Buser, Marc; Felizeter-Kessler, Monika; Lenggenhager, Daniela; Maeder, Micha T (2015). Rapidly progressive pulmonary hypertension in a patient with pulmonary tumor thrombotic microangiopathy. American Journal of Respiratory and Critical Care Medicine, 191(6):711-712. ...

Although TMAs are highly heterogeneous pathological conditions, one-third of TMA patients have severe deficiency of ADAMTS13: AC, and rapid ADAMts13:AC assays are therefore prerequisite to appropriately treat T MA patients. BACKGROUND Thrombotic microangiopathies (TMAs) are pathological conditions characterized by generalized microvascular occlusion by platelet thrombi, thrombocytopenia, and microangiopathic hemolytic anemia. Two typical phenotypes of TMAs are hemolytic-uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Severe deficiency of plasma ADAMTS13 activity (ADAMTS13: AC) is more specific for TTP, but not for HUS. Since 1998, our laboratory has functioned as a nationwide referral center for TMAs by analyzing ADAMTS13. METHODS Of 1,564 patients tested from 426 hospitals, 919 were positive for TMA. Levels of ADAMTS13: AC and the ADAMTS13 neutralizing autoantibody (ADAMTS13: INH) were determined by chromogenic act-ELISA and/or by classic von Willebrand factor multimer assay.

Eppsteiner, R. W., Fowlkes, J. W., Anderson, C. M., Robinson, R. A. & Pagedar, N. A. (2017). Aggressive Salivary Malignancies at Early Stage: Outcomes and Implications for Treatment. The Annals of otology, rhinology, and laryngology, 3489417702655. PMID: 28474964.. De Andrade, J. P., Lorenzen, A. W., Wu, V. T., Bogachek, M. V., Park, J. M., Gu, V. W., Sevenich, C. M., Cassady, V. C., Beck, A. C., Kulak, M. V., Robinson, R. A., Lal, G. & Weigel, R. J. (2017). Targeting the SUMO pathway as a novel treatment for anaplastic thyroid cancer. Oncotarget, 8(70), 114801-114815. PMID: 29383121.. Story, M., Kwon, S. K., Robinson, R. & Fortis, S. (2017). Acute cor pulmonale due to pulmonary tumour thrombotic microangiopathy from renal cell carcinoma. BMJ case reports, 2017. PMID: 28659364.. Wilson, T. C., MA, D., Tilak, A., Tesdahl, B. & Robinson, R. A. (2016). Next generation sequencing in salivary gland basal cell adenocarcinoma and basal cell adenoma. Head and Neck Pathology.. Reed, M. J., Sperry, S. M., ...

Among various lupus renal vascular changes, thrombotic microangiopathy (TMA) presented with the most severe clinical manifestations and high mortality. The pathogenesis of TMA in systemic lupus erythematosus (SLE) was complicated. The aim of this study was to assess clinical manifestations, laboratory characteristics, pathological features and risk factors for clinical outcomes of lupus nephritis patients co-existing with renal TMA in a large cohort in China. Clinical and renal histopathological data of 148 patients with biopsy-proven lupus nephritis were retrospectively analyzed. Serum complement factor H, A Disintegrin and Metalloprotease with Thrombospondin type I repeats 13 (ADAMTS-13) activity, antiphospholipid antibodies and C4d deposition on renal vessels were further detected and analyzed. In the 148 patients with lupus nephritis, 36 patients were diagnosed as co-existing with renal TMA based on pathological diagnosis. Among the 36 TMA patients, their clinical diagnoses of renal TMA were as

Primary thrombotic microangiopathy (TMA) syndromes encompass diseases that present with thrombosis in small and medium sized blood vessels due to endothelial injury. They are specific disorders that require specific treatment. The initial assessment is focused on confirming that the patient has true microangiopathic hemolytic anemia (MAHA) with or without thrombocytopenia. If MAHA and thrombocytopenia are…

Publication date: Available online 16 February 2018 Source:Pregnancy Hypertension Author(s): M. Gupta, B.B. Feinberg, R.M. Burwick Thrombotic microangiopathy (TMA) disorders are characterized by microangiopathic hemolytic anemia, thrombocytopenia and end-organ injury. In pregnancy and postpartum, TMA is most commonly encountered with HELLP (hemolysis, elevated liver enzymes, low platelet count sy...

Case Presentation: In our Morning Report at WCH, we discussed a case of a patient presenting acute anemia and thrombocyotopenia (recent CBC 2 weeks prior = normal). Subsequent investigations were compatible with microangiopathic hemolytic anemia, also referred to as thrombotic microangiopathy (TMA). Learning Points: The Acute Drop in Hemoglobin Hemolysis Work-Up Definition and types of…

Publication date: September 2019Source: Advances in Chronic Kidney Disease, Volume 26, Issue 5Author(s): Elizabeth S. Kotzen, Sanjeet Roy, Koyal JainAntiphospholipid syndrome (APS) and other causes of thrombotic microangiopathy (TMA) negatively impact the renal outcomes of patients with systemic lupus erythematosus (SLE) and lupus nephritis. Here we review the diagnosis and management of occlusive...

This is a Phase 2, uncontrolled, 3-stage, ascending-dose-escalation study in patients with 1 of 3 forms of TMA: atypical hemolytic uremic syndrome (aHUS), thrombotic thrombocytopenia (TTP), and hematopoietic stem cell transplant - associated TMA (HSCT-associated TMA). In Stage 1 of the study, OMS721 was administered to 3 cohorts, with dose escalation by cohort to identify the optimal dosing regimen. In Stage 2, the dose selected in the first stage was administered to expanded cohorts of patients with distinct etiologies (aHUS alone in 1 cohort and TTP or HSCT-TMA in the other cohort). Patients completing Stage 2 were eligible for continued treatment in Stage 3 if they tolerated OMS721 treatment and derived clinical benefit. Enrollment in the study has been completed ...

TY - JOUR. T1 - Snakebite associated thrombotic microangiopathy. T2 - A protocol for the systematic review of clinical features, outcomes, and role of interventions. AU - Noutsos, Tina. AU - Currie, Bart J.. AU - Isbister, Geoffrey K.. PY - 2019/8/22. Y1 - 2019/8/22. N2 - Background: Thrombotic microangiopathy is an uncommon complication of snake envenoming associated with a subset of snakebite cases presenting with venom-induced consumption coagulopathy. It presents with microangiopathic haemolytic anaemia and thrombocytopenia. Available studies are predominantly small retrospective observational studies only. Renal end organ injury appears common. It has variably been likened to either thrombotic thrombocytopenic purpura or atypical haemolytic uraemic syndrome. Many studies report acute kidney injury, with dialysis required in a subset of patients. Some studies suggest a role for treatment with plasmapheresis. Interpretation of the literature is complicated by variable nomenclature and ...

Microangiopathies may cause ischemic brain lesions and are of fundamental importance in vascular dementia. Risk factors include high age, hypertension, diabetes and Alzheimers disease. In addition, recent studies have focused on autosomal dominant types of arteriopathy causing leukoencephalopathy,psychiatric disturbances, stroke and dementia (CADASIL). This thesis concerns various collagens andbasal lamina components which are deposited in vascular walls of cases presenting cerebral microangiopathy. In addition, endothelin-like immunoreactivity has been studied in CADASIL cases andsome other brain diseases.. CADASIL cases described by Sourander and Wålinder (1977) were re-investigated. Those with longduration of the disease presented marked expression of fibrillary collagen types I, Ill, V and VI and of thebasal lamina components, collagen type IV and laminin. Deposits appeared also in non-familial casespresenting hyalinosis and in cases with the Binswanger type of leukoencephalopathy. Media ...

Acquired thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are appropriately at the top of a clinicians differential when a patient presents with a clinical picture consistent with an acute thrombotic microangiopathy (TMA). However, there are several additional diagnoses that should be considered in patients presenting with an acute TMA, especially in patients with non-deficient ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity (,10%). An increased awareness of drug-induced TMA is also essential as the key to their diagnosis more often is an appropriately detailed medical history to inquire about potential exposures. Widespread inflammation and endothelial damage are central in the pathogenesis of the thrombotic microangiopathy (TMA), with the treatment directed at the underlying disease if possible. TMA presentations in the critically ill, drug-induced TMA, cancer-associated TMA, and hematopoietic ...

Six patients with prolonged acute courses of thrombotic microangiopathy are reviewed. These patients had in common courses of acute disease requiring plasma support for more than 3 months, with subsequent complete remission. Plasma support requirements may be prodigious, and the acute course may require more than 100 plasma exchanges before a stable remission is achieved. These patients appear to represent a subset of thrombotic microangiopathy distinct from the more common acute T.T.P. course, which resolves in 3-6 weeks, and the chronic relapsing pattern, which may have a short or prolonged acute course.

TY - JOUR. T1 - Acute Kidney Injury in Pregnancy. AU - Jim, Belinda. AU - Garovic, Vesna D. PY - 2017/7/1. Y1 - 2017/7/1. N2 - Summary: Pregnancy-related acute kidney injury (AKI) has declined in incidence in the last three decades, although it remains an important cause of maternal and fetal morbidity and mortality. Pregnancy-related causes of AKI such as preeclampsia, acute fatty liver of pregnancy, HELLP (Hemolysis, Elevated Liver function tests, Low Platelets) syndrome, and the thrombotic microangiopathies (thrombotic thrombocytopenic purpura, atypical hemolytic-uremic syndrome [HUS]) exhibit overlapping features and often present as diagnostic dilemmas. Differentiating among these conditions may be difficult or impossible based on clinical criteria only. In difficult and rare cases, a renal biopsy may need to be considered for the exact diagnosis and to facilitate appropriate treatment, but the risks and benefits need to be carefully weighed. The use of eculizumab for the treatment of ...

Background: Vascular endothelial cells (ECs) express and release protein components of the complement pathways, as well as secreting and anchoring ultra-large von Willebrand factor (ULVWF) multimers in long string-like structures that initiate platelet adhesion during hemostasis and thrombosis. The alternative complement pathway (AP) is an important nonantibody- requiring host defense system. Thrombotic microangiopathies can be associated with defective regulation of the AP (atypical hemolytic-uremic syndrome) or with inadequate cleavage by ADAMTS-13 of ULVWF multimeric strings secreted by/anchored to ECs (thrombotic thrombocytopenic purpura). Our goal was to determine if EC-anchored ULVWF strings caused the assembly and activation of AP components, thereby linking two essential defense mechanisms. Methodology/Principal Findings: We quantified gene expression of these complement components in cultured human umbilical vein endothelial cells (HUVECs) by real-time PCR: C3 and C5; complement factor ...

B TALBOT1,2, J OTHMAN2, RCF CHAN2, M KRISHNASWAMY2, K ARCHER2, V CHEN2,3, S SEN2. 1The George Institute, Sydney, NSW; 2Concord Repatriation General Hospital, Sydney, NSW; 3The University of Sydney, Sydney, NSW.. Background:. Thrombotic microangiopathy (TMA) describes a pathological process of microvascular thrombosis, consumptive thrombocytopenia and microangiopathic haemolytic anaemia leading to end-organ ischaemia and infarction. Patients may present with acute renal failure and/or cerebral dysfunction. TMA is a feature of several clinical disorders and rarely can be associated with malignancy.. Case Report: A 71 year old gentleman presented with flank pain, fevers and deteriorating renal function. He was known to have unilateral hydronephrosis and a poorly defined hilar soft tissue density in the left kidney.. On arrival he was septic and haemodynamically unstable. Investigations revealed microcytic anaemia, acute kidney injury and raised inflammatory markers. Significant fragmentation was ...

14:52 - The punchline: aHUS and TTP diagnosis algorithm. Publications. Stromsness B. et al. Physician Interpretation of Equivocal Results for aHUS Genetic Testing Varies Greatly and is Frequently at Odds with Laboratory Views. J Clin Apheresis. 2019; (abstract P-82).. Ero, MP, Kain, JS, inventors; Machaon Diagnostics, Inc., assignee. 2018 Dec 18. Method of diagnosis of complement-mediated thrombotic microangiopathies. United States patent US 10,155,983.. Tao J. et al. A rare case of Alport syndrome, atypical hemolytic uremic syndrome and Pauci-immune crescentic glomerulonephritis. BMC Nephrology. 2018;19:355.. Kain J. et al. Additional Genes Associated with Atypical Hemolytic Uremic Syndrome. ASN 2018 Abstract TH-PO713. 2018; (abstract).. Switala L. et al. Complement factor abnormalities detected in patients with suspected Heparin-induced Thrombocytopenia (HIT) but not in Thrombotic Thrombocytopenia Purpura (TTP). ISLH 2017 Abstract Proceedings. 2017; (abstract).. Ipe T. et al. An extremely rare ...

14:52 - The punchline: aHUS and TTP diagnosis algorithm. Publications. Stromsness B. et al. Physician Interpretation of Equivocal Results for aHUS Genetic Testing Varies Greatly and is Frequently at Odds with Laboratory Views. J Clin Apheresis. 2019; (abstract P-82).. Ero, MP, Kain, JS, inventors; Machaon Diagnostics, Inc., assignee. 2018 Dec 18. Method of diagnosis of complement-mediated thrombotic microangiopathies. United States patent US 10,155,983.. Tao J. et al. A rare case of Alport syndrome, atypical hemolytic uremic syndrome and Pauci-immune crescentic glomerulonephritis. BMC Nephrology. 2018;19:355.. Kain J. et al. Additional Genes Associated with Atypical Hemolytic Uremic Syndrome. ASN 2018 Abstract TH-PO713. 2018; (abstract).. Switala L. et al. Complement factor abnormalities detected in patients with suspected Heparin-induced Thrombocytopenia (HIT) but not in Thrombotic Thrombocytopenia Purpura (TTP). ISLH 2017 Abstract Proceedings. 2017; (abstract).. Ipe T. et al. An extremely rare ...

Dr Noris with Len Woodward of the aHUS alliance at the Research Centre in Bergamo during the whistle top tour of European aHUS Expert Centres ( read here). The alliance registered to attend the webinar. Starting on time the talk proved to be an advanced and up to date learning opportunity about aHUS and the alternative pathway of Complement.. Beginning with describing Thrombotic Microangiopathies (TMAs) , of which aHUS is the one caused by dysregulation of the Complement System. aHUS has an incidence of 0.5 to 2 per million of the population ( which means between 4000 and 15000 new cases globally annually) and without treatment 80% of those patients would die or go into chronic kidney failure.. Marina introduced the components of the pathways of Complement focusing on the Alternative path and the creation of the C5 converteses which sets off the Membrane Attack Complex from a state of continuous tickover. Then spent time explaining the controls, in particular CFH and how in three ways its ...

TY - JOUR. T1 - Thrombotic microangiopathy in pregnancy. AU - DAngelo, Armando. AU - Fattorini, Annalisa. AU - Crippa, Luciano. PY - 2009. Y1 - 2009. UR - http://www.scopus.com/inward/record.url?scp=65549128053&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=65549128053&partnerID=8YFLogxK. M3 - Article. C2 - 19217478. AN - SCOPUS:65549128053. VL - 123. JO - Thrombosis Research. JF - Thrombosis Research. SN - 0049-3848. IS - SUPPL. 2. ER - ...

Gastrointestinal Bleeding -- Liver Failure in Infants and Children -- Acute Pancreatitis -- Abdominal Compartment Syndrome in Children -- Obesity in Critical Illness -- Nutrition in the PICU -- Diabetic Ketoacidosis -- Hyperglycemia, Dysglycemia and Glycemic Control in Pediatric Critical Care -- Hypoglycemia -- The Adrenal Glands in Critical Illness and Injury -- Thyroid and Growth Hormone Axes Alteration in the Critically Ill Child -- Applied Renal Physiology in the PICU -- Electrolyte Disorders in the PICU -- Acid-Base Disorders in the PICU -- Acute Kidney Injury -- Kidney Disorders in the PICU: Thrombotic Microangiopathies and Glomerulonephritis -- Kidney Pharmacology -- Renal Replacement Therapy -- Transfusion Medicine -- Hematologic Emergencies in the PICU -- Coagulation Disorders in the PICU -- Therapeutic Apheresis in the Pediatric Intensive Care Unit -- Thromboembolic Disorders in the PICU -- Care of the Oncology Patient in the PICU -- Critical Illness as a Result of Anti-Neoplastic ...

Aims/Introduction It is idea that adipocytokines contribute to the increased risk of vascular complications in type 2 diabetes. the patients in the lowest tertile of adiponectin level. Conclusions Levels of adipocytokines were significantly different according to the presence of each microangiopathy. In particular, higher serum adiponectin was independently associated with increased odds for the presence of neuropathy. Future prospective studies with larger numbers of patients are required to establish a direct relationship between plasma adipocytokine concentrations and the development or severity of diabetic microangiopathies. Keywords: Adipocytokines, Diabetic microangiopathies Introduction Adipose tissue secretes adipocytokines, which influence glucose and lipid metabolism, inflammatory processes, and other bioactivities1. It is thought that adipocytokines contribute to the increased risk of vascular complications in patients with type 2 diabetes by modulating vascular function and affecting ...

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INTRODUCTION:Autoantibody effects of monoclonal proteins have been described in multiple organ systems. We previously found a 5-fold higher prevalence than expe

In diabetes-associated microangiopathies and atherosclerosis, there are alterations of the extracellular matrix (ECM) in the intima of small and large arteries. High levels of circulating nonesterified fatty acids (NEFAs) are present in insulin resistance and type 2 diabetes. High concentrations of NEFAs might alter the basement membrane composition of endothelial cells. In arteries, smooth muscle cells (SMCs) are the major producers of proteoglycans and glycoproteins in the intima, and this is the site of lipoprotein deposition and modification, key events in atherogenesis. We found that exposure of human arterial SMCs to 100-300 micromol/albumin-bound linoleic acid lowered their proliferation rate and altered cell morphology. SMCs expressed 2-10 times more mRNA for the core proteins of the proteoglycans versican, decorin, and syndecan 4 compared with control cells. There was no change in expression of fibronectin and perlecan. The decorin glycosaminoglycan chains increased in size after ...

The main findings of the present study are fourfold. Firstly, we observed a high prevalence of AD in T2DM females, with 35% affected, similar to that observed in T2DM males. Secondly, the AD ratio log(TG)/HDL-C is an easy means to estimate IR, and was strongly related to a cardiometabolic phenotype characterized by IR, MetS, hyperinsulinemia, central fat accretion, sarcopenia, liver steatosis and sedentary lifestyle. Thirdly, this ratio was linked to a stepwise gradient for residual risk of future CAD. Lastly, this ratio was related to decreased insulin secretion, β-cell function loss, poorer glycemic control and higher frequency of microangiopathies. The AD ratio may therefore allow to easily identifying a comprehensive modifiable component of non-LDL, lipid-related residual vascular risk, as well as pinpoint worsening in glucose homeostasis determinants[5-7].. The hallmark of AD is decreased HDL-C level together with raised TG, with LDL-C often only marginally elevated[2-5, 33-40]. Computing ...

NASDAQ: OMER) today announced new results from the companys ongoing Phase 2 study of OMS721 evaluating patients with hematopoietic stem cell transplant-associated thrombotic microangiopathy (HCT-TMA). The data demonstrate an increase in median overall survival in HCT-TMA patients treated with OMS721 compared to a matched historical control (347 days vs. 21 days, respectively, by Kaplan-Meier analysis; p , 0.0001 by log-rank test). Historical control data are typically used for comparison when it is impractical or unethical to include a placebo arm in a clinical trial. In addition to and consistent with the survival data reported today, updated assessments of platelet count, lactate dehydrogenase (LDH) and haptoglobin - all markers of TMA activity - continue to demonstrate clinically meaningful and statistically significant improvements in the HCT-TMA patients treated with OMS721. A total of 19 HCT-TMA patients have been treated to date with OMS721, 18 in the ongoing study and one patient under ...

Masias, Camila, Sumithira Vasu, and Spero R. Cataland. None of the above: thrombotic microangiopathy beyond TTP and HUS. Blood 129.21 (2017): 2857-2863. Web. 23 Feb. 2018. ...

Sberro-Soussan, B. Severino, N.S. Sheerin, A. Trivelli, L.B. Zimmerhackl, T. Goodship, and C.1,2 This syndrome is due to defects in regulation of the complement system. These defects are inherited, acquired, or both, plus they bring about chronic, uncontrolled activation of the complement system1-4 which leads to platelet, leukocyte, and endothelial-cell activation and systemic thrombotic microangiopathy.1,5-9 […]. Read More ...

A safety review was initiated to evaluate the possible risk of thrombotic microangiopathy (TMA) associated with the use of vascular endothelial growth factor (VEGF) receptor inhibitors.

Pulmonary Langerhans cell histiocytosis (PLCH) Lymphangioleiomyomatosis (LAM) Sarcoidosis Chronic eosinophilic pneumonia Aspiration pneumonia Pulmonary tumor thrombotic microangiopathy (PTTM) Minute pulmonary meningothelial like nodul

TY - JOUR. T1 - Treatment of thrombotic microangiopathy after hematopoietic stem cell transplantation with recombinant human soluble thrombomodulin. AU - Fujiwara, Hideaki. AU - Maeda, Yoshinobu. AU - Sando, Yasuhisa. AU - Nakamura, Makoto. AU - Tani, Katsuma. AU - Ishikawa, Tatsunori. AU - Nishimori, Hisakazu. AU - Matsuoka, Ken Ichi. AU - Fujii, Nobuharu. AU - Kondo, Eisei. AU - Tanimoto, Mitsune. N1 - Publisher Copyright: © 2015 AABB. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.. PY - 2016/4/1. Y1 - 2016/4/1. N2 - BACKGROUND Transplant-associated thrombotic microangiopathy (TA-TMA) after hematopoietic stem cell transplantation (HSCT) remains a severe complication associated with underlying endothelial damage. TMA has a high mortality rate with no definite treatments and effective treatments are needed. STUDY DESIGN AND METHODS The study objective was to retrospectively analyze the outcome of patients receiving recombinant human soluble thrombomodulin (rTM), which has ...

Idiopathic thrombocytopenic purpura. Primary ITP is mediated by platelet autoantibodies that accelerate destruction. Secondary ITP is related to an underlying condition: common culprits include HIV, HCV, SLE and CLL. The clinical presentation is one of insidious mucocutaneous bleeding. CBC reveals an isolated thrombocytopenia with platelet count ,100,000/µL. Primary ITP is a diagnosis of exclusion, made after other potential etiologies have been ruled out. There are no specific associated laboratory findings. Anti-platelet antibodies are neither sensitive nor specific, and are not required for diagnosis.. Hemolytic uremic syndrome/Thrombotic thrombocytopenic purpura. Both HUS and TTP fall in the spectrum of thrombotic microangiopathies, a pathological entity of abnormal arteriolar and capillary vessel walls, leading to microvascular thrombosis and thrombocytopenia with hemolytic anemia. In the case of TTP, this is due to a decrease in ADAMTS13 protease activity, leading to large von Willebrand ...

For thrombotic microangiopathies (TMAs), the diagnosis of atypical hemolytic uremic syndrome (aHUS) is made by ruling out Shiga toxin-producing Escherichia coli (STEC)-associated HUS and ADAMTS13 activity-deficient thrombotic thrombocytopenic purpura (TTP), often using the exclusion criteria for secondary TMAs. Nowadays, assays for ADAMTS13 activity and evaluation for STEC infection can be performed within a few hours. However, a confident diagnosis of aHUS often requires comprehensive gene analysis of the alternative complement activation pathway, which usually takes at least several weeks. However, predisposing genetic abnormalities are only identified in approximately 70% of aHUS. To facilitate the diagnosis of complement-mediated aHUS, we describe a quantitative hemolytic assay using sheep red blood cells (RBCs) and human citrated plasma, spiked with or without a novel inhibitory anti-complement factor H (CFH) monoclonal antibody. Among 45 aHUS patients in Japan, 24% (11/45) had moderate-to-severe (

We have developed an ex vivo test with human endothelial cells from the microcirculation to monitor, at the endothelial level, the activation of the complement induced by serum from patients with thrombotic microangiopathies, such as hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (PTT). This test allowed us to demonstrate that serum from patients that was collected during the acute phase, but not in remission, induced more extensive complement deposits than serum from healthy subjects on unstimulated cells. On stimulated cells, the serum from patients who were in remission also increased C3 and C5b-9 deposits. These data suggest that in HUS and PTT there is uncontrolled activation of the complement at the endothelial level that leads to thrombosis in the microcirculation. This test allows us to monitor disease activity and the efficacy of standard treatment. Furthermore, we used this test to evaluate activity at the endothelial level of potential new complement inhibitor ...

ADAMTS-13 (a disintegrin-like and metalloproteinase with thrombospondin type 1 motif 13) is an enzyme (vWF-cleaving protease or vWF-CP) that specifically cleaves von Willebrand Factor (vWF) multimers, a large protein involved in blood clotting. It is secreted in blood and degrades large vWF multimers. If the activity of ADAMTS-13 is decreased, unusually large vWF multimers may accumulate within blood causing thrombosis due to platelet aggregation, which in turn may lead to TTP (thrombotic thrombocytopenic purpura). Differentiation of TTP from other thrombotic microangiopathies (TMA) is challenging. Read more…. ...

All patients received open-label eculizumab administered intravenously on the following dose schedule: Induction dose - 900 mg per week for four weeks and a dose of 1200 mg one week later; Maintenance dose - 1200 mg every two weeks. Patients who received plasma exchange or infusion during the eculizumab treatment period received a supplemental dose of 600 mg within one hour before plasma infusion or within one hour after the completion of each plasma exchange ...

The primary purpose is to assess the efficacy and safety of eculizumab in pediatric patients with aHUS to control TMA as characterized by thrombocytopenia, hemolysis and renal impairment.

A diagnosis of thrombotic microangiopathy on kidney biopsy in a patient presenting with hypertensive emergency has historically elicited the diagnosis of malignant hypertension-associated thrombotic microangiopathy. Recent studies, however, have raised awareness that a number of these patients may actually represent atypical hemolytic uremic syndrome. To further investigate this premise, we performed next-generation sequencing to interrogate the coding regions of 29 complement and coagulation cascade genes associated with atypical hemolytic uremic syndrome in 100 non-elderly patients presenting with severe hypertension, renal failure and a kidney biopsy showing microangiopathic changes limited to the classic accelerated hypertension-associated lesion of arterial intimal edema (mucoid intimal hyperplasia) in isolation and without accompanying glomerular microthrombi ...

Atypical hemolytic uremic syndrome (aHUS) is frequently associated in humans with loss-of-function mutations in complement-regulating proteins or gain-of-function mutations in complement-activating proteins. Thus, aHUS provides an archetypal complement-mediated disease with which to model new therapeutic strategies and treatments. Herein, we show that, when transferred to mice, an aHUS-associated gain-of-function change (D1115N) to the complement-activation protein C3 results in aHUS. Homozygous C3 p.D1115N (C3KI) mice developed spontaneous chronic thrombotic microangiopathy together with hematuria, thrombocytopenia, elevated creatinine, and evidence of hemolysis. Mice with active disease had reduced plasma C3 with C3 fragment and C9 deposition within the kidney. Therapeutic blockade or genetic deletion of C5, a protein downstream of C3 in the complement cascade, protected homozygous C3KI mice from thrombotic microangiopathy and aHUS. Thus, our data provide in vivo modeling evidence that ...

A growing body of evidence has recently accumulated about the pathogenic role of the complement system in AAV (1). In 2007, Xiao et al. (4) demonstrated how infusion of ANCA antibodies in wild-type mice could induce glomerular lesions typical of pauci-immune NCGN; interestingly, no lesion was observed when ANCA were injected in mice knocked out for C5 or complement factor B, whereas RPGN fully developed in C4-knockout mice; because C5 belongs to the terminal part of the complement cascade and complement factor B belongs to the cAP, while C4 is a key molecule of the classic pathway, these findings clearly showed that cAP plays a central role in experimental AAV (4). In keeping with this, Gou et al. showed that patients with active AAV have serologic signs of activation of the cAP (augmented serum levels of activated complement proteins, such as C3a, C5a, sC5b9, and Bb), which correlated with acute-phase reactants, number of crescents, and severity of kidney histology (9). The same group ...

若限制補體活化的調節蛋白缺陷(ex. Complement H、Complement factor I、CD46等)，會造成補體不正常的活化，造成血管內皮和腎臟細胞的傷害。此狀況可能為先天性，也可能是後天產生(產生自體抗體). ...

The Hemolytic Uremic Syndrome (HUS) is a rare thrombotic microangiopathy (TMA), affecting both children and adults. HUS is characterized by the abnormal occurrence of diffuse thrombosis in the microcirculation resulting in the occurrence of ischemic events affecting especially the kidneys and is associated with hemolytic anemia. One of the major problems encountered in the management of HUS is the absence of reliable marker of treatment response or relapse; conventional hematological markers being too insensitive to judge therapeutic efficacy or identify early relapse. Data from the literature suggest that the endothelial cell is a major target of this syndrome. Our hypothesis is that an initial micro-endothelial activation plays a critical role in the initiation and / or relapse of the disease.The main objective of this study is to define a

ANSWER: C. Shiga toxin-producing E. coli is one of the most common pathogens involved in foodborne disease outbreak linked to raw dairy products. Patients develop hemolytic uremic syndrome characterized by bloody diarrhea, hemolytic anemia, thrombotic microangiopathy and kidney failure.. ...

Horváth, Orsolya and Kállay, Krisztián and Csuka, Dorottya and Mező, Blanka and Sinkovits, György and Kassa, Csaba and Sinkó, János and Prohászka, Zoltán and Kriván, Gergely (2018) Early Increase in Complement Terminal Pathway Activation Marker sC5b-9 Is Predictive for the Development of Thrombotic Microangiopathy after Stem Cell Transplantation. BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 24 (5). pp. 989-996. ISSN 1083-8791 Kállay, Krisztián and Csomor, Judit and Ádám, Emma and Bödör, Csaba and Kassa, Csaba and Simon, Réka and Kovács, Gábor and Péter, György and Ottóffy, Gábor and Bartyik, Katalin and Kiss, Csongor and Masát, Péter and Réti, Marienn and Tóth, Blanka and Kriván, Gergely (2018) Korszakváltás a gyermekkori szerzett csontvelő-elégtelenséggel járó kórképek kezelésében Magyarországon = Change in paradigm in the treatment of pediatric acquired bone marrow failure syndromes in Hungary. Orvosi Hetilap, 159 (42). pp. 1710-1719. ISSN 0030-6002 ...

At just 18-months-old, Roman Fariello was diagnosed with Stage 4 Neuroblastoma.. He fought hard through six rounds of chemotherapy and one round of high dose chemotherapy that killed his bone marrow in preparation for a stem cell transplant.. After each round of chemo, Romans blood and platelet counts would plummet, said Jody, Romans mom. He would need numerous blood and platelet transfusions to replenish his counts.. When he was going through the process of a stem cell transplant, Roman needed even more blood and platelets to help him rebound.. Post transplant, Roman needed an abundant amount of platelets because he came down with a side effect from transplant called Thrombotic Microangiopathy (TMA), said Jody.. He was receiving platelets about every two days.. If Roman did not get the blood and platelets that he needed throughout his entire protocol, he would not be where he is today, Jody said. He is alive and breathing!. Jody says she would love to have met the donors who helped ...

Recombinant full-length human DGKE was expressed by baculovirus in Sf9 insect cells using an N-terminal GST tag. Diacylglycerol kinase epsilon (DAG kinase epsilon) is the only member of class III diacylglycerol kinase family.

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TY - JOUR. T1 - An immunocompetent case of capnocytophaga canimorsus infection complicated by secondary thrombotic microangiopathy and disseminated intravascular coagulation. AU - Tani, Naoki. AU - Nakamura, Keiji. AU - Sumida, Kosuke. AU - Suzuki, Michio. AU - Imaoka, Koichi. AU - Shimono, Nobuyuki. PY - 2019/1/1. Y1 - 2019/1/1. N2 - A 62-year-old woman with no previous history developed a Capnocytophaga canimorsus infection followed by thrombotic microangiopathy (TMA) and disseminated intravascular coagulation (DIC). She was treated with antibiotics and plasma exchange (PE) and recovered. C. canimorsus sepsis sometimes causes not only DIC but also TMA. The mortality of TMA is extremely high, so we should not hesitate to perform PE when a patient shows TMA symptoms.. AB - A 62-year-old woman with no previous history developed a Capnocytophaga canimorsus infection followed by thrombotic microangiopathy (TMA) and disseminated intravascular coagulation (DIC). She was treated with antibiotics and ...

For kidney fans, this review article on atypical hemolytic-uremic syndrome in this months New England Journal of Medicine (subscription required) is a must read. It details recent advances in the genetics of atypical hemolytic-uremic syndrome. What was previously a confusing mess of similar-appearing diseases - hemolytic-uremic syndrome, atypical hemolytic-uremic syndrome, drug-induced hemolytic-uremic syndrome, and thrombotic thrombocytopenic purpura - may finally be understandable ...

Fingerprint Dive into the research topics of Thrombotic microangiopathy caused by severe graft dysfunction after living donor liver transplantation: Report of a case. Together they form a unique fingerprint. ...

Atypical hemolytic uremic syndrome (aHUS) is frequently associated in humans with loss-of-function mutations in complement-regulating proteins or gain-of-function mutations in complement-activating proteins. Thus, aHUS provides an archetypal complement-mediated disease with which to model new therapeutic strategies and treatments. Herein, we show that, when transferred to mice, an aHUS-associated gain-of-function change (D1115N) to the complement-activation protein C3 results in aHUS. Homozygous C3 p.D1115N (C3KI) mice developed spontaneous chronic thrombotic microangiopathy together with hematuria, thrombocytopenia, elevated creatinine, and evidence of hemolysis. Mice with active disease had reduced plasma C3 with C3 fragment and C9 deposition within the kidney. Therapeutic blockade or genetic deletion of C5, a protein downstream of C3 in the complement cascade, protected homozygous C3KI mice from thrombotic microangiopathy and aHUS. Thus, our data provide in vivo modeling evidence that ...

Atypical hemolytic-uremic syndrome (aHUS) is a rare, potentially lethal systemic disorder, capable of affecting both adults and children, causing thrombotic microangiopathy (TMA) that leads to the formation of thrombus within small blood vessels with multiple organ failure. The pathogenesis of the aHUS is part of a sort of chronic and uncontrolled activation of the complement system by genetic mutation of some proteins usually responsible for its self-regulation. Today, the rapid diagnosis of the disease and the timely start of treatment with eculizumab, improve outcomes of renal failure, stroke and heart attack. Fabry disease is a rare tesaurismosis, X linked, due to the deficiency of the lysosomal enzyme alpha-galactosidase A, necessary for the physiological catabolism of glycosphingolipids. Multisystem clinical manifestations lead to a serious degenerative pathology. The diagnostic suspicion based on anamnesis and careful research of the symptoms and then confirmed by the enzymatic dosage of ...

CASE REPORT: A 4-year-old boy presented with nephrotic syndrome, arterial hypertension, and chronic anemia but no signs of hemolysis. Renal biopsy showed TMA with ischemic glomerular collapse, foot process effacement, and tubulointerstitial fibrosis. Elevated serum levels of homocysteine suggested a cobalamin C disorder. This was confirmed by the identification of compound heterozygous mutations in the MMACHC gene. Initial therapy consisted of antihypertensive treatment including angiotensin converting enzyme inhibitor (ACEi) leading to blood pressure control and a significant reduction of proteinuria. After a definite diagnosis of CblC deficiency, hydroxocobalamin was introduced. Thereafter, homocysteine levels decreased, anemia resolved, and a further decline of proteinuria with normalization of serum protein levels was noted. Renal function remained stable ...

POLAINA-RUSILLO, Manuel et al. Renal cortical necrosis secondary to thrombotic microangiopathy in the context of acute promyelocytic leukaemia blast crisis. Nefrología (Madr.) [online]. 2013, vol.33, n.6, pp.845-848. ISSN 1989-2284. https://dx.doi.org/10.3265/Nefrologia.pre2013.Sep.12162.. A 37-year-old patient was transferred to Haematology from the ENT Emergency Department where he had been admitted due to tonsillitis. He displayed anaemia and leukopenia and had agranulocytosis in the study. A day later the patient had blast crisis, and was diagnosed with myeloid acute leukaemia. Due to blast crisis the patient experienced sudden back pain, with oliguria and renal function deterioration followed by anaemia, in the context of haemolysis consistent with thrombotic microangiopathy, and as such, we were consulted. We began treatment with plasmapheresis and on the following day we performed haemodialysis (we carried out a total of 12 sessions of plasmapheresis until haemolysis disappeared). Five ...

Hemolytic Uremic Syndrome (HUS), including life threatening cases, has been reported in patients treated with LUMOXITI and is characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and progressive renal failure. In the combined safety database of HCL patients treated with LUMOXITI, HUS occurred in 7% (9/129) of patients, including Grade 3 in 3% (4/129) and Grade 4 in 0.8% (1/129). Most cases of HUS occurred in the first 9 days (range: 1 to 16) of a treatment cycle, however, cases have also been reported on other days throughout the cycle. The median time to resolution of HUS was 11.5 days (range: 2 to 44). All cases resolved, including those who discontinued LUMOXITI.. Avoid LUMOXITI in patients with prior history of severe thrombotic microangiopathy (TMA) or HUS. Administer prophylactic intravenous fluids before and after LUMOXITI infusions. In Study 1053, patients with a platelet count ≥ 100,000/mm3 received low-dose aspirin on Days 1 through 8 of each 28-day ...

We discuss the case of a patient with PAH of multiple etiologies, and report to the best of our knowledge the first case of APS and factor V deficiency associated with MMM.. The etiology of PAH in this case was not that of emphysema or interstitial lung disease as evidenced by minimal parenchymal involvement on imaging studies. However, negative perfusion lung scan and doppler ultrasound of lower extremities could not exclude the possibility of pulmonary microthrombosis (6,8). Thrombotic microangiopathy has been associated with APS (10,26), and MPD (8,18). In fact, recurrent pulmonary embolism is assumed to be the major cause of PAH in APS (5,10); and, thromboembolism secondary to thrombophilia (in MMM) is well described (7,8,18).. Although titers of aPL were not available in our patient, the diagnosis of APS was satisfied by other major criteria. These major criteria were past episodes of vascular thrombosis (microangiopathic hemolytic anemia, myocardial infarction, and stroke), laboratory ...

Eculizumab is a monoclonal antibody that prevents complement activation. It has been found to be an effective treatment for atypical hemolytic-uremic syndrome (aHUS). This retrospective study is the largest collection of previously published and unpublished cases to date. Eculizumab was effective at both preventing and treating recurrence of aHUS.. ...

Recurrent haemolytic uraemic syndrome (HUS) is a genetic form of thrombotic microangiopathy that is mostly associated with low activity of complement factor H. The disorder usually develops in families, leads to end stage renal disease, and invariably recurs after kidney transplantation. We did a si …

Inherited kidney diseases represent the fifth most common cause of end-stage renal disease after diabetes, hypertension, glomerulonephritis, and pyelonephritis. Nearly all children and at least 10% of adults who receive renal-replacement therapy (RRT) have an inherited renal disease. In most cases, inherited kidney diseases are severe diseases with insufficient knowledge and insufficient treatment options available.. Our research activity is currently focused on thrombotic microangiopathy (TMA), which is a severe glomerulopathy, and on autosomal-dominant tubulointerstitial kidney disease - UMOD (ADTKD-UMOD).. TMA is a morphological symptom occurring in numerous glomerulopathies like in hemolytic uremic syndrome (HUS), as side effects of drugs or in preeclampsia. Common pathogenic mechanism of TMA irrespective of the cause is a primary endothelial injury. In the Munich ENU mutagenesis project, a mutant mouse line with glomerular specific TMA was generated and is currently investigated to evaluate ...

SARS-CoV-2 is hard to detect in the brain, compared with other organs. Tests like real time-polymerase chain reaction (RT-PCR) often fail to detect the virus in the brain(7), possibly because the ACE2 receptor, that the virus uses to entry, is not expressed enough in brain cells(7). This is the reason why many researchers consider that the most probable explanation of neurological complications in patients with COVID-19 is the immunologic response of the human body to the coronavirus infection(7). Other hypothesis that should not be ignored is related to the medications used for the treatment of COVID-19: tocilizumab and chloroquine may frequently induce headache as a side effect. Also, case reports about multifocal cerebral thrombotic microangiopathy and demyelinating disorders associated to tocilizumab treatment have been published(8),(9). Seizures, peripheral neuropathy, dizziness, paresthesia and hypoesthesia may be side effects of chloroquine and hydroxychloroquine(10). Hypoxia may further ...

We read with great interest the article by Nicholson et al1 that described 4 patients with coronavirus disease 2019 (COVID-19) presenting with parenchymal hemorrhages during their critical care admission. We agree with the authors proposal that a thrombotic microangiopathy may cause hemorrhagic neurologic manifestations in COVID-19. This is supported by imaging features of coagulopathy and endothelial dysfunction in multiple organ systems observed in such patients. However, there remains a degree of uncertainty with regard to potentially shared underlying pathophysiologic mechanisms in the critically ill COVID-19 cohort.. Herein, we present 2 male patients with COVID-19 (48 and 65 years of age) with CT findings of isolated intraventricular hemorrhage (IIVH) during their prolonged critical care admission. Both patients were treated for COVID-19-related respiratory failure, requiring mechanical ventilation, and were placed on Continuous Veno-Venous Hemofiltration (CVVH; ...

We describe the largest cohort of patients with DGKE nephropathy. The combined analysis of the ten newly identified cases with all previously published patients provides convincing evidence that this condition is a genetically and phenotypically distinct disease entity. However, the larger sample size has helped uncover findings that deviate from that of the original reports.. The predominant phenotype of DGKE nephropathy is early-onset relapsing HUS with chronic proteinuria and long-term progression to CKD. On the basis of the original report by Lemaire et al.5 and the reports that followed,7-10 DGKE-HUS appeared to be a disease with onset during early infancy. Aggregated data analysis show that indeed most patients with DGKE-HUS (86%) are diagnosed within the first year of life. However, there are now five patients diagnosed between the ages of 1 and 4 years. On that basis, it would be helpful to screen for DGKE mutations in all patients with aHUS, irrespective of age at diagnosis.. Chronic ...

In 9 of 10 patients with diarrhea and in 4 of 6 patients with steatorrhea carbohydrate metabolism poorly monitored throughout the period of diabetes . In 8 out of 10 patients with diabetic retinopathy diarrhea was observed, and 4 patients - neuropathy. In 6 of the 10 diabetic patients with ...

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کنترل زمان گل‌دهی یکی از مهم‌ترین اجزای اثر متقابل بین گیاهان و محیط رشد آن‌ها می‌باشد که نه تنها برای میزان محصول تولیدی بلکه برای کیفیت دانه برنج نیز عامل مهمی به‌-حساب می‌آید. در این تحقیق مطالعات فنوتیپی و مولکولی بر روی 45 رقم برنج محلی و اصلاح شده انجام شد. ابتدا چندشکلی ژن‌های Ehd1 و Ehd3 در بین ارقام و سپس ارتباط این دو ژن با زمان خوشه‌دهی مورد بررسی قرار گرفت. نتایج مطالعات فنوتیپی حاکی از وجود تنوع بیشتر در ارقام محلی نسبت به ارقام اصلاح شده بود. ارقام محلی به‌طور متوسط 8 روز زودرس‌تر از ارقام اصلاح شده بودند و تفاوت زمان خوشه‌دهی آن‌ها معنی‌دار