a severe life-threatening complication associated with solid organ transplantation. We retrospectively investigated the incidence, risk factors, and appropriate treatment of TMA following adult living donor liver transplantation (LDLT). MATERIAL AND METHODS The subjects were 129 adult patients who underwent LDLT in our department from 1997 to 2014. Patients with TMA were identified retrospectively based on diagnostic criteria. We calculated the incidence of TMA and performed a risk factor analysis for TMA occurrence...
December 13, 2016: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/27932157/belatacept-and-eculizumab-for-treatment-of-calcineurin-inhibitor-induced-thrombotic-microangiopathy-after-kidney-transplantation-case-report
#18
J Merola, P S Yoo, J Schaub, J D Smith, M I Rodriguez-Davalos, E Tichy, D C Mulligan, W Asch, R Formica, M Kashgarian, S Kulkarni
Thrombotic microangiopathy (TMA) after kidney transplantation is an uncommon and challenging cause of graft dysfunction and is associated with early graft loss. An idiosyncratic endothelial reaction to calcineurin inhibitors (CNIs) has been implicated as a frequent cause of TMA. This reaction is marked by uncontrolled activation of complement and subsequent cellular destruction. Usual therapy consists of withdrawal of the inciting drug and plasmapheresis to minimize levels of circulating complement. Recently, eculizumab, a monoclonal antibody to complement component C5, has been used for the treatment of atypical hemolytic uremic syndrome...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27913483/atypical-hemolytic-uremic-syndrome
#19
Vahid Afshar-Kharghan
Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy (TMA) that affects multiple organs and the kidneys in particular. aHUS can be sporadic or familial and is most commonly caused by dysregulation of the alternative complement pathway. The initial attack of aHUS can occur at any age, and is associated with a high rate of progression to end stage renal disease. Many aHUS patients relapse in the native or transplanted kidneys, and require close monitoring and long-term management. Availability of anticomplement therapy has revolutionized the management of aHUS, and can change the natural course of aHUS by inducing hematologic remission, improving or stabilizing kidney functions, and preventing graft failure...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27892947/danaparoid-reduces-the-incidence-of-hematopoietic-stem-cell-transplantation-associated-thrombotic-microangiopathy
#20
S Machida, M Onizuka, M Toyosaki, Y Aoyama, H Kawai, J Amaki, R Hara, A Ichiki, Y Ogawa, H Kawada, K Ando
No abstract text is available yet for this article.
February 2017: Bone Marrow Transplantation
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