TTP-HUS 2007
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