Atypical Hemolytic Uremic Syndrome in a Patient with Acute Promyelocytic Leukemia: A Case Report

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.

溶血性尿毒综合征(Hemalytic—Uremic Syndrome, HUS)的治疗

溶血性尿毒综合征,其主需临床表现是:微血管病性溶血性贫血、血小板减少和急性肾病。主要见于婴幼儿,也可见于成人。病理改变是双侧肾皮质坏死,肾小球弥漫性或限局性坏死伴有输入小动脉内纤维蛋白沉积:肾小球毛细血管丛栓塞;肾小球内毛细血管及小动脉内皮细胞和上皮细胞肿胀增生。此外有25%的病例存在着透明血栓。本病主要发生于婴幼儿,也见于青少年。典型者在胃肠炎或上呼吸道感染后数天到二周突然发病,出现贫血、溶血、皮肤和粘膜出血、急性肾功衰竭,血象中出现畸形和碎片红细胞。本病的治疗,虽然不甚满意,但由于应用下列方法,取得了明显进步:一、抗血小板药物本病的主要病理改变是在微小血管中血小板血栓形成,因此,是应用抗血小板药物的适应症。常用阿斯匹林和潘生丁。

Update on hemolytic uremic syndrome:Diagnostic and therapeutic recommendations

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.

Streptococcal pneumonia-associated hemolytic uremic syndrome treated by T-antibody-negative plasma exchange in children: Two case reports

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.

A case of severe preeclampsia diagnosed as post-partum hemolytic uremic syndrome

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.

Clinical characteristics of hemolytic uremic syndrome secondary to cobalamin C disorder in Chinese children

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.

Successful Renal Transplantation in a Patient with Atypical Hemolytic Uremic Syndrome Treated with Eculizumab in China

Hemolytic uremic syndrome （HUS） is a rare disease characterized by thrombocytopenia and acute renal failure. Atypical HUS （aHUS） accounts for approximately 10% of all HUS cases. The pathogenesis of aHUS is mainly associated with gene mutations in complement factor H, complement factor I, and membrane cofactor protein （MCP）. The prognosis of aHUS is generally poor.

Hemolytic uremic syndrome in Argentina:An attack scenario

The recent Escherichia coli epidemic in Germany gave a lesson at an international level.There is no time to solve food security problems when an epidemic is on the way.The epidemic in Germany exposed the fissures in the control systems of the Federal Risk Evaluation Institute of this country,as well as showing the incompetency of health authorities,who had great difficulty in resolving the situation.To summarize,the possibility of prevention was confused with the utopian idea of non-occurrence.It was not less important the public’s recognition and the“awakening”of health ministers in the European Union as regards the proven fact that pathogenic and even lethal microorganisms may be present in the food we eat.Argentina has the highest incidence of hemolytic uremic syndrome in the world,and the next epidemic is likely not to occur in Germany,but in any other country,such as Argentina.In order to avoid complicity,we do not wish to remain silent about the situation in Argentina.Therefore,this is the writer’s motive for writing this article,which describes the scientific advances and the ethical pitfalls related to a disease transmitted by food,particularly hemolytic uremic syndrome,in Argentina.

Lupus-associated thrombotic thrombocytopenic purpura-like microangiopathy

Recently reported cases of lupus complicated by a thrombotic thrombocytopenic purpura （TTP）-like syndrome suggest a survival beneft to early treatment with plasma exchange. The following is a report of the eighth such case in the last ten years. A 44-year-old lady known for lupus presented with the nephrotic syndrome and a renal biopsy was consistent with class 4G lupus nephritis. She was given high-dose steroids and cytotoxic therapy, but her induction therapy was complicated by the classic pentad of TTP. She was subsequently treated with another course of high-dose steroids, a different cytotoxic agent, and plasma exchange, with clinical resolution shortly thereafter. Similar to seven recently reported cases of microangiopathy in lupus, this lady’s TTP-like syndrome improved dramatically after initiation of plasma exchange, despite not having a severely deficient ADAMTS13. This has implications on both current clinical practice and on the pathogenesis of TTP-like syndromes in lupus.

Combined liver-kidney transplantation for rare diseases

Combined liver and kidney transplantation(CLKT)is indicated in patients with failure of both organs,or for the treatment of end-stage chronic kidney disease(ESKD)caused by a genetic defect in the liver.The aim of the present review is to provide the most up-to-date overview of the rare conditions as indications for CLKT.They are major indications for CLKT in children.However,in some of them(e.g.,atypical hemolytic uremic syndrome or primary hyperoxaluria),CLKT may be required in adults as well.Primary hyperoxaluria is divided into three types,of which type 1 and 2 lead to ESKD.CLKT has been proven effective in renal function replacement,at the same time preventing recurrence of the disease.Nephronophthisis is associated with liver fibrosis in 5%of cases and these patients are candidates for CLKT.In alpha 1-antitrypsin deficiency,hereditary C3 deficiency,lecithin cholesterol acyltransferase deficiency and glycogen storage diseases,glomerular or tubulointerstitial disease can lead to chronic kidney disease.Liver transplantation as a part of CLKT corrects underlying genetic and consequent metabolic abnormality.In atypical hemolytic uremic syndrome caused by mutations in the genes for factor H,successful CLKT has been reported in a small number of patients.However,for this indication,CLKT has been largely replaced by eculizumab,an anti-C5 antibody.CLKT has been well established to provide immune protection of the transplanted kidney against donor-specific antibodies against class I HLA,facilitating transplantation in a highly sensitized recipient.