Hemolytic Uremic Syndrome Triad of thrombocytopenia microangiopathic hemolytic
Hemolytic Uremic Syndrome
Triad of thrombocytopenia, micro-angiopathic hemolytic anemia and acute renal failure
• The most common cause of HUS is systemic uptake of Shiga-like toxin (Stx or verotoxin) from Stx-producing Escherichia coli (STEC) O 157: H 7, ( enterohemorrhagic E. coli or diarrhoeal-associated (D+HUS). • 5 -10% of people infected with Shiga-like toxin will develop D+HUS
10% of cases, which are referred to as atypical HUS (a. HUS) or D-HUS.
• HUS is the most frequent intrinsic renal cause of acute renal failure in children and a common reason for renal transplant
• The age group that is most vulnerable to D+HUS is infants/ children, especially those aged between 6 months and 4 years. • In children the infection is mainly spread by faeco-oral transmission.
• Stx is the main pathogenic agent in the development of D+HUS • HUS presents as a multiorgan system disease characterised by damage of endothelial cells. • This damage occurs via the inhibition of protein synthesis and production of inflammatory mediators, leading to tissue ischaemia and dysfunction. • Stx induces damage of the mesangial cells, as well as glomerular and renal tubular epithelial cells, through the interaction with its globotriaosylceramide receptor
Hemolytic-Uremic Syndrome D Neg HUS • Genetic: factor H deficiency, membrane cofactor protein (CD 46) abnormalities , factor 1 deficiency , factor B mutation, C 3 mutations • Acquired anti-C 3 AB • Immune-mediated factor H deficiency • ADAMTS 13 abnormalities • Infectious: HIV • Antiphospholipid syndrome • Lupus, Scleroderma, Malignant hypertension, Malignancy, Pregnancy • Mitomycin Quinidine Ticlopidine Clopidogrel Calcineurin inhibitors Oral contraception • Deficiency in cobalamin C • Transplant-associated TMA
CLINICAL FEATURES • • The commonest clinical presentation of HUS is Acute pallor Oliguria Diarrhea or dysentery It occurs commonly in children between 1 -5 years of age HUS develops about 5 -10 days after onset of diarrhea Hematuria and hypertension Complications of fluid overload: Pulmonary edema: Hypertensive encephalopathy • Despite thrombocytopenia, bleeding manifestations are rare • Neurological symptoms like: Irritability, Encephalopathy & Seizures
Investigations • CBC, Peripheral blood smears, Reticulocyte count, Schistocytes • LDH • Bili unconjugated • Cr & BUN • Urine analysis, Hemoglobinuria, Hematuria , Proteinuria
• Investigations to Identify Cause • dairrhea, identification of pathogenic EHEC or Shigella : Stool culture, Further serotyping by agglutination or enzyme immunoassay • Bacteriological cultures of body fluids are indicated in suspected pneumococcal disease; Sputum, CSF, Blood, Pus
MANAGEMENT • • Supportive Therapy Antibiotics Plasma Therapy Miscellaneous
Supportive therapy • Close clinical monitoring of : Fluid status , Blood pressure, Neurological , Ventilatory parameters, Blood levels of glucose, electrolytes, creatinine and hemoglobin • The use of antimotility therapy for diarrhea has been associated with a higher risk of developing HUS
• Plasma Therapy • In a. HUS due to : complement factor abnormality, ADAMTS 13 deficiency • Replacement of the deficient factor with FFP • Daily plasma infusions (10 to 20 m. L/kg/day)� Exchange of 1. 5 times plasma volume ( 60 to 75 m. L/kg/day) using FFP
Miscellaneous • In infants with HUS associated with cobalamin abnormalities: Treatment with hydroxycobalamin, Oral betaine , Folic acid Normalizes the metabolic abnormalities can help to prevent further episodes. • In patients with persistent ADAMTS 13 antibodies and poor response to plasma exchange: Immunosuppressive therapy with high dose steroids/cyclophosphamide/ cyclosporin/rituximab /Splenectomy
• Eculizemab
Prognosis HUS • • Early recognition, intensive supportive care mortality D+ HUS is <5% in Dialysis in half of pt 5% dialysis dependent 30% CKD Pneumococci associated 20% mortality The familial and the genetic; progressive or relapsing, poor prognosis and recurrence
Which of the following are NOT typical laboratory findings in HUS? A. Moderate leukocytosis and hemolytic anemia with elevated reticulocyte count B. Presence of Schistocytes (fragmented, deformed, irregular or helmet-shaped red cells) in the peripheral blood smear C. Abnormal prothrombin time, activated partial thromboplastin time and fibrinogen levels D. Markedly elevated blood urea nitrogen and creatinine Sterile blood cultures
• What percentage of children with HUS will require renal replacement therapy (dialysis) in the acute phase? A. 50 -80% B. 20 -40% C. 40 -50% D. 5 -15% E. None
• . What is the impact of antibiotics during the acute enteric phase of STEC infection? • They are potentially harmful • May increase the release of Shiga-like toxins during the diarrhoeal illness
• Which of the following statements are true regarding complications of HUS? A. Complications can include intussusception, renal failure, hypertension, encephalopathy, pancreatitis and seizures Insulindependent diabetes mellitus may present as a long-term complication B. 2. 5 -10% of patients will either die during the acute illness or have permanent renal failure C. Patients with a. HUS are less likely to develop complications with recurrent disease episodes, severe hypertension, pancreatitis, hepatitis, cardiac failure, chronic and endstage renal failure D. Patients with genetic HUS have a high risk of graft loss from disease recurrence or thrombosis
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