I recently tweeted asking whether the rightward shift of our O2 dissociation curve (ODC) (reduced O2 affinity, increased O2 offloading in tissues) when we climb a mountain is a good thing.
2/7
I pointed out that animals that have evolved at high altitude (e.g., bar-headed goose, llama) actually shift their curve to the left (they have a special mutation in their Hb).
3/7
Similarly, human fetuses, who are normally exposed to limiting amounts of O2 from mom's circulation, shift their ODC to the left (a characteristic feature of fetal Hb).
4/7
To further address the question of whether a left or right shift is adaptive at high altitude, a 1974 paper in Science reported that rats chemically manipulated to shift their ODC to the left fared better when exposed to simulated high altitude.
5/7
This was followed by a classic study by Bob Hebbel, a hematologist at the University of Minnesota. He reasoned that if a shift to the left is adaptive at high altitude, then humans with congenital high-affinity hemoglobin should do better under these conditions.
6/7
Indeed, this is what he found. He took 2 subjects with Hb Andrew-Minneapolis and 2 of their normal siblings up to about 9,000 ft. for 10 days and showed that the ones with Hbopathy fared better.
Such a cool experiment that would NEVER be funded in this era!
7/7
The bottom line then is that in situations where environmental oxygen is limiting (high altitude, in the womb), the benefit of increasing O2 uptake in lungs/fetus with a shift to the left outweighs the disadvantage of unloading less O2 to the tissues.
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I tweeted a poll asking how you would treat a case of uncomplicated IDA with oral iron. The options and responses are shown below:
2/10
There is no one right answer, though existing data (notwithstanding clinical practice guideline recommendations) support the use of a single dose of oral iron on alternative days. Most of you concurred.
3/10
The poll prompted a really good discussion.
There was wide recognition that a dose of oral iron increases serum hepcidin at 24 h, which inhibits further iron absorption (hence the rationale for every other day dosing).
I tweeted a poll yesterday asking for the correct description of the CBC shown in the graphic.
There was a pretty even split between the 1st 3 options.
The correct answer is hyperleukocytosis.
2/7
DEFINITIONS
Definitions may seem trivial, but they matter because medical terminology allows all medical professionals to understand each other and communicate effectively, promoting accuracy, safety, and efficiency in patient care.
So, let's review some definitions!
3/7
LEUKEMOID REACTION (LR)
Defined as a WBC count > 50 (usually with left shift) in the absence of a primary hematological malignancy.
It is reactive and typically transient.
Since the CBC doesn't provide evidence for reactive vs. clonal leukocytosis, we can't label it LR.
The 2 most common causes of microcytic anemia are IDA and thalassemia trait. According to the morphological classification of anemia, microcytic anemia is divided into normochromic and hypochromic subtypes.
2/9
As a general rule IDA is hypochromic, thalassemia normochromic. But the MCHC is by no means perfect at discriminating between the two conditions.
Many other discriminant indices and formulas have been proposed over the years (graphic).
3/9
Perhaps the most commonly used formula is the Mentzer index which is MCV/RBC count.
I tweeted about a case in which the labs showed anemia, thrombocytopenia, elevated PT and D-dimers above assay. I asked whether this could be DIC and if so, what the circumstances might be.
2/7
No single lab test is sufficiently sensitive/specific to diagnose DIC. Diagnosis is facilitated by use of clinical prediction scores, most commonly the ISTH score.
In this case, the ISTH score is:
PLT 55 - 1 point
Elevated D-dimer - 3 points
PT - 1 point
Fbn - 0 points
3/7
TOTAL SCORE: 5 pts
5 points is compatible with overt DIC.
What is unusual about this patient's labs is that the fibrinogen is so high. What might explain this?
1. Pregnancy - fibrinogen levels increase during pregnancy and are often "normal" in the setting of DIC.
Yesterday, I tweeted 2 CBCs from a patient 4 months apart and asked for an explanation of the de novo macrocytosis. I also showed a WBC differential and asked whether the patient was neutropenic.
2/8
Lots of awesome responses!
Shout out to @UsuarezMD and @plainJai for correctly answering both questions.
Let's deal with the 2nd question 1st. The neutrophil count was 1% but none of you fell for the trap and labeled this neutropenia. The ANC was a healthy 3.3 x 10^9/L!
3/8
Now for the first question. Many of you guessed that the patient developed AIHA as a complication of evolving CLL, with reticulocytosis-associated macrocytosis. That works, but there are two pieces of data that is tough to reconcile:
Pregnancy is often stated to be a physiological cause of macrocytosis. It appears on many differential diagnosis lists for macrocytosis, and UpToDate states:
2/8
"Macrocytosis (with mild or no anemia) may be seen in newborns... or during pregnancy."
3/8
What is the evidence that pregnancy is associated with macrocytosis?
Well, published data support the notion that the MCV increases by about 5 fL during pregnancy, but rarely to the macrocytic range (i.e., MCV > 100 fL).