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Anemia of Chronic Disease (ACD) or Anemia of Inflammation (AI) (TREATMENT,…
Anemia of Chronic Disease (ACD) or Anemia of Inflammation (AI)
PATHOPHYSIOLOGIC ETIOLOGY
DECREASED RED CELL LIFE SPAN
: shortened red cell life span may occur in acute inflammation which are characterized by increased macrophage activity which release cytokines
:!!:
HEPCIDIN-INDUCED ALTERATIONS IN IRON METABOLISM
: reduced iron absorption in GI tract and trapping of iron in macrophages ---> reduced plasma iron levels =
hypoferremia
, iron unavailable for new hemoglobin synthesis
SUPPRESSED ERYTHROPOIESIS RESPONSE
: serum erythropoietin (EPO) levels somewhat elevated in ACD but no increase in erythropoiesis, possibly due to increased apoptosis of red cell precursors in bone marrow
DECREASE IN ERYTHROPOIETIN (EPO) PRODUCTION
:
:!!:
CYTOKINES
:
underlying inflammatory condition releases
cytokines such as
interleukins (e.g. IL-1, IL-6)
and
tumor necrosis factor (TNF-alpha)
by activated monocytes results in secretion of
interferon (IFN)-beta
and
IFN-gamma
by T lymphocytes
decreased bone marrow responsiveness to erythropoietin
which may cause apoptosis of red cells precursors as well as downregulation of erythropoietin receptors on progenitor cells. This is induced particularly from cytokines
IL-1 beta and TNF-alpa
IL-6
affects hepatocytes and
increases release of peptide hepcidin
, which regulates activity of
ferroportin
(primary transporter for export of iron from macrophages to plasma).
Increased hepcidin levels--> decreased ferroportin activity and suppressed iron release
BACTERIAL TOXINS
: direct action of these toxins such as
Clostridium perfringens
(cause food poisoning) produces
alpha toxin
which has an
enzymatic activity that disrupts cell membrane
like erythrocyte's cell membrane
TREATMENT
:check:
Iron supplementation
:check:
Erythropoiesis-stimulating agents
(ESAs) treatment
:star: :star:
Treat the underlying medical condition
whether inflammatory, autoimmune, malignant, infectious
:!:Transfusion (only for emergency situations)
HEPCIDIN THERAPY
eHepcidin antagonist: Sotatercept, Luspatercept
Hepcidin binding proteins: Lipocalin e.g. Anticalin (PRS-080)
Hepcidin production inhibitors, BMP inhibitors: Dorsomorphin, Anti-BMP6 monoclonoal antibody
Heparin
Anti-IL6 monoclonal antibody: Siltuximab
FGF23 inhibitor
FPN stabilizers: anti-ferroportin monoclonal antibody
CAUSATIVE FACTORS
& RELATION TO
IMMUNITY, INFLAMMATION & INFECTION
RISK FACTORS
:warning:
People with chronic systemic disease or inflammation at greater risk
cancer and hematological malignancies
infections
immune -mediated diseases
chronic kidney disease
obesity
chronic obstructive pulmonary disease (COPD)
congestive heart failure
anemia of critical illness (accelerated course)
chronic liver disease
:!:
elderly > 65 years
:explode:
INFLAMMATION
disorders that cause
chronic or systemic inflammation
(i.e. RA, COPD, IBS, CKD) commonly have ACD due to inflammation causing
increased levels of hepcidin in circulation which alters iron metabolism
:warning:
INFECTION OR INJURY
causes an immune response like the
inflammatory process
from bacterial (TB), viral (including HIV), parasitic, fungal infections, which contributes to ACD since inflammation response
releases cytokines
:red_flag:
IMMUNITY
- the
innate immune system
responds with an
inflammatory process
due to autoimmune disorders such as SLE, sarcoidosis, vasulitis, that
releases cytokines
from macrophages, lymphoctes and affected tissue that
contributes to ACD
DIAGNOSTIC TESTS
IRON STUDIES - STANDARD
transferrin saturation
serum ferritin
total iron-binding capacity (TIBC), transferrin
reticulocyte hemoglobin equivalent (Ret-he or CHr)
serum iron
C-reactive protein
Erythrocyte protoporphyrin
Soluble transferrin receptor
COMPLETE BLOOD COUNT - STANDARD
mean corpscular volume (MCV)
red cell distribution width (RDW)
hemoglobin concentration
red blood cell count
OTHER TESTS
sTfR- ferritin index (used more to distinguish between ACD and IDA [iron deficiency anemia])
bone marrow studies (not performed often)
peripheral blood smear
hepcidind assay (helpful but not widely available)
COMMON FINDINGS
:warning:
mild to moderate
normocytic (normal size and shape), normochromic (normal in iron and hemoglobin content), hypoproliferative (i.e. no evidence for an increased erythropoietic rate)
anemia
with few complications
:red_flag:
5 KEY LAB FINDINGS PRESENT INDICATIVE OF ACD
Elevated erythrocyte sedimentation rate
(Normal: 0 to 20 mm/hour [men], 0 to 30 mm/hour [women]) or
elevated C-reactive protein
(Normal: <3 mg/L for most subjects)
Normal to increased serum ferritin
(Normal: 40 to 200 ng/mL or 40 to 200 mcg/L; 90 to 449 picoM/L)
Low transferrin saturation
Normal to low serum transferrin
(total iron binding capacity) (Normal: 300 to 360 mcg/dL or 3 to 3.6 mg/L; 54 to 64 microM/L)
Low serum iron
(Normal: 60 to 150 mcg/dL or 0.6 to 1.5 mg/L; 11 to 27 microM/L)
abundant iron stores in bone marrow macrophages (unless concurrently blood loss has happened) with decreased, if not absent, numbers of sideroblasts
serum erythropoietin (EPO) levels are inappropriately low given degree of anemia and intact renal function
low plasma concentrations of iron and transferrin (measured as total iron binding capacity [TIBC]) in the presence of normal or increased plasma ferritin concentrations