Hemolytic uremic syndrome

HEMOLYTIC UREMIC SYNDROME

JINU JANET VARGHESE

GROUP: 4

YEAR: 5

TBILISI STATE MEDICAL UNIVERSITY

DEFINITION

• Hemolytic uremic syndrome (HUS), a disease that destroys red blood cells, is the most common cause of sudden, short-term acute kidney failure in children.

• It is a triad of:

• Micro-angiopathic hemolytic anemia

• Thrombocytopenia.

• Acute kidney injury (acute renal failure)

EPIDEMOLOGY

• Hemolytic uremic syndrome (HUS) is a rare disorder with an annual incidence of 6.1 cases per 100,000 children aged under 5 years (compared with an overall incidence of 1 to 2 cases per 100,000).

• Over 90% of cases in children are secondary to infection. Approximately 15% of cases of E. coli O157 infection will develop HUS. The development of HUS may occur up to two weeks after the initial onset of symptoms, and may develop after apparent recovery from the initial acute illness. Cases may be sporadic or occur as part of larger outbreaks. The largest documented outbreak in England occurred in Cumbria in 1999, and was associated with pasteurized milk.

• About 10% of HUS cases are atypical and are not caused by Shiga toxin-producing bacteria or streptococci.

TYPES OF HUS

Classified into 2 main categories, depending on whether it is associated with Shiga-like toxin or not.

1. TYPICAL HUS:

• Typical HUS follows a diarrheal infection often caused by E. coli OH157:H7. Infection related Shiga toxin producing E.coli/Shigella Pneumococcal infection HIV Typical Other viral or bacterial infections. Only the diarrheal form of HUS is considered to be typical HUS and is usually a disease of infants and children younger than 3 years of age

2. ATYPICAL HUS

• caused by exposure to certain medications (eg ciclosporin, tacrolimus), genetic mutations in the complement pathway[4] and systemic conditions, including lupus, cancer and pregnancy.

PATHOGENESIS

• Specifically, E coli serotype O157:H7 has been associated with more than 80% of infections leading to Hemolytic Uremic Syndrome.

• The shiga-like toxin affects endothelial cells and initiates intravascular thrombo-genesis. After entering the circulation via the gastrointestinal mucosa, the toxin preferentially localizes to the kidneys, inhibiting protein synthesis and eventually leading to cell necrosis or apoptosis.

• Endothelial cell damage subsequently potentiates renal microvascular thrombosis by promoting activation of the blood coagulation cascade.

• Platelet aggregation results in a consumptive thrombocytopenia. Microangiopathic hemolytic anemia results from mechanical damage to red blood cells circulating through partially occluded microcirculation.

CAUSES

Hemolytic-uremic syndrome (HUS) predominantly occurs in infants and children after prodromal diarrhea. In summer epidemics, the disease may be related to infectious causes.

BACTERIAL INFECTIONS :

• S dysenteriae

• E coli

• Salmonella typhi

• Campylobacter jejuni

• Yersinia pseudotuberculosis

• Neisseria meningitidis

• S pneumoniae

• Legionella pneumophila

• Mycoplasma species

VIRAL INFECTIONS :

• Human immunodeficiency virus (HIV)

• Coxsackievirus

• Echovirus

• Influenza virus

• Epstein-Barr virus

• Herpes simplex virus

OTHER CAUSES:

• Fungal infections, Vaccinations, Pregnancy, Quinine, Oral contraception, Cancers, Chemotherapeutic agents, Antiplatelet agents, Collagen-vascular disorder, Primary glomerulopathies, etc.

SIGNS & SYMPTOMS

HUS develops about 5-10 days after onset of diarrhea

EARLY SYMPTOMS:

• Blood in the stools

• Irritability

• Fever

• Lethargy

• Vomiting and diarrhea

• Weakness

LATER SYMPTOMS:

• Bruising

• Decreased consciousness

• Low urine output

• No urine output

• Pallor

• Seizures -- rare

• Skin rash that looks like fine red spots (petechiae)

• Yellow skin (jaundice)

DIAGNOSIS

• Findings of hemolysis and thrombocytopenia on a complete blood count are required to establish the diagnosis.

• Anemia: invariable finding and usually severe

• Thrombocytopenia: Platelet survival time is shortened in HUS.

• The peripheral blood smear reveals fragmented RBCs (e.g., schistocytes, spherocytes, segmented RBCs)

• Reticulocytosis (proportional to hemolysis) and circulating free hemoglobin may be found

• Increased serum thrombo-modulin levels may be found and are a marker for endothelial injury in HUS.

• Leukocytosis: moderate leukocytosis in post diarrheal cases indicates renal failure due epithelial injury

• disseminated intravascular coagulopathy (elevated fibrin split products, prolongation of the activated partial thromboplastin time, and low anti-thrombin III levels)

Healthy red blood cells (left) are smooth and round. In hemolytic uremic syndrome, toxins destroy red blood cells (right). These misshapen cells may clog

the tiny blood vessels in the kidneys.

Schistocytes as seen in a person with hemolytic-uremic syndrome

A bloody diarrhea is followed in a few days by renal failure caused by endothelial

injury from the toxin, leading to the characteristic fibrin thrombi in glomerular and interstitial capillaries.

• Because of intravascular hemolysis, direct bilirubin values are elevated with elevated serum lactate dehydrogenase (LDH) level

• Renal function and electrolytes: a rise in urea and creatinine may be due to dehydration

• Azotemia

• Elevated C-reactive protein level

• Negative Coombs’ test

• Stool culture positive for Shiga toxin–roducing Escherichia coli O157:H7

• Hematuria on urinalysis

COMPLICATIONS

GASTROINTESTINAL NEUROLOGIC RENAL

• Intestinal strictures/perforations

• Intussusception• Pancreatitis• Severe colitis

• Altered mental status• Focal neurologic signs• Seizures

• Chronic renal failure• Hematuria• Hypertension• Proteinuria

DIFFERNTIAL DIAGNOSIS

• Acute abdomen

• Acute gastroenteritis

• Appendicitis

• Colitis

• Disseminated intravascular coagulation

• Inflammatory bowel disease

• Lupus

• Thrombotic thrombocytopenia

TREATMENT & MANAGEMENT

• Hemolytic uremic syndrome requires treatment in the hospital. To ease immediate signs and symptoms and prevent further problems, hemolytic uremic syndrome treatment may include:

• FLUID REPLACEMENT: The key treatment for HUS is fluid replacement. This treatment replaces electrolytes that the body needs to function. Fluid replacement also increases blood flow through the kidneys. The extra fluids help offset the impaired blood flow that occurs due to the breakdown of red blood cells.

• KIDNEY DIALYSIS

• PLASMA EXCHANGE

• PLATELET TRANSFUSIONS

• RED BLOOD CELL TRANSFUSIONS: Low RBCs result in chills, fatigue, short of breath, rapid heart rate, yellow skin and dark urine. Transfusions (IV) can relieve these symptoms.

• Antibiotics and antimotility agents are not recommended as treatments for hemolytic uremic syndrome during the diarrheal stage of the disease. Some children who were diagnosed with Shigella dysenteriae type 1 and treated with ampicillin developed hemolytic uremic syndrome.

• Use of monoclonal antibodies which block complement activity. Case reports of experimental treatments with eculizumab is used to treat congenital atypical hemolytic uremic syndrome, as well as severe shiga-toxin associated hemolytic uremic syndrome.

• These have shown promising results. Eculizumab was approved by the U.S. Food and Drug Administration on September 23, 2011 for the treatment of atypical hemolytic uremic syndrome (aHUS) It was approved by the European Medicines Agency on November 29, 2011 for the treatment of aHUS.

• Trials of gamma globulin are under way, with promising preliminary results. Findings suggest the possibility of some benefit in children.

• Azathioprine and vincristine are potent drugs with potential benefit in the management of HUS.

PROGNOSIS

• Typical hemolytic uremic syndrome (HUS) with a diarrheal prodrome usually has a good prognosis. The two British Pediatric Surveillance Unit prospective surveys in the UK and Ireland (1985-1988 and 1997-2001) of HUS in children under 16 years reported a mortality rate of HUS in the first of these surveys to be 5.6% and this had decreased to 1.8% in the second survey.

• Death due to HUS is nearly always associated with severe extra-renal disease, including severe central nervous system involvement.

• Fatality is highest in infants, small children and the elderly.

• Whilst renal recovery is the norm, there have been permanent and serious renal sequelae(hypertension, proteinuria, diminishing glomerular filtration rate) found in 5-25% of HUS patients.

• Atypical HUS often has a poorer prognosis, with death rates reportedly as high as 25%, and progression to end-stage renal disease in 50%.

PREVENTION

• The organism is very common in cattle and a low level of infection causes clinical disease. Prevention is based on reducing fecal contamination during slaughtering and processing.

• Good personal hygiene measures, e.g. hand-washing before and after food-handling and eating, after toilet use and after contact with farm animals.

• Increased public awareness about good food hygiene, eg cook meat and meat products well, especially where minced or in burger form; avoid cross-contamination between raw and cooked food.

• Early diagnosis enables early supportive treatment and better ultimate prognosis. Similarly, early identification of an outbreak enables public health measures to be put in place to prevent further cases. Separating known cases from their younger siblings may also be an appropriate measure.

• Conjugate vaccines against E. coli O157 are in development - phase 3 trials are awaited.

REFERENCES

• http://emedicine.medscape.com/article/1183555-treatment

• http://www.patient.co.uk/doctor/Haemolytic-Uraemic-Syndrome.htm

• http://www.healthline.com/health/hemolytic-uremic-syndrome

• https://www.clinicalkey.com/topics/hematology/hemolytic-uremic-syndrome.html

• http://en.wikipedia.org/wiki/Hemolytic-uremic_syndrome#Treatment

• http://www.mayoclinic.org/diseases-conditions/hemolytic-uremic-syndrome/basics/treatment/con-20029487

• http://www.aafp.org/afp/2006/0915/p991.html