ANEMIA OF CHRONIC DISEASE

Dwi Lingga Utama

SubBagian Infeksi dan Penyakit Tropis
Bag/SMF Ilmu Kesehatan Anak
FK UNUD-RSUP Sanglah Denpasar

OUTLINE
PENGERTIAN ACD
BAGAIMANA TERJADINYA ACD
PENGENALAN KLINIS DAN PENELUSURAN PENUNJANG
PENANGANAN
TAKE HOME MESSAGE

NAMA
UMUR
JENIS KELAMIN
DIAGNOSIS
high risk
prokemoterapi

: IK
: 9 tahun 8 bulan
:L
:
Neuroblastoma
stadium IV

HGB :10,52 gr/dl

MCV : 90,51 fL
MCHC : 31,17 gr/dL

HGB : 6,60 gr/dl

MCV : 74,62 fl

MCHC : 29,66 gr/dl

SI : 26 g/dl
TIBC : 211 g/dl

Ferritin : 562,3 ng/dl

Definition

Anemia of chronic disease (ACD)= anemia of inflammation(AI)

mild to moderately severe anemias ([Hb] 7-12 g/dl)
associated with chronic infections and inflammatory disorders
and some malignancies.

characterized by:
Inadequate erythrocyte production
Low serum iron
Low binding capacity (i.e low transferrin)
The erythrocytes usually are normocytic and normochromic
but can be mildly hypochromic and microcytic.

Epidemiology

The high prevalence of infectious diseases , hospitalized

patient and the high prevalence of inflammatory and
malignant

second

or third most common form of anemia after

iron-deficiency anemia (IDA) and thalasemia .

Etiology
Infections

(acute and chronic)

Viral infections, including HIV infection
Bacterial including tuberculosis, osteomyelitis and sepsis
Parasitic including malaria
Fungal

Cancer

Hematologic including multiple myeloma and lymphoma

Solid tumor including carcinoma

Etiology ..

Autoimmune

Rheumatoid arthritis and other rheumatologic disorders

Systemic lupus erythematosus
Connective-tissue diseases
Vasculitis
Sarcoidosis
Inflammatory bowel disease
systemic inflammatory response syndrome

Pathogenesis
Interleukin
Inhibition

-6 & other cytokin ,Hepcidin ,and Hypoferremia

of Intestinal absorption of iron

iron concentrations AND iron released from

Macrophages and Hepatocytes

Serum

Red

cell destruction

Inadequate

erythropoietin secretion

Erythropoiesis

as a result of iron unavailability

LIPOPOLISAKARIDA

Mikroorganisme,
Sel malignan,autoimun

HEPSIDIN

MONOSIT
DUODENUM
ABSORBSI FE

IL-6
SEL T

IL-10

IL-1
TNF
INTERFERON

FERRITIN

TRANSFERRIN
RESEPTOR

DEGRADASI &
FAGOSIT
SENESCENT
ERITOSIT
DMT 1
UPTAKE FE

FERROPORTIN-1
PENGELUARAN FE

PRODUKSI
ERITROPOETIN

INHIBISI
ERITROPOESIS

Weiss G. n engl j med. 2005; 352:10

Control of Body Iron Homeostasis by Hepcidin

Luminal

Baso-lateral

Enterocyte

Macrophage

Tf Fe3+

Fe3+
DcytB

HO-1

Heph
Fe2+

Fe2+
DMT1

Heme

Fpn1

Fe2+

Fe2+

HCP-1?

Heph

Fe

Fpn1

Fe2+
HO-1
+

Hepcidin
Tf-Fe+3

Fe2+

+
Tf-Fe+3

Liver

Slide courtesy of Dr. G. Weiss. Hentze MW, et al. Cell. 2010;142:24-28

Hepcidin

Tf Fe3+

Inflammation (IL-6, LPS)

Hepcidin-mediated regulation of iron homeostasis.

(A) Increased hepcidin expression by the liver results from inflammatory stimuli. High levels of hepcidin in the bloodstream result in the
internalization and degradation of the iron exporter ferroportin. Loss of cell surface ferroportin results in macrophage iron loading,
low plasma iron levels, and decreased erythropoiesis due to decreased transferrin-bound iron. The decreased erythropoiesis gives
rise to the anemia of chronic disease.
(B) Normal hepcidin levels, in response to iron demand, regulate the level of iron import into plasma, normal transferrin saturation, and
normal levels of erythropoiesis.
(C) Hemochromatosis, or iron overload, results from insufficient hepcidin levels, causing increased iron import into plasma, high
transferrin saturation, and excess iron deposition in the liver.

Clinical features
The

clinical manifestations of AI usually are

obscured by the signs and symptoms of the
underlying disease.

Moderate

anemia (Hg<10) can exacerbate the

symptoms of the preexisting disease comorbidity

 The

erythrocytes in AI are normocytic and normochromic

but, with increasing severity and duration, can become
hypochromic and eventually microcytic.
The absolute reticulocyte count is normal or slightly
elevated.
Hypoferremia and decreased serum transferrin
Interleukin -6, Hepcidin, and Hypoferremia
Normal to increased serum ferritin
Marrow iron stain

Weiss G. n engl j med. 2005; 352:10

Marrow iron stain

Marrow aspiration or biopsy is rarely required for
diagnosis of AI. In general, the marrow morphology and
stainable iron are normal, unless the underlying disease
alters the picture.

The most important information that obtained from

marrow examination is the content of and distribution of
iron.

Differential diagnosis
Most patients with chronic infections, inflammatory diseases, or neoplastic
disorders are anemic.
The diagnosis of AI should be made only if the anemia is mild to moderate, the
serum and iron binding capacity are low, and the serum ferritin is elevated.
Drug-induced marrow suppression or drug-induced hemolysis
Chronic blood loss
Renal impairment
Endocrine disorders
Anemia resulting from metastatic invasion of the bone marrow
Thalassemia minor
Dilution anemia

Algorithm for the Differential Diagnosis

Therapy and prognosis

Anemia that presents in the setting of infection, inflammation,
or malignancy requires sufficient diagnostic studies to more
threatening causes, such as occult hemorrhage; iron, B12, and
follate deficiency; hemolysis and drug reaction.

If the anemia can be designated as AI after such studies,

effective treatment of the underlying disease resolves the
anemia

Therapeutic Options for ACD

TAKE HOME MESSAGE

ACD sering ditemukan pd pasien rawat inap (keganasan,
infeksi, autoimun)

ACD: lebih sering normositik normokromik

Patogenesis: kompleks, diawali mediator pro inflamasi
Klinis: lebih kepada penyakit yang mendasari

Penting untuk membedakan dg anemia defisiensi Fe

Tatalaksana: tangani penyakit dasar