Evaluation of Patients with Hemolytic Uremic Syndrome

Genetic studies into inherited and sporadic hemolytic uremic syndrome

Genetic studies into inherited and sporadic hemolytic uremic syndrome

Historical review - the birth of the haemolytic uraemic syndrome, commentary on the relationships between HUS and TTP, with musings on the problems concerning the definition of a syndrome epidemiology of HUS - the haemolytic uraemic syndromes in the United Kingdom, childhood haemolytic uraemic syndrome in Canada - a multicentre study, haemolytic uraemic syndrome in Asia, HUS in Johannesburg, South Africa - epidemiology and long-term-follow-up, the haemolytic uraemic syndrome in Argentina clinical manifestations of HUS - gastrointestinal features of the haemolytic uraemic syndrome, central nervous system involvement in the haemolytic uraemic syndrome, pancreatic involvement in the haemolytic uraemic syndrome, cardiovascular involvement in the haemolytic syndrome atypical haemolytic uraemic syndrome, haemolytic uraemic syndrome and transplantation, bone marrow transplantation-associated thrombotic microangiopathy causes of HUS - the association of verocytotoxins and the classical haemolytic uraemic syndrome, haemolytic uraemic syndrome in families, an analysis of the association of the haemolytic uraemic syndrome and the birth control pill, haemolytic uraemic syndrome in association with pregnancy, inborn errors of cobalamin metabolism and the haemolytic uraemic syndrome, cancer and chemotherapy-associated thrombotic microangiopathy, haemolytic uraemic syndrome/thrombotic thrombocytopenic purpura associated with human immunodeficiency virus and acquired immunodeficiency syndrome pathology - pathology of the haemolytic uraemic syndrome pathogenesis - oxygen-derived free radicals in the pathogenesis of the haemolytic uraemic syndrome, haemolytic uraemic syndrome, thrombotic thrombocytopenic purpura, the generalized Shwartzman reaction, coagulation, and fibrinolysis, the pivotal role of the endothelial cell in the pathogenesis of HUS, pathogenesis of Shiga toxin (verotoxin)-induced endothelial cell injury treatment - treatment of haemolytic uraemic syndrome with antithrombotic agents, treatment of haemolytic uraemic syndrome with fresh-frozen plasma or with plasmapheresis, long-term outcome of haemolytic uraemic syndrome in children, follow-up of haemolytic uraemic syndrome in Argentina thrombotic thrombocytopenic purpura - von Willebrand factor abnormalities in thrombotic thrombocytopenic purpura and the haemolytic uraemic syndrome, platelet-agglutinating/aggregating proteins from the plasma of patients with thrombotic thrombocytopenic purpura, role of prostacyclin in the pathogenesis and therapy of thrombotic thrombocytopenic purpura, pathological features of thrombotic thrombocytopenic purpura, an animal model of thrombotic thrombocytopenia with von Willebrand factor deficiency - the role of botrocetin in studies of human TTP, treatment of thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome - the role of Vincristine, antiplatelet agents on thrombotic thrombocytopenic purpura. (Part contents)

Is ADAMTS-13 deficiency specific for thrombotic thrombocytopenic purpura? No

Deficiency of ADAMTS-13 in thrombotic and thrombocytopenic purpura

Escherichia coli O157:H7-associated hemolytic uremic syndrome and acute hepatocellular cholestasis: a case report.

Hemolytic uremic syndrome (HUS), a common cause of acute renal failure (ARF) in children, consists of triad of microangiopathic haemolytic anemia (MAHA), thrombocytopenia, and ARF. The aim of the present article is to have a recent overview of HUS including its incidence, etiopathogenesis, clinical profile and management. It consists of two types a) Diarrhoea associated i.e. classical also called D+ HUS b) Non-diarrhoea associated i.e. atypical also called D- HUS. D+ HUS is caused mostly by Escherichia coli or occasionally by Shigella dysenteriae. The causes of HUS are infections, genetic defects, systemic diseases and drugs. The atypical form commonly presents with recurrent or chronic persistent attack. Thrombotic microangiopathy (TMA), the pathologic hallmark, includes HUS, atypical HUS (aHUS), thrombotic thrombocytopenic purpura (TTP) which is characterized by endothelial cell damage and microvascular injury. In the vast majority of aHUS susceptibility factors are familial and not acquired. In D+ HUS, following an attack of diarrhoea or dysentery the child abruptly develops pallor, irritability, swelling of body, oligoanuria, hematuria, and hypertension. Central nervous system disturbances like seizure, obtundation and encephalopathy may occur but less common than aHUS or TTP. Diagnosis of HUS is established by presence of MAHA in the peripherl blood smear i.e. schistocytes, burr cells, helmet cells etc. Thrombocytopenia is nearly always seen. ARF is reflected in elevated blood urea and creatinine level. Coagulation studies like prothrombin time (PT), activated partial thromboplastin time (APTT), will be normal unlike disseminated coagulopathy (DIC). D-dimer level will be raised in HUS similar to DIC. Interestingly, direct Coomb’s test will be positive in Streptococcus pneumonia induced D- HUS. With excellent supportive care and often dialysis D+ HUS will show remarkable recovery whereas in addition plasmapheresis or plasma infusion outcome is poor in most of the D-HUS cases. Though incidence of gastroenteritis is very high in our country, only few patients may develop HUS, the reason of which remains unclear. The incidence of HUS as a cause for ARF in India may be reviewed further. Indiscriminate use of antimicrobials is to be avoided as far as possible to prevent HUS related mortality. Facilities for dialysis may be enhanced in most of the health care facilities in our country as a life saving measure to reduce HUS related mortality and morbidity.

Relative Nephroprotection During<i>Escherichia coli</i>O157:H7 Infections: Association With Intravenous Volume Expansion

In children, haemolytic uraemic syndrome (HUS) is associated with high plasma plasminogen activator inhibitor type 1 (PAI-1), which may contribute to the persistence of renal glomerular and arteriolar thrombi. HUS has been described in HIV-infected patients, but the pathophysiology of HUS in these patients is poorly understood. The aim of the study was to investigate plasma fibrinolytic activity in 18 patients with HIV-associated HUS. We measured tissue type plasminogen activator (t-PA) and PAI-1 activities in the plasma of 18 HIV-infected patients with biopsy-proven HUS (HIV+/HUS+) and 48 HIV-infected patients without HUS (HIV+/HUS-). Patients with HUS had a significantly higher serum creatinine, a lower platelet count and an increased incidence of cytomegalovirus (CMV) infection (72% of patients HIV+/HUS+, vs 25% of patients HIV+/HUS-). Unexpectedly, plasma PAI-1 activity was similar in both groups. However, t-PA activity was significantly higher in HUS cases (11.5 vs 4.5 U/ml, P=0.001). Patients with CMV infection, with or without HUS, had significantly increased t-PA level (P=0.01). Multivariate analysis identified high t-PA (RR=9.21) and CMV infection (RR=3.36) as risk factors for HUS. This study provides evidence that HIV-infected patients with HUS have high plasma t-PA activity. PAI-1 plasma activity is not significantly increased, as opposed to non-HIV-associated HUS. Thus, in the setting of HIV infection, HUS cannot be attributed to decreased fibrinolytic activity.

Is severe deficiency of ADAMTS-13 specific for thrombotic thrombocytopenic purpura? Yes

Journal of the American Society of Nephrology : JASN 9(6):p 1126-1133, June 1998. | DOI: 10.1681/ASN.V961126

The thrombotic microangiopathies consist of a heterogeneous group of diseases which have common clinical manifestations including nonimmune hemolytic anemia, thrombocytopenia, and acute kidney injury. They also share in common endothelial cell injury and microthrombus formation as the central pathologic features (Fig. 1). While they share common clinical and pathologic manifestations, they have quite different and unique etiologies, presentations, pathogenesis, and therapies [1–6]. The most common cause of hemolytic uremic syndrome (HUS) is infectious agents with Shiga toxin-producing Escherichia coli (STEC) being the predominant cause of infectious HUS (Fig. 2). Atypical HUS (aHUS) can result from genetic mutations in complement regulatory proteins including complement factors H (FH), I (FI), and B (FB), as well as other factors. Thrombotic thrombocytopenia purpura (TTP) is caused by an inherited genetic mutation or an acquired immune deficiency in a disintegrin and metalloprotease with thrombospondin type 1 repeats 13 (ADAMTS13). ADAMTS13 cleaves von Willebrand factor (VWF) facilitating its release from endothelial cells, thereby preventing the accumulation of prothrombotic ultralarge VWF oligomers. Other less common causes of HUS include drug-induced HUS, cobalamin deficiency HUS, transplant-associated HUS, and other secondary causes of HUS such as systemic lupus erythematosus and malignant hypertension. STEC HUS is usually associated with diarrhea and has been called diarrhea-positive HUS. In contrast, atypical HUS and TTP have been classified as diarrhea-negative HUS, but clearly some cases of STEC HUS have minimal gastrointestinal symptoms and some case of atypical HUS have prominent gastrointestinal symptoms [1–5]. In the majority of STEC HUS, the diarrhea is prominent, usually bloody, and associated with severe crampy abdominal pain. Diarrhea has typically begun to subside at the time HUS is developing. In contrast, diarrhea in atypical HUS is less prominent and not usually bloody. It is important to take the history, clinical findings, and laboratory values into consideration when classifying the thrombotic microangiopathies. This chapter will review the different etiologies, clinical manifestations, management, and therapy of the different causes of infectious HUS, atypical HUS, and TTP.

Association of a Factor H Mutation With Hemolytic Uremic Syndrome Following a Diarrheal Illness

Phenotypic expression of factor H mutations in patients with atypical hemolytic uremic syndrome

Acute inflammation in the pathogenesis of hemolytic-uremic syndrome