Setting: office
CC: “I didn’t know my blood count was low.”
VS: normal
HPI: A 28-year-old woman comes for preemployment screening tests prior to her first job as a fellow in orthopedic surgery. She has never had a CBC before and did not know her hematocrit was low.
Hematocrit: 28%
Hemoglobin: 10 g/dL
MCV: 65 fL
Smear: target cells
Which is most likely to be found in this patient?
a. Her RBC count is elevated.
b. Her platelet count is elevated.
c. Her TIBC is elevated.
d. Her iron level is elevated.
Answer a. Her RBC count is elevated.
Thalassemia is associated with an increase in the RBC count. This patient most likely has thalassemia because it is a microcytic anemia with a very low MCV and no symptoms. This is because the RBC count goes up, which maintains the hematocrit. Also, target cells are most likely in a person with thalassemia. Platelet count elevation (choice b) is found in iron deficiency anemia.
Iron studies are ordered and the patient returns in 2 days to discuss the results. Which of the following is most likely to be found?
Answer b. Normal (iron, TIBC, ferritin)
Iron studies are normal in thalassemia. High circulating iron (choice a) level indicates sideroblastic anemia. The most accurate test for sideroblastic anemia is a Prussian blue stain. Low iron level with a low iron-binding capacity is the anemia of chronic disease. Choice d is iron deficiency anemia. Up to one-third of those with iron deficiency anemia can have a normal ferritin level. This is because ferritin is an acute phase reactant and its level increases with infection, cancer, and stress in the same way a white count or sedimentation rate would.
Prussian blue is an iron stain. Sideroblastic anemia has iron built up in RBC mitochondria.
Target Cells = Low Hemoglobin (Hb) in the Large RBC Membrane
The patient comes back to discuss her CBC and iron study results. She does not understand how her RBC count can be up, and her hematocrit level can be down.
What else besides thalassemia can do this?
a. Hypoxia and polycythemia vera
b. Leukemia and essential thrombocytosis
c. Hereditary spherocytosis
d. Autoimmune hemolysis
Answer a. Hypoxia and polycythemia vera
Besides thalassemia, hypoxia causes an increased RBC count. These patients and those with polycythemia vera will have an excessively high hematocrit concentration. Thalassemia is a cause of anemia. It is easy to confuse hypoxia with polycythemia vera because both have supranormal high hematocrit levels.
The repeat CBC and iron studies are normal. You inform the patient that she likely has thalassemia trait. You do not offer an electrophoresis because it will not change your management of this patient’s medical care. She is requesting the electrophoresis because she “just wants to know.”
What do you tell her?
a. You refuse because you do not want to be manipulated by another doctor.
b. You refuse, because it will not change her treatment.
c. You agree because you should do any test that is not harmful or expensive.
d. You agree because she has a right to know what type of thalassemia she has.
Answer d. You agree because she has a right to know what type of thalassemia she has.
The patient does not know if she has alpha-thalassemia or beta-thalassemia and she wants to know. Patients do not have a right to “any test they want.” This is true even if they are paying cash and the test is uncomplicated. For example, I do not have a right to demand an abdominal computed tomography (CT) “just because I want to know.” The physician is not obligated to perform tests unless they have direct medical benefit.
You perform the hemoglobin electrophoresis and reschedule the patient in a week to discuss results.
Which electrophoresis result is most likely in this patient?
Answer a. Normal
This person has thalassemia trait. Alpha-thalassemia trait will give a normal electrophoresis. This is very hard for most people to understand. The electrophoresis does not tell the total amount of hemoglobin. It tells the relative percentages of each subtype. In alpha-thalassemia trait, all the types of hemoglobin are decreased, but they are decreased in normal proportions.
Choice b is more severe alpha-thalassemia. This would present with a lower hematocrit level and symptoms. Choice c is beta-thalassemia major, not beta-thalassemia trait.
HbH = Tetrads of Four Beta-chains
Four genes are needed to fully produce alpha-chains.
How many genes are deleted in this patient?
a. 1
b. 2
c. 3
d. 4
Answer b. 2
Alpha-thalassemia trait is defined at the deletion of two of the normal four genes responsible for alpha-chain production. One gene deletion is clinically normal. One gene deletion is a “silent carrier” in which the CBC is normal. Four gene deletions is not compatible with life. The fetus would die in utero of heart failure. You cannot survive without any alpha-chains.
• Hemoglobin Bart’s (HbBart) = Four Genes Deleted
• HbH = Three Genes Deleted
• Silent Carrier = One Gene Deleted
The patient is informed that she has alpha-thalassemia trait with two genes deleted. She is always asymptomatic. There is no treatment for her to correct the disorder.
What benefit is there in knowing she has alpha-thalassemia trait?
a. There is no benefit except for her own knowledge.
b. The trait progresses to thalassemia major in some cases.
c. The patient can have genetic counseling for reproductive purposes.
Answer c. The patient can have genetic counseling for reproductive purposes.
For a person considering reproduction, thalassemia trait has enormous significance. A person may choose not to reproduce with a person who also has a thalassemia trait to avoid a risk of thalassemia major. The couple may choose to have amniocentesis or other testing done during pregnancy to assess a baby that has been conceived.
What is the most precise method of determining this patient’s type of thalassemia?
a. Genetic testing
b. Bone marrow
c. Electrophoresis—as precise as it gets
Answer a. Genetic testing
The only way to be certain of the number of genes deleted is by genetic testing. Bone marrow shows nothing specific.
Which form of thalassemia has high reticulocytes?
a. Alpha-thalassemia trait
b. Three-gene-deleted alpha-thalassemia
c. Beta-thalassemia trait
d. Beta-thalassemia major
Answer b. Three-gene-deleted alpha-thalassemia
The deletion of three genes results in a much lower hematocrit that needs periodic transfusion. The RBCs are made in increased number, but they have a very short survival.