IDA, ACD, Virus, HIV Anemia

Three issues in Heme Synthesis

1. RBC production is impaired

2. RBC life span is shortened (hemolysis)

3. RBCs are lost

Where does iron absorption occur, and how much is absorbed?

1. Small intestine

2. 10-20% daily

What regulates iron absorption, where is it produced, and how is it related to EPO?

1. Hepcidin (hormone)

2. Liver

3. Inversely related to EPO

What transports iron throughout circulation? What stores iron?

1. Transferrin

2. Ferritin

Where is ferritin found?

1. Hepatocytes

2. Macrophages

3. Enterocytes

Where is Hemosiderin found?

In macrophages in BM

What is the plasma level of iron regulated by?

1. Amount of iron in storage sites

2. Amount of iron in EPO tissues

What form of iron is transported and stored?

Fe3+

How much iron is excreted each day?

1 mg

How is iron excreted? How is it recycled?

1. Excreted through menstruation and exfoliation of epithelial cells or bile, urine, feces

2. Iron from senescent RBCs recycled.

How is serum Fe measured?

What is TIBC?

The amount of iron available for EPO / Transferrin in serum that functionally can bind to iron.

What is the formula for Transferrin Saturation?

TS = (serum Fe/TIBC) x 100

How much transferrin is saturated with iron? What does the transferrin that is not saturated with iron do?

1. 1/3 is saturated with iron

2. 2/3 is the reserve capacity (UIBC)

Transferrin reference range

200-370 mg/dL

Serum Fe reference range

35-165 ug/dL

TIBC reference range

25-35% saturated

Where is Ferritin located, and what relationship does it have to iron storage?

1. Liver

2. BM

3. Spleen

4. Proportional

Ferritin reference range male

20-300 ng/mL

What is ferritin classified as?

Acute Phase Reactant

What does the Iron Prussian Blue stain show?

Hemosiderin stores in the BM, liver, and other RES tissue

What is TfR?

A transferrin receptor on the surface of all cells that admits iron. Serum TfR reflects total cellular TfR.

sTfR is _____________ proportional to the amount of body iron.

Inversely

How does IDA affect sTfR?

sTfR increases in IDA

What is sTfR useful for differentiating between?

IDA from ACD

How is sTfR measured?

Immunoassay

What is formed in the last step in HGB synthesis?

Erythrocyte Protoporphyrin is iron complexes with heme.

Low levels of iron lead to what?

Higher levels of ZPP (Zinc complexed with Protoporphyrin as a substitute for iron)

How is Protoporphyrin measured?

Fluorometric assay using “hematofluorometer”

What are the benefits of measuring Protophorphyrin?

1. Easy to do

2. Cheaper than serum ferritin

3. More sensitive than HCT

What are the downsides to Protoporphyrin measurement?

1. Indirect

2. Lacks specificity

What population is recommended to get tested with Ancillary lab tests? What do ancillary lab tests include?

1. > 50 years old

2. Hemoccult slides and fecal occult blood

What disease is IDA correlated to?

GI cancers

What does Reticulocyte Hemoglobin measure?

Hemoglobin concentration in retics

What method does Reticulocyte Hemoglobin use?

Flow cytometry

What are two benefits to the Reticulocyte Hemoglobin concentration?

1. Very sensitive to developing IDA

2. Retic hemoglobin is decreased before HGB in total blood

Which population is especially vulnerable to Iron Deficiency Anemia?

Non-pregnant women

What is the main cause of IDA in adult females?

Insufficient dietary intake

What are six other causes of IDA?

1. Malabsorption

2. Acute blood loss

3. Chronic bleeding

4. Chronic intravascular hemolysis

5. Runner’s anemia

6. Hookworm infection

How quickly does IDA develop?

Slowly

What are the stages of IDA development?

1. Depletion of Fe stores through progressive loss

2. Exhaustion of storage iron causes impairment of erythropoiesis.

3. Full-blown iron deficiency anemia

What can be seen of IDA during stage 1?

No evidence in PB CBC but decreased ferritin

What can be seen of IDA during stage 2?

Decreasing H & H, increased ZPP

What can be seen of IDA in stage 3?

1. Decreased H & H

2. Microcytes

3. Hypochromia

How does Anemia affect EPO production?

It increases

In IDA, there is (more/less) HGB/RBC so RBC are (larger/smaller) than normal.

1. Less

2. Smaller

IDA lab findings

1. Decreased H & H

2. Decreased MCV, MCH, MCHC

3. Increased RDW (during development)

4. Decreased (variable) retic count

5. Increased platelets

6. Variable WBC count

7. Increased ZPP

How does IDA affect serum Fe, TIBC, Transferrin, Transferrin Saturation, serum Ferritin, sTfR, and CHr?

1. Serum Fe < 30 ug/dL

2. Increased TIBC

3. Decreased Transferrin Saturation (<16%)

4. Decreased serum ferritin

5. Increased sTfR

6. Decreased CHr

What does the BM look like in IDA?

1. Hyperplasia

2. Abnormal erythroid precursors

3. Decreased iron storage

How common is it to do a BM exam for IDA?

Not common

Treatment of IDA

Iron supplements

What is the most common anemia of hospitalized patients?

Anemia of chronic disorders / Anemia of inflammation

What conditions can anemia of chronic disorders be found in?

1. Chronic infection

2. Malignancy

3. Inflammation (SLE, RA)

4. Organ failure

How does inflammation cause anemia?

1. Increases Hepcidin Production, which decreases iron absorption and increases iron sequestration

2. Decreases EPO sensitivity

3. Reduces RBC Lifespan

4. Cytokines suppress BM → hypoproliferation

How does ACD impact serum Fe, TIBC, storage iron (ferritin), and sTfR?

1. Low serum Fe

2. Low TIBC

3. Normal - increased Ferritin

4. sTfR normal

When determining Ferritin levels in people with inflammatory states, what should you do?

Divide Ferritin by 3 since inflammation naturally increases Ferritin since it’s an acute phase reactant.

ACD PB characteristics?

1. Mild to moderate anemia (rarely severe)

2. N, N or hypochromic, microcytic

3. Decreased retic count

BM ACD characteristics

Hypoplasia

ACD treatment

Treat underlying disorder

What is used to differentiate Anemia of Viral Infection from ACD?

WBC changes and N, N anemia

How does a virus cause anemia?

1. Interference with iron release

2. Aplasia of RBC precursors (parvovirus)

How can HIV/AIDS anemia be distinguished from Anemia caused by other viruses?

AIDS patients also have accompanying tumors and infections. AZT worsens anemia.