Hemolytic uremic syndrome （HUS） is a rare disease. In this work the authors review the recent findings on HUS, considering the different etiologic and patho-genetic classifications. New findings in genetics and, in ...Hemolytic uremic syndrome （HUS） is a rare disease. In this work the authors review the recent findings on HUS, considering the different etiologic and patho-genetic classifications. New findings in genetics and, in particular, mutations of genes that encode the complement-regulatory proteins have improved our understanding of atypical HUS. Similarly, the comple-ment proteins are clearly involved in all types of thrombotic microangiopathy： typical HUS, atypical HUS and thrombotic thrombocytopenic purpura （TTP）. Fur-thermore, several secondary HUS appear to be related to abnormalities in complement genes in predisposed patients. The authors highlight the therapeutic as-pects of this rare disease, examining both “traditional therapy” （including plasma therapy, kidney and kidney-liver transplantation） and “new therapies”. The latter include anti-Shiga-toxin antibodies and anti-C5 mono-clonal antibody “eculizumab”. Eculizumab has been recently launched for the treatment of the atypical HUS, but it appears to be effective in the treatment of typical HUS and in TTP. Future therapies are in phases Ⅰ and Ⅱ. They include anti-C5 antibodies, which are more purifed, less immunogenic and absorbed orally and, anti-C3 antibodies, which are more powerful, but potentially less safe. Additionally, infusions of recombinant complement-regulatory proteins are a potential future therapy.展开更多
BACKGROUND Thrombocytopenia associated with acute kidney injury is a challenging disorder. Thrombotic microangiopathy (TMA) is a potentially life- or organ-threatening syndrome that can be induced by several disorders...BACKGROUND Thrombocytopenia associated with acute kidney injury is a challenging disorder. Thrombotic microangiopathy (TMA) is a potentially life- or organ-threatening syndrome that can be induced by several disorders or medical interventions. There is overlap between the clinical presentation and pathophysiology of thrombotic thrombocytopenia purpura and hemolytic uremic syndrome (HUS), and to a lesser extent, disseminated intravascular coagulation (DIC). We describe a case to illustrate the potential diagnostic difficulty, especially at initial presentation. CASE SUMMARY We reported a case of a 44-year-old woman that presented with diarrhea, thrombocytopenia, schistocytes, elevated serum lactate dehydrogenase (LDH) level and acute kidney injury. While the clinical presentation resembled that of Shiga toxin–induced HUS, the disease course was more consistent with gastrointestinal infection-related DIC. To aid in the accurate diagnosis of TMA and other associated disorders, we have undertaken a review and provided a clear interpretation of some typical biomarkers including schistocytes, LDH and platelet count, coagulation profile and more specific indexes of ADAMTS13, complement profile, and the isolation of Shiga toxin-producing Escherichia coli (commonly referred to as STEC). CONCLUSION The use and correct interpretation of classical indexes of schistocyte, LDH, and platelet count is vital in diagnosing TMA and associated disorders. Understanding the characteristics of these biomarkers in the context of thrombocytopenia purpura, HUS and DIC will facilitate the accurate diagnosis and early initiation of appropriate treatment.展开更多
IGA nephropathy （IgAN） is one of the most commontypes of primary glomerulonephritis, which occursmore frequently in patients of reproductive age.Atypical hemolytic uremic syndrome （aHUS）without diarrhea is rare an...IGA nephropathy （IgAN） is one of the most commontypes of primary glomerulonephritis, which occursmore frequently in patients of reproductive age.Atypical hemolytic uremic syndrome （aHUS）without diarrhea is rare and has a poor prognosis. In theabsence of appropriate therapy, pregnancy-related aHUSis associated with high morbidity and mortality.展开更多
Objective:To decrease or delay the major un-wanted clinical consequences to improve the quality of life in the involved patients.Methods:A retrospective case series study has been made on the forty five pediatric pati...Objective:To decrease or delay the major un-wanted clinical consequences to improve the quality of life in the involved patients.Methods:A retrospective case series study has been made on the forty five pediatric patients admitted to nephrology department of Ali-Asghar Hospital during a period of nearly 10 years.The patients have been divided into two groups of good and poor prognoses according to their clinical outcomes.The routine laboratory records and clinical manifestations extracted and statistically analyzed as independent variables both by univariate and multivariate methods.Results:Forty three patients have been managed successfully with only two deaths occurred.According to clinical findings,nineteen patients were classified as poor prognosis and the rest were categorized as good prognosis.Multivariate statistical analyses showed that lesser age at the time of admission(age【46 months,P【0.015) and the higher initial WBC count(count】15 000,P【0.226) were well-interrelated to ominous clinical consequences like convulsion,coma and peritonitis and statistically different between the two groups of patients.Conclusion:Despite the importance of predictive variables in the course of Hemolytic uremic syndrome(HUS) in children and their critical influence on the clinical outcome,many aspects of these parameters have been remained to be elucidated comprehensively.Our study showed that simultaneous low age of child at the time of admission with simultaneous high WBC count will result in the poorer prognoses of the patients.This may warn the clinicians to provide more supportive cares for this group of patients.展开更多
BACKGROUND The occurrence of Streptococcus pneumoniae-associated hemolytic uremic syndrome(SP-HUS)is increasing.Thomsen-Friedenreich antigen activation is highly involved in the pathogenesis of SP-HUS,and T-antibody-n...BACKGROUND The occurrence of Streptococcus pneumoniae-associated hemolytic uremic syndrome(SP-HUS)is increasing.Thomsen-Friedenreich antigen activation is highly involved in the pathogenesis of SP-HUS,and T-antibody-negative plasma exchange(PE)may be effective in the treatment of severe cases of SP-HUS.CASE SUMMARY We retrospectively reviewed two pediatric patients with SP-HUS.Both clinical features and laboratory examination results of the children were described.Tantibody-negative PE was performed in both cases.Both children made a full recovery after repeated PE and remained well at a 2 year follow-up.CONCLUSION Streptococcal pneumonia continues to be an uncommon but important cause of HUS.The successful treatment of the presented cases suggests that T-antibodynegative PE may benefit patients with SP-HUS.展开更多
Objective: To ascertain the role of serum potassium levels in predicting clinical outcomes in diarrhea-associated hemolytic uremic syndrome (HUS D+). Methods: We reviewed clinical and laboratory data from HUS D+ patie...Objective: To ascertain the role of serum potassium levels in predicting clinical outcomes in diarrhea-associated hemolytic uremic syndrome (HUS D+). Methods: We reviewed clinical and laboratory data from HUS D+ patients at our tertiary care institution from 2001 to 2008. Serum potassium concentration at presentation and during the acute phase of acute renal failure were recorded and related to laboratory parameters and clinical outcomes. Results: 15 HUS D+ cases were identified. E. coli 0157:H7 was found in 9/15 cases (70%). Potassium levels were not predictive of clinical outcomes. Normal serum potassium levels were found in the majority of patients. Potassium levels <3.6 mmol/L were evident at presentation in 3/15 patients (23%), and no patient manifested hyperkalemia even when creatinine levels were concurrently increase. Conclusions: This study suggests the presence of vigorous compensatory mechanisms in the homoestasis of serum potassium levels during HUS D+ disease since neither the increase stool volumes associated with diarrhea nor the presence of renal failure resulted in clinically significant changes in serum potassium levels.展开更多
Thrombotic microangiopathies(TMA) are microvascular occlusive disorders characterized by platelet aggregation and mechanical damage to erythrocytes, clinically characterized by microangiopatic haemolytic anemia, throm...Thrombotic microangiopathies(TMA) are microvascular occlusive disorders characterized by platelet aggregation and mechanical damage to erythrocytes, clinically characterized by microangiopatic haemolytic anemia, thrombocytopenia and organ injury. We are reporting a case of a woman patient with severe hemolytic uremic syndrome associated to infectious diarrhoea caused by Shiga toxin-producing pathogen, who were admitted to our intensive care unit. The patient described developed as organ injury, neurological failure and acute renal failure, with need of haemodialysis technique. Due to the severity of the case and the delay in the results of the additional test that help us to the final diagnose, we treated her based on a syndromic approach of TMA with plasma exchange, with favourable clinical evolution with complete recovery of organ failures. We focus on the syndromic approach of these diseases, because thrombotic thrombocytopenic purpura, one of the disorders that are included in the syndromes of TMA, is considered a haematological urgency given their high mortality without treatment; and also review the TMA in adults: Their pathogenesis, management and outcomes.展开更多
Nowadays acute gastroenteritis infection caused by Escherichia coli(E. coli) O157:H7 is frequently associated with hemolytic uremic syndrome(HUS), which usually developed after prodromal diarrhea that is often bloody....Nowadays acute gastroenteritis infection caused by Escherichia coli(E. coli) O157:H7 is frequently associated with hemolytic uremic syndrome(HUS), which usually developed after prodromal diarrhea that is often bloody. The abdominal pain accompanied by failure kidney is a suspicious symptom to develop this disorder. Their pathological characteristic is vascular damage which manifested as arteriolar and capillary thrombosis with abnormalities in the endothelium and vessel walls. The major etiological agent of HUS is enterohemorragic(E coli) strain belonging to serotype O157:H7. The lack of papers about HUS associated to gastroenteritis lead us to report this case for explain the symptoms that are uncommon. Furthermore, this report provides some strategies to suspect and make an early diagnosis, besides treatment approach to improving outcomes and prognosis for patients with this disorder.展开更多
Introduction: Acute Promyelocytic Leukemia (APL) is highly associated with hemostasis alterations. The atypical hemolytic uremic syndrome (aHUS) is a rare type of Thrombotic Microangiopathy (TMA) due to an overactivat...Introduction: Acute Promyelocytic Leukemia (APL) is highly associated with hemostasis alterations. The atypical hemolytic uremic syndrome (aHUS) is a rare type of Thrombotic Microangiopathy (TMA) due to an overactivation of the alternative complement pathway. Case Presentation: A 48-years-old woman was diagnosed with APL and achieved molecular remission after induction therapy. During the second consolidation cycle she presented with TMA. She began treatment with plasma exchange plus corticotherapy but due to aggravation of symptoms Eculizumab was initiated. Thrombotic thrombocytopenic purpura, infections and drug toxicity causes were ruled out. There was no evidence of relapse of the APL. Genetic studies of the hereditary anomalies of the alternative complement pathway were negative and the decision of stopping Eculizumab was made. During maintenance therapy for the APL she presented a severe relapse of the aHUS, requiring dialysis. She re-started treatment with Eculizumab with a progressive hematologic recovery and improvement of renal function. She completed APL treatment without relapse of the leukemia for the moment and continues to be treated with Eculizumab. Conclusion: This is the first published case of coexisting aHUS and APL successfully treated with Eculizumab.展开更多
Post-partum hemolytic uremic syndrome （PHUS） is a severe thrombotic microangiopathy clinically characterized by hemolytic anemia, renal dysfunction, and low platelets after birth with rapid progression and poor prog...Post-partum hemolytic uremic syndrome （PHUS） is a severe thrombotic microangiopathy clinically characterized by hemolytic anemia, renal dysfunction, and low platelets after birth with rapid progression and poor prognosis. Here, we reported a rare case of severe preeclampsia diagnosed as hemolytic uremic syndrome after birth. The patient was diagnosed with PHUS and underwent intermittent plasma exchange with supportive treatment including glucocorticoid injections and transfusion of suspended red blood cells. After these treatments, the patient experienced no apparent remission and chronic renal dysfunction occurred on her. PHUS is a severe emergency with acute onset, rapid progress, and poor prognosis. Early detection, diagnosis, and treatment can significantly improve the prognosis.展开更多
Background:The present study was undertaken to investigate the clinical characteristics of hemolytic uremic syndrome(HUS)secondary to cobalamin C disorder(cbl-C disorder).Methods:We reviewed retrospectively the medica...Background:The present study was undertaken to investigate the clinical characteristics of hemolytic uremic syndrome(HUS)secondary to cobalamin C disorder(cbl-C disorder).Methods:We reviewed retrospectively the medical records of 3 children with HUS secondary to cbl-C disorder who had been treated between April 1,2009 and October 31,2013.Results:The 3 patients with HUS secondary to cbl-C disorder presented with progressive hemolytic anemia,acute renal failure,thrombocytopenia,poor feeding,and failure to thrive.Two of the 3 patients once had high blood pressure.The mutations of c.609G>A(P.W203X),c.217C>T(p.R73X)and c.365A>T(p.H122L)in the methylmalonic aciduria(cobalamin deficiency)cbl-C type,with homocystinuria gene were detected in the 3 patients.In these patients the levels of lactate dehydrogenase and homocysteine in serum were elevated and the level of methylmalonic acid(MMA)in urine was also elevated.After treatment with hydroxocobalamin,2 patients were discharged with no obvious abnormal growth and neurological development and 1 patient died of multiple organ failure.Conclusions:The results of this study demonstrated that cbl-C disorder should be investigated in any child presenting with HUS.The high concentrations of homocysteine and MMA could be used for timely recognization of the disease.Once the high levels of plasma homocystein and/or plasma or urine MMA are detected,the treatment with parenteral hydroxocobalamin should be prescribed immediately.The early diagnosis and treatment would contribute to the good prognosis of the disease.展开更多
文摘Hemolytic uremic syndrome （HUS） is a rare disease. In this work the authors review the recent findings on HUS, considering the different etiologic and patho-genetic classifications. New findings in genetics and, in particular, mutations of genes that encode the complement-regulatory proteins have improved our understanding of atypical HUS. Similarly, the comple-ment proteins are clearly involved in all types of thrombotic microangiopathy： typical HUS, atypical HUS and thrombotic thrombocytopenic purpura （TTP）. Fur-thermore, several secondary HUS appear to be related to abnormalities in complement genes in predisposed patients. The authors highlight the therapeutic as-pects of this rare disease, examining both “traditional therapy” （including plasma therapy, kidney and kidney-liver transplantation） and “new therapies”. The latter include anti-Shiga-toxin antibodies and anti-C5 mono-clonal antibody “eculizumab”. Eculizumab has been recently launched for the treatment of the atypical HUS, but it appears to be effective in the treatment of typical HUS and in TTP. Future therapies are in phases Ⅰ and Ⅱ. They include anti-C5 antibodies, which are more purifed, less immunogenic and absorbed orally and, anti-C3 antibodies, which are more powerful, but potentially less safe. Additionally, infusions of recombinant complement-regulatory proteins are a potential future therapy.
文摘BACKGROUND Thrombocytopenia associated with acute kidney injury is a challenging disorder. Thrombotic microangiopathy (TMA) is a potentially life- or organ-threatening syndrome that can be induced by several disorders or medical interventions. There is overlap between the clinical presentation and pathophysiology of thrombotic thrombocytopenia purpura and hemolytic uremic syndrome (HUS), and to a lesser extent, disseminated intravascular coagulation (DIC). We describe a case to illustrate the potential diagnostic difficulty, especially at initial presentation. CASE SUMMARY We reported a case of a 44-year-old woman that presented with diarrhea, thrombocytopenia, schistocytes, elevated serum lactate dehydrogenase (LDH) level and acute kidney injury. While the clinical presentation resembled that of Shiga toxin–induced HUS, the disease course was more consistent with gastrointestinal infection-related DIC. To aid in the accurate diagnosis of TMA and other associated disorders, we have undertaken a review and provided a clear interpretation of some typical biomarkers including schistocytes, LDH and platelet count, coagulation profile and more specific indexes of ADAMTS13, complement profile, and the isolation of Shiga toxin-producing Escherichia coli (commonly referred to as STEC). CONCLUSION The use and correct interpretation of classical indexes of schistocyte, LDH, and platelet count is vital in diagnosing TMA and associated disorders. Understanding the characteristics of these biomarkers in the context of thrombocytopenia purpura, HUS and DIC will facilitate the accurate diagnosis and early initiation of appropriate treatment.
文摘IGA nephropathy （IgAN） is one of the most commontypes of primary glomerulonephritis, which occursmore frequently in patients of reproductive age.Atypical hemolytic uremic syndrome （aHUS）without diarrhea is rare and has a poor prognosis. In theabsence of appropriate therapy, pregnancy-related aHUSis associated with high morbidity and mortality.
文摘Objective:To decrease or delay the major un-wanted clinical consequences to improve the quality of life in the involved patients.Methods:A retrospective case series study has been made on the forty five pediatric patients admitted to nephrology department of Ali-Asghar Hospital during a period of nearly 10 years.The patients have been divided into two groups of good and poor prognoses according to their clinical outcomes.The routine laboratory records and clinical manifestations extracted and statistically analyzed as independent variables both by univariate and multivariate methods.Results:Forty three patients have been managed successfully with only two deaths occurred.According to clinical findings,nineteen patients were classified as poor prognosis and the rest were categorized as good prognosis.Multivariate statistical analyses showed that lesser age at the time of admission(age【46 months,P【0.015) and the higher initial WBC count(count】15 000,P【0.226) were well-interrelated to ominous clinical consequences like convulsion,coma and peritonitis and statistically different between the two groups of patients.Conclusion:Despite the importance of predictive variables in the course of Hemolytic uremic syndrome(HUS) in children and their critical influence on the clinical outcome,many aspects of these parameters have been remained to be elucidated comprehensively.Our study showed that simultaneous low age of child at the time of admission with simultaneous high WBC count will result in the poorer prognoses of the patients.This may warn the clinicians to provide more supportive cares for this group of patients.
文摘BACKGROUND The occurrence of Streptococcus pneumoniae-associated hemolytic uremic syndrome(SP-HUS)is increasing.Thomsen-Friedenreich antigen activation is highly involved in the pathogenesis of SP-HUS,and T-antibody-negative plasma exchange(PE)may be effective in the treatment of severe cases of SP-HUS.CASE SUMMARY We retrospectively reviewed two pediatric patients with SP-HUS.Both clinical features and laboratory examination results of the children were described.Tantibody-negative PE was performed in both cases.Both children made a full recovery after repeated PE and remained well at a 2 year follow-up.CONCLUSION Streptococcal pneumonia continues to be an uncommon but important cause of HUS.The successful treatment of the presented cases suggests that T-antibodynegative PE may benefit patients with SP-HUS.
文摘Objective: To ascertain the role of serum potassium levels in predicting clinical outcomes in diarrhea-associated hemolytic uremic syndrome (HUS D+). Methods: We reviewed clinical and laboratory data from HUS D+ patients at our tertiary care institution from 2001 to 2008. Serum potassium concentration at presentation and during the acute phase of acute renal failure were recorded and related to laboratory parameters and clinical outcomes. Results: 15 HUS D+ cases were identified. E. coli 0157:H7 was found in 9/15 cases (70%). Potassium levels were not predictive of clinical outcomes. Normal serum potassium levels were found in the majority of patients. Potassium levels <3.6 mmol/L were evident at presentation in 3/15 patients (23%), and no patient manifested hyperkalemia even when creatinine levels were concurrently increase. Conclusions: This study suggests the presence of vigorous compensatory mechanisms in the homoestasis of serum potassium levels during HUS D+ disease since neither the increase stool volumes associated with diarrhea nor the presence of renal failure resulted in clinically significant changes in serum potassium levels.
文摘Thrombotic microangiopathies(TMA) are microvascular occlusive disorders characterized by platelet aggregation and mechanical damage to erythrocytes, clinically characterized by microangiopatic haemolytic anemia, thrombocytopenia and organ injury. We are reporting a case of a woman patient with severe hemolytic uremic syndrome associated to infectious diarrhoea caused by Shiga toxin-producing pathogen, who were admitted to our intensive care unit. The patient described developed as organ injury, neurological failure and acute renal failure, with need of haemodialysis technique. Due to the severity of the case and the delay in the results of the additional test that help us to the final diagnose, we treated her based on a syndromic approach of TMA with plasma exchange, with favourable clinical evolution with complete recovery of organ failures. We focus on the syndromic approach of these diseases, because thrombotic thrombocytopenic purpura, one of the disorders that are included in the syndromes of TMA, is considered a haematological urgency given their high mortality without treatment; and also review the TMA in adults: Their pathogenesis, management and outcomes.
文摘Nowadays acute gastroenteritis infection caused by Escherichia coli(E. coli) O157:H7 is frequently associated with hemolytic uremic syndrome(HUS), which usually developed after prodromal diarrhea that is often bloody. The abdominal pain accompanied by failure kidney is a suspicious symptom to develop this disorder. Their pathological characteristic is vascular damage which manifested as arteriolar and capillary thrombosis with abnormalities in the endothelium and vessel walls. The major etiological agent of HUS is enterohemorragic(E coli) strain belonging to serotype O157:H7. The lack of papers about HUS associated to gastroenteritis lead us to report this case for explain the symptoms that are uncommon. Furthermore, this report provides some strategies to suspect and make an early diagnosis, besides treatment approach to improving outcomes and prognosis for patients with this disorder.
文摘Introduction: Acute Promyelocytic Leukemia (APL) is highly associated with hemostasis alterations. The atypical hemolytic uremic syndrome (aHUS) is a rare type of Thrombotic Microangiopathy (TMA) due to an overactivation of the alternative complement pathway. Case Presentation: A 48-years-old woman was diagnosed with APL and achieved molecular remission after induction therapy. During the second consolidation cycle she presented with TMA. She began treatment with plasma exchange plus corticotherapy but due to aggravation of symptoms Eculizumab was initiated. Thrombotic thrombocytopenic purpura, infections and drug toxicity causes were ruled out. There was no evidence of relapse of the APL. Genetic studies of the hereditary anomalies of the alternative complement pathway were negative and the decision of stopping Eculizumab was made. During maintenance therapy for the APL she presented a severe relapse of the aHUS, requiring dialysis. She re-started treatment with Eculizumab with a progressive hematologic recovery and improvement of renal function. She completed APL treatment without relapse of the leukemia for the moment and continues to be treated with Eculizumab. Conclusion: This is the first published case of coexisting aHUS and APL successfully treated with Eculizumab.
文摘Post-partum hemolytic uremic syndrome （PHUS） is a severe thrombotic microangiopathy clinically characterized by hemolytic anemia, renal dysfunction, and low platelets after birth with rapid progression and poor prognosis. Here, we reported a rare case of severe preeclampsia diagnosed as hemolytic uremic syndrome after birth. The patient was diagnosed with PHUS and underwent intermittent plasma exchange with supportive treatment including glucocorticoid injections and transfusion of suspended red blood cells. After these treatments, the patient experienced no apparent remission and chronic renal dysfunction occurred on her. PHUS is a severe emergency with acute onset, rapid progress, and poor prognosis. Early detection, diagnosis, and treatment can significantly improve the prognosis.
基金supported by a grant from the Special Program for Clinical Research of the Beijing Municipal Commission of Science and Technology and WU JIE PING Medical Foundation,China(Grant Z121107005112008)
文摘Background:The present study was undertaken to investigate the clinical characteristics of hemolytic uremic syndrome(HUS)secondary to cobalamin C disorder(cbl-C disorder).Methods:We reviewed retrospectively the medical records of 3 children with HUS secondary to cbl-C disorder who had been treated between April 1,2009 and October 31,2013.Results:The 3 patients with HUS secondary to cbl-C disorder presented with progressive hemolytic anemia,acute renal failure,thrombocytopenia,poor feeding,and failure to thrive.Two of the 3 patients once had high blood pressure.The mutations of c.609G>A(P.W203X),c.217C>T(p.R73X)and c.365A>T(p.H122L)in the methylmalonic aciduria(cobalamin deficiency)cbl-C type,with homocystinuria gene were detected in the 3 patients.In these patients the levels of lactate dehydrogenase and homocysteine in serum were elevated and the level of methylmalonic acid(MMA)in urine was also elevated.After treatment with hydroxocobalamin,2 patients were discharged with no obvious abnormal growth and neurological development and 1 patient died of multiple organ failure.Conclusions:The results of this study demonstrated that cbl-C disorder should be investigated in any child presenting with HUS.The high concentrations of homocysteine and MMA could be used for timely recognization of the disease.Once the high levels of plasma homocystein and/or plasma or urine MMA are detected,the treatment with parenteral hydroxocobalamin should be prescribed immediately.The early diagnosis and treatment would contribute to the good prognosis of the disease.
