In this lecture, we're going to review Hemolytic-Uremic Syndrome in Children. Hemolytic-uremic
syndrome is a combination of a few different findings. These patients have a microangiopathic
hemolytic anemia. They'll have acute kidney injury and they'll have thrombocytopenia. So,
anemia and thrombocytopenia as well as kidney injury. This disease typically happens in
children under 5 years of age and it's the most common cause of acute kidney injury in
children. If it's preceded by diarrhea, the mortality is fairly low, 4% although those odds are
what you would like for your own child. If it's not preceded by diarrhea, the mortality is high,
25%. Hemolytic-uremic syndrome used to be classified into diarrhea positive and diarrhea
negative types. But that classification has been replaced by an etiologic classification because
diarrhea can be associated with different etiologies. The updated classification of HUS includes
acquired and hereditary types. There are several points to highlight in this large classification.
Note that Shiga toxin-producing E. coli or STEC accounts for 90% of the cases in the US
whereas Shigella dysenteriae type 1 is a more common cause in developing countries.
Streptococcus pneumoniae accounts for 40% of non-STEC cases. Hereditary types are mostly
caused by mutations in the genes' coding for complement components or in those coding for
proteins involved in the coagulation pathway. We typically see patients getting E. coli 0157
from undercooked meats, unpasteurized milk, unwashed fruit and vegetables or petting zoos.
We tend to see little outbreaks happen sometimes from petting zoos where that bacteria has
become prevalent and patients are perhaps not cleaning their hands appropriately after
petting the farm animals. Non-STEC-HUS cases are most often caused by Streptococcus
pneumoniae lung infections especially if they're associated with pleural effusions, but this is
rare. HIV can also cause non-STEC-HUS. Infectious HUS is typically an illness that starts with
bloody diarrhea. So in a large study at the Children's Hospital of Philadelphia, they looked
at many decades and they only found a handful of cases, but in those cases it is usually from
patients who had complicated pneumonia with pleural effusions. Medications such as
cyclosporine or tacrolimus can also cause non-STEC-HUS. Also, HIV can cause the problem and
so we might see this in patients with HIV. So, infectious HUS is typically an illness where it
starts with a bloody diarrhea. Patients may have vomiting and fever with the acute illness
from the usually E. coli 0157. This diarrhea may resolve or it may still be present when the
new symptoms occur. And the new symptoms will be an acute onset of lethargy, irritability,
and key pallor. These patients will develop oliguria. They're developing oliguria because their
kidneys are shutting down. They may have neurologic syndromes present as well such as
altered mental status or seizure. The point is that these children can be very sick, 10% of
them can go into congestive heart failure. They can have all kinds of substantial problems and
we have to watch them very carefully. Here is an example of what a slide might look like if you
are to look at the blood of a patient with hemolytic-uremic syndrome. They will have
schistocytes or other evidence of a normocytic anemia; however, there will be evidence of
the microangiopathic nature of this anemia. Remember, these cells are being viciously split
apart inside the blood vessels. Additionally, patients typically have a low platelet level usually
between 20,000 to 100,000 platelets. This is because, again, of a consumptive coagulopathy.
In patients with hemolytic-uremic syndrome, the Coombs test should be negative. This is not
an antibody-mediated disease, these cells are being broken apart because it's a
microangiopathic state. A urinalysis will show hematuria and proteinuria. Additionally, we
may get a chem-7. The chem-7 will show a high BUN and creatinine consistent with intrarenal
disease. If it's severe, the patient may have high potassium from renal failure or from cell
lysis in combination from renal failure. And because of their hemolysis, patients will have a
high LDH and often a high indirect bilirubin and maybe frankly jaundiced. In patients with
hemolytic-uremic syndrome, they have a bloody diarrhea caused by E. coli 0157:H7. It may be
tempting to give them antibiotics to treat that E. coli and to think that that might prevent the
hemolytic-uremic syndrome. On the contrary, it seems that treatment may, in some patients,
actually increase risk of HUS. So we do not treat patients with antibiotics in this condition.
What we will do is treat people symptomatically for their problems. First, we need to be very
careful with fluid and electrolyte management. Remember, we're trying to maintain a situation
where the child is remaining hydrated and yet in the child there may be some renal failure.
Also, a high potassium is an emergency because patients may have arrhythmias. So we have
to keep an eye on that potassium. Close monitoring of both fluid and electrolytes is absolutely
indicated. If patients end up in trouble, we may have to do dialysis to try to control levels of
electrolytes and the fluid in the blood. We also want to control their hypertension. We can't
let that get out of control and we may provide medications for that purpose. If patients are
seizing, we need to control the seizures as well and we'll provide seizure medications. It's
important to transfuse children if they are symptomatic and have tachycardia. We usually try
to keep them above approximately the level of 7, but do not transfuse platelets. It would be
rare for these children to get into a trouble zone say less than 5000 to 10,000 and the
platelets almost immediately get consumed. So, you'll just worsen the coagulopathic state.
In resource rich countries, the mortality rate of HUS is less than 5%, but another 5% of
patients have significant sequelae for example stroke or end-stage renal disease and 30-50%
of children will show evidence of irreversible renal injury manifesting as hypertension, mild
proteinuria, a subclinical decline in glomerular filtration rate, and chronic kidney disease. The
mortality rate of HUS in underdeveloped countries remains as high as 72%. However, some
patients progressed to end-stage renal disease and may eventually need a transplant. The key
thing here is that we have to promote handwashing and safe processing of foods and certainly
handwashing when visiting the petting zoo. That's a summary of hemolytic-uremic syndrome.
Thanks for your attention.