Setting: office
CC: “I feel tired.”
VS: R: 18 breaths/minute; BP: 110/70 mm Hg; P: 87 beats/minute; T: 97.8°F
HPI: A 32-year-old woman with several weeks of increasing tiredness and fatigue visits your office. She says she feels worse after walking up stairs and improves with rest. Her menstrual periods last 5 days and are regular.
PE:
General appearance: normal
Cardiovascular: normal
Chest: clear to auscultation
Initial Orders:
Complete blood count (CBC)
Thyroid function tests (thyroxine [T4], thyroid-stimulating hormone [TSH])
Oximeter
The patient does not return for her scheduled office visit the following week. She comes 2 months later because her fatigue has worsened and now interferes with functioning. She is now dyspneic with significant exertion, such as walking two flights of stairs.
Previous Laboratory Test Results:
Thyroid function: normal
Oximeter: 98%
CBC:
Hematocrit: 28%
Hemoglobin: 9 g/dL
Mean corpuscular volume (MCV): 74 fL
White blood cells (WBCs): 7000/μL
Platelets: 378,000/μL
Which of these does not cause this patient’s type of anemia?
a. Sideroblastic
b. Folic acid deficiency
c. Iron deficiency
d. Chronic disease
e. Thalassemia
Answer b. Folic acid deficiency
Folic acid deficiency is associated with macrocytosis and large cells. The others all cause microcytic anemia. Expect an MCV >100 fL in folic acid deficiency.
Orders:
CBC
Iron, total iron-binding capacity (TIBC), ferritin level
Reticulocyte count
Peripheral smear
Schedule an office visit for the following day (laboratory test results should be back by then)
The computer-based case simulation (CCS) always tells you precisely when the results of the laboratory tests return. It will say “Report Available” and give a precise time.
Which of these can be associated with target cells?
a. Autoimmune hemolysis
b. Iron deficiency
c. Folic acid deficiency
d. Vitamin B12 deficiency
Answer b. Iron deficiency
Any of the microcytic anemias can be associated with target cells. The most likely of all the anemias to cause target cells is thalassemia. Both alpha- and beta-thalassemia can cause target cells and thalassemia can also be caused by thalassemia trait. Autoimmune hemolysis causes spherocytes, not target cells.
What is the mechanism of target cell formation?
a. Precipitation of hemoglobin in the red blood cell (RBC) membrane
b. Excess cell membrane bunching up on the surface
c. Loss of membrane from protein loss
d. Cellular dehydration
e. Ankyrin and spectrin deficiency
Answer b. Excess cell membrane bunching up on the surface
Target cells are formed exclusively from excess RBC membrane. The amount of hemoglobin is too small for the size of the covering. The excess membrane “bunches up” on the cell surface.
The patient returns the following day. You never have to be uncertain about the time to have the patient come back on CCS, because when you order the tests, it will tell you when the report will be back.
CBC:
Hematocrit: 23%
Hemoglobin: 7 g/dL
MCV: 70 fL
WBCs: 7,400/μL
Platelets: 578,000/μL
Iron: low
TIBC: elevated
Ferritin level: low
Reticulocyte count: 1%
Peripheral smear: microcytic, hypochromic cells; no target cells; no schistocytes or fragmented cells
Red blood cell distribution width (RDW): elevated
What is the mechanism of elevated TIBC?
a. Decreased saturation of the transferrin transport protein
b. Decreased saturation of transferring in storage in marrow
c. Increased hepcidin
d. Iron is locked in macrophages
Answer a. Decreased saturation of the transferrin transport protein
Transferrin transport two iron atoms on each molecule. This is the fast transporter in plasma of iron to be incorporated into hemoglobin and into cells. A high capacity on a protein such as transferrin means that it is empty or unoccupied. Iron locked in macrophages is the mechanism of the anemia of chronic disease.
Ferritin is a hollow ball of proteins that stores iron in tissue. Free iron is toxic.
What is the significance of the high platelet count?
a. None, it is an expected part of iron deficiency anemia.
b. It is a marker of additional disease and needs investigation.
c. Essential thrombocytosis will develop. Order a Janus kinase 2 (JAK2) mutation test.
Answer a. None, it is an expected part of iron deficiency anemia.
Platelet elevation is an expected feature of iron deficiency anemia. The etiology may be that erythropoietin has some stimulatory effect on megakaryocytes. No further evaluation is needed.
Thrombocytosis in iron deficiency needs no further investigation.
RDW is found to be elevated. What is the mechanism?
a. In iron deficiency, new cells are larger.
b. In iron deficiency, new cells are smaller.
c. Microcytosis becomes stable.
Answer b. In iron deficiency, new cells are smaller.
As you run out of iron, the cells become smaller. The RBC is a “bad of hemoglobin.” If there is no iron to make hemoglobin from, then the cells become smaller. It is like making smaller sandwiches when you run low on food.
The patient returns feeling tired. Her stool is heme negative. The presumed mechanism of her iron deficiency anemia is menstruation in a woman. Her menstrual periods do tend to be somewhat heavy. Oral ferrous sulfate is started, and you ask her to return in 2 weeks.
What will change first in response to iron replacement?
a. MCV
b. Reticulocyte count
c. Hemoglobin level
d. RDW
Answer b. Reticulocyte count
Reticulocytes are the measure of new cell formation. Reticulocyte concentration has to increase first for any of the other features of a CBC to change.
Reticulocytes: Methylene blue stains ribosomal RNA from residual endoplasmic reticulum.
The patient returns in 2 weeks. The repeat hematocrit test shows that the level rose from 23% to 25%. The reticulocyte count rises only from 1% to 2.5%.
Which of the following over-the-counter substances may be impeding the absorption of iron?
a. Cimetidine
b. Vitamin C
c. Vitamin D
d. Carbonated beverages
Answer a. Cimetidine
Anything that raises the gastric pH will inhibit iron absorption. H2-blockers, proton pump inhibitors, and liquid antacids can all impair iron absorption. Carbonated beverages and vitamin C can increase iron absorption because they acidify the stomach.
High pH (basic) inhibits iron absorption. Acid, like vitamin C, increases iron absorption.
The patient admits to taking both liquid antacids and H2-blockers. She did not think to tell you because she did not consider them important, saying, “Well, I don’t need a prescription for them, so I didn’t think of them as a medication.” You ask her to stop taking them and start taking vitamin C. She continues the oral ferrous sulfate. Move the clock forward another 2 weeks. She returns feeling better except that her stool, she says, is black and she is constipated.
Oral ferrous sulfate causes constipation and black stool.
Everyone on iron should be given a stool softener, such as docusate.
How can you differentiate the effect of oral ferrous sulfate from gastrointestinal bleeding?
a. Iron is stool-guaiac negative.
b. Iron is stool-guaiac positive.
c. Upper endoscopy is needed to be sure.
d. Colonoscopy is needed to be sure.
Answer a. Iron is stool-guaiac negative.
Oral ferrous sulfate, or elemental iron, causes constipation because only 1% to 2% of it is absorbed. The remaining iron in the bowel lumen causes constipation. It is also guaiac or heme negative. Colonoscopy would not be useful even if there was upper gastrointestinal (GI) tract bleeding.
FerroUS iron is normal in the U.S.
What is the normal function of hepcidin?
a. Stores iron in the liver
b. Stores iron in the marrow
c. Master regulator of the rate of iron absorption in the bowel
d. Liver regulator of excretion bilirubin
e. Transports iron from destroyed RBCs to the liver for recycling
Answer c. Master regulator of the rate of iron absorption in the bowel
Hepcidin is made by the liver to stop excess iron absorption in the bowel. Hepcidin prevents hemochromatosis by blocking iron transport from enterocytes in the bowel wall into the portal system. Hepcidin keeps iron in the bowel.
Iron is absorbed in the duodenum.
Eight weeks after the starting iron and stopping antacids, the patient returns. Her symptoms are resolved and her hematocrit is 36%.