38 Anemia of Chronic Disease Flashcards
Term more reflective of the pathophysiology of ACD
Anemia of inflammation (AI)
A condition that presents similarly to anemia of chronic disease but develops within days of the onset of illness
Anemia of critical illness
An anemia similar to AI is seen in some older patients in the absence of an identifiable chronic disease
Unexplained anemia of elderlies or anemia of aging
Cytokine dyregulation
Older patients in this defined subset typically have an elevated sedimentation rate and/or elevated C-reactive protein (CRP), a high plasma interleukin-6 (IL-6) concentration, and frailty.
Key characteristic of AI
- Inadequate erythrocyte production in the setting of low serum iron and low iron-binding capacity (ie, low transferrin) despite preserved or even increased macrophage iron stores in the marrow
- The erythrocytes are usually normocytic and normochromic but can be mildly hypochromic and microcytic.
Patients with_____________ are often at least partially spared, likely because cysts cause local ischemia with resultant increased local EPO production
Polycystic kidney disease
Pathophysiology of anemia of chronic kidney disease (anemia of CKD)
Relative EPO deficiency
Others:
Systemic inflammation, true iron deficiency, and decreased clearance of hepcidin
The second or third most common form of anemia after iron deficiency anemia (IDA) and possibly thalassemia
Anemia of inflammation (AI)
The term that describes rare disorders where hemophagocytosis by activated macrophages is the predominant cause of anemia
“Consumptive anemia of inflammation”
Cytokines that exert a suppressive effect on erythroid colony formation
Tumor necrosis factor-α (TNF-α), IL-1, and Interferon-γ
One of the defining features of AI that develops within hours of the onset of inflammation
Hypoferremia
Induces the iron-regulatory hormone, hepcidin
IL-6
Amount of iron that daily enters the plasma iron/transferrin pool comes from macrophage recycling of senescent erythrocytes and from hepatocyte iron stores
20–25 mg
Amount of iron derived from dietary iron
1–2 mg
Amount of iron bound to transferrin
2–4 mg
Hepcidin acts by binding to cell membrane–associated ________ molecules that are the only conduits for iron export, and inducing occlusion, internalization, and degradation.
Ferroportin
As an intermediate step during the synthesis of heme, iron becomes incorporated into protoporphyrin_____.
Protoporphyrin IX
Mineral that is an alternative protoporphyrin ligand
Zinc
In AI (as well as IDA), zinc protoporphyrin is (increased or decreased).
Increased
In AI, the number of sideroblasts is (increased or decreased)
Decreased
TRUE OR FALSE
In AI, iron deficiency contribute to the anemia, in that coadministration of parenteral iron can resolve the resistance of AI to EPO
TRUE
In AI, iron deficiency contribute to the anemia, in that coadministration of parenteral iron can resolve the resistance of AI to EPO
In AI, the absolute reticulocyte count is
Normal or slightly elevated
In AI, transferrin is (increased or decreased).
Decreased
The decrease in transferrin concentrations develops more slowly than the decrease in serum iron levels because of the longer half-life of transferrin (8–12 days) compared with the turnover of plasma iron (approximately 90 minutes).
In AI, ferritin is (increased or decreased).
Increased
Decreased in iron deficiency
Depending on the severity of inflammation, coexisting iron deficiency should be suspected if ferretin level is less than _______ in the presense of significant inflammation.
Ferritin is an acute-phase protein and inflammatory cytokines increase ferritin synthesis.
Less than 100 mcg/L
Soluble transferrin receptor (sTfR) levels (increased or decreased) during infection or inflammation.
Decreased
sTfR is increased in iron deficiency
Another promising marker that may differentiate AI from systemic iron deficiency is serum ________, because very low serum levels in hypoferremia are diagnostic of systemic iron deficiency.
Hepcidin
TRUE OR FALSE
Marrow aspiration or biopsy is required for the diagnosis of AI.
FALSE
Marrow aspiration or biopsy is rarely required for the diagnosis of AI.
The most important information obtained from marrow examination is the
Content and distribution of iron
Iron in a marrow preparation can be found as
- Storage iron in the cytoplasm of macrophages
- Functional iron in nucleated red cells
Approximately one-third of nucleated red cells contain 1–4 blue inclusion bodies by light microscopy, and such cells are called
Sideroblasts
In AI, sideroblasts are (increased or decreased) , but macrophage iron is (increased or decreased)
Decreased or absent
Increased
Marrow staining that could be considered the gold standard for differential diagnosis of AI and iron deficiency
Prussian blue stain
TRUE OR FALSE
When AI and chronic blood loss coexist, serum ferritin usually indicates the predominant disorder, although the level can increase as a result of inflammation itself.
TRUE
When AI and chronic blood loss coexist, serum ferritin usually indicates the predominant disorder, although the level can increase as a result of inflammation itself.
Treatment of AI
Treatment of the underlying disease
EPO is recommended in treating patients with Hb less than ______ g/dL
10 g/dL
Modification to reduce the ESA dose is appropriate when Hb reaches a level sufficient to avoid transfusion or the increase exceeds 1 g/dL in any two-week period to avoid excessive ESA exposure.
The FDA-approved starting dose of epoetin
150 U/kg three times per week or 40,000 U weekly
The FDA-approved starting dose of darbepoetin
2.25 mcg/kg weekly or 500 mcg every 3 weeks
Continuing epoetin or darbepoetin treatment beyond ______weeks in the absence of response (achieving less than 1–2 g/dL rise in Hb) does not appear to be beneficial and EPO therapy should be discontinued.
6–8 weeks
For adult patients, these guidelines recommend that a newly anemic patient with CKD should have laboratory studies to rule out B12 and folate deficiency, and a therapeutic trial of intravenous iron if their transferrin saturation level is _______and ferritin is less than ______ ng/mL.
30% or lower
less than 500 ng/mL
CKD
The guidelines recommend that individualized therapy with ESAs may be started when Hb concentrations fall below _____ g/dL, and then adjusted to maintain Hb to ______ g/dL or lower,
Below 10 g/dL
11.5 g/dL or lower
TRUE OR FALSE
Concerns exist that iron supplementation in AI or CKD may increase susceptibility to infections, but epidemiologic studies have generally not detected this risk.
TRUE
Concerns exist that iron supplementation in AI or CKD may increase susceptibility to infections, but epidemiologic studies have generally not detected this risk.
However, the use of high-bolus doses of iron in patients with intravenous catheters may be associated with increased infections.
