Anemia of Chronic Disease
Dairion Gatot, Soegiarto Gani, Savita Handayani
Divisi Hematologi Onkologi MedikDepartemen Penyakit Dalam
Anemia of Chronic Disease (ACD)
= Anemia of Chronic Inflammation• Can be due to infection, Can be due to infection,
inflammation, malignancy, DM, heart disease, trauma.heart disease, trauma.
• Typically: normochromic normocytic hypoproliferativenormocytic hypoproliferative.
PathogenesisPathogenesis• Reduction in RBC production in BM:p
Iron trapping in macrophages pp g p gunavailable usage of Fe
Increased apoptotic death of red cell precursor
Blunted response toward EPO
• Decreased RBC survival
ACD FeaturesACD Features
• low serum iron (unavailability of Fe)• high ferritin (acute phase protein)high ferritin (acute phase protein)• blunted response to EPO
HepcidinHepcidin
• An acute phase reactant protein• Predominant negative regulator Predominant negative regulator
of Fe absorption from the intestine, and also Fe release intestine, and also Fe release from macrophage.
• Release of hepcidin from the • Release of hepcidin from the liver is dependent upon level of IL 6IL-6.
Acute event-related anemia • Variant of ACD in conditions:
after surgery, major trauma, g y, j ,myocardial infarction or sepsis.
• = Anemia of critical illness Anemia of critical illness • Features ≈ ACD
Laboratory findingsLaboratory findings
• Most patients have mild anemia • More severe anemia (Hb<8) ≈ 20%( )• Absolute reticulocyte count is
frequently low (<25,000/microL) frequently low (<25,000/microL) decrease in RBC production.
• Elevation in cytokines (eg IL 6) and • Elevation in cytokines (eg, IL-6) and acute phase reactants (fibrinogen, erythrocyte sedimentation rate Cerythrocyte sedimentation rate, C-reactive protein)
Laboratory Findings….Laboratory Findings
• Serum iron (SI) and total iron binding capacity, (TIBC) are both low and the percent saturation of transferrin is usually normal / increase.S f iti i i d f i • Serum ferritin is a poor index of iron stores in chronic inflammatory diseases because ferritin is also an acute phase because ferritin is also an acute phase reactant.
Laboratory Findings….Laboratory Findings
• Bone marrow:
macrophages normal or increased amounts of Fe storage
erythroid precursors Fe staining / (-)/ (-)
Differential DiagnosisDifferential Diagnosis• As a normochromic hypoproliferative As a normochromic hypoproliferative
anemia that does not affect other blood cell lines DD:blood cell lines DD:chronic renal failure and several endocrine disorders endocrine disorders (hyperthyroidism, hypothyroidism, panhypopituitarism and primary and panhypopituitarism, and primary and secondary hyperparathyroidism)
Differential Diagnosis ….Differential Diagnosis
• Prominent ACD (Hb<8 g/dL) with hypochromic and microcytic DD:
fchronic Fe deficiency, thalassemia variants, and the sideroblastic
i t f th MDS variants of the MDS. • ACD vs IDA = truncated forms of
transferrin receptors (sTfR). IDA cellular membrane transferrin receptor density increases sTfR
TreatmentTreatment
• Correction of underlying disorder
• Treat other complicating factors: blood loss, Fe/B12/folate factors: blood loss, Fe/B12/folate deficiency
Treatment EPO….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
i t d ith th associated with cancer therapy found that EPO significantly decreased the percent of patients decreased the percent of patients transfused (relative risk 0.38).
Assessing the causeAssessing the cause…
• Blood loss anemia
• Increased RBC destruction (hemolytic anemia)(hemolytic anemia)
• Decreased red blood cell production (hypoproliferative anemia)
Malignancy relatedMalignancy related
• Direct effects of the neoplasmP d t f th l• Products of the neoplasm
• Effects of treatment directed against the neoplasm
Anemia due to direct effects of cancer
• Bleeding• Impaired Iron absorptionImpaired Iron absorption• Bone marrow replacement
(myelophthisic)(myelophthisic)leukoerythroblastic features
Anemia due to product pof cancer.
• Cytokines (interferon (IFN)-α, IFN-β, Cytokines (interferon (IFN) α, IFN β, IFN-γ, TNF-α, TGF-β, IL-1 and IL-6)
block in iron utilization & block in iron utilization & inhibiting erythropoietin mRNA synthesis anemiasy t es s a e a