The Oklahoma Blood Institute and University of Oklahoma
It is hard to have an illness that neither you nor your family have ever heard of before. This information is written with the help of our patients, to help you understand what your doctor has told you.
TTP-HUS describes an illness for which the full name is too long to remember:
T is for Thrombotic, a term describing blood clots, which are called thrombi. In TTP-HUS, thrombi caused by clumps of platelets block small blood vessels. That can cause damage to organs such as the kidneys, heart, and brain.
T is for Thrombocytopenic, a term describing low platelet counts. Platelets are blood cells that are needed to stop bleeding. In TTP-HUS, they are used up in the abnormal clots that occur throughout the body.
P is for Purpura, a term describing the bruises and the small purple bleeding spots that are caused by too few platelets.
H is for Hemolytic, a term describing the anemia. Anemia means too few red blood cells. The anemia is caused by red blood cell damage, as blood forces its way through the thrombi (clots) that partially block the small blood vessels.
U is for Uremic, a term describing kidney failure.
S is simply for Syndrome, a term describing symptoms that occur together. Doctors use the word “syndrome” when there are no specific and defining diagnostic tests (such as a culture for strep throat or a biopsy for breast cancer).
WHAT IS TTP-HUS?
TTP-HUS was first recognized in 1924; in 1966 five key signs and symptoms were established: (1) thrombocytopenia, (2) hemolytic anemia, (3) kidney failure, (4) neurologic abnormalities (such as trouble with thinking or seeing, or actual stroke), and (5) fever. When these 5 problems occurred together, without an apparent cause, the “syndrome” of TTP-HUS was diagnosed. In that era almost all patients with TTP-HUS died. In 1975, it was discovered that plasma exchange could cure most patients with TTP-HUS. (Plasma exchange treatment is described below.) This created urgency to make the diagnosis and to begin treatment. Now patients are diagnosed earlier in their disease. The diagnosis is often made only when a low blood platelet count and anemia is present, when there is no kidney failure, no neurologic abnormalities, and no fever.
There is no specific diagnostic test that defines TTP-HUS. Therefore we begin plasma exchange treatment as soon as we have strong suspicion. This means we begin treatment on some patients who may not have TTP-HUS. In some patients, another diagnosis, such as a serious infection, is diagnosed and then we stop plasma exchange treatments. However we continue to carefully follow all patients whom we have treated with plasma exchange for TTP-HUS, including patients in whom another diagnosis was made. We do this by calling all of our former patients twice a year. Long-term follow-up helps us to improve our diagnosis and treatment.
We think of most diseases as problems with specific parts of the body: for example, pneumonia involves the lungs; hepatitis involves the liver; glaucoma involves the eyes. Some illnesses, such as allergic reactions to a food or medicine, cause a rash on the skin, sometimes over all of our body. In this example, the skin represents a single involved organ. TTP-HUS is a disease that involves the cells (called “endothelial cells”) that cover the inside of all of our small blood vessels throughout the body. Like our skin, these cells are also similar to each other and represent a single organ. Their main function is to prevent circulating blood cells from sticking to the vessel wall. The vessel wall lining is like Teflon – it prevents blood clotting.
These cells that form the inside lining of the vessel wall are the “organ” that is abnormal in TTP-HUS. They can be injured by the different causes of TTP-HUS listed below. When these cells are injured, the smooth flow of blood cells is disrupted. Blood platelets are consumed at the many points of injury, because the function of blood platelets is to seal any leaks that occur in blood vessels and prevent bleeding. When these cells are damaged throughout the body, platelets stick to the damaged areas and the platelet count may decrease to very low levels. The platelets can also stick to each other and block blood flow. This is the critical problem that occurs in TTP-HUS; these platelet clumps are the blood clots or thrombi described by the first “T” in TTP-HUS. Since the blood vessels and their lining cells are similar in all the organs of our body, all parts of our body can be affected in TTP-HUS.
WHAT CAUSES TTP-HUS?
In most patients there is no explanation for the occurrence of TTP-HUS. However we do know many things about this illness: (1) TTP-HUS is not contagious. (2) TTP-HUS is not inherited (except for very rare families). (3) TTP-HUS can occur at all ages. (4) TTP-HUS occurs more often in women. (5) Many patients with TTP-HUS are overweight. (6) TTP-HUS can occur during or immediately following pregnancy. In pregnant women the diagnosis of TTP-HUS is difficult because all of its features can also be present in preeclampsia (sometimes also called “toxemia of pregnancy”). Preeclampsia is typically only a problem of high blood pressure that resolves after delivery. (6) TTP-HUS can be caused by an allergic reaction to a medicine. The most common drug that can cause TTP-HUS is quinine, the remedy many people use for leg cramps. (7) TTP-HUS can be caused by infection with the bacteria, E. coli 0157:H7, which can be in undercooked beef or hamburger. In this form of TTP-HUS, patients initially have bloody diarrhea; this occurs most commonly in young children. (8) Some types of TTP-HUS have an autoimmune cause, in which the patient makes an antibody that blocks the function of one of their own enzymes, named ADAMTS13. ADAMTS13 helps to prevent the formation of platelet thrombi. Immunity describes the normal development of antibodies against foreign substances, such as bacteria, viruses, or a transplanted organ. These diseases are called “autoimmune” because the patients make antibodies against their own tissues. Some patients with TTP-HUS may have symptoms similar to other illnesses that are described as “autoimmune”, such as lupus.
WHAT IS THE TREATMENT FOR TTP-HUS?
Plasma exchange is the most important treatment for all patients except young children whose illness follows diarrhea; they usually get well without plasma exchange. It is done with a machine that removes patient plasma and replaces it with fresh plasma, similar to the machines used for routine blood donations. The reason for the effectiveness of plasma exchange, like the cause of the disease, is not known. The exchange may remove a harmful substance from the patient and provide an essential new substance in the fresh plasma. Plasma exchange has risk. A catheter needs to be inserted into one of the large veins of the shoulder, neck, or groin area. That creates a risk for serious infection. Allergic reactions to the infused plasma are common; most reactions cause only hives, but some can also cause breathing problems.
We continue plasma exchange daily until the platelet count is normal. Then we may decrease treatments to every other day, or we may stop. However if the TTP-HUS is still active, the platelet count will fall again and daily treatments must be resumed. Patients usually get better in several days and then need one to three weeks of treatment to make sure that they stay well. Other treatments, such as steroids and related medicines, are sometimes also used to help patients recover more quickly.
WHAT IS THE FREQUENCY OF TTP-HUS?
We see all of the patients with TTP-HUS in Central and Western Oklahoma because the Oklahoma Blood Institute (OBI) does all of the plasma exchange treatments in our region. During the past 18 years we have treated 368 patients. We treat about 20 patients each year in all hospitals in Oklahoma City, Midwest City, Norman, and Edmond.
WHAT IS THE OUTCOME OF TREATMENT FOR TTP-HUS?
Some patients with TTP-HUS still die. Most of our patients who died never had a chance for effective treatment; patients who have begun plasma exchange treatment have almost always survived. Because some patients who were critically ill have completely recovered, we initiate aggressive treatment with full life supporting measures in everyone. Patients who respond to treatment usually recover completely, but some problems, such as kidney failure, may be permanent.
WHAT IS THE FUTURE FOR PATIENTS WHO RECOVER FROM TTP-HUS?
Some patients may have another episode of TTP-HUS after they recover. Most recurrences happen within the first year after the initial episode, and almost all occur in patients who have the autoimmune cause for their TTP-HUS, with deficient activity of their enzyme, called ADAMTS13. Patients with other causes of TTP-HUS almost never have another episode. Patients with recurrences do well, because their disease was responsive to treatment the first time and because there is no delay in diagnosis the next time. Because TTP-HUS often occurs in young women, some of whom are pregnant when the first diagnosis is made, the question about safety of subsequent pregnancies is critical. Our experience is that TTP-HUS can recur during pregnancy, but this is uncommon. Most women have uncomplicated, successful pregnancies.
WHAT RESEARCH IS BEING DONE ON TTP-HUS IN OKLAHOMA?
Our most important research is to carefully follow all of our patients forever. Part of our program is to have meetings of former patients and their families at the OBI three times each year. We began these meetings in 1996, and they have been well attended each time. These meetings have been important for us to provide information to our former patients and their families. We also learn a lot from our patients. We contact every patient whom we have treated for the diagnosis of TTP-HUS every six months. Because there is often no clear distinction between patients who have TTP-HUS and patients who may have had another cause for their illness, we continue to stay in touch with everyone whom we have treated with plasma exchange. This includes some patients whom we feel may not have had TTP-HUS. We also stay in contact with the patient’s doctor, to keep current records of his or her medical care and laboratory data. To measure completeness of recovery, we do a questionnaire with each patient every year called a “Quality-of-Life” survey. The value of the “Quality-of-Life” survey is that it goes beyond routine medical evaluation and actually describes how patients are doing in their daily activities. We save blood samples from the time of our first plasma exchange treatment to develop tests that may help with diagnosis and understanding of TTP-HUS. We ask all of our patients to sign a consent form that allows us to keep their records, to stay in contact, and to do the blood test research.
HOW CAN I LEARN MORE ABOUT TTP-HUS?
Our Website, http://moon.ouhsc.edu/jgeorge, has the stories of some of our patients. These stories can tell you a lot about TTP-HUS.
HOW CAN YOU HELP PATIENTS WITH TTP-HUS?
Consider becoming a plasma donor. For each plasma exchange procedure, about 10 plasma donors are required, and each patient requires about 20 procedures, or 200 donations. For information, call the OBI at (405) 297-5700.
James N. George, M.D.
The University of Oklahoma Health Sciences Center
Revised March 19, 2007