Macrocytic Anemias Flashcards
define macrocytosis
increase in MCV relative to a patient’s baseline
- Don’t forget! Normal range for MCV is AGE DEPENDENT
- Don’t forget! There is a broad normal range for MCV - Use your database (when available) to see what is normal for your patient
- Don’t forget! MCV changes only gradually for any given individual; a rapid change could indicate laboratory ERROR
What makes red cells big?
- Artifact (sticking together!)
- Immature red cells
- Too much membrane
- Too much stuffing
- Stressed red cell production
How do you figure out that a macrocytosis may be due to artifact?
Use the formula and call the lab!
How do immature cells cause macrocytosis?
– A young reticulocyte has an MCV of 140 fl
– The normal range for MCV in adults is 80-100 fl
– If you are hemolyzing and have a marked reticulocytosis you can, conceivably, drive up your MCV
Let s try it!
Let s say you have acute, or maybe even subacute, hemolysis with 20% reticulocytes and your baseline MCV is 95 fl.
– 0.2 X 140 fl + 0.8 X 95 fl = 104 fl
Obviously 20% is a very high reticulocyte count but it is worth being aware that a marked reticulocytosis (which is very frequently accompanied by folate deficiency) can give you a slight macrocytosis
19 year old male college student with sore throat and fatigue RBC L Hgb 10.9 L Hct 31% L Formula: 1.7 MCV 101 MACRO RDW 18 --> Retic! MCHC 35 N
Reticulocytes 25% HIGH
Macrocytic anemia with elevated reticulocyte count….eventually found to have EBV
If MCV is slightly elevated what is the first thing you shoiuld check?
reticulocyte count! (REMEMBER, this may be already available with the CBC you ordered and you just need to call and request that it be reported in the computer!)
If reticulocyte count is ELEVATED think…
– Is this patient on erythropoietin or somehow producing excess
erythropoietin?
– If not, it is time to order HEMOLYSIS LABS (which may
include a blood smear review - tomorrow s lecture)
What causes too much membrane that makes RBC big?
• When there is excess unesterified cholesterol in the circulation, this cholesterol is taken up by the red cell membrane making the cells larger - typically a mild increase in MCV
What are the 2 acquired conditions that can lead to increased levels of circulating unesterified cholesterol?
liver disease
hypothyroidism
If the MCV is only mildly elevated and the absolute/corrected retic count is LOw/normal think…
– Could this person have liver disease or be hypothyroid?
– Liver and/or thyroid function tests
Too much membrane leads to ____ shaped cells
target shaped!
what is megaloblastosis?
too much stuffing
– Vast majority of too much stuffing in red cells can be placed in the general category of megaloblastosis
– An unusual cause of too much stuffing is increased red cell water that can be seen with chronic hypercapnia (lung disease with CO2 retention)
– This is ALSO a general term for situations where you can make PROTEIN but you can t make DNA
– This means that the cells can get bigger and bigger (as long as there is a nucleus) but they can’t divide
Under what circumstances can nucleated cells make protein but not DNA causing megaloblastosis?
– Vitamin B12 or folate deficiency
– Drugs that block DNA synthesis
– Drugs that inhibit vitamin B12 or folate utilization
– Congenital metabolic abnormalities • Lesch Nyhan syndrome
• Methylmalonic aciduria
• Homocysteinuria without methylmethioninuria
– Myelodysplastic syndromes (“pre-leukemia”) or myeloid leukemias that impair DNA synthesis
When someone is severely “megaloblastic” their oversized red cell precursors and red cells are destroyed in the bone marrow and other lab tests (LDH, haptoglobin, indirect bilirubin, etc) will mimic the findings of ….
HEMOLYSIS!!!
What are the limits of B12 measurement?
– B12 (7 years worth) stored in liver
– Any inflammation (particularly liver) falsely increases the measured B12 level
– If you suspect B12 deficiency despite a low normal level you can verify functional deficiency with serum homocystiene and methylmethionine levels
**An important point not in the slides: Inflammation falsely increases the measured B12 levels because you don’t directly measure the B12. You measure its carrier protein. To confirm do homocystiene and MMA levels.
What are the limits of folate measurement?
– Folate (3 months worth) is mainly stored in red cells
– Serum levels may not reflect storage levels – Red cell folate level is more reliable
How does “stressed” red cell production lead to macrocytosis?
“Stressed” red cell production refers to the production of red cells with a lot of erythropoetin. These cells are actually mildly macrocytic whether from disease or exogenous use.
– Any cause of decreased numbers of erythroid precursors in bone marrow
• Aplastic anemia
• Chronic hepatitis C
• Some B-cell lymphomas
How do you differentiate between what makes RBC big?
artifact
100-120
FORMULA!!! Hct trick!!
How do you differentiate between what makes RBC big?
immature red cells
MCV 100-105
look at reticulocyte count
How do you differentiate between what makes RBC big?
too much membrane
MCV 100-110
liver/thyroid fxn test and history
How do you differentiate between what makes RBC big?
too much stuffing
100-130
B12/folate levels, history
blood smear/bone marrow bx
How do you differentiate between what makes RBC big?
stressed
100-105
history
blood smear morphology/BM bx
68 year old retired attorney who is having difficulty walking.
RBC 3.49 L Hgb 13.6 Low normal Anemia Hct 39 Low normal Formula: 1.8 MCV 110 MACROCITIC RDW 14.4 NORMAL MCHC normal
next step?
B12 deficiency
MCV increased gradually by the time it was 100 he laready had the sxs
33 year old agricultural chemical salesman with a sore throat and
unexplained bruising.
RBC L Hgb L Hct L MCV macrocytosis RDW H (retics)
This case was of a rare leukemia that has been described in chemical salesman. The point was that a toxin caused the macrocytic anemia.
A 67 year old male with a long history of seizure disorder is admitted to the MICU after successful resuscitation from full cardiac arrest suffered during a witnessed seizure at his workplace
Hgb 12.5 ANEMIA Hct Trendig down RBC 2.9 ANEMIA MCV 109 (trending up) MCHC 29.4 (trending down)
Case of a cardiac arrest because of status, who had rapid shifts in pH and potassium and these are what lead to rapid changes in his MCV over the course of a few days.
