• aHUS overview
  • Who gets aHUS?
  • A genetic disease
  • The associated risks
  • Signs and Symptoms
  • Diagnosis
  • What to expect with aHUS
  • Living with aHUS
  • Communicating about aHUS
  • Resources and links
  • References

What is atypical Haemolytic Uraemic Syndrome (aHUS)?

 

aHUS is a rare, life-threatening, genetic disease that can damage vital organs such as the kidneys, brain and heart.2,6 The underlying cause is a dysfunction in the complement system, which is part of the immune system.2

The key feature of the disease is the formation of very small blood clots (thrombi) in small blood vessels throughout the body. These small blood clots accumulate at sites throughout the body and can severely damage the vital organs affected, such as the kidneys, brain and heart. The accumulation of these blood clots and the associated damage and swelling within small blood vessels is known as thrombotic microangiopathy (TMA).5

Click on image below to enlarge

  • Platelets are cells in the blood that help the formation of small blood clots in blood vessels. The formation of these clots damages blood vessels1,6
  • Red blood cells shatter as they flow through the damaged blood vessels5,6

The destruction of red blood cells causes a cascade of effects. Red blood cells carry oxygen around the body. Their destruction means that oxygen isn’t transported properly around the body, so tissues and organs, particularly the heart and brain, may not be able to function efficiently.

 

  • This results in damage to tiny blood vessels
  • The damage that occurs throughout the body is known as TMA 2,3
  • TMA can lead to problems in the kidneys and other vital organs2,3

Fortunately, our understanding of aHUS is growing rapidly and, with early diagnosis and good management, the risks associated with aHUS can be reduced. Today, for many people with aHUS, the disease can be effectively managed.

The name: atypical Haemolytic Uraemic Syndrome. The ‘atypical’ is to distinguish this disease from the more common HUS, a condition linked to bacterial infection1. ‘Haemolytic’ refers to the destruction of red blood cells and ‘Uraemic’ means ‘urea in the blood’. Urea is one of the primary components of urine, and under normal circumstances is not found in such high levels in the blood.

Who gets aHUS?



  • aHUS can occur at any age, with nearly half all people diagnosed aged 18 and older6
  • aHUS is caused by mutations (changes) to genes involved in the immune system1
  • Not everyone who has an identified genetic mutation develops aHUS6
  • If one person in a family has aHUS, this does not necessarily mean that other members of the family will also develop the disease6

aHUS is a genetic disease


The genetic change underlying aHUS causes 
chronic, uncontrolled activation of
 the complement system, which is part of the
 body’s immune system.2

This part of the immune system is always turned ‘on’, ready to attack foreign invaders, such as bacteria or viruses.4 During a time of ‘attack’, a healthy complement system has proteins that are able to protect the body’s own healthy cells.

When the Complement system is working normally, foreign or invading cells are the target; healthy body cells are not affected.

When the Complement system is uncontrolled, both foreign and healthy body cells are targeted.

These regulators are faulty in aHUS – the result of changes, or mutations, in the genes that produce them. As a result, the complement attack is directed against both foreign and healthy body cells, such as the inner lining of blood vessels. The genetic mutations result in permanent, uncontrolled, and excessive activation of the complement system which can do great damage to vital organs if it is left undiagnosed and untreated.4

Although aHUS is a genetic disease, many people with aHUS have none of the genetic mutations identified so far. Additionally, even when mutations are identified in a family, 50% of family members with the mutation remain healthy.6 This is an area in which much more research is needed.

There are serious risks associated with aHUS


aHUS is not a predictable disease and, as a result, people with aHUS and their families need to be aware of the signs and symptoms of an acute episode. If unmanaged or untreated, aHUS can cause a sudden and serious deterioration in health.5


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  • aHUS damages the kidneys. The kidneys’ job is to clean toxins from the blood and eliminate them through the urine. Kidney impairment affects the majority of people with aHUS, this may result in long-term dialysis and the need for a kidney transplant1,7,8
  • Approximately 48% of people with aHUS experience neurological symptoms, including stroke, brain damage and seizures1,3,9,10
  • Many people with aHUS experience cardiovascular symptoms, including heart attack, abnormal blood clotting, blood vessel damage and high blood pressure9,11,12
  • Diarrhoea and other gastrointestinal complications, such as inflammation of the bowel, nausea and vomiting are common in people with aHUS10,13,14
  • Other complications include colon and digestive tract inflammation, and lung, liver and pancreatic damage1,3,24

    Signs and Symptoms



    • Understanding aHUS and being able to recognise its signs and symptoms are important steps in managing the disease
    • People with aHUS face a life-long risk of sudden, life-threatening complications due to TMA5
    • The signs and symptoms of aHUS include:4,10,12,15-17

      • confusion
      • diarrhoea
      • nausea and vomiting
      • shortness of breath
      • heart symptoms
      • kidney symptoms

    Diagnosis


    The diagnosis of aHUS is not straightforward. The signs and symptoms of aHUS are similar to those of other diseases and people with aHUS may have other medical conditions as well as aHUS. Additionally, there is no specific diagnostic test for aHUS. Instead doctors need to rule out other diseases with similar signs and symptoms. Loss of kidney function may be one of the early signs of aHUS.5


    • aHUS is usually diagnosed by a nephrologist or a haematologist as the results of a series of tests5
    • Blood tests: the levels of red blood cells and platelets are likely to be low in a person with aHUS5
    • Kidney function: Creatinine is a chemical waste product excreted by the kidneys; raised creatinine levels are a sign that the kidneys are not functioning well5
    • Genetic testing is not necessary for the diagnosis of aHUS and the absence of an identified genetic mutation does not rule out aHUS2
    • A specialised blood test, known as the ADAMTS13 laboratory test can differentiate aHUS from other diseases21

    What you can expect

     

    Anyone who is diagnosed with aHUS can expect close, lifelong medical attention and support. The GP, Haematologist and Nephrologist are key to ongoing care, though other medical professionals, such as nurses, are often involved also. To help ensure that the best care is provided at all times, patients with aHUS need to keep in close contact with their medical team, alerting them promptly to any changes in health.

    aHUS treatment decisions are based on the extent of any organ damage, especially kidney damage, and the symptoms experienced. Patients may receive any of the following treatments:

    Plasma exchange or plasma infusion is frequently used by doctors to manage aHUS. During this process a plasma infusion is given over several hours at specialised treatment centres. Treatment with plasma does not, however, treat the underlying disease.5,22

    Dialysis may be needed as a result of kidney damage. Dialysis sessions are likely to be at regular intervals and takes place at specialised treatment centres5,11

    Kidney transplant can be an option for some people with aHUS. It is, however, associated with significant risks and is not a cure for aHUS.23

    Treatment advances: Other treatment options (such as blocking the body’s inflammatory response) are available. Your doctor will be able to discuss this treatment with you. e.g. complement inhibitors.

    Monitoring aHUS: There are a number of important regular blood tests that can help show how well aHUS is being controlled.11

    Renal function:. One of the tests to monitor kidney function measures the level of a substance called creatinine in the blood. High levels of creatinine are an indicator of kidney damage.19,20

    Red blood cells:. These cells are responsible for delivering oxygen and removing waste from the body. Red blood cell levels are affected by aHUS, so tests help in monitoring the disease.18

    Platelets: Also called ‘thrombocytes’, these cells play a key role in stopping bleeding. Platelet levels are affected by aHUS, so regular testing helps to monitor the disease.18

    Regular visits to your GP are important for monitoring your general health and it is recommended that you visit your nephrologist or haematologist every three to six months.11

    Living with aHUS


    aHUS is a serious disease and living with it can be stressful. Understanding the disease can help in the management of signs and symptoms. Keeping track of things is important.


    • Track signs and symptoms: A doctor should be informed of any change in health, even if it may not be related to aHUS. Tracking and reporting infections is particularly important

    Living with aHUS can be difficult as the disease is unpredictable and serious. Here are some suggestions that may make day-to-day living easier.


    • Keeping a journal of symptoms can be useful as it may reveal links between general health and the incidence of TMA.
    • A doctor should be informed of any infection that occurs; this includes common infections such as a respiratory infection and gastroenteritis. An infection can be the catalyst for TMA and the serious symptoms TMA can cause.
    • A doctor should be aware of all medications being taken – prescription and non-prescription.
    • For people with aHUS who are on dialysis, it is important that appointments are kept. If an appointment cannot be kept, the dialysis centre involved should be notified and a replacement session booked for the earliest possible date
    • A doctor should be notified of any invasive procedures (eg, dental work, surgery) that are planned.
    • Eat a healthy diet and drink plenty of water. For people with aHUS a kidney-friendly diet is important; referral to a dietician can help with this.
    • Seeking help: aHUS can have a wide range of damaging effects on the body, so asking for help, when it’s needed, is essential.

    The following section offers tips that may help aHUS patients talk about aHUS to family and friends.

    Talking to others about aHUS11


    Talking about your disease may help make life with aHUS a bit easier. For people who have been diagnosed recently, here’s why talking to others about aHUS might be important:


    • Understanding: aHUS can cause pain, discomfort and, because of its unpredictability, can be stressful. Living with such a chronic disease can affect people’s mood and outlook
    • Emotional support: The family and friends of someone with aHUS can provide vital support in helping them manage the condition
    • Information: Family and friends welcome information about aHUS. Websites, such as this, can help answer their questions

    Resources and links


    The aHUS Patient Support Group Australia (aPSGA)
    http://ahusaustralia.org.au
    The aPGSA works on behalf of people living with aHUS, their family and carers. It aims to provide support for affected families, raise awareness in the community and improve treatment for the disease.


    Rare Voices Australia (RVA)
    http://www.rarevoices.org.au
    RVA is a national organisation that advocates on behalf of people who live with a rare disease. RVA works with governments, researchers, clinicians and industry to promote research, diagnosis, treatment and services for all rare diseases in Australia.

    References


    1. 1. Loirat C, et al. Pediatr Nephrol. 2008;23:1957-1972.
    2. 2. Noris M, et al. Clin J Am Soc Nephrol. 2010;5:1844-1859.
    3. 3. Ohanian M, et al. Clin Pharmacol 2011;3:5-12.
    4. 4. Noris M, et al. N Engl J Med. 2009;361:1676-1687.
    5. 5. Laurence J. Clin Adv Hematol Oncol. 2012;10(suppl 17): 1-12.
    6. 6. Loirat C, et al. Orphan J Rare Dis. 2011; Doi:10.1186/1750-1172-6-60.
    7. 7. Kavanagh D, Goodship T. Pediatr Nephrol 2010; 25: 2431–2442.
    8. 8. Caprioli J, et al. Blood 2006;108:1267-1279.
    9. 9. Ariceta G, et al. Pediatr Nephrol 2009;24:687-696.
    10. 10. Neuhaus TJ, et al. Arch Dis Child. 1997;76:518-521.
    11. 11. The Foundation for Children with Atypical HUS. http://www.atypicalhus.org/page/a-parents-perspective-ahus.
    12. 12. Sallee N, et al. Nephrol Dial Transplant. 2010;25:2028-2032.
    13. 13. Kavanagh D, et al. Br Med Bull 2006;77-78:5-22.
    14. 14. Zuber J, et al. Nat Rev Nephrol 2011;7:23-35.
    15. 15. Dragon-Durey M-A, et al. J Am Soc Nephrol 2010;21:2180-2187.
    16. 16. Zuber J, et al. Nat Rev Nephrol. 2010; doi:10.1038/nrneph.2010.155.
    17. 17. Scheiring J, et al.. Eur J Pediatr. 2010;169:7-13.
    18. 18. Platelet count. Lab Tests Online. American Association for Clinical Chemistry. http://www.labtestsonline.org/understanding/analytes/platelet/tab/all?printpreview=1. Accessed March 15, 2012.
    19. 19. Creatinine - blood. MedlinePlus. http://www.nlm.nih.gov/medlineplus/ency/article/003475.htm. Accessed March 15, 2012.
    20. 20. Serum creatinine. RnCeus. com. http://www.rnceus.com/renal/renalcreat.html. Accessed March 15, 2012.
    21. 21. Tsai H-M. Int J Hematol 2010;91:1-19.
    22. 22. Loirat C, et al. Semin Thromb Hemost 2010;36:594-610.
    23. 23. Bresin E, et al.Clin J Am Soc Nephrol 2006;1:88-99.
    24. 24. Langman CB. Haematologica. 2012;97(suppl1):Abstract 0490.
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