A Parent's Perspective - aHUS BOOTCAMP

A Parent's Perspective - aHUS BOOTCAMP

You or your child have been diagnosed with Atypical HUS - Now What?

by Cheryl Biermann, Linda Burke, and Jodi Kayler

So, you or your child's symptoms have lead you to the doctor or straight to the hospital. Symptoms may have included extreme fatigue, puffiness, vomiting, paleness, fever, and perhaps some diarrhea. It is possible that you noticed swelling as well as dark or strong smelling urine. Your child's appetitie may have completely vanished and you are struggling to get him or her to eat. Since the medical diagnosis of atypical HUS (hemolytic uremic syndrome) you're now hearing terms like schistocytes, blood smears, platelets, red and white blood cell counts, and protein in the urine! What does it all really mean?

Types of Hemolytic Uremic Syndrome (HUS) There are two types of HUS: typical HUS (caused by E coli or other othen food/water borne pathogens) and atypical HUS (usually a genetic mutation but sometimes triggered by other illnesses or even by unknown causes)

*HUS (Typical HUS) Typical HUS can be triggered by E coli bacteria or other, often food borne pathogens (such as with the 2007 contaminated spinach outbreak). This can cause an immune system response that causes hemolysis (shattering of red blood cells) and kidney failure. In typical HUS, most cases will not occur again after the initial onset (typically lasting 4-6 weeks). Cases can see long-term kidney damage and issues with high bloood pressure.

*atypical HUS Atypical HUS can be triggered for a variety of reasons such as genetic mutation, pneumonia, or gastro-intestinal illness - as well as unknown reasons (ideopathic). The biggest difference between types is that atypical HUS is unpredictable and can/will relapse or recurr with some frequency. It is estimated that there are from 300 to 600 aHUS patients in the United States, most of them young children, but each case is quite different. Some cases will relapse intermittently - often triggered by exposure to a virus- while others have chronic symptoms and never truly reach remission. Some relapses are relatively mild and easily controlled while other aHUS events come on devastatingly quick.

What happens to the body during the attack?

With aHUS the red blood cells break apart and these cell fragments travel to the kidneys, making tiny microscopic clots causing severe anemia and kidney failure. When the kidneys fail to work, the body fails to rid itself of toxins, the urine output declines, and the amount of protein in the urine will increase. This process can permanently damage the kidneys. Poorly functioning kidneys also lead to high blood pressure and swelling which can stress the heart and lungs. In rare cases blood clots may develop somewhere else in the body, with some aHUS patients also experiencing neural events such as seizure activity. Platelets are consumed during aHUS activity and LDH levels will rise, so lab tests must be ordered to give the physican an overview of the disease process. Treatment will be determined by lab test results, so expect blood draws to be ordered by your doctor and their results to discussed with you (CBC, BMP, and LDH are lab tests commonly ordered).

About the Doctors

Atypical HUS is a very rare disease, estimated at 300 to 600 cases in America and about 1000 patients worldwide. Having knowledgeable specialists is critical for successful treatment, though due to the rarity of this disease few doctors have experience with treating another aHUS case. Typically these are the types of doctors that will be primarily involved in an aHUS case (although others may be consulted): Nephrologists are experts of kidney dieases. This doctor will monitor kidney function, electrolytes, blood pressure, disease activity, and dialysis (when necessary). Kidneys are very sensitive organs and care can be complex/difficult due to the wide range of issues. This doctor should be a primary link for aHUS cases and should be heavily involved in a patient's treatment and care plan. Hematologists are experts in blood diseases. This doctor will closely monitor aHUS activity and its' effects on the body's blood. Sometimes a consulting physican may be an oncologist, a doctor who specializes in cancer and who may asked for their opinion on other blood diseases. Many hospitals place aHUS in the care category of nephrologists, still others choose to send aHUS cases to hemotolgists. Physicans entrusted with aHUS cases must have expertise in both kidney and blood aspects.

Treatment Types

Be aware that aHUS cases DO NOT have a standard 'treatment protocol' as is common in most other diseases. Due to the complexity and variability of aHUS symptoms, expect that your physician will try one or more of the options below and await lab results to see the degree of treatment's effectiveness. Some patients respond well to one treatment type chosen, while others' lab work will indicate that another treatment yields better lab values. Blood samples drawn from the aHUS patient will yield lab test results, the critical keys that determine treatment type and frequency. Some aHUS patients who do not respond to plasma products may respond to treatments that target the immune system. Sometimes IVIG (intravenous immune globulin) is used in conjunction with, or instead of, plasma products. IVIG is a man-made blood product that can help to regulate the immune system. Steroids, such as Predisone, are also sometimes effective but can lead to increased blood pressure in aHUS patients and should be used only under very close medical care. Due to the ongoing nature of the disease process and subsequent damage to the kidneys, nearly all aHUS patients will need some kind or combination of blood pressure medication. Managing high blood pressure (hypertension) is critical to keep the heart and kidneys from being stressed.

*Blood Transfusions: Some type of blood product transfusion is almost always the first line of treatment. Typically, aHUS patients are admitted to the hospital with lab tests indicating low red blood cells and low platetlet numbers. Depending on the doctor's decision, a patient may receive packed red blood cells, whole blood, and/or platelets in order to stabilize their current situation. These products help to return the blood to a more normal level for a brief time but do not treat the disease. When blood products are given, doctors have to closely manage fluid levels in the body. If the kidneys are not working properly, the extra fluid can cause stress on the heart and lungs.

*Plasma Therapies such as Plasmapheresis (also known as Plasma Exchange or Pheresis or Apheresis) and Plasma Infusion, Plasma therapy is the most traditional way to treat patients with aHUS. By transfusing FFP (Fresh Frozen Plasma) from a healthy donor into an aHUS patient in the process known as Plasma Infusion, its potential benefit is supplementing chemical compounds found deficient or absent in the patient's body. Plasma is the liquid component of the blood which transports the cells (red and white blood cells as well as platelets) and also carries various chemical compunds throughout the body. Plasma can be thought of as "the glue that holds the blood together and prevents the blood from shattering". Some aHUS cases do not respond to plasma infusion or patients can prove sensitive to adding the extra volume of fluid, so plasmaphersis is indicated for plasma therapy. A special pheresis machine is used to filter out all of the body's original plasma, replacing it with plasma from a healthy blood donor. In smaller aHUS patients, total blood volume is low and requires that the tubing of the pheresis machine be primed with a donor unit of packed red blood cells. Requiring surgery to place a 'central line' for plasmapheresis access, this process is more invasive but can also help to get control of the disease faster. Keeping the central line dry and sterile is of utmost importance. Patients with genetic mutations seem to respond especially well to plasma therapies.

*Soliris (generic name: Eculizumab)

A recent development in aHUS treatment was the FDA approval in Sept. 2011 of Soliris (eculizumab), a 'first in class' complement inhibitor approved for treatment of adults and children with aHUS.  Made by Alexion Pharmaceuticals, Soliris is an intravenous (IV) drug was that was originally FDA approved to prevent hemolysis (red blood cell destruction) in adult patients with the rare disease PNH.  This is the first treatment specifically approved for atypical HUS and the only one that targets the cause of the disease: over-activation of complement proteins that the body uses to fight infection.

In clinical trials, Soliris inhibited complement and reduced the blood clots that damage blood vessels, kidneys and other organs in patients with atypical HUS. Soliris also maintained or restored kidney function and improved quality of life in patients in the studies.  If given soon upon initial presentation/diagnosis of aHUS, early intervention with Soliris therapy can maintain kidney function and prevent long-term damage to the kidneys.  For more infromation, visit our website's Soliris Forum at http://atypicalhus.ning.com/forum/topics/soliris-1

 Access Choices

Accessing a patient's veins for treatment can be one of the most stressful times for aHUS patients and their family. In order to treat the disease, doctors must have quality intravenous (IV) lines to use. There are a large variety of IV lines such and while the standard or common IV line familiar to most people, most often the frequency of aHUS treatments and lab work monitoring will require a longer-term solution such as a picc line or the longest term choices of 'central line' such as a port-a-cath (under the skin) or a broviack or tessio line (external, with a dressing that needs to be dry and sterile). No matter the type of bloodstream access, it is imperative that STERILE PROCEDURES are implemented each and every time the line is accessed or de-accessed. A line infection can be life-threatening. (See this site's Line Care Forum.) Plasma infusions can be done with the familiar vein p