38 Anemia of Chronic Disease

Question 1

Term more reflective of the pathophysiology of ACD

Answer 1

Anemia of inflammation (AI)

Question 2

A condition that presents similarly to anemia of chronic disease but develops within days of the onset of illness

Answer 2

Anemia of critical illness

Question 3

An anemia similar to AI is seen in some older patients in the absence of an identifiable chronic disease

Answer 3

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.

Question 4

Key characteristic of AI

Answer 4

• 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.

Question 5

Patients with_____________ are often at least partially spared, likely because cysts cause local ischemia with resultant increased local EPO production

Answer 5

Polycystic kidney disease

Question 6

Pathophysiology of anemia of chronic kidney disease (anemia of CKD)

Answer 6

Relative EPO deficiency

Others:
Systemic inflammation, true iron deficiency, and decreased clearance of hepcidin

Question 7

The second or third most common form of anemia after iron deficiency anemia (IDA) and possibly thalassemia

Answer 7

Anemia of inflammation (AI)

Question 8

The term that describes rare disorders where hemophagocytosis by activated macrophages is the predominant cause of anemia

Answer 8

“Consumptive anemia of inflammation”

Question 9

Cytokines that exert a suppressive effect on erythroid colony formation

Answer 9

Tumor necrosis factor-α (TNF-α), IL-1, and Interferon-γ

Question 10

One of the defining features of AI that develops within hours of the onset of inflammation

Answer 10

Hypoferremia

Question 11

Induces the iron-regulatory hormone, hepcidin

Answer 11

IL-6

Question 12

Amount of iron that daily enters the plasma iron/transferrin pool comes from macrophage recycling of senescent erythrocytes and from hepatocyte iron stores

Answer 12

20–25 mg

Question 13

Amount of iron derived from dietary iron

Answer 13

1–2 mg

Question 14

Amount of iron bound to transferrin

Answer 14

2–4 mg

Question 15

Hepcidin acts by binding to cell membrane–associated ________ molecules that are the only conduits for iron export, and inducing occlusion, internalization, and degradation.

Answer 15

Ferroportin

Question 16

As an intermediate step during the synthesis of heme, iron becomes incorporated into protoporphyrin_____.

Answer 16

Protoporphyrin IX

Question 17

Mineral that is an alternative protoporphyrin ligand

Answer 17

Zinc

Question 18

In AI (as well as IDA), zinc protoporphyrin is (increased or decreased).

Answer 18

Increased

Question 19

In AI, the number of sideroblasts is (increased or decreased)

Answer 19

Decreased

Question 20

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

Answer 20

TRUE

In AI, iron deficiency contribute to the anemia, in that coadministration of parenteral iron can resolve the resistance of AI to EPO

Question 21

In AI, the absolute reticulocyte count is

Answer 21

Normal or slightly elevated

Question 22

In AI, transferrin is (increased or decreased).

Answer 22

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).

Question 23

In AI, ferritin is (increased or decreased).

Answer 23

Increased

Decreased in iron deficiency

Question 24

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.

Answer 24

Less than 100 mcg/L

Question 25

**Soluble transferrin receptor (sTfR)** levels (increased or decreased) during infection or inflammation.

Answer 25

Decreased ## Footnote sTfR is increased in iron deficiency

Question 26

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.

Answer 26

Hepcidin

Question 27

# TRUE OR FALSE Marrow aspiration or biopsy is required for the diagnosis of AI.

Answer 27

FALSE Marrow aspiration or biopsy is **rarely required** for the diagnosis of AI.

Question 28

The most important information obtained from marrow examination is the

Answer 28

Content and distribution of iron

Question 29

Iron in a marrow preparation can be found as

Answer 29

* **Storage iron** in the cytoplasm of **macrophages** * **Functional iron** in **nucleated red cells**

Question 30

Approximately **one-third of nucleated red cells** contain **1–4 blue inclusion bodies** by light microscopy, and such cells are called

Answer 30

Sideroblasts

Question 31

In AI, **sideroblasts** are (increased or decreased) , but **macrophage** iron is (increased or decreased)

Answer 31

Decreased or absent Increased

Question 32

Marrow staining that could be considered the gold standard for differential diagnosis of AI and iron deficiency

Answer 32

Prussian blue stain

Question 33

# 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.

Answer 33

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.

Question 34

Treatment of AI

Answer 34

Treatment of the underlying disease

Question 35

EPO is recommended in treating patients with Hb less than ______ g/dL

Answer 35

10 g/dL ## Footnote 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.

Question 36

The FDA-approved starting dose of epoetin

Answer 36

150 U/kg three times per week or 40,000 U weekly

Question 37

The FDA-approved starting dose of darbepoetin

Answer 37

2.25 mcg/kg weekly or 500 mcg every 3 weeks

Question 38

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.

Answer 38

6–8 weeks

Question 39

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.

Answer 39

30% or lower less than 500 ng/mL

Question 40

# 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,

Answer 40

Below 10 g/dL 11.5 g/dL or lower

Question 41

# 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.

Answer 41

TRUE Concerns exist that iron supplementation in AI or CKD may **increase susceptibility to infections**, but *epidemiologic studies have generally not detected this risk.* ## Footnote However, the use of high-bolus doses of iron in patients with intravenous catheters may be associated with increased infections.