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).

Anemia in Malignancyg y

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

Anemia due to cancer therapy

• Radiotherapy• ChemotherapyChemotherapy