Essential Thrombocythemia
Subj: Essential Thrombocytisis (ET)
Date: Sat, Mar
30, 1996 3:17 PM EDT
(XGYZ79A@MSN.COM) Joyce
Niblack
Dear Robert,
As you requested, I have drafted a write up on
Essential Thrombocytosis for
you to provide new ET people who sign onto the
list to supplement the
information you send out on your own variant of the
Myeloproliferative
Disorders (MPD), polycythemia vera (PV). We probably
should also have one
for myelofibrosis.
For the sake of accuracy, I have referred to the
description of ET in Dr.
Harriet Gilbert's excellent review article entitled
"Myeloproliferative
Disorders", Clinics in Geriatric Medicine, Vol. 1, No. 4,
November, 1985
but have tried to simplify the language where possible and
have supplement it
with my own experiences. I will be happy to send a copy of
this 21 page
article to anyone who is interested with the caveat that
additional
information has been developed on newer treatment options since
this article
was written. It also discussed PV, AMM (agnogenic myeloid
metaplasia) and
CML (chronic myelogenous leukemia).
When I was first diagnosed and living in Illinois, a
young hematologist fresh
out of a residency at Harvard Medical school said In
simple terms, in these
disorders, the bone marrow goes nuts, revs up and
produces too much of what
its suppose to produce and much of what it produces
can be abnormal which can
cause complications; that if allowed to go
unchecked, the marrow gets
scarred from years of hyperactivity, goes into a
spent phase where is slows
down production and causes other
problems.
According to Gilbert, the hallmark of any
myeloproliferative disorder is
evidence of involvement of more than one cell
line. In my case, platelet
counts at diagnosis were 980,000, WBC 27,000 and
HCT and HG were also
elevated. The four disorders (essential thrombocytosis
(ET) , polycythemia
vera (PV), agnogenic myeloid metaplasia (AMM) and chronic
myelogenous
leukema (CML) each have predominant features which permit
classifications
which are named for the cell type showing the most marked
involvement. There
is a great deal of overlap in the features of these
various syndroms and
transition from one to another is common.
Thrombocythemia (or thrombocytosis) is defined as the
occurence of a platelet
count in excess of 400,000 per microliter in the
setting of a
myeloproliferative disease. When this is the predominant
abnormality, the
sydrome is classified as essential thrombocytosis. Abnormal
megakarocyte
proliferation is seen in all variants of MPD and elevated
platelet counts is
common in PV, CML and the proliferative states of AMM. On
the other hand,
ET patients can also have elevated WBC, HCT and HG counts so
a careful
differential diagnosis is essential.
The diagnosis of essential thrombocytosis is primarily
one of exclusion.
If platelet counts are elevated with: 1) no identifiable
cause of secondary
thrombocytis i.e. from infection, cancer or other disease
state); 2) the
red cell volume is normal (excludes polycythemia vera); 3)
iron is present in
the bone marrow or reduced iron stores have been repleted
by oral iron
administration for one month withot inducing an increase in
hemoglobin; 4)
collagen fibrosis is absent from the bone marrow
biopsy(excludes
myelofibrosis; and 5) the Philadelphia chromosome is absent
from the bone
marrow aspirate (excluses chronic myelogenous
leukemia).
In essential thrombocytosis, in addition to elevated
platelet counts,
platelets generally are abnormal in size, shape, density and
function.
Spontaneous aggregation can occur putting ET patients at higher
risk for
clotting events. There can also be an increased risk
of
bleeding.Complications can arise either from bleeding or clotting.
According
to Gilbert, clinical manifestations are dominated by hemorrhage
(bruising,
epistaxis, unexplained gastrointestinal bleeding, and
postoperative
hemorrhage) and microvascular occlusions (cyanosis in fingers
and toes,
erythema and burning as well as a host of neurological complaints
such as
headache, parathesis-numbness and tingling and transient ischemic
attacks).
The hematogist who has been treating me since we moved
to Arizona several
years ago, and who is presently treating me with
anagrelide, told me he has
seen more bleeding than clotting problems in his
patients but the one that
stands out in his mind is a man whose platelet
counts were controlled in the
200,000's, came in complaining of breathing
difficulty and turned out to
have multiple embolisms in his lungs. He said
when they looked at blood and
bone marrow, plaletets and megakoryctes were
aggregating and forming clumps
like crazy. So this patient needs to safeguard
against future clotting by
taking heparin while since my clotting and
bleeding times have been normal
since IFN treatment and I just take a baby
aspirin a day as a precaution. I
haven't heard from anyone with a bleeding
problem so if you are out there,
tell us how that is handled.
Supposedly thrombocytosis in the absence of
erythrocytosis (elevated HCT and
HG) does not increase the risk of large
vessel occlusion and thrombotic events
in ET patients are no more frequent
than in aged matched controls. But if
elevated platelet counts are present
with increased blood viscosity from
erythemia, there is greater risk for
large vessel thrombosis.
Bottom line is, we all need to be monitored carefully
and we need to work
with our hematologists in reaching an informed decision
about whether or not
treatment is appropriate and if so, which treatment
option. Since I
probably had a mixed disorder because spleen was very large,
bone marrow had
expanded to knees and at one point I had a mild transition to
myelofibrosis
which was reversed with IFN therapy, I personally believe in
treatment to
either prevent or at least slow down progression to something
more
troublesome. Since I take a baby aspirin a day, I periodically have
both
bleeding and clotting times checked.
There are a whole gaggle of metabolic abnormalities
that go along in patients
with myeloproliferative disorders. These
include:
-Elevated uric acid accounts are seen in about half of
MPD patients during
the course of their disease. If untreated, this leads to
uric acid stones,
uric acid neuropathy, acute gout, and chronic gouty
arthritis.
-Low cholesterol levels (hypocholestoremia),
particularly in those with
enlarged spleens.
-Elevated histamine levels. Symptoms of increased
histamine release include
puritis (characteristically produced by bathing or
showering), heartburn,
acid eructation, peptic ulcer, small bowel
hypermotility, flushing and
angioneurotic edema. This occurs in 2/3rds of MPD
patients and correlates
with presence of elevated basophil count and
hyperhistaminemia.
-Hypermetabolism which commonly manifests as weakness
and fatigue in the
absence of anemia.
There are varying views on treatment. Gilbert's
article was written when
myelosuppressive (chemotherapy or P32) was the main
treatment option and
because of the risks and complications of chemotherapy,
including an
increased risk of developing a secondary acute leukemia from the
chemotherapy,
and the unpredictable nature of complications, the thinking in
1985 was that
aggressive reduction of platelet counts may not be indicated,
particularly in
young and asymptomatic patients. Observations at that time
were made before
the differential effect on prostaglandin metabolism of low
and high dose
aspirin were appreciated, before interferon was used by many
hematologists
and before anagrelide was available.
There is a body of literature on the use of interferon
in treating essential
thrombocytois as well as literature on anagrelide which
is presently available
under compassionate use protocols. When I consulted
with Dr. Gilbert, she
told me to expect to be on alternating cycles of
interferon and anagrelide
for life. As long as my spleen remains normal,
anagrelide is fine. If my
spleen starts enlarging again or other cell lines
go goofy, I'll be back on
interferon in a heart beat. Others in the group are
happy with Hydrea, or
have opted to have their spleens removed rather than go
back on IFN but that
causes other problems-difficulty in controlling counts.
These are all very
personal choices that have to be made in the context of
what will provide the
most acceptable quality of life options for each of
us.
When I was first diagnosed, because of a family
emergency which required me
to be away from home for a period of time, I was
treated with Hydrea
(hydroxyurea) to rapidly knock down counts and reduce the
risk of further
clotting events. Because I was 49 at the time, both
hematologists (home town
and diagnosing) felt I was too young to take Hydrea
for any length of time
because of its potential to cause a secondary
leukemia. Other
chemotherapeutic agents carry an ever greater
risk.
So I was subsequently treated with inteferon which
went a long way to
normalize my bone marrow status. I started out in a
clinical trial at 3MU
daily which normalized blood counts but did not improve
bone marrow status.
had the best result following Dr. Gilbert's
recommendations for 5MU daily. My
blood counts remained normal for 3 years
after stopping IFN and once platelets
started to rise, I was placed on
anagrelide which has kept them at
350,000-380,000 for the past 17 months.
Apart from several silent migranes
and a transient vision loss in one eye
shortly before I was placed on
anagrelide (platelets 540,000), I have had no
further complications from my
disease
My 89 year old father (will be 90 this July) also has
essential
thrombocytosis. He has never had any complications that we know of
from his
disorder and since diagnosis, has only been treated with short
bursts of
Hydrea (hydroxyurea) to rapidly knock down his platelet counts
before major
surgery. He did go into congestive heart failure several years
ago and does
have stress angina but its more likely that his diabetes
contributed to this.
He walks at least an hour a day and that probably
contributed not only to his
recovery from the congestive heart failure but
his joy of life. Who knows.
We should all live so long and be so healthy at
his age!