1. A PRESENTATION ON POSSIBLE CAUSES OF
ANEMIA IN A PATIENT WITH RHEUMATOID
ARTHRITIS
BY
DR JOSEPH UCHENNA VICTOR
MEDICAL FACULTY
GROUP 5(CLINICAL PRACTICAL SKILLS)
4TH COURSE

2. Introduction
Possible Causes of Anemia in RA Patient
-Non-drug associated
-Drug associated
Conclusion

3. Rheumatoid arthritis is a chronic inflammatory
(autoimmune) disorder that typically affects the
joints in hands and feet especially small joints
causing a painful swelling that can eventually
result in bone erosion and joint deformity. Aside
from joint symptoms, anemia is the most common
problem for people with rheumatoid arthritis. Studies
show as many as 60% of people with rheumatoid
arthritis are anemic. Anemia is a below-normal level
of hemoglobin* or hematocrit*.

4. Anemia can be a temporary condition, a
consequence of other health conditions, or it can
be a chronic problem. People with mild anemia
may not have any symptoms or may have only
mild symptoms. People with severe anemia may
have problems carrying out routine activities and
can feel tired or experience shortness of breath
with activity.

5. Anemia and rheumatoid arthritis are linked to
each other as this can affect the bone marrow and
thus the blood count. Sex, age, duration and renal
function play important role on the development
of anemia. Prevalence of anemia is higher in
women (73%) than in men (38%). The prevalence
also is more frequent in younger and older
women, with the highest hemoglobin levels in
patients >58years.

6. There can be many reasons a person with rheumatoid
arthritis experiences anemia. According to general classification
of causes, it can be grouped into 2 major categories;
A. Non-drug associated:
Non-drug associated includes, Anemia of Chronic Disease
(ACD) and concomitant disease induced.
B. Drug associated:
In drug associated, it is noted that the anemia is not part of RA
but as a result of side-effects of drugs used in the treatment.
E.g. NSAIDs, (DMARDs) Disease Mediating Anti-Rheumatic
Drugs: Methotrexate and other heavy metal-containing drugs
like gold.

7. Overall, anemia in RA is classified as an anemia
of chronic disease (ACD) and it is considered the
most frequent cause of anemia in RA. The anemia
develops slowly during the first month of illness and
has been found to be associated with a higher degree
of disease activity. ACD is usually mild and
nonprogressive, characterized by decreased plasma
iron, decreased total iron-binding capacity, decreased
iron saturation of transferrin, decreased bone marrow
sideroblast, and normal or increased
reticuloendothelial iron.

8. One cause is inflammation associated with
rheumatoid arthritis. Inflamed tissues secrete small
proteins that have effects on iron metabolism, bone
marrow, and erythropoietin production by the
kidneys (a hormone that controls production of red
blood cells).
The development of ACD in patients suffering from
RA is related to the inflammation associated with the
condition. The increased production of inflammatory
cytokines results in decreased availability of
erythropoietin, decreased erythropoietic response in the
bone marrow and inadequate erythropoiesis.

10. Numerous cytokines, including TNF, IL-1, IL-10,
IFN-Υ and IL-6, mediate ACD. Hepcidin, a
peptide that controls iron homeostasis, is an acute
phase protein that is influenced by inflammation.
Hepcidin, secondary to the effects of IL-6 is also
associated with ACD. IL-6 has a significant effect,
through the increased production of hepcidin, on
decreased duodenal iron absorption and reduced
iron transport to macrophages, as well as the
storage of ferritin in macrophages.

12. The outline effects of cytokines due to inflammation in RA include;
1.Iron utilization is impaired, with decreased serum iron
and transferrin concentrations and an increased synthesis
of ferritin. There is increased lactoferrin which binds and
lowers serum iron.
2. Reduced erythropoietin levels
3. Decreased bone marrow response to erythropoietin.
4. Premature destruction of red blood cells. Red blood cell life
span may be reduced.
Hence in ACD, the anemia is most often normocytic and
monochromic. Different inflammatory substances depress
reticular processes causing anemia of different forms.

13. The degree of anemia in RA is related to the
activity of the underlying disease and
inflammation. Proven effect was also observed on
secondary disease activity characteristics for the
number of swollen joints, pain score, and patient's
global assessment of disease activity. A combination
of rheumatoid arthritis, splenomegaly, leucopenia,
pigmented spots on lower extremities, and other
evidence of hypersplenism (anemia and
thrombocytopenia).

14. Concomitant diseases causes secondary anemia (Iron
deficiency) in RA patient by causing internal bleeding or
by destruction of bones which directly affects
erythropoiesis and hematopoietic disorders in kidney. They
include Osteoarthritis, Leucopenia, disease of thyroid gland, Cancer
etc.
Rheumatoid arthritis as a disease may cause a warm
autoimmune hemolytic anemia. The red cells are of normal
size and color (normocytic and normochromic). A low white
blood cell count (neutropenia) usually only occurs in patients
with Felty's syndrome with an enlarged liver and spleen. The
mechanism of neutropenia is complex. An increased platelet
count (thrombocytosis) occurs when inflammation is
uncontrolled, as does the anemia.

16. Mostly results to Iron-deficiency anemia
(hypochromic, microcytic ) and sometimes
megaloblastic anemia. NSAIDs and DMARDs are the
main cause of drug related anemia in patient with
RA. This anemia is secondary because it’s not as a
result of the disease. Pain killers, NSAIDs,
Methotrexate are among drugs use in treatment of RA
which have side effects on patients blood cell count.
This iron deficiency is usually caused by gastrointestinal
bleeding, or a problem getting the iron from within the
bone marrow into the red blood cells.

18. NSAID induced bleeding (menstrual bleeding in
women) and secondary iron deficiency while bone
marrow suppression is caused from drug therapy
i.e. gold, Penicillamine, Methotrexate. Generally, they
prevent the release of iron for incorporation into red
blood cells. This type of anemia is characterized by
decreased or absent iron stores, low serum iron
concentration, low transferrin saturation, and low
hemoglobin concentration or hematocrit value. The
erythrocytes are hypochromic and microcytic and the
iron binding capacity is increased.

19. The most common causes of anemia in patients with
rheumatoid arthritis are the anemia of chronic disease
(ACD) and iron deficiency anemia (IDA). ACD is
more common than IDA in RA patients, occurring in
up to 77% of anemic RA patients. In fact, anemia in
RA patients has served as a model for the anemia of
chronic disease. Differentiating the types of anemia is
important in planning diagnostic testing and in
guiding therapy. In ACD, hemoglobin levels are
higher than in IDA, ferritin levels tend to be steady or
increasing, but if ferritin is decreased, and the anemia
is hypochromic, IDA is much more likely.

20. It is estimated that iron deficiency anemia occurs in
approximately 23% of anemic RA patients. However, Iron
deficiency anemia often coexists with ACD in RA
patients. It is generally a hypochromic, microcytic anemia
most commonly due to gastrointestinal bleeding
secondary to nonsteroidal anti-inflammatory drugs
(NSAIDs), or corticosteroid therapy. “It’s important to
recognize that iron deficiency anemia is not part of RA.
It’s the drugs we use to treat our patients, such as the NSAIDs
and the DMARDs (disease-modifying antirheumatic drugs); it
can also be from the secondary effects of other concomitant
conditions resulting in gastrointestinal blood loss that causes
IDA in the patients.

21. THANK
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