Hemolytic Uremic Syndrome

Hemolytic Uremic Syndrome is the most common cause of acute renal failure in children and is characterized by:

Microangiopathic hemolytic anemia
Thrombocytopenia
Acute kidney injury

There are three subgroups of hemolytic anemia (1):

STEC-HUS is used to describe hemolytic-uremic syndrome mediated by Shiga toxin (Stx)–producing Escherichia coli. This is also called classic, typical, Stx, diarrhea-positive, or D ⁺ hemolytic-uremic syndrome.*

Atypical HUS (aHUS) is used to describe hemolytic-uremic syndrome not mediated by Shiga toxin. This is also called diarrhea-negative, non–diarrhea-associated, or D ^– hemolytic-uremic syndrome. This disease is usually mediated by abnormalities of the complement system or other heritable factors.

Pneumococcal-associated HUS is a subtype of atypical hemolytic-uremic syndrome, mediated by neuraminidase in the presence of infection withStreptococcus pneumoniae. This is also called neuraminidase-associated hemolytic-uremic syndrome.

*For an outstanding brief review of E. coli and of Shigella toxin producing E. coli see E. Coli General Information from the Centers For Disease Control

The differential diagnosis for Hemolytic Uremic Syndrome is (2):

Differential Diagnoses

Acute Poststreptococcal Glomerulonephritis

Bacterial Sepsis

Disseminated Intravascular Coagulation

Henoch-Schonlein Purpura

Immune Thrombocytopenic Purpura (ITP)

Systemic Lupus Erythematosus (SLE)

Thrombotic Thrombocytopenic Purpura (TTP)

Vasculitis and Thrombophlebitis

The clinical presentation of hemolytic uremic syndrome is (3):

Patients with Shiga toxin–producing E coli hemolytic-uremic syndrome (STEC-HUS) experience several days of diarrhea, with or without vomiting, followed by sudden onset of symptoms such as irritability and pallor. In more than 80% of patients, the diarrhea is visibly bloody. Other symptoms include restlessness, oliguria, edema, and macroscopic hematuria. In some patients, the prodrome may improve as hemolytic-uremic syndrome symptoms begin. The clinical picture may mimic that of an acute abdomen. In patients infected with a Shiga toxin (Stx)–producing strain of E coli, hemolytic-uremic syndrome occurs in 5-15%.

. . . most cases of STEC-HUS are sporadic, with no clearly identifiable source of infection, even when stool culture yields a toxigenic organism.

Atypical hemolytic-uremic syndrome (aHUS) may follow a respiratory illness, especially when caused by S pneumoniae.

Features of all forms of hemolytic-uremic syndrome include the following:

Hematology: Hemolysis occurs in all patients with hemolytic-uremic syndrome. It can proceed rapidly, resulting in a rapid fall of the hematocrit. Platelet counts usually fall below 40,000/µL. However, the degree of thrombocytopenia does not correlate with the severity of hemolytic-uremic syndrome, and some children can maintain relatively normal kidney function despite severe hematologic abnormalities. Many patients have petechiae, purpura, and oozing from venipuncture sites. Overt bleeding is less common.

CNS: Patients often present with sudden onset of lethargy and irritability. Other findings may include ataxia, coma, seizures, cerebral swelling, hemiparesis, and other focal neurologic signs. CNS changes may be caused by cerebral ischemia from microthrombi, effects of hypertension, hyponatremia, or uremia. aHUS tends to be associated with a greater number of neurologic symptoms than STEC-HUS.

Renal system: Acute renal insufficiency usually begins with the onset of hemolysis. Although patients have decreased urine output, frequent diffuse watery stools may mask this sign. If renal insufficiency is not recognized and treated, hyponatremia, hyperkalemia, severe acidosis, ascites, edema, pulmonary edema, and hypertension ensue.

GI tract: STEC-HUS is usually preceded by 3-12 days of watery or bloody diarrhea. Vomiting and crampy abdominal pain are also common. Note that diarrhea may improve as the other hemolytic-uremic syndrome symptoms begin (eg, thrombocytopenia, renal insufficiency). Life-threatening complications include intestinal perforation or necrosis. Even without these complications, the colitis of hemolytic-uremic syndrome may cause severe abdominal pain, which may persist for several days into the illness.

Infectious signs: Fever is present in 5-20% of patients. The presence of fever, leukocytosis, or both is a prognostic indicator of the risk of developing more severe hemolytic-uremic syndrome.

Pancreas: Mild pancreatic involvement is common but can be severe on occasion, with necrosis, pseudocysts, or both, which can leave the patient with type 1 diabetes and, on rare occasion, exocrine dysfunction.

Cardiovascular: Congestive heart failure may occur.

I’ve included a link to the YouTube video Hemolytic Uremic Syndrome (8:a5) by Dr. Larry Mellick. The video published July 17, 2015 discusses the clinical case of a young girl who developed hemolytic uremic syndrome.

The mother in the video provides a clear description of the clinical course of the child’s illness.

What follows is the mother’s history of the child’s illness. It seems that the illness began on a Wednesday when she was seen by the pediatrician. Then continued on through the following week. The child was seen again by the pediatrician on Monday of the following week when both he and the mother agreed the child was improving. However, the illness continued for [it seems from the video] for four or five more days at which time the child presented to the emergency department [so it seems that the child presented to the ED perhaps nine or ten days after the start of her illness]:

The mother states that the child got sick last week. She had bloody diarrhea. She saw the pediatrician and he ordered a stool sample.

Mother reports that the results of the stool culture came back over the weekend and was negative. [I believe that toxigenic e. coli requires special non-routine culture].

Wednesday, Thursday, and Friday were the bad days for the bloody diarrhea. By Saturday it had slowed down to 4 or 5 or maybe 3 or 4.

Sunday she finished – no more vomitting, no more diarrhea – so we’re thinking we just need to get her rehydrated and eating again (she wasn’t eating anything) and she would be better.

Monday we took her back to the pediatrician again just to double check. She had lost about six pounds. And the pediatrician was thinking she doesn’t look dehydrated so just push fluids and try to get her to eat small amounts of food.

Starting Tuesday, every morning when she wakes up she feels really queezy and vomits. Then she kind of feels better and she can eat a little bit and drink a little bit throughout the day. And she’d really perk up in the afternoon once she got a little food in her.

Then we’d start the same thing the next morning. She’d feel nauseous; we’d give her Zofran to keep her from being nauseous, and she’d would eat and start to feel a little better.

After 5 days of this, mother states I thought, there must be something else going on. And I think this is when mother went to ED.

The child, mother states when asked, has been peeing normally which for her is not much. She normally doesn’t drink a lot and doesn’t pee a lot. She probably pees 3 to 4 times a day which is typical for her.

At 4:10 Dr. Mellick asks “When she was having her bloody diarrheas, how many bloody diarrheal stools a day was she having?”

Mother answers Wednesday and Thursday and even into Friday she was having bloody diarrhea constantly – every 15 minutes. And terrible stomach cramping. I forgot to mention that [earlier]. She’d just double over in pain. She was up all night Wednesday night and Thursday night.

Wednesday and Thurday and Friday were the bad days for the bloody diarrhea. By Saturday, it had slowed down to maybe 3 or 4.

By Sunday, I hadn’t noticed any more blood in her stool. It is still loose and it is not quite normal and she’s not going frequently.