Anemia – 1: Intro to Lab Tests

Anemia is not a symptom per se, rather an abnormal laboratory test we just happen to find for whatever reason we ordered a blood count (CBC) to begin with.  But once we detect anemia, we deal with it as a presenting problem, and pursue diagnostic pathways.

DON’T just prescribe Iron!  May be useless, even harmful.

Anemia is common, and involves lots of tricky subtleties (which make it both confusing & also fun).  A few introductory concepts will start us off.

Anemia deals with red blood cells (RBC), best defined in terms of grams of Hemoglobin (Hb) and percent of whole blood that’s RBC mass (vs. serum), i.e. the Hematocrit (Hct).  Total number of RBCs in the CBC rarely helps much.

• Hct = Hb x3
• A 3-point change in Hct (1 gm in Hb) is a standard error that can be ignored.  In other words, if the Hct “drops” from 36 to 33, they’re really the same [no change].
• RBC life span is about 120 days

HOW BAD is the Anemia?

• Normal Hct values are around 42-47 for males & non-menstruating females, 3 points lower during menstrual years.  This “normal” range is highly variable in terms of age, altitude, athleticism, race, etc…
• Pale conjunctiva — Hct <24
• Pale skin — Hct <18
• Start considering Transfusion  —  Hct <21
• But primarily transfuse based on symptoms (SOB, edema, & anginal chest pain above all)
• Symptoms depend upon a) rapid onset of anemia; and b) underlying cardiopulmonary disease.

I had a 22-year-old patient with Hct of 7 and minimal symptoms [!!!].  He had a hereditary renal disease, his creatinine was 19 [!!!!!], the anemia must have developed over months-to-years & was well-compensated [well… say ‘somewhat compensated’].

CONFOUNDERS:

Acute blood loss presents with No Anemia (normal Hct/Hb).  Imagine a person with normal values.  Then you withdraw 50% of circulating volume; the next ml. of blood will have baseline values.  It takes 36-48 hours for the body to pull extracellular fluid into the vascular space & fully hemodilute.

• In E.D. setting, to evaluate acute blood loss, run in 2L NS IV & recheck; the IV hemodilutes for you & saves time [& lives].  Run 2L in a healthy person & they pee it right out.

Dehydration, conversely, causes an artificially high Hct/Hb.

SYMPTOMS  —  The cardinal symptom generating a CBC to R/O any type of Anemia is Dyspnea on Exertion.  As noted, seek Anemia in the work-up of patients with new Heart Failure, Angina, Pedal Edema.

However, some people harbor conditions that can ultimately lead to anemia, but initially manifest differently.  They may complain of a variety of unrelated symptoms:

• Neuropathy (paresthesias, ataxia): Vitamin B12 Deficiency
• Cognitive Deficits: Vitamin B12 Deficiency
• Pica (cravings to eat starch, dirt, ice, paper…):  Iron Deficiency
• Beeturia (eating beets → red urine): Iron Deficiency (iron decolorizes the beet pigment)
• Jaundice is often the presenting Sx of Hemolytic Anemia

WORK-UP  OF  ANEMIA

WBCs & PLATELETS  —  Before you start considering types of Anemia, make sure the WBCs & Platelets are normal.  If they’re both reduced, you’re dealing with Pancytopenia [= “all cell-type” -penia] due to bone marrow suppression.

From now on, we’re talking about reduced RBC mass alone, i.e. Anemia.

TO BEGIN — Look at the “Indices,” primarily the Mean Corpuscular Volume (MCV)

RBC Indices are averages for size (MCV), hemoglobin (MCH), & hemoglobin concentration (MCHC) per RBC.  They all parallel each other; clinicians only refer to the MCV.

MCV values define the type of Anemia:

• Microcytic (small cells)  —  MCV <80 fL (femtoliters)
• Normocytic (normal cells)  —  MCV 80-100 fL
• Macrocytic (big cells)  —  MCV >100 fL

From now on we’ll leave off the units.  I bet you’ll meet few clinicians of any stripe who know that the MCV is measured in fL’s, much less what an fL is (1-quadrillionth of a liter = 10^-15).  [Imagine how we functioned in the pre-Google era.]

The MCV defines the Type of Anemia:

DIFFERENTIAL DIAGNOSIS OF ANEMIA

Of course, “Normocytic 80-100” looks nice & neat, but some macrocytic etiologies might only produce an MCV of 98 or 99.  Avoid pettifoggery.

Before we start with Microcytic Anemia, a word about MCV confounders.  The MCV is an average.  Suppose a patient has a mixed anemia, some microcytic RBCs from iron deficiency & macrocytes from B12 deficiency.  Iron deficiency alone might give an MCV of 65, B12 deficiency alone an MCV of 115, so the patient’s MCV comes out 90.

Look at the “Red Cell Distribution Width” (RDW), a value that’s usually given by automated counters.  The RDW estimates the extent of differences in RBC sizes (the word “width” refers to a histogram plot of the different sizes, not the RBC diameter).  Normal is <13%.  So an elevated RDW of, say, 18% indicates clinically-significant difference in sizes of RBCs present (>20% is pretty high).

An increased RDW may mean:

• Mixed anemia (microcytes & macrocytes together)
• Early anemia (e.g. iron deficiency has recently begun, new RBCs are microcytic, older cells normocytic)
• Hemolytic Anemia (fragmented RBCs)

Some counters report “Anisocytosis” graded 1+ to 4+ instead of an RDW.  This means “Unequal-sized Cells” [An-Iso-Cytosis].  Same thing.  When laboratorians or hematologists visualize a peripheral smear under the microscope, they also report this in degrees of anisocytosis.

When in doubt about anemia, order a “peripheral smear” to be viewed manually [or is it visually?].  This is sort of a gold standard, but requires an add-on order (if lab held an original slide) or another blood draw.  It’s most useful when suspecting either mixed or hemolytic anemias.

Today’s posting was short, but I hope interesting, & not too anemic.  The next will be longer, as we get into specific types of anemia: Microcytic, then Macrocytic and Normocytic.