HEMOLYTIC UREMIC SYNDROME, ATYPICAL, SUSCEPTIBILITY TO, 1

Diagnosis and Treatment

Hemolytic-Uremic Syndrome (HUS) is characterized by the formation of platelet thrombi in the affected organs. Its clinical manifestations are marked by the triad of microangiopathic hemolytic anemia, acute renal failure and thrombocytopenia (low platelet number).

HUS consists of a type of thrombotic microangiopathy, as well as thrombotic thrombocytopenic purpura (TTP).

Hemolytic-uremic syndrome (HUS) can be divided in the typical form, with episodes of diarrhea (SHU-typical) and the atypical (atypical HUS) form usually with little or no episodes of diarrhea.

The Typical SHU are mainly characterized by infectious and diarrheal episodes.

The most common etiology of typical HUS is Shiga toxin Escherichia coli (STEC) representing over 70% of cases of HUS after diarrhea in the United States. It has been described in different strains of EHEC associated with HUS episodes worldwide.

About 3 days after ingestion of E. coli, patients develop abdominal pain, diarrhea, vomiting and fever.

By the third day of diarrhea, the disease progresses to episodes of bloody diarrhea that would have rarely bleeding on the first day of diarrhea.

In 80-90% of children with positive culture for E. coli, the presence of blood in the stool was found.

Patients usually have normal levels of platelets, creatinine, and hematocrit.

 

 

Other etiologies that also contribute to episodes of typical form of HUS:

  • Streptococcus pneumonia
  • Viral infections related to Human Immunodeficiency (HIV positive patients?!)
  • Drug toxicity, particularly in transplanted patients and patients under cancer treatment.
  • Rare occurrences have been reported in pregnant women carrier of autoimmune diseases, especially with a history of Systemic Lupus Erythematosus.

 

The atypical HUS is related to alterations in the complement system caused by mutations in genes that control the this system and also complement B factor antibodies.

The atypical HUS bites, although described as no episodes of diarrhea in some patients may be associated s also the presence of diarrhea.
 

      

 

Usually the clinical diagnosis of HUS is based on clinical and laboratory findings: an episode of diarrhea due to bacteria producing STEC, followed by the abrupt onset of the triad of microangiopathic hemolytic + anemia thrombocytopenia + acute renal failure, is strongly suggestive of HUS. To confirm the diagnosis, it is not required in molecular diagnostics to identify genetic mutations specific to SHU.

Below there is a flowchart for the diagnosis of HUS.

The prognosis of Hemolytic-uremic syndrome (HUS) has improved greatly due to the early institution of supportive therapy, intensive care, renal replacement therapy and biological therapy.

Some important points in symptomatology that deserve a special attention:

  • Anemia
  • Thrombocytopenia
  • Disorders of fluids and electrolytes
  • Acute kidney injury (AKI)
  • Hypertension
  • Neurological alterations
  • Involvement of other organs, including colon, heart, pancreas and lung

 

Treatment

Anemia

Patients with HUS may present important and rapidly evolving anemia.
The possibility of blood transfusion must be evaluated when the hemoglobin concentration is <6 g / dL and hematocrit concentrations are <18% for avoiding cardiovascular complications and pulmonary diseases. Around 80% of children with HUS require blood transfusion.


Thrombocytopenia

Platelet transfusion is indicated for patients with HUS episodes of clinically significant bleeding or against an invasive procedure. Platelet transfusions are uncommon; the significant clinical bleeding is rare because the platelet count rarely drops below 10,000 / mm3.

 

Intravascular fluids

The volume of fluid of patients with HUS should be carefully monitored. The control of intravascular volume decreased or increased is critical to avoid potential complications of HUS.
Episodes of vomiting, decreased oral intake of fluids or diarrhea, may result in decreased intravascular volume, while episodes of oliguria or anuria may increase intravascular volume.
In some cases, the expansion of the fluid can be indicated to neutralize in patients with renal hypoperfusion volume depletion. In contrast, the fluid restriction may be necessary for patients with increased intravascular volume leading to oliguria or anuria.
Weight gain initially may not be a good marker of intravascular volume because hypoalbuminemia and capillary leakage of fluid can cause edematous state, resulting in an increase in the volume of total body water.
The fluid balance should be monitored as a function of intravascular fluid volume and renal function of the patient.
Patients with increased intravascular volume may need dialysis for removal of fluids, especially if there are cardiac and pulmonary accumulation.
The frequent monitoring of fluid balance, weight and vital signs is imperative for the proper control of these patients. At the first sign of hypertension or cardiac overload of fluid intake should be restricted. The use of diuretics rarely reverses episodes of anuria, however, the use of furosemide (2 to 5 mg / kg per dose) can be tried to induce diuresis, especially in patients with overhead circulation.
Diuretics should not be continued in patients who fail to respond to treatment. Therapy with dialysis is required if the fluid restriction and administration of diuretics or fail to improve the patient's cardiorespiratory compromise in a timely manner.

 

Electrolytes

Electrolyte abnormalities are common usually due to acute renal failure, including episodes of hyperkalemia, hyperphosphatemia, and metabolic acidosis.
The management of these disorders is not different from the methods usually applied in other pathologies.


Acute Renal Failure (ARF)

Patients with HUS that develop kidney failure should avoid nephrotoxic drugs. The dosage of drugs that are excreted via the kidney should also be adjusted according to the renal dysfunction.
There is no evidence that early dialysis provides improved clinical outcome. Indications for dialysis in children with HUS resemble those of children with other causes of ARF.


Hypertension

In patients with HUS, hypertension is caused by the expansion of the intravascular volume or ischemia-induced renin-angiotensin system. Treatment must be based on the control and correction of the fluid volume and the use of antihypertensive agents.

 

Neurological dysfunction

The complications of the Central Nervous System (CNS) reactions such as seizures and strokes are predictive of poor prognosis. In any patient presenting HUS with severe neurological dysfunction, radiological examinations should be performed periodically to monitor possible complications in the CNS.
In severe CNS manifestations must be taken into account the systematic control of the arterial hypertensive patients with mostly severe hypertension. In these patients, blood pressure control may result in significantly higher resolution of some of the CNS manifestations.

 

Involvement of other organs

Although not as common as renal and neurological complications, patients may develop serious gastrointestinal complications, cardiac dysfunction and pancreatitis, respiratory complications secondary to increased intravascular volume.
These complications should be treated with an appropriate conduct for the underlying pathology.

 

Gastrointestinal Complications

The colitis is a complication that can occur and eventually severe episodes that eventually may progress to necrosis and intestinal perforation.
Patients with these complications should be monitored frequently.
Cardiac dysfunction may be a result of ischemia or heart fluid overload, including pericarditis episodes that might be associated with uremia.

 

Pancreatitis

Episodes of acute pancreatitis can occur with clinically significant deficiency of insulin, in which cases insulin therapy may be needed for the treatment of hyperglycemia.

 

The pulmonary complications

Pulmonary edema and stroke can occur as a result of intravascular fluid overload. The control and fluid restriction, use of diuretics, dialysis, and ventilatory support may be necessary.

 

Specific Therapy

Eculizumab is a monoclonal antibody to the complement factor C5 that acts by blocking the complement activation and it has been used to treat patients with HUS complement mediated.
Eculizumab may also be beneficial in patients with HUS STEC with CNS involvement (cite literature referencing it).

The initial dose for treating Eculizumab HUS STEC is dependent on the body weight of the patient as follows:

  • 5 to <10 kg - 300 mg
  • 10 to <40 kg - 600 mg
  • ≥ 40 kg - 900 mg

The decision to further increase the doses of Eculizumab is dependent on the patient's clinical status. If the plasmapheresis therapy is also being performed, a repeated dose may be done after each plasmapheresis session