Yesterday I posted CBCs from a patient, posed three questions and asked for a diagnosis.
Kudos to @EltonWandira for coming up with the answers and diagnosis within minutes of posting!
The dx is CAD.
2/9
Answers to questions:
Q1. Which value at time 0 is physiologically impossible?
A1. The MCHC of 65.4 g/dL. Hb is almost supersaturated under normal conditions, and rarely increases above 40 g/dL.
3/9
Q2. What does the notation 4 refer to at time 0?
A2. Spun Hct. Note that the Hb is reported as 8.5 g/dL, the Hct as 26.5%. Recall that the MCHC = Hb/Hct, which in this case would = 32 g/dL, a far cry from the reported MCHC of 65.4 g/dL!
4/9
Q3. What has the lab technician done to the blood to obtain 4 h results?
A3: They have warmed the blood to disassemble the cold agglutinins from the RBCs, converting clumps to single cells.
5/9
Instead of simply memorizing this pattern of CBC changes in CAD, let's think our way through it.
In automated hematology analyzers ('CBC machines'), RBCs normally pass in single file as their numbers are counted and their volume measured using the Coulter principle.
6/9
In CAD, clumps of 3 or more RBCs cannot squeeze through the aperture used for counting/sizing cells, so fewer cells get through, leading to falsely low RBC count. Doublets can pass through, but are counted as single cells, resulting in falsely high MCV and reduced RBC count.
7/9
These artefactual changes can be incorporated in the equation Hct = RBC count x MCV. Because the RBC takes a double hit, it is disproportionately decreased relative to the change in MCV, resulting in a reduction in Hct.
8/9
Finally because the Hct is falsely low (and the Hb is one of the few parameters unaffected in CAD), the MCHC is falsely elevated.
9/9
We can put it all together in table format with findings and explanations.
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Spherocytic RBCs result from a loss of membrane surface area and, consequently, exhibit increased cell sphericity and reduced cellular deformability. Two major causes are hereditary spherocytosis (HS) and autoimmune hemolytic anemia (AIHA).
2/6
Mechanisms of spherocyte formation:
1. In HS, increased propensity of abnormal RBCs to shed membrane in the circulation due to improper assembly of membrane proteins.
2. In AIHA, partial macrophage-mediated phagocytosis of circulating RBCs bound by antibodies.
3/6
Common to both conditions:
1. Presence of spherocytes on the peripheral smear 2. Anemia 3. Elevated MCHC 4. Reticulocytosis 5. Increased osmotic fragility
(Diameter of RBCs smaller than normal, but MCV typically normal)
I recently tweeted about how the relationship between Hct/Hb and O2 delivery results in a bell-shaped curve, with anemic patients lying on the ascending part, polycythemic patients on the descending part.
The peak of the curve represents the optimal Hct/Hb.
2/7
I was asked a couple of interesting questions I would like to address.
Q1. What is the evidence that the optimal Hct is conserved across mammalian species?
A1. Pretty good, actually. Check out the Hct measurements from multiple mammalian species in the graphic.
3/7
Q2. What is the evidence for the descending part of the curve?
A2. The evidence is based on both in vitro and in vivo experiments as well as modeling. The graphic below shows supportive in vitro data.
Here is a fun graphic that ties together the relationships between RBC parameters:
1. RBC count gives us no information about Hct or Hb, but it can be used to help distinguish between thal minor and iron deficiency anemia (e.g., Mentzer index).
2/7
2. The only way to get from RBC count to Hct (without a spun Hct) is to consider the MCV (Hct = RBC count x MCV).
3. If the RBC count is held constant, the larger the cells the higher the Hct. Laws of physics!
3/7
4. With the Hct in hand, we can make predictions about blood viscosity and its negative effect on cardiac output and oxygen delivery, but we cannot accurately derive the Hb from the Hct alone.
I saw a patient in the ICU (diagnosis doesn't matter for purposes of this discussion) whose Hb suddenly dropped over a 5 h period from 9.3 to 5.7 g/dL (see graphic).
Not knowing anything about the patient, what are possible explanations?
Well, if it is the patient must have been administered massive quantities of crystalloid (remember, we bleed out whole blood, so our Hb is initially normal and only drops after re-equilibration of fluids (from extra to intravascular space) +/- IV fluids.
Anemia of inflammation (AI) is believed to represent an evolutionarily trade-off whereby the advantages of starving bugs (e.g. siderophilic bacteria) of much needed iron outweigh the disadvantages of collateral iron-deficient erythropoiesis.
2/4
So why does AI occur in non-infectious inflammatory states? One possible explanation is the smoke detector principle (SDP). According to this theory, the body is unable to differentiate - at least initially - between infectious and non-infectious causes of inflammation.
3/4
As a result, it assumes the worse and by default activates the innate immune system. Most of these cases will be false alarms, but like smoke detector alarms, such minor annoyances – the argument goes - are necessary to avoid possible catastrophes.
Check out the CBC time series in the graphic and without fast forwarding in this thread, try to come up with a story!
2/12
The first thing I like to do with a time series is to check out the dates - when is the 1st CBC, when is the most recent? Are there periods when the dates are contiguous, and/or are there major gaps in the dates, c/w outpatient? Are there any missing data or notations?
3/12
Next, we have two options. One is to look for patterns over time (type 1 thinking), the other is to move from ground up with the initial CBC. Let's take the latter approach. How would you describe the initial CBC in the fewest words possible?