Labs

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Labs (2 of 18 slides)

What do expect to find on the CBC?

a
Low hemoglobin
So far, the history suggests the possibility of anemia.
b
High mean corpuscular hemoglobin concentration (MCHC)
The MCHC may be low – not high – in iron deficiency anemia.
c
Elevated red cell distribution width (RDW)
The RDW is often elevated in iron deficiency anemia. In other words, these patients have anisocytosis.
d
Thrombocytosis
Correct. About 10% of patients with iron deficiency anemia develop reactive (or secondary) thrombocytosis. The mechanisms underlying iron-deficiency-mediated thrombocytosis remain unclear (previous studies have shown normal thrombopoietin levels in this setting).
e
Microcytosis (low MCV)
Patients with iron deficiency anemia often have a low MCV.

Labs (3 of 18 slides)

Assuming the patient has iron deficiency anemia, which hemoglobin (Hb g/dL)-hematocrit (Hct, %) pair in the above complete blood counts (CBCs) are you most likely to find?

a
A
b
B
c
C
Right. MCHC = Hb/Hct. In iron deficiency anemia, the MCHC is typically decreased. Therefore, for any Hb level (in this case, 6.2 g/dL), the Hct will be higher than that predicted by the 1:3 rule (Hb:Hct = 1:3 when the MCHC = 33 g/dL) (see NOTES page for more details).

Labs (4 of 18 slides)

WBCHbHctMCVMCHCRDW-SDPLT
6.222 ?

What’s what: WBC, white blood cell count; Hb, hemoglobin; MCV, mean cell volume; MCHC, mean cellular hemoglobin concentration; RDW-SD, red cell distribution width-standard deviation; platelets, PLT; Normal values: WBC 5-10 x 109/L, RBC 4-6 x 1012/L, Hb 12-16 g/dL, Hct 35-47%, MCV 80-100 fL, MCHC 32-36 g/dL, RDW-SD < 45%, platelets (PLT) 150-450 x 109/L

What is the patient’s mean corpuscular hemoglobin concentration (MCHC)?

a
33 g/dL
33 g/dL is a normal MCHC, and does not apply to this case.
b
28 g/dL
Yes, MCHC = Hb/Hct = 6.2 g/dL/0.22 = 28 g/dL
c
55 g/dL
Red cells cannot achieve such a high MCHC under any conditions. Hb would come out of solution!

Labs (5 of 18 slides)

WBCHbHctMCVMCHCRDW-SDPLT
6.222 ?28

What’s what: WBC, white blood cell count; Hb, hemoglobin; MCV, mean cell volume; MCHC, mean cellular hemoglobin concentration; RDW-SD, red cell distribution width-standard deviation; platelets, PLT; Normal values: WBC 5-10 x 109/L, RBC 4-6 x 1012/L, Hb 12-16 g/dL, Hct 35-47%, MCV 80-100 fL, MCHC 32-36 g/dL, RDW-SD < 45%, platelets (PLT) 150-450 x 109/L

What is the patient’s mean cell volume (MCV) likely to be?

a
Low
Correct. In iron deficiency anemia, especially in severe cases such as this, the MCV is typically low.
b
Normal
c
High

Labs (6 of 18 slides)

The MCV is indeed low (normal is 80-100 fL); now let’s look at the rest of the CBC:

WBCHbHctMCVMCHCRDW-SDPLT
4.36.222722858290

What’s what: WBC, white blood cell count; Hb, hemoglobin; MCV, mean cell volume; MCHC, mean cellular hemoglobin concentration; RDW-SD, red cell distribution width-standard deviation; platelets, PLT; Normal values: WBC 5-10 x 109/L, RBC 4-6 x 1012/L, Hb 12-16 g/dL, Hct 35-47%, MCV 80-100 fL, MCHC 32-36 g/dL, RDW-SD < 45%, platelets (PLT) 150-450 x 109/L

Labs (7 of 18 slides)

Which cell best represents the average red cell in this patient? Consider the left-most cell to be of normal size with a normal hemoglobin concentration (represented by the ratio of red color to the total red + white [central pallor] color).

a
A
This cell captures the hypochromia but not the microcytosis.
b
B
Yes! This cell is pale (hypochromic) and small (microcytic).
c
C
This cell captures the reduced size, but not the hypochromia. It is more typical of thalassemia minor.

Labs (8 of 18 slides)

Let’s look at another schematic of red cells, only this time a population of cells; which population most closely represents that of our patient? Note the normal red cell at top.

a
A
These cells are small and well hemoglobinized, and they lack variation in cell size. They are more typical of thalassemia minor.
b
B
Some of the cells are smaller than normal, but all are well hemoglobinized, There is anisocytosis (variation in cell size), but not hypochromia.
c
C
All cells are small and poorly hemoglobinized, but they lack variation in size.
d
D
Correct. Here the red cells are smaller and paler than normal (that is they are microcytic and hypochromic) and they show variation in size (anisocytosis) – all classic findings of iron deficiency anemia, and all consistent with our patient’s results.

Labs (9 of 18 slides)

Notice that in the CBC provided earlier, the mean corpuscular hemoglobin result was not provided. Why?

The answer is on the next slide.

Labs (10 of 18 slides)

Because the mean corpuscular hemoglobin (MCH), with few exceptions, is not helpful!

The MCH is the mean weight of red cells in hemoglobin. Imagine if we were to take a single red cell, lyse it, and collect all its hemoglobin on a weighing scale. The weight, when averaged across multiple red cells, is the MCH. The MCH is reported in picograms. A normal MCH ranges from 27 to 31 pg.

Labs (11 of 18 slides)

There are two ways to change the MCH: by changing the red cell volume or by changing the MCHC. These relationships are shown in the following schematic. The MCH (x-axis) increases as the MCV (y-axis) increases, and as the MCHC increases (dotted line). In other words, MCH tracks with the MCV and MCHC and since we are already considering these latter two values, there is no reason to be concerned with the MCH in daily practice (there are cases when the MCH provides clues about in vitro artifacts of red cell indices, but these are not our concern here).

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MCHC – an important red cell index
MCH – a dispensable red cell index
How to remember:

The acronym with an extra letter (MCHC) rules!

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Let’s look at the patient’s peripheral smear:

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Which single test would your order to order to confirm or rule out a diagnosis of iron deficiency anemia?

a
Serum iron
Serum iron is the least helpful of the iron indices for diagnosing iron deficiency because levels are highly influenced by recent dietary intake and they follow a diurnal variation. That being said, there is no evidence that fasting levels are any more helpful than random samples.
b
Total iron binding capacity (TIBC)
TIBC is typically high in iron deficiency anemia, but this effect may be blunted by concomitant inflammation.
c
Ferritin
Yes! A ferritin < 10 ng/ml is diagnostic of iron deficiency. A ferritin > 100 ng/ml rules out iron deficiency in most cases, even if the patient is inflamed (exceptions include those with conditions associated with leakage of ferritin from injured cells, for example, acute hepatitis, and – for reasons not entirely clear – those on hemodialysis). See NOTES page for explanation of competing effects of iron and inflammatory mediators on ferritin levels.
d
Mean cell hemoglobin (MCH)
Remember, MCH is not very helpful. In this case it will be low because both the MVC and MCHC are decreased. Maybe it could be argued that because MCH is a sensor for both MCV and MCHC that is a more sensitive indicator of early iron deficiency when both MCV and MCHC are minimally reduced, but it is hardly worth the effort of putting the parameter on your daily radar screen.

Labs (15 of 18 slides)

Lab tests in iron deficiency viewed from pathophysiological angle

  1. In iron deficiency, liver expression of transferrin is increased, resulting in increased circulating levels of transferrin, which “mops up” (binds) every last atom of iron (Fe) to deliver to developing erythrocytes in the bone marrow. Transferrin can be directly assayed. However, many labs report the total iron binding capacity (TIBC) as a surrogate marker for the transferrin level. Each transferrin molecule can bind up to 3 iron atoms. The TIBC measures the total amount of iron that the patient’s transferrin can bind. In iron deficiency, because transferrin levels (and TIBC) in blood are high and iron levels are low, the transferrin saturation (TSAT) is low.
  2. Liver hepatocyte and macrophage expression of ferritin is reduced in iron deficiency (figure shows liver-derived ferritin), leading to lower levels of circulating ferritin. Circulating ferritin has no known function (though it is a very convenient marker of iron stores). However, the reduced levels of intracellular ferritin result in less sequestration and increased availability of iron for transfer to erythroid progenitors in the bone marrow.
  3. In iron deficiency, the liver expresses less hepcidin. The lower levels of hepcidin (which is not routinely assayed) “open the floodgates” for iron release from cells (especially macrophages) and enterocytes into the blood. These changes serve to maximize the amount of circulating iron.
  4. Iron-deficiency causes red cell precursors to increase surface expression of transferrin receptors, which can then mediate more intracellular entry of iron.

Labs (16 of 18 slides)

Iron indices

You order iron studies, also called iron indices

Iron 17 ug/dL
TIBC420 ug/dL
TSAT?
Ferritin 7 ng/ml

Can you calculate the transferrin saturation (TSAT)? See next slide

Labs (17 of 18 slides)

Iron indices

You order iron studies, also called iron indices

Iron 17 ug/dL
TIBC420 ug/dL
TSAT0.04
Ferritin 7 ng/ml

TSAT = Fe/TIBC = 17/420 = 0.04 or 4%

Note that transferrin saturation (TSAT), as the term is used, suggests the denominator is transferrin. In practice, however, the denominator is total iron binding capacity (TIBC). TIBC the the total amount of iron that could be bound by the patient’s circulating transferrin (3 atoms per molecule of transferrin). It is an indirect measurement of transferrin availability.

Labs (18 of 18 slides)

In summary, the labs show:

  • Microcytic, hypochromic anemia
  • Anisocytosis
  • Low serum iron
  • Elevated TIBC
  • Low ferritin

Each of these findings is consistent with iron deficiency anemia. The low ferritin is diagnostic of iron deficiency. Collectively, the data are diagnostic of iron deficiency anemia.