Autoimmune Leukopenia

Gordon Starkebaum, M.D.

David C. Dale, M.D.
The terms "autoimmune leukopenia," "autoimmune granulocytopenia," and "autoimmune
Neutropenia" are often used synonymously to describe conditions in which autoantibodies to
mature neutrophils, or their precursors, lead to cell destruction and a reduced blood
neutrophil count. Leukopenia is generally defined as a reduction in the total white blood cell
count to less than 4,000 cells per deciliter; Neutropenia is defined as a neutrophil count of
less than 1,800 cells per deciliter. Neutropenia has numerous causes and mechanisms; the
most frequent cause is reduced cell production by the bone marrow. Neutropenia also occurs
because of abnormalities in the distribution of cells between the circulating and marginated
pools of cells in the blood and accelerated cell destruction. Autoimmune leukopenia can be
caused by any of these mechanisms.
Although the term "leukopenia" often implies "Neutropenia", there are many pathologic
conditions in which not only neutrophils but also lymphocytes, monocytes, eosinophils, and
basophils are concomitantly or specifically reduced. Lymphocytopenia is a common feature
of the stress response to many infections and acute inflammatory illnesses. It occurs in
systemic lupus erythematosus (SLE) and other collagen vascular diseases. Lymphocytopenia,
monocytoenia, and eosinopenia are regularly seen with corticosteroid therapy. Reductions in
any of the white blood cell elements may reflect an important ongoing pathologic process.
Other Conditions Associated with Neutropenia
There are a number of other conditions that include neutropenia as part of the symptoms.
Depending on the nature of the main condition the way neutropenia is managed may differ
from the treatment of "pure" SCN.
The main conditions that may include neutropenia are:
Severe Aplastic anaemia
Viral illnesses
Post chemotherapy or radiotherapy
Other drug-induced situations
Fanconi Anemia
There may be some other very rare disorders, congenital or acquired, that may be associated
with neutropenia, e.g. myelokathexis, Hyper IgM, or Combined Immunodeficiency. This list
may be incomplete and more information about diseases associated with neutropenia is being
discovered all the time.

A chronic disorder with unknown etiology, systemic lupus erythematosus (SLE) is the most
diverse autoimmune disorder with a relapsing and remitting course that may affect any organ
in the body. SLE has a broad spectrum of clinical presentations with higher mortality than
general population. These diverse clinical manifestations are mainly due to SLE complex
immunopathology in which B cells produce autoantibodies against mainly intracellular auto
antigen targets, and form complement fixing immune complex deposits resulting in
irreversible organ damage. More than one hundred autoantibodies have been found in SLE,
but only few of them are associated with the SLE manifestations.
There are almost always autoantibodies against one or more cell components in the blood of
SLE patients. Hematologic complications of SLE are among the most common
manifestations of this disorder, and almost all patients have hematologic abnormality at some
stage of the disease.
In 1971, American college of rheumatology established the SLE criteria in which hemolytic
anemia, leukopenia, and thrombocytopenia were the individual criterion. In revised version in
1982, these criteria classified as a group in hematologic system:
What do I need to know about anemia?
Dr. Michael Rosove is a Medical Oncologist in Los Angeles, CA and a Clinical Professor of
Medicine at the University of California-Los Angeles, School of Medicine.
See all of Michael Rosove, MD's answers.
The most common blood disorder is anemia, affecting about half of all people with active
lupus. Anemia can be measured and discussed in several different ways, including a low red
blood cell count, low hemoglobin, or low hematocrit. Each doctor usually has a preference
for using a particular term. In the most important sense, anemia means too little hemoglobin.
Hemoglobin is the protein inside red cells that carries oxygen from the lungs to all the tissues
of the body. Fatigue, a very common lupus symptom, is generally the first and most common
symptom of anemia.
Anemia affects about half of all people with active lupus. Fatigue is usually the first and
most common symptom.
Common Causes of Anemia
Normal red blood cells live only 120 days (about four months) and must constantly be
produced by the bone marrow. The most common explanation for anemia is reduced red cell
production. This may be due to a variety of causes, including:
Inflammation
Inadequate erythropoietin, a hormone produced by the kidneys, that stimulates the
marrow to make more red cells
Iron deficiency -- Iron is necessary for the production of hemoglobin. Iron (as part of
the protein hemoglobin) carries oxygen from the lungs throughout the body. Having too
little hemoglobin is called anemia. Iron deficiency also may result from menstrual
bleeding or from intestinal bleeding due to non-steroidal anti-inflammatory drugs.
Intestinal bleeding can be obvious if the stool is red, maroon, or black in color, but often
bleeding is so slow and gradual that special stool tests are needed to detect it.
Loss of bone marrow caused by certain drugs used to treat lupus (such as azathioprine
or cyclophosphamide)

Thrombocytopenia means low platelets. Thrombocyte is the medical term for platelet and
penia means few, so it is translated to 'few platelets.' Platelets have a lot to do with blood
clotting. If platelets are significantly deficient, a person is more susceptible to bleeding;
either minor bleeding or more serious bleeding if a patient bangs their head, etc.
Antiplatelet drugs such as aspirin, Plavix, and most of the non-steroidal anti-inflammatory
drugs can also exert an effect on platelets getting together as a group, called platelet
aggregation. They can reduce this platelet aggregation and interfere with clotting to an
extent. For that reason they can be useful in preventing serious blood clots causing heart
attacks and strokes, but they can also promote bleeding.

In lupus, thrombocytopenia is generally due to antibodies that form against platelets and
destroy them. This destruction can occur in the blood or in the spleen, an organ in the left
upper part of the abdomen. Sometimes the spleen enlarges in patients with immune
thrombocytopenia. So if the antibodies damage the platelets and the bone marrow cannot
make new platelets fast enough, the platelet count drops. Sometimes a bone marrow
aspiration is done. This can be momentarily painful, but it assesses the blood-making cells.
 Blood cells such as white blood cells, red blood cells, and platelets are made in the marrow
of long bones. If there are plenty of precursors to platelets (called megakaryocytes), then the
destruction of platelets must be occurring outside the bone marrow and in the blood, spleen,
etc. This is immune thrombocytopenia such as in lupus in which sufficient platelets are
made, but there is an overactive response at destroying them.

Unless the platelet levels are extremely low, such as less than 10,000, when about 140,000 to
400,000 is considered normal, bleeding usually does not occur unless there is trauma. But
even moderately low platelet counts in the range of 80,000 to 100,000 can be related to
immune thrombocytopenia, and lupus and is one of the characteristics of the disease. But it is
not present in most lupus patients.

Therapy for thrombocytopenia in lupus is generally directed at the underlying disease with
steroids if the thrombocytopenia is severe enough and immunosuppressive drugs to reduce
the level of autoimmune antiplatelet antibodies. But one has to be careful with
immunosuppressive drugs because you do not want them to suppress platelet production in
the bone marrow. Since immunosuppressives can affect rapidly dividing cells such as the
megakaryocytes (the precursors to platelets in the bone marrow), the physician needs to be
judicious in the use of immune-suppressing drugs for this disorder. Rituximab, a monoclonal
antibody to B-lymphocytes, can also be used in some cases of immune thrombocytopenia.
Most patients tolerate rituximab well, and it works for a long time. It is not always
indicated, but could be used in some cases of lupus thrombocytopenia.

Our reader wants to know why she has terrible leg pain in conjunction with the low platelet
count. She commented she is already taking 60 mg of prednisone for one week and that her
platelet count went up in response to the steroids, but the leg pain did not respond. Without
getting into specifics in a case where I do not know the details, it sounds like the leg pain and
immune thrombocytopenia are not directly connected, and there is another explanation for the
leg pain, but again, I do not really want to go there in this type of column in terms of trying to
make a more specific diagnosis.

When you go to see your physician, you might ask questions about which tests the doctor
feels are important in following your lupus, how your lupus was diagnosed and what specific
tests need to be followed. If the platelet count is one of them, jot down what your platelet
count is and what the normal values are. Then from time to time you can review your lab
work with your physician or by yourself to determine how your platelet count is responding.
The same with other commonly done tests in lupus, including the white blood cell count,
which can also be low, the red blood cell count, various antibodies such as anti-double-
stranded DNA antibodies, proteins in the blood called complements and especially C3 and C4
components of complement, the sed rate and C-reactive protein, which tend to increase due to
inflammation caused by lupus, the urine protein level, and sometimes other tests that your
doctor indicates are important in your particular case. If you go to read about certain medical
issues regarding lupus, choose reliable websites such as the Lupus Foundation of America
and the Illinois chapter, the Mayo Clinic website, WebMD, various university medical
websites, etc.

Robert S. Katz, M.D.