Characteristics

• • Defined as triad of microangiopathic hemolytic anemia, AKI, and thrombocytopenia

Epidemiology

• • Mainly affects children age <5 years

  • Most common cause of AKI in children

  • Incidence is 1-2 cases/100,000

  • Mortality is low (3%-5%) with D+ (plus diarrhea) HUS but nears 25% with D - (minus diarrhea) HUS

Causes

D+HUS

• • Escherichia coli serotype O157:H7 is most common cause in children; acquired by eating undercooked meats, unpasteurized milk, and fruits or vegetables, or contact with farm animals (petting zoos)

  • Shigella dysenteriae type I is another cause and may result in more severe disease

D-HUS (atypical HUS)

• • Includes Group Of Various Etiologies

  • S. pneumoniae is a leading cause

  • Drugs and toxins (e.g.., cyclosporine, tacrolimus, clopidogrel)

  • Other infections including HIV

  • Genetic Causes Have Been

    • Inherited deficiencies of von Willebrand factor-cleaving protease complement factors

    • Inherited deficiency of vitamin B metabolism

    • Other familial inherited disorders

Secondary HUS

• • diseases associated with microvascular injury including SLE, antiphospholipid-antibody syndrome, and malignant HTN

Risk factors

• • eating undercooked hamburgers and age <5 years

Pathophysiology

• • Microvascular injury with endothelial cell damage is characteristic

    • In classic D+ forms of HUS, toxin causes direct damage to endothelial cells → intravascular thrombogenesis → ↓ decreased GFR

    • Platelet aggregation → consumptive thrombocytopenia

    • Microvascular injury and partial vascular occlusion → mechanical damage to RBCs → microangiopathic hemolytic anemia

  • Genetic causes may be triggered by inciting event like infection

Clinical features

Historical findings

• • Typically present with abdominal pain, preceded by bloody diarrhea (in 90%), vomiting, and fever

  • Acute onset of pallor, irritability, and lethargy follows initial illness Oliguria can be seen early

  • Neurologic symptoms like seizures, irritability, or altered mental status

Physical exam depends on organ systems involved

• • Abdominal pain is prominent and exam may demonstrate acute abdomen with signs of peritonitis with potential for pancreatitis

  • GI bleeding is often noted; bowel perforation is possibility

  • Cardiac involvement occurs in about 10% of cases

    • Symptoms may include congestive heart failure (CHF) mainly due to volume overload and arrhythmias

    • Acute respiratory failure (acute respiratory distress syndrome) may also rarely occur

  • Vital signs may demonstrate fever, HTN, or tachycardia (related to fever or dehydration)

Diagnosis

Essentials of Diagnosis

• • HUS caused by Shiga toxin producing E. coli O157:H7 is the MCC AKI in peds

  • Petechial rash, hypertension, acute-to-subacute renal failure

  • Often preceded by gastroenteritis or exposure to offending medication

  • Frequently associated with antecedent Campylobacter infection (may be very mild to occult)

  • Laboratory reports notable for thrombocytopenia, anemia, renal failure, elevated LDH, normal prothrombin time and partial thromboplastin time as well as fibrin and fibrinogen degradation products

Differential diagnosis

• • Other causes of microvascular injury and bleeding including TTP and disseminated intravascular coagulation (DIC) can present similarly

  • Gastroenteritis in general can present similarly to HUS but does not typically have associated laboratory findings

  • Autoimmune processes like SLE and antiphospholipid syndrome can have findings similar to HUS

Laboratory findings

• • CBC will demonstrate thrombocytopenia (usually 20,00o-lOO,OOO/mm3) , anemia (may be mild initially but quickly progresses), and leukocytosis i. Reticulocyte count typically high

  • Prothrombin time (PT) and partial thromboplastin time (PTT) are normal

  • Coombs test for autoimmune hemolysis is typically negative; haptoglobin will be low, supporting hemolytic process

  • Urinalysis with microscopic hematuria and proteinuria

  • Stool cultures for E. coli 0157:H7 are positive >90% of time if obtained during 1st week of illness

  • Renal panel will demonstrate elevated BUN and creatinine

  • Hemolysis (elevated lactate dehydrogenase and indirect bilirubin)

Imaging studies are not indicated

Treatment

Therapy is primarily supportive

• • Fluid and electrolyte management; dialysis is indicated for refractory acidosis, hyperkalemia, fluid overload, and/or uremia

  • HTN control

  • Seizure control

  • RBC transfusion to keep hemoglobin >7 gldL

  • Consultation with nephrologist or hematologist

Complications

• • MC complications are proteinuria, renal insufficiency, and HTN

Prognosis

• • For patients with D+HUS is generally good with complete recovery, but if residual HTN renal insufficiency persists beyond 1 year, they require close follow-up due to risk of CKD

  • Mortality <5%

  • Adult prognosis worse than kids

pPx

• • Prevention of D+HUS is best achieved with good handwashing to prevent spread of infection

Essentials of Diagnosis

• • Petechial rash, mucosal bleeding, fever, altered mental status, renal failure; many cases in HIV infection

  • Laboratory reports are notable for anemia, dramatically elevated LDH, normal prothrombin and partial thromboplastin times, fibrin degradation products, and thrombocytopenia

  • Most cases probably related to acquired inhibitor of von Willebrand factor (vWF)–cleaving protease; may also be secondary to drugs, chemotherapy, or cancer

  • Demonstrating decreased activity of vWF-cleaving protease inhibitor (ADAMTS13) may be diagnostic

Differential Diagnosis

• • Disseminated intravascular coagulation

  • Pre-eclampsia–eclampsia

  • Other microangiopathic hemolytic anemias

  • Catastrophic antiphospholipid antibody syndrome

  • Hemolytic-uremic syndrome

Treatment

• • Immediate plasmapheresis

  • Fresh-frozen plasma infusions help if plasmapheresis not readily available

  • Splenectomy and immunosuppressive or cytotoxic medications for refractory cases