Haemolytic Uremic Syndrome

 

Mrs. Kavitha. D

Nursing Tutor, College of Nursing, Sri Ramakrishna Institute of Paramedical Sciences, Coimbatore

 

ABSTRACT:

CASE HISTORY:

 

 

INTRODUCTION:

Hemolytic Uremic Syndrome (HUS) is a group of blood disorders characterized by low red blood cells, acute kidney failure, and low platelets. Initial symptoms typically include bloody diarrhea, fever, vomiting, and weakness. Kidney problems and low platelets then occur as the diarrhea is improving. While children are more commonly affected, adults may have worse outcomes.⁽¹⁾⁽²⁾

 

EPIDERMIOLOGY:

The country with the highest incidence of HUS is Argentina and it performs a key role in the research of this condition. In the United States, the overall incidence of HUS is estimated at 2.1 cases per 100,000 persons/year, with a peak incidence between six months and four years of age.

 

In May, 2011 an epidemic of bloody diarrhea caused by E. coli O104:H4-contaminated fenugreek seeds hit Germany. Tracing the epidemic revealed more than 3,800 cases, with HUS developing in more than 800 of the cases, including 36 fatal cases. Nearly 90% of the HUS cases were in adults. (8)

 

CAUSES AND RISK FACTORS:

TYPICAL HUS.  

Enterohemorrhagic Escherichia coli (EHEC), of which E. coli O157: H7 is the most common serotype.

 

ATYPICAL HUS:

Atypical hemolytic uremic syndrome:

Atypical HUS (aHUS) represents 5–10% of HUS cases and is largely due to one or several genetic mutations that cause chronic, uncontrolled, and excessive activation of complement. This results in platelet activation endothelial cell damage, and white blood cell activation, leading to systemic TMA, which manifests as decreased platelet count, hemolysis (breakdown of red blood cells), damage to multiple organs, and ultimately death. Early signs of systemic complement-mediated TMA include thrombocytopenia (platelet count below 150,000 or a decrease from baseline of at least 25%) and evidence of microangiopathic hemolysis, which is characterized by elevated LDH levels, decreased haptoglobin, decreased hemoglobin (the oxygen-containing component of blood), and/or the presence of schistocytes. Despite the use of supportive care, an estimated 33–40% of patients will die or have end-stage renal disease (ESRD)(3)

 

SIGNS AND SYMPTOMS:

Early symptoms can include diarrhea (which is often bloody), stomach cramps, Mild fever, Vomiting that results in dehydration and reduced urine. HUS typically develops about 5–10 days after the first symptoms, but can take up to 3 weeks to manifest, and occurs at a time when the diarrhea is improving. Related symptoms and signs include lethargy, decreased urine output, blood in the urine, kidney failure, low platelets, (which are needed for blood clotting), Destruction of red blood cells (microangiopathic hemolytic anemia),  (a yellow tinge in skin and the whites of the eyes), Seizures, Bleeding into the skin, Thrombotic Microangiopathy (TMA), which can include abdominal pain, low platelet count, elevated lactate dehydrogenase LDH, (a chemical released from damaged cells, and which is therefore a marker of cellular damage) decreased haptoglobin (indicative of the breakdown of red blood cells) anemia (low red blood cell count), schistocytes (damaged red blood cells, elevated creatinine (a protein waste product generated by muscle metabolism and eliminated renally),proteinuria (indicative of kidney injury), Acute kidney failure, Hypertension (high blood pressure), Myocardial infarction (heart attack), stroke, lung complications, Pancreatitis (inflammation of the pancreas), Liver necrosis (death of liver cells or tissue), Encephalopathy (brain dysfunction). Failure of neurologic, cardiac, renal, and gastrointestinal (GI) organs, as well as death, (3)

 

PATHOPHYSIOLOGY:

HUS is one of the thrombotic microangiopathies, a category of disorders that includes STEC-HUS, aHUS, and thrombotic thrombocytopenic purpura (TTP). STEC-HUS occurs after ingestion of a strain of bacteria expressing Shiga toxin (s), usually types of E. coli, that expresses verotoxin. These Shiga toxins bind GB3 receptors, globotriaosylceramide, which are present in renal tissue more than any other tissue and are also found in central nervous system neurons and other tissue,asymptomatic carriers. Once the bacteria colonize, diarrhea followed by bloody diarrhea, hemorrhagic colitis, typically follows. STEC-HUS is usually preceded by a prodrome of diarrhea, the typical pathophysiology of HUS involves the binding of Shiga-toxin to the globotriaosylceramide  receptor on the surface of the glomerular endothelium. Additionally, the binding action of Shiga-toxin inactivates a metalloproteinase called ADAMTS13, the deficiency of which causes the closely related TTP. Once ADAMTS13 is disabled, multimers of von Willebrand Factor (vWF) form and initiate platelet activation, causing microthrombus formations, which have adhered to the endothelium via large multimeric vWF. Through a mechanism known as microangiopathic hemolysis, the growing thrombi lodged in smaller vessels destroy red blood cells (RBCs) as they squeeze through the narrowed blood vessels, forming schistocytes, or fragments of sheared RBCs. The presence of schistocytes is a key finding that helps to diagnose HUS. Typically, this hemolysis results in a hemoglobin level of less than 80 g/L.The consumption of platelets as they adhere to the thrombi lodged in the small vessels typically leads to mild or moderate thrombocytopenia with a platelet count of less than 60,000 per microliter, and ischemia may develop. The kidneys and the central nervous system (brain and spinal cord) are the parts of the body most critically dependent on high blood flow, and are thus the most likely organs to be affected. However, in comparison to TTP, the kidneys tend to be more severely affected in HUS, and the central nervous system is less commonly affected, the kidneys may show patchy or diffuse renal cortical necrosis. STEC- aHUS does not follow STEC infection and is thought to result from one or several genetic mutations that cause chronic, uncontrolled, and excessive activation of complement. This leads to platelet activation, endothelial cell damage, and white blood cell activation, leading to systemic TMA, which manifests as decreased platelet count, hemolysis, damage to multiple organs, and ultimately, death (6)(9).

 

TREATMENT:

Treatment involves supportive care and may include dialysis, steroids, blood transfusions, and plasmapheresis. While eculizumab is being used to treat atypical hemolytic uremic syndrome, no evidence as of 2018 supports its use in the main forms of HUS. Scientists are trying to understand how useful it would be to immunize humans or cattle. (9)(10)

 

PREVENTION:

The effect of antibiotics in shiga toxin producing E. coli is unclear. While some early studies raised concerns more recent studies show either no effect or a benefit. (7)

 

PROGNOSIS:

Acute renal failure occurs in 55–70% of people with STEC-HUS, although up to 70–85% recovers renal function. Patients with aHUS generally have poor outcomes, with up to 50% progressing to ESRD or irreversible brain damage; as many as 25% die during the acute phase. However, with aggressive treatment, more than 90% of patients survive the acute phase of HUS, and only about 9% may develop ESRD. Roughly one-third of persons with HUS have abnormal kidney function many years later, and a few require long-term dialysis. Another 8% of persons with HUS have other lifelong complications, such as high blood pressure, seizures, blindness, paralysis, and the effects of having part of their colon removed. The overall mortality rate from HUS is 5–15%. Children and the elderly have a worse prognosis.⁽⁵⁾⁽⁷⁾

 

REFERENCES:

1.        "Haemolytic uremic syndrome". Genetic and Rare Diseases Information Center (GARD). Retrieved 21 November 2018.

2.        Salvadori, M; Bertoni, E (6 August 2013). "Update on hemolytic uremic syndrome: Diagnostic and therapeutic recommendations". World Journal Nephrology 2 (3):566. Doi:10.5527/wjn.v2.i3.56. PMC 3832913. PMID 24255888.

3.        Ferri, Fred F. (2010). Ferri's Differential Diagnosis E-Book: A Practical Guide to the Differential Diagnosis of Symptoms, Signs, and Clinical Disorders. Elsevier Health Sciences. p. 219. ISBN 978-0323081634.

4.        Noris, M; Remuzzi, G (2009). "Atypical hemolytic–uremic syndrome". N Engl J Med. 361 (17): 761687. Doi:10.1056/NEJMra0902814. PMID 19846853.

5.        Benz, K; Amann, K (2010). "Thrombotic microangiopathy: new insights". Current Opinion in Nephrology and Hypertension. 19 (3): 242–247. Doi:10.1097/MNH.0b013e3283378f25. PMID 20186056.

6.        Gasser C, Gautier E, Steck A, Siebenmann RE, Oechslin R (September 1955). "Hemolytic–uremic syndrome: bilateral necrosis of the renal cortex in acute acquired hemolytic anemia". Schweiz Med Wochenschr (in German). 85 (38–39): 905–9. PMID 13274004.

7.        Centers for Disease Control and Prevention. U.S. Department of Health & Human Services. 2017-11-30. Retrieved 22 November 2018.

8.        "Hemolytic uremic syndrome (HUS)". Center for Acute Disease Epidemiology. Iowa Department of Public Health. Retrieved 21 November 2018.

9.        Boyer, O; Niaudet, P (August 2011). "Hemolytic Uremic Syndrome: New Developments in Pathogenesis and Treatments". Int J Nephrol. 2011: 908407. Doi:10.4061/2011/908407. PMC 3159990. PMID 21876803.

10.     Kumar, V; Cotran, RS; Robbins, SL, eds. (2002). Robbins Basic Pathology. Philadelphia, PA: Saunders. ISBN 978-0721692746.

 

 

Received on 05.03.2020          Modified on 08.04.2020

Accepted on 29.04.2020      ©A&V Publications All right reserved