Anemia of Chronic

Disease

Departemen Penyakit Dalam
Anemia of Chronic Disease
(ACD)
= Anemia of Chronic Inflammation
Can be due to infection,
inflammation, malignancy, DM,
heart disease, trauma.
Typically: normochromic
normocytic hypoproliferative.
Pathogenesis
Reduction in RBC production in BM:

Iron trapping in macrophages
unavailable usage of Fe

Increased apoptotic death of red cell
precursor

Blunted response toward EPO

Decreased RBC survival
ACD Features
low serum iron (unavailability of Fe)
high ferritin (acute phase protein)
blunted response to EPO
Hepcidin
An acute phase reactant protein
Predominant negative regulator
of Fe absorption from the
intestine, and also Fe release
from macrophage.
Release of hepcidin from the
liver is dependent upon level of
IL-6.
Acute event-related
anemia
Variant of ACD in conditions:
after surgery, major trauma,
myocardial infarction or sepsis.
= Anemia of critical illness
Features ACD
Laboratory findings
Most patients have mild anemia
More severe anemia (Hb<8) 20%
Absolute reticulocyte count is
frequently low (<25,000/microL)
decrease in RBC production.
Elevation in cytokines (eg, IL-6) and
acute phase reactants (fibrinogen,
erythrocyte sedimentation rate, C-
reactive protein)
.Laboratory Findings
Serum iron (SI) and total iron binding
capacity, (TIBC) are both low and the
percent saturation of transferrin is
usually normal / increase.
Serum ferritin is a poor index of iron
stores in chronic inflammatory diseases
because ferritin is also an acute phase
reactant.
.Laboratory Findings
Bone marrow:

macrophages normal or
increased amounts of Fe storage

erythroid precursors Fe staining
/ (-)
Differential Diagnosis
As a normochromic hypoproliferative
anemia that does not affect other
blood cell lines DD:
chronic renal failure and several
endocrine disorders
(hyperthyroidism, hypothyroidism,
panhypopituitarism, and primary and
secondary hyperparathyroidism)
.Differential Diagnosis
Prominent ACD (Hb<8 g/dL) with
hypochromic and microcytic DD:
chronic Fe deficiency, thalassemia
variants, and the sideroblastic
variants of the MDS.
ACD vs IDA = truncated forms of
transferrin receptors (sTfR).
IDAcellular membrane transferrin
receptor density increases sTfR
Treatment
Correction of underlying
disorder
Treat other complicating
factors: blood loss, Fe/B
12
/folate
deficiency

.Treatment..EPO
EPO levels <500 IU/mL frequently
respond to rHuEPO.
A meta-analysis of 22 trials involving
the use of EPO for the anemia
associated with cancer therapy
found that EPO significantly
decreased the percent of patients
transfused (relative risk 0.38).
Assessing the cause
Blood loss anemia

Increased RBC destruction
(hemolytic anemia)

Decreased red blood cell production
(hypoproliferative anemia)
Malignancy related
Direct effects of the neoplasm
Products of the neoplasm
Effects of treatment directed
against the neoplasm
Anemia due to direct
effects of cancer
Bleeding
Impaired Iron absorption
Bone marrow replacement
(myelophthisic)
leukoerythroblastic features
Anemia due to product
of cancer.
Cytokines (interferon (IFN)-, IFN-,
IFN-, TNF-, TGF-, IL-1 and IL-6)
block in iron utilization &
inhibiting erythropoietin mRNA
synthesis anemia
Anemia due to cancer
therapy
Radiotherapy
Chemotherapy