Hemolytic And Uremic Syndrome Research Articles

Predictors of acute ischemic cerebral lesions in immune-mediated thrombotic thrombocytopenic purpura and hemolytic uremic syndrome.

The immune form of thrombotic thrombocytopenic purpura (iTTP) and the hemolytic and uremic syndrome (HUS) are two major forms of thrombotic microangiopathy (TMA). Their treatment has been recently greatly improved. In this new era, both the prevalence and predictors of cerebral lesions occurring during the acute phase of these severe conditions remain poorly known. The prevalence and predictors of cerebral lesions appearing during the acute phase of iTTP and Shiga toxin-producing Escherichia coli-HUS or atypical HUS were evaluated in a prospective multicenter study. Univariate analysis was performed to report the main differences between patients with iTTP and those with HUS or between patients with acute cerebral lesions and the others. Multivariable logistic regression analysis was used to identify the potential predictors of these lesions. Among 73 TMA cases (mean age 46.9 ± 16years (range 21-87years) with iTTP (n = 57) or HUS (n = 16), one-third presented with acute ischemic cerebral lesions on magnetic resonance imagery (MRI); two individuals also had hemorrhagic lesions. One in ten patients had acute ischemic lesions without any neurological symptom. The neurological manifestations did not differ between iTTP and HUS. In multivariable analysis, three factors predicted the occurrence of acute ischemic lesions on cerebral MRI: (1) the presence of old infarcts on cerebral MRI, (2) the level of blood pulse pressure, (3) the diagnosis of iTTP. At the acute phase of iTTP or HUS, both symptomatic and covert ischemic lesions are detected in one third of cases on MRI. Diagnosis of iTTP and the presence of old infarcts on MRI are associated with the occurrence of such acute lesions as well as increased blood pulse pressure, that may represent a potential target to further improve the therapeutic management of these conditions.

Urine Protein/Creatinine Ratio in Thrombotic Microangiopathies: A Simple Test to Facilitate Thrombotic Thrombocytopenic Purpura and Hemolytic and Uremic Syndrome Diagnosis.

Background: Early diagnosis of thrombotic thrombocytopenic purpura (TTP) versus hemolytic and uremic syndrome (HUS) is critical for the prompt initiation of specific therapies. Objective: To evaluate the diagnostic performance of the proteinuria/creatininuria ratio (PU/CU) for TTP versus HUS. Patients/Methods: In a retrospective study, in association with the “French Score” (FS) (platelets < 30 G/L and serum creatinine level < 200 µmol/L), we assessed PU/CU for the diagnosis of TTP in patients above the age of 15 with thrombotic microangiopathy (TMA). Patients with a history of kidney disease or with on-going cancer, allograft or pregnancy were excluded from the analysis. Results: Between February 2011 and April 2019, we identified 124 TMA. Fifty-six TMA patients for whom PU/CU were available, including 35 TTP and 21 HUS cases, were considered. Using receiver–operating characteristic curves (ROC), those with a threshold of 1.5 g/g for the PU/CU had a 77% sensitivity (95% CI (63, 94)) and a 90% specificity (95% CI (71, 100)) for TTP diagnosis compared with those having an 80% sensitivity (95% CI (66, 92)) and a 90% specificity (95% CI (76, 100) with a FS of 2. In comparison, a composite score, defined as a FS of 2 or a PU/CU ≤ 1.5 g/g, improved sensitivity to 99.6% (95% CI (93, 100)) for TTP diagnosis and enabled us to reclassify seven false-negative TTP patients. Conclusions: The addition of urinary PU/CU upon admission of patients with TMA is a fast and readily available test that can aid in the differential diagnosis of TTP versus HUS alongside traditional scoring.

Shiga Toxins as Antitumor Tools.

Shiga toxins (Stxs), also known as Shiga-like toxins (SLT) or verotoxins (VT), constitute a family of structurally and functionally related cytotoxic proteins produced by the enteric pathogens Shigella dysenteriae type 1 and Stx-producing Escherichia coli (STEC). Infection with these bacteria causes bloody diarrhea and other pathological manifestations that can lead to HUS (hemolytic and uremic syndrome). At the cellular level, Stxs bind to the cellular receptor Gb3 and inhibit protein synthesis by removing an adenine from the 28S rRNA. This triggers multiple cellular signaling pathways, including the ribotoxic stress response (RSR), unfolded protein response (UPR), autophagy and apoptosis. Stxs cause several pathologies of major public health concern, but their specific targeting of host cells and efficient delivery to the cytosol could potentially be exploited for biomedical purposes. Moreover, high levels of expression have been reported for the Stxs receptor, Gb3/CD77, in Burkitt’s lymphoma (BL) cells and on various types of solid tumors. These properties have led to many attempts to develop Stxs as tools for biomedical applications, such as cancer treatment or imaging, and several engineered Stxs are currently being tested. We provide here an overview of these studies.

Shiga Toxin-Associated Hemolytic Uremic Syndrome: A Narrative Review.

The severity of human infection by one of the many Shiga toxin-producing Escherichia coli (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.

SHU et syndromes de microangiopathie thrombotique apparentés : épidémiologie, physiopathologie et tableaux cliniques

Thrombotic microangiopathies (TMA) represent an eclectic group of conditions, which share hemolytic anemia and thrombocytopenia as a common defining basis. Remarkable breakthroughs in the physiopathological setting have allowed for a thorough recomposition of the disparate syndromes, which form the constellation of TMA. In this view, clinicians now discriminate thrombocytopenic thrombotic purpura (TTP) defined by a severe deficiency in ADAMTS13, which is rarely associated with a severe renal involvement and the hemolytic and uremic syndrome (HUS) in which renal impairment is the most prominent clinical feature. HUS can result from toxins stemming from bacterial infections of the digestive tract, alternate complement pathway abnormalities, metabolic or coagulation disorders or, lastly, drug and various toxic compounds. The diverse forms of HUS reflect the insights gained in the understanding of the pathophysiological mechanisms underpinning TMA. In this first part, a broad overview of the epidemiological, physiopathological and clinical aspects of HUS and related TMA syndromes is presented.

PTT ou SHU atypique ? À propos d’un cas révélant une maladie de Berger

Thrombotic microangiopathy includes a set of conditions characterized by the association of mechanical hemolytic anemia, thrombocytopenia and organ failure which accurate diagnosis is sometimes difficult. We report the case of a patient who presented a thrombotic microangiopathy (TMA) due to an atypical hemolytic and uremic syndrome (HUS) associated with an immunoglobulin A (IgA) nephropathy with a favorable outcome under corticosteroid.

Syndrome hémolytique et urémique atypique et déficit en ADAMTS 13

Hemolytic and uremic syndrome (HUS) is a classical form of thrombotic microangiopathies characterized by the association of hemolytic anemia with schizocytes, thrombocytopenia, and acute renal failure. Two forms of HUS have been described: the typical form that occurs after ingestion of a strain of bacteria, usually Escherichia coli types, which expresses verotoxin (also called shiga-like toxin), typically followed by bloody diarrhea, and atypical HUS, which is rare during childhood and can also be revealed by bloody diarrhea. We report a case of a 25-month-old infant who presented with hematuria and pallor after an episode of diarrhea. Biological tests revealed anemia, thrombocytopenia, and renal failure. The diagnosis of typical HUS was made, but the causal microorganism was not identified. Progression was favorable within 5 days of plasma transfusions. Two months later, the patient presented with the same symptoms and neurological impairment without any diarrhea. Von Willebrand factor-cleaving protease activity (ADAMTS 13) was low. Therefore, the diagnosis of atypical HUS by severe deficiency of ADAMTS 13 was suggested. The treatment was based on plasma transfusions resulting in remission. Atypical HUS associated with severe ADAMTS 13 deficiency rarely occurs in childhood. The prognosis, usually threatening, has been completely transformed thanks to a better understanding of the pathogenesis and to therapeutic progress.

Response to "Predictors of survival in thrombotic thrombocytopenic purpura" Haematologica 2013;98(5):e58

The French TMA Reference Center recently described in this Journal a predictive model for death in patients with idiopathic acquired thrombotic thrombocytopenic purpura (TTP).1 In their paper, Chaturvedi and Bhatia claimed that our model may not be applicable to the majority of patients with TTP because we only considered patients with severe ADAMTS13 deficiency.2 These authors suggest that all patients with an apparent diagnosis of idiopathic or secondary TTP should have been analyzed, irrespective of ADAMTS13 activity. We disagree with this view. Indeed, the association of a microangiopathic hemolytic anemia with peripheral thrombocytopenia and organ failure are not specific to TTP. Rather, these features define a heterogeneous group of disorders that have overlapping clinical manifestations and are grouped under the broader term of thrombotic microangiopathy (TMA), which includes not only TTP, but also other distinct diseases, such as the hemolytic and uremic syndrome (HUS), and TMA associated with various conditions (i.e. cancer, allogeneic hematopoietic stem cell transplantation, chemotherapy, human immunodeficiency virus infection, etc.). All these diseases have now been clearly characterized as having specific features in terms of pathophysiology, prognosis and treatment, and, therefore, cannot be considered as a single disease. TMA syndromes are currently classified on the basis of their pathophysiological mechanisms.3,4 This new molecular classification is more adapted to the increasing use of targeted therapies, such as B-cell depleting therapies (rituximab; Mabthera®, Roche) for acquired TTP and complement blockers (eculizumab; Soliris®, Alexion) for atypical HUS.5–7 Moreover, Chaturvedi and Bhatia wrongly consider TTP and TTP-HUS to be the same entity. The term TTP-HUS was used by some authors to group TTP and HUS together in their studies, due to the absence of explicit criteria to distinguish between the diseases on the basis of their clinical presentation and standard biology.8 However, TTP-HUS includes distinct diseases, as reflected by the variable frequency (33–75%) of severe ADAMTS13 deficiency in this group of patients.8–10 Conversely, 75–100% of patients diagnosed with TTP on the basis of mild renal involvement display severe ADAMTS13 deficiency, whereas most patients with severe renal failure, and considered, therefore, as having features of HUS, have detectable ADAMTS13 activity.9,11 Likewise, the distinction of idiopathic TMA on the basis of ADAMTS13 activity (severe deficiency and detectable enzyme activity) closely matches the diagnoses of TTP and HUS, respectively.10,12–15 Clearly, TMA can no longer be considered as a single disease in the era of molecular diagnosis and targeted therapies. Accordingly, the aim of our work was to identify original prognostic factors in a specific and homogeneous subset of patients with TMA (i.e. acquired idiopathic TTP) who were identified accurately on the basis of severe ADAMTS13 deficiency and for whom targeted therapies are available.6 In conclusion, the comment by Chaturvedi and Bhatia revives the old issue of the crucial need for the use of a rigorous terminology in the field of TMA that is acknowledged by all national collaborative groups.12 This requires international efforts to define consensual diagnostic criteria, treatment modalities and definitions of treatment response to allow a common language to be developed and international studies and fruitful meta-analyses to be conducted.

Syndrome hémolytique et urémique àEscherichia coli : quels enseignements tirer après l’épidémie européenne de 2011 ?

Hemolytic and uremic syndrome (HUS) is the most feared complication of infections with enterohemorrhagic Escherichia coli. During summer 2011, Europe was the scene of a large outbreak of shiga-toxin producing E. coli gastroenteritis, occasioning more than 800 cases of HUS, highlighting this public health problem. Last years, many advances have occurred, on the physiopathology, microbiology or therapeutics. We review here these different aspects, from molecular identification of the German bacteria, to the use of targeted therapies as eculizumab in severe forms, or even the major role of complement activation in the physiopathology of HUS.

Quantitative risk assessment for Escherichia coli O157:H7 in frozen ground beef patties consumed by young children in French households

A quantitative risk assessment for Escherichia coli O157:H7 in frozen ground beef patties consumed by children under 10 years of age in French households was conducted by a national study group describing an outbreak which occurred in France in 2005. Our exposure assessment model incorporates results from French surveys on consumption frequency of ground beef patties, serving size and consumption preference, microbial destruction experiments and microbial counts on patties sampled from the industrial batch which were responsible for the outbreak. Two different exposure models were proposed, respectively for children under the age of 5 and for children between 5 and 10 years. For each of these two age groups, a single-hit dose-response model was proposed to describe the probability of hemolytic and uremic syndrome (HUS) as a function of the ingested dose. For each group, the single parameter of this model was estimated by Bayesian inference, using the results of the exposure assessment and the epidemiological data collected during the outbreak. Results show that children under 5 years of age are roughly 5 times more susceptible to the pathogen than children over 5 years. Exposure and dose-response models were used in a scenario analysis in order to validate the use of the model and to propose appropriate guidelines in order to prevent new outbreaks. The impact of the cooking preference was evaluated, showing that only a well-done cooking notably reduces the HUS risk, without annulling it. For each age group, a relation between the mean individual HUS risk per serving and the contamination level in a ground beef batch was proposed, as a tool to help French risk managers.

Syndrome hémolytique et urémique chez l’enfant

Hemolytic and uremic syndrome (HUS) is characterized by the association of hemolytic anemia with sckizocytes, thrombopenia and renal involvement secondary to thrombotic microangiopathy. The typical form is the most frequent in children occurring after an episode of diarrhea caused by Escherichia coli. Other microorganisms may be responsible for HUS such as Shigella dysenteriae or streptococcus pneumoniae. Acute renal failure is reversible in most cases, but long-term renal sequelae are seen in one third of patients when the anuria at onset of disease has lasted more than one week. Treatment of typical HUS is only supportive (blood transfusion, treatment of acute renal failure). Atypical HUS is less frequent but of poorer prognosis. Atypical HUS may be associated with mutations in complement regulator genes, von Willebrand factor-cleaving protease deficiency, congenital intracellular defects of vitamin B12 metabolism or may be of unknown origin. Familial forms are frequent. Recurrence of HUS following renal transplantation is exceptional in the typical form but is frequent in atypical HUS.

Thrombotic Microangiopathy in a Child With Acute Pancreatitis

Thrombotic Microangiopathy in a Child With Acute Pancreatitis

Syndrome hémolytique et urémique et ischémie mésentérique aiguë lors d’un traitement par interféron alpha-2b pour une maladie de Kaposi associée au VIH

Interferon alpha is approved for the treatment of Kaposi's sarcoma in HIV infected patients. Hemolytic and uremic syndrome (HUS) is a rare side-effect of interferon alpha and has been reported primarily in chronic myelogenous leukemia. A 44-year-old HIV-infected woman from Cameroon was admitted for treatment of cutaneous Kaposi's sarcoma. Two days later, she presented severe HUS. Abdominal pains subsequently revealed non-occlusive mesenteric ischemia. The patient rapidly improved after interferon withdrawal. To our knowledge this is the first case of HUS induced by interferon alpha given for Kaposi's sarcoma. Further, no cases of acute mesenteric ischemia have been reported with interferon alpha. It is possible that the condition may have been induced or aggravated by HUS or a low infusion rate. Interferon can exert vascular toxicity on both the mesenteric vessels and the renal vessels in a setting of microangiopathy.

Syndrome hémolytique et urémique chez l'enfant

Hemolytic and uremic syndrome (HUS) is characterized by the association of hemolytic anemia with sckizocytes, thrombopenia and renal involvement secondary to thrombotic microangiopathy. The typical form is the most frequent in children occurring after an episode of diarrhea caused by Escherichia coli. Other microorganisms may be responsible for HUS such as Shigella dysenteriae or streptococcus pneumoniae. Acute renal failure is reversible in most cases, but long-term renal sequelae are seen in one third of patients when the anuria at onset of disease has lasted more than one week. Treatment of typical HUS is only supportive (blood transfusion, treatment of acute renal failure). Atypical HUS is less frequent but of poorer prognosis. Atypical HUS may be associated with mutations in complement regulator genes, von Willebrand factor-cleaving protease deficiency, congenital intracellular defects of vitamin B12 metabolism or may be of unknown origin. Familial forms are frequent. Recurrence of HUS following renal transplantation is exceptional in the typical form but is frequent in atypical HUS.