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Clinical Journal of the American... Feb 2018Thrombotic microangiopathy can manifest in a diverse range of diseases and is characterized by thrombocytopenia, microangiopathic hemolytic anemia, and organ injury,... (Review)
Review
Thrombotic microangiopathy can manifest in a diverse range of diseases and is characterized by thrombocytopenia, microangiopathic hemolytic anemia, and organ injury, including AKI. It can be associated with significant morbidity and mortality, but a systematic approach to investigation and prompt initiation of supportive management and, in some cases, effective specific treatment can result in good outcomes. This review considers the classification, pathology, epidemiology, characteristics, and pathogenesis of the thrombotic microangiopathies, and outlines a pragmatic approach to diagnosis and management.
Topics: Acute Kidney Injury; Animals; Complement Inactivating Agents; Disease Progression; Hemolytic-Uremic Syndrome; Humans; Plasma Exchange; Prognosis; Purpura, Thrombocytopenic; Risk Assessment; Risk Factors
PubMed: 29042465
DOI: 10.2215/CJN.00620117 -
Toxins Dec 2022Shiga toxin-producing (STEC)-associated hemolytic uremic syndrome (STEC-HUS) is a clinical syndrome involving hemolytic anemia (with fragmented red blood cells), low... (Review)
Review
Shiga toxin-producing (STEC)-associated hemolytic uremic syndrome (STEC-HUS) is a clinical syndrome involving hemolytic anemia (with fragmented red blood cells), low levels of platelets in the blood (thrombocytopenia), and acute kidney injury (AKI). It is the major infectious cause of AKI in children. In severe cases, neurological complications and even death may occur. Treating STEC-HUS is challenging, as patients often already have organ injuries when they seek medical treatment. Early diagnosis is of great significance for improving prognosis and reducing mortality and sequelae. In this review, we first briefly summarize the diagnostics for STEC-HUS, including history taking, clinical manifestations, fecal and serological detection methods for STEC, and complement activation monitoring. We also summarize preventive and therapeutic strategies for STEC-HUS, such as vaccines, volume expansion, renal replacement therapy (RRT), antibiotics, plasma exchange, antibodies and inhibitors that interfere with receptor binding, and the intracellular trafficking of the Shiga toxin.
Topics: Child; Humans; Shiga-Toxigenic Escherichia coli; Escherichia coli Infections; Hemolytic-Uremic Syndrome; Anti-Bacterial Agents; Acute Kidney Injury
PubMed: 36668830
DOI: 10.3390/toxins15010010 -
F1000Research 2019The thrombotic microangiopathies (TMAs) are a group of diseases characterised by microangiopathic haemolysis, thrombocytopenia, and thrombus formation leading to tissue... (Review)
Review
The thrombotic microangiopathies (TMAs) are a group of diseases characterised by microangiopathic haemolysis, thrombocytopenia, and thrombus formation leading to tissue injury. Traditionally, TMAs have been classified as either thrombotic thrombocytopenic purpura (TTP) or haemolytic uremic syndrome (HUS) based on the clinical presentation, with neurological involvement predominating in the former and acute kidney injury in the latter. However, as our understanding of the pathogenesis of these conditions has increased, it has become clear that this is an over-simplification; there is significant overlap in the clinical presentation of TTP and HUS, there are different forms of HUS, and TMAs can occur in other, diverse clinical scenarios. This review will discuss recent developments in the diagnosis of HUS, focusing on the different forms of HUS and how to diagnose and manage these potentially life-threatening diseases.
Topics: Acute Kidney Injury; Hemolysis; Hemolytic-Uremic Syndrome; Humans; Purpura, Thrombotic Thrombocytopenic; Thrombotic Microangiopathies
PubMed: 31598213
DOI: 10.12688/f1000research.19957.1 -
Pediatric Nephrology (Berlin, Germany) Sep 2022The syndrome of thrombotic microangiopathy (TMA) is a clinical-pathological entity characterized by microangiopathic hemolytic anemia, thrombocytopenia, and end organ... (Review)
Review
The syndrome of thrombotic microangiopathy (TMA) is a clinical-pathological entity characterized by microangiopathic hemolytic anemia, thrombocytopenia, and end organ involvement. It comprises a spectrum of underlying etiologies that may differ in children and adults. In children, apart from ruling out shigatoxin-associated hemolytic uremic syndrome (HUS) and other infection-associated TMA like Streptococcus pneumoniae-HUS, rare inherited causes including complement-associated HUS, cobalamin defects, and mutations in diacylglycerol kinase epsilon gene must be investigated. TMA should also be considered in the setting of solid organ or hematopoietic stem cell transplantation. In this review, acquired and inherited causes of TMA are described with a focus on particularities of the main causes of TMA in children. A pragmatic approach that may help the clinician tailor evaluation and management is provided. The described approach will allow for early initiation of treatment while waiting for the definitive diagnosis of the underlying TMA.
Topics: Child; Complement System Proteins; Hematopoietic Stem Cell Transplantation; Hemolytic-Uremic Syndrome; Humans; Purpura, Thrombotic Thrombocytopenic; Thrombotic Microangiopathies
PubMed: 35041041
DOI: 10.1007/s00467-021-05370-8 -
Toxins Jan 2020The severity of human infection by one of the many Shiga toxin-producing (STEC) is determined by a number of factors: the bacterial genome, the capacity of human... (Review)
Review
The severity of human infection by one of the many Shiga toxin-producing (STEC) is determined by a number of factors: the bacterial genome, the capacity of human societies to prevent foodborne epidemics, the medical condition of infected patients (in particular their hydration status, often compromised by severe diarrhea), and by our capacity to devise new therapeutic approaches, most specifically to combat the bacterial virulence factors, as opposed to our current strategies that essentially aim to palliate organ deficiencies. The last major outbreak in 2011 in Germany, which killed more than 50 people in Europe, was evidence that an effective treatment was still lacking. Herein, we review the current knowledge of STEC virulence, how societies organize the prevention of human disease, and how physicians treat (and, hopefully, will treat) its potentially fatal complications. In particular, we focus on STEC-induced hemolytic and uremic syndrome (HUS), where the intrusion of toxins inside endothelial cells results in massive cell death, activation of the coagulation within capillaries, and eventually organ failure.
Topics: Animals; Bacterial Zoonoses; Escherichia coli Infections; Hemolytic-Uremic Syndrome; Humans; Shiga Toxin; Shiga-Toxigenic Escherichia coli; Virulence
PubMed: 31973203
DOI: 10.3390/toxins12020067 -
Journal of the Formosan Medical... May 2023Atypical hemolytic uremic syndrome (aHUS), characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury, is a rare but life-threatening...
Atypical hemolytic uremic syndrome (aHUS), characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury, is a rare but life-threatening systemic disorder caused by the dysregulation of the complement pathway. Current advances in molecular analysis and pathogenesis have facilitated the establishment of diagnosis and development of effective complement blockade. Based on this recent consensus, we provide suggestions regarding the diagnosis and management of aHUS in Taiwan. The diagnosis of aHUS is made by the presence of TMA with normal ADAMTS13 activity without known secondary causes. Although only 60% of patients with aHUS have mutations in genes involving the compliment and coagulation systems, molecular analysis is suggestive for helping establish diagnosis, clarifying the underlying pathophysiology, guiding the treatment decision-making, predicting the prognosis, and deciding renal transplantation. Complement blockade, anti-C5 monoclonal antibody, is the first-line therapy for patients with aHUS. Plasma therapy should be considered for removing autoantibody in patients with atypical HUS caused by anti-CFH or complement inhibitor is unavailable.
Topics: Humans; Atypical Hemolytic Uremic Syndrome; Taiwan; Consensus; Complement System Proteins; Prognosis
PubMed: 36323601
DOI: 10.1016/j.jfma.2022.10.006 -
Canadian Medical Association Journal Dec 1977
Topics: Child, Preschool; Diagnosis, Differential; Hemolytic-Uremic Syndrome; Humans; Hypertension, Malignant; Prognosis; Purpura, Thrombocytopenic
PubMed: 562706
DOI: No ID Found -
Orphanet Journal of Rare Diseases Jun 2022Patients with Hemolytic Uremic Syndrome (HUS) face late diagnosis and lack of appropriate treatment because of a lack of knowledge and experience in this field. A...
BACKGROUND
Patients with Hemolytic Uremic Syndrome (HUS) face late diagnosis and lack of appropriate treatment because of a lack of knowledge and experience in this field. A prerequisite for such knowledge is the development of research infrastructures such as a registry system. Therefore, this study aimed to develop and describe the HUS registry in accordance with the Iranian health system and implement its software system.
METHODS
We first interviewed 10 pediatric nephrologists and after analyzing the interviews, we identified the features and requirements and the data related to HUS. Then, during two rounds of the Delphi technique (the first round with 23 participants and the second round with 18 participants), the model of this registry was finalized based on the agreement of at least 75% of specialists. At the next step, based on the agreed requirements, IRI.HUS.Reg (Iranian Hemolytic Uremic Syndrome Registry) software was developed and implemented in a pediatric hospital.
RESULTS
We classified 369 meaning units of interviews in 41 codes and 7 final themes including purposes of the registry (10 codes), inclusion criteria (7 codes), data collection method (4 codes), data quality control (6 codes), data sources (4 codes), data analysis (3 codes) and software features (7 codes). These 7 feature groups (67 subgroups) and 12 data classes (138 data elements) include demographic data, referrals, examinations, clinical signs, causes, laboratory tests, medical histories, paraclinical measures, treatments, outcomes, patient's status at discharge, and follow-up data were reviewed by the Delphi panelists, and finally, 64 features and 131 data elements were accepted by at least 78% agreement. Then, we developed and implemented a registry software system in a hospital.
CONCLUSION
We implemented IRI.HUS.Reg based on related features, 12 data classes agreed by specialists, literature review, and comparison with other existing registries. Therefore, the data collected in this registry can be compared with other data from existing registries in other countries.
Topics: Hemolytic-Uremic Syndrome; Humans; Iran; Registries
PubMed: 35710568
DOI: 10.1186/s13023-022-02376-9 -
Clinical Journal of the American... Aug 2017Pregnancy is associated with various forms of thrombotic microangiopathy, including hemolytic uremic syndrome. A previous small French study suggested that...
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.
RESULTS
Eighty-seven patients with pregnancy-associated hemolytic uremic syndrome were included. Hemolytic uremic syndrome occurred mainly during the first pregnancy (58%) and in the postpartum period (76%). At diagnosis, 56 (71%) patients required dialysis. Fifty-six (78%) patients underwent plasma exchanges, 21 (41%) received plasma infusions, and four (5%) received eculizumab. During follow-up (mean duration of 7.2 years), 41 (53%) patients reached ESRD, 15 (19%) had CKD, and 18 (28%) patients experienced hemolytic uremic syndrome relapse. Twenty-four patients (27%) received a kidney transplant and a recurrence of hemolytic uremic syndrome occurred in 13 (54%) patients. Variants in complement genes were detected in 49 (56%) patients, mainly in the (30%) and genes (9%).
CONCLUSIONS
Pregnancy-associated hemolytic uremic syndrome and atypical hemolytic uremic syndrome nonrelated to pregnancy have the same severity at onset and during follow-up and the same frequency of complement gene variants.
Topics: Adolescent; Adult; Antibodies, Monoclonal, Humanized; Complement Activation; Complement Factor H; Complement Factor I; Complement Inactivating Agents; Disease Progression; Europe; Female; Genetic Predisposition to Disease; Genetic Variation; Hemolytic-Uremic Syndrome; Humans; Kidney Failure, Chronic; Middle Aged; Phenotype; Plasma Exchange; Postpartum Period; Pregnancy; Pregnancy Complications; Recurrence; Renal Dialysis; Renal Insufficiency, Chronic; Retrospective Studies; Time Factors; Treatment Outcome; Young Adult
PubMed: 28596415
DOI: 10.2215/CJN.00280117 -
Current Opinion in Pediatrics Apr 2013Complement mediated hemolytic uremic syndrome (aHUS) accounts for a significant proportion of non-shiga toxin HUS. The purpose of this review is to outline the... (Review)
Review
PURPOSE OF REVIEW
Complement mediated hemolytic uremic syndrome (aHUS) accounts for a significant proportion of non-shiga toxin HUS. The purpose of this review is to outline the pathophysiology, clinical features and therapeutic options for aHUS.
RECENT FINDINGS
In the last decade, strides have been made in identifying several new disease-causing mutations in complement-regulating proteins.
SUMMARY
Complement mediated HUS (aHUS) has a worse prognosis compared with shiga toxin mediated HUS, often resulting in end stage renal disease. Early identification of aHUS is crucial so that plasma therapy can be initiated. After renal transplantation, there is very high risk of disease recurrence and graft loss. Eculizumab and combined liver-kidney transplantation offer promise for improved prognosis.
Topics: Atypical Hemolytic Uremic Syndrome; Complement Activation; Complement System Proteins; Hemolytic-Uremic Syndrome; Humans; Kidney Failure, Chronic; Kidney Transplantation; Plasma Exchange; Prognosis; Recurrence
PubMed: 23399570
DOI: 10.1097/MOP.0b013e32835df48a