ahus A PATIENT S GUIDE To learn more about ahus, visit Copyright 2011, Alexion Pharmaceuticals, Inc. All rights reserved.

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1 To learn more about ahus, visit ahus A PATIENT S GUIDE Copyright 2011, Alexion Pharmaceuticals, Inc. All rights reserved. SOL 1169

2 BECOME EMPOWERED By learning more and taking control of ahus atypical Hemolytic Uremic Syndrome (ahus) is a serious, life-threatening disease that can have devastating consequences. It may be scary to find out that you are living with ahus. You may have questions and concerns about the disease and how it affects your body. Learning about your disease is important, and it can empower you to start taking control of it. 1 GET THE RIGHT INFORMATION, RIGHT FROM THE START If you have been diagnosed with ahus, you probably have a lot of questions. What is ahus? What does ahus do? What are the risks of having ahus? How do I get ahus? How do I know if I have ahus? How is ahus treated? WHAT IS ahus? atypical Hemolytic Uremic Syndrome (ahus) is a rare, life-threatening, genetic disease that can damage vital organs such as the kidneys, heart, and brain. In patients with ahus, blood clots form in small blood vessels throughout the body, a process known as systemic thrombotic microangiopathy, or TMA. The disease can occur at any age and can lead to potentially devastating consequences. In the past, even with management about 50% of all people with ahus die, needed dialysis, or had damage to their kidneys within 1 year of being diagnosed. 2,3 ahus is a rare and serious disease that can affect people throughout their lives. There is no cure, and it is a genetic, lifelong disease; but you and your healthcare team can work together to manage the disease once it has been diagnosed. As with other rare diseases, diagnosis is often difficult ahus has a wide range of signs and symptoms that are often similar to those of other diseases. Understanding ahus and being able to recognize its signs and symptoms are important steps in managing the disease s effects. 1,4 As you are reading: Find the meaning of underlined words in the Glossary on page ahus affects only children. Although ahus does affect children, almost one-half of people affected are adults. EVIDENCE A study of ahus patients shows that 40% are diagnosed at over 18 years of age. 2 3

3 START LEARNING More about ahus WHAT DOES ahus DO? ahus is a disease of chronic uncontrolled complement activation, in which complementmediated systemic TMA can result in catastrophic consequences for patients. The complement system is part of the immune system that is always on and ready to attack any foreign or invading cells. The complement system is normally controlled by a group of genes. These genes keep the complement system under control by producing proteins that prevent the complement system from being overactive. When certain complement proteins are missing or working improperly, the body does not have the ability to control the complement system. This is known as ahus. 1 UNCONTROLLED N O R M A L ON ON ahus affects platelets, another part of the body s natural defense system. Normally, platelets help protect the body by forming clots in damaged areas and assisting in other important activities. Clots help the body to stop bleeding, inside and out. They work only when they are specifically activated. When your complement system is uncontrolled, cells along blood vessel walls become damaged and platelets become overactive. This can result in clots, low red blood cell and platelet counts, and damage to organs that these blood vessels go to, such as the kidneys, heart, and brain. 1,5,6 If uncontrolled, the body s complement system causes abnormal clotting and inflammation This results in damage to small blood vessels ON C O M P L E M E N T OFF C O M P L E M E N T The damage that occurs throughout the body is known as TMA TMA can also lead to problems in the body s vital organs, such as the kidney, heart, brain, and blood 4 ahus is not a long-lasting disease. ahus is an ongoing disease that currently has no cure. It occurs because of abnormal genes that you were born with. These genes cause the complement system to be uncontrolled and triggered at any time. EVIDENCE The abnormal genes in your body are the underlying cause of ahus. If left unmanaged, ahus can lead to damage throughout the body. 1,6 5

4 WHAT ARE THE RISKS OF HAVING ahus? Brain People with ahus have a lifelong risk of sudden, catastrophic, and life-threatening complications. ahus is systemic because it occurs throughout the body, affecting all vital organs, such as the kidneys, heart, and brain. As the disease continues to damage small blood vessels, vital organs can suddenly fail to function or slowly lose their ability to function over time. Many people with ahus will need long-term dialysis or kidney transplant if their kidneys stop working. 1,3,7,8 Because ahus occurs throughout the body, many important organs are affected by the disease. Complications of ahus: 48 percent of patients experience neurological symptoms 2,9,10 Neurological complications can include confusion, stroke, brain damage, and seizures 43 percent of patients experience problems with their cardiovascular, or CV, system 7,9 CV complications can include heart attack, abnormal blood clotting, damaged blood vessels, and high blood pressure Problems with the renal system 3,5,7 Complications of the kidneys can include high levels of creatinine (a chemical filtered by the kidneys), dialysis, transplant, edema, and extremely high blood pressure, all of which result from or lead to kidney failure 30 percent of patients experience diarrhea 2,5,10,11 Other complications associated with the digestive system include an inflamed colon, liver damage, nausea/vomiting, abdominal pain, and severe inflammation of the digestive tract Lung Heart Liver Kidney Bowel 6 ahus is a disease of just the kidneys. ahus is much more than a disease of just the kidneys. EVIDENCE ahus affects not only your kidneys, but also damages other vital organs, such as the heart and brain. 1,2,7 7

5 HOW D0 I GET ahus? ahus results from changes, or mutations, in the genes that produce the proteins that help control the complement system, which is part of your body s natural immune defense system. Examples of affected proteins are factor H, factor I, membrane cofactor protein (MCP), factor B, and factor C3. The genetic mutations or defects result in permanent, uncontrolled, and excessive activation of the complement system. When this system is uncontrolled, it can attack the body it normally protects. As a result, ahus can do great damage to vital organs if it is left undiagnosed and untreated. 1 Although ahus is a genetic disease, 30% to 50% of people with ahus will not have genetic mutations that can be identified through genetic tests. Testing for specific genes is not necessary for your doctor to diagnose you with ahus. The absence of genetic mutation does not rule out ahus 2 Because ahus can be caused by a genetic mutation, it is known as a chronic disease. The underlying cause of the disease is always present and the disease is lifelong. Currently, there is no cure, but there are things you and your doctor can do to help you avoid its devastating consequences. 1,12 HOW DO I KNOW IF I HAVE ahus? ahus can be difficult to diagnose, which is why it is important for you and your doctor to be able to recognize the disease s signs and symptoms. Some of the signs and symptoms of ahus are 3,7,9-11,13 : Confusion Diarrhea, nausea, and vomiting Dyspnea, or shortness of breath Fatigue Impaired quality of life Cardiac-related symptoms Renal symptoms One of the most common signs of ahus is kidney failure, which can help lead doctors to the diagnosis of ahus. 1 Your doctor can also examine your blood by taking certain laboratory tests. In particular, he or she can look at your red blood cell and platelet counts to see if they are low. Creatinine levels can also be measured to monitor how well your kidneys are working. If any of these results are abnormal, your doctor may suspect ahus. 4 To make an accurate diagnosis, your doctor will need to rely on signs, symptoms, laboratory test results, and frequent follow-up visits with you. It is very important to continue to see your treating physician regularly, because ahus is a chronic disease that never goes away. 8 Your doctor needs to identify a genetic mutation in order to confirm that you have ahus. Your doctor doesn t need to identify a genetic mutation to diagnose ahus. EVIDENCE In 30%-50% of patients with ahus, genetic mutations cannot be identified through genetic tests. There are other tests, such as ADAMTS13 and Shiga-toxin EHEC tests, that can help with diagnosis. 2,4,14 9

6 MAKING A DIAGNOSIS ahus is difficult to diagnose because it has signs and symptoms similar to those of other diseases. Your doctor can perform certain tests to help determine if your disease is ahus or another disease, such as thrombotic thrombocytopenic purpura (TTP) or Shiga-toxin producing E coli hemolytic uremic syndrome (STEC-HUS). These are two diseases that have signs and symptoms similar to those of ahus, but which have different underlying causes. 14 ADAMTS13 A LABORATORY TEST TO HELP DIFFERENTIATE ahus FROM OTHER DISEASES Like ahus, TTP also causes clots that damage small blood vessels in the body. But unlike ahus, TTP is caused by low amounts of a certain protein in the blood, called ADAMTS13. Therefore, to determine if someone has TTP, your doctor can measure levels of ADAMTS13 activity. If someone has 5% of normal ADAMTS13 activity levels, then TTP is the likely disease. An ADAMTS13 level >5% is likely to be ahus. As part of the diagnostic process, this test can help a doctor differentiate TTP from ahus. 14 STEC-HUS AND STEC BACTERIA STEC-HUS and ahus are different diseases. STEC-HUS is caused by an E coli infection in the body, but ahus is not. Because STEC-HUS is associated with E coli, people who have this disease most likely have diarrhea. The diarrhea and other symptoms will go away when the infection is gone. A doctor can perform a test (via stool sample) to see if the STEC bacteria are present. 4,12,15 HOW IS ahus TREATED? Your doctor may recommend plasma exchange or plasma infusion, although infusion does not treat the underlying cause of the disease. However, there have been no clinical studies conducted to show that plasma infusion or exchange is effective and safe as a treatment for ahus. The infusion process itself takes hours to complete and requires access and traveling to specialized centers. Plasma exchange/infusion is not a cure and symptoms may return over time. 4,8,12,15 As a result of having ahus, some people may develop kidney failure and need dialysis, while others may opt for a kidney transplant; however, dialysis and transplantation do not specifically treat ahus. In some cases, transplantation is not an option, because there is a great chance of ahus occurring in the new kidney. Both dialysis and transplantation have significant risks associated with them. 15,17,18 Monoclonal antibodies are some of the latest advancements in the treatment of ahus. Known as targeted treatments, they aim to address the underlying cause of the disease and help regulate the complement system. 6 Talk with your doctor about a management plan that includes treatment and frequent follow-up or monitoring of your rare disease. A person with ahus can also get a STEC infection, too. In ahus, the cause is genetic, so the disease occurs throughout a person s life. If you have been told you have STEC-HUS but your symptoms continue or reoccur, you may actually have ahus. Talk with your doctor if your symptoms reoccur. 16 ahus may be safely and effectively treated with plasma exchange/infusion. Plasma exchange/infusion has not been shown to be either safe or effective

7 GLOSSARY ADAMTS13: a type of protein that occurs naturally in the body. It helps break up a different protein that can help produce clots. An ADAMTS13 test can identify patients with TTP because they have low levels of ADAMTS13. ahus patients have normal or only slightly reduced levels Atypical: something that is irregular; an unusual type atypical Hemolytic Uremic Syndrome (ahus): a disease of the blood that causes low red blood cell and platelet counts, kidney failure, and damage to other vital organs, such as the heart and brain Complement system: a network of proteins and enzymes that interact with each other to protect the body against foreign substances, like bacteria and other invading organisms. ahus is a disease in which the complement system has trouble figuring out who is one of us and who is one of them Creatinine: a chemical excreted by the kidneys, which when measured, shows whether the kidneys are functioning properly Colon: the lower part of the large intestine Dialysis: a treatment for kidney failure. Normally, the kidneys work to filter the blood and remove waste, excess salt, and water. Kidney failure, also called end-stage renal disease, occurs when the kidneys stop working completely. During hemodialysis, a machine takes over the job of the kidney by filtering the blood outside of the body, and then returning the filtered blood back to the body E coli: bacteria that normally exist in the lower intestines of humans and other animals, which can cause illness Edema: swelling of certain parts of the body due to the presence of abnormally large amounts of fluid Enzyme: a protein that starts a chemical reaction within the body Immune system: a complex group of cells, proteins, and other molecules that work together to identify foreign organisms and substances, such as bacteria; the main role of the system is to protect the body against these foreign organisms Infusion: a process during which fluid is introduced into the body through a vein Microangiopathy: a disease of very small blood vessels Monoclonal antibodies: special proteins designed to target other very specific cells or proteins in the body Mutation: a permanent change in genetic material, usually in a single gene Plasma: the pale yellow liquid part of whole blood, in which the red and white blood cells and various other elements are suspended Plasma exchange: a process of removing, treating, and returning plasma to the body Purpura: any condition characterized by bleeding in the skin and mucous membranes, which can appear as bruises on the surface of the skin Shiga-toxin: a poison produced by E coli bacteria that causes severe diarrhea Shiga-toxin producing E coli hemolytic uremic syndrome (STEC-HUS): a syndrome triggered by Shiga-toxin producing E coli. The disease is characterized by diarrhea that is often bloody and followed by acute renal failure Stroke: damage to the brain. Strokes can happen when an artery in the brain becomes clogged or starts bleeding and cuts off the blood supply to that portion of the brain Syndrome: a set of symptoms that occur together in a pattern Systemic: spread throughout the body Thrombotic: producing blood clots Thrombocytopenia: decreased numbers of platelets Thrombotic Microangiopathy (TMA): clotting and inflammation that damages small blood vessels throughout the body; this is a symptom or a result of diseases such as ahus and TTP Thrombotic Thrombocytopenic Purpura (TTP): a rare condition that causes blood clots to form in small blood vessels throughout the body, leading to widespread thrombotic microangiopathy Uremia: signs and symptoms of kidney failure; signs and symptoms of uremia can include nausea, vomiting, metallic taste in the mouth, muscle pain, and swelling 12 13

8 ADDITIONAL RESOURCES FOR ahus EDUCATION AND SUPPORT: The Foundation for Children with Atypical HUS Website: Genetic and Rare Diseases (GARD) Information Center PO Box 8126 Gaithersburg, MD Phone: Toll-free: Website: References: 1. Noris M, Remuzzi G. N Engl J Med. 2009;361: Noris M, Caprioli J, Bresin E, et al. Clin J Am Soc Nephrol. 2010;5: Caprioli J, Noris M, Brioschi S, et al; International Registry of Recurrent and Familial HUS/TTP. Blood. 2006;108: Ariceta G, Besbas N, Johnson S, et al; European Paediatric Study Group for HUS. Pediatr Nephrol. 2009;24: Ståhl AL, Vaziri-Sani F, Heinen S, et al. Blood. 2008;111: Hirt-Minkowski P, Dickenmann M, Schifferli JA. Nephron Clin Pract. 2010;114:c219-c Sallée M, Daniel L, Piercecchi MD, et al. Nephrol Dial Transplant. 2010;25: Loirat C, Garnier A, Sellier-Leclerc AL, Kwon T. Semin Thromb Hemost. 2010;36: Neuhaus TJ, Calonder S, Leumann EP. Arch Dis Child. 1997;76: Ohanian M, Cable C, Halka K. Clin Pharmacol Adv Appl. 2011;3: Zuber J, Le Quintrec M, Sberro-Soussan R, Loirat C, Frémeaux-Bacchi V, Legendre C. Nat Rev Nephrol. 2010; doi: /nrneph Scheiring J, Rosales A, Zimmerhackl LB. Eur J Pediatr. 2010;169: Dragon-Durey MA, Sethi SK, Bagga A, et al. J Am Soc Nephrol. 2010;21: Tsai H-M. Int J Hematol. 2010;91: Loirat C, Noris M, Fremeaux-Bacchi V. Pediatr Nephrol. 2008;23: Bitzan M, Schaefer F, Reymond D. Semin Thromb Hemost. 2010;36: Kavanagh D, Goodship THJ, Richards A. Br Med Bull. 2006;77-78: Bresin E, Daina E, Noris M, et al; International Registry of Recurrent and Familial HUS/TTP. Clin J Am Soc Nephrol. 2006;1: National Organization for Rare Disorders (NORD) 55 Kenosia Avenue PO Box 1968 Danbury, CT Phone: Toll-free: Website: