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Case Studies
Differentiation Between Sickle Cell Anemia
and S/β0 Thalassemia
Vichaka Fanestil, BS, MLS(ASCP)CM,1* Carleen Van Siclen, MS, MT(ASCP) 2
Lab Med Summer 2015;46:e79-e81
DOI: 10.1309/LMKW5VWNUK26LKAX
Clinical History
Patient: 37-year-old man of half African and half Italian ethnicity.
Chief Complaint: Sickle cell crisis (SCC).
History of Present Illness: The patient had severe pain in his lower
back that radiated to both thighs. He had been admitted twice in the
previous 2 weeks at another hospital due to SCC. Each time, he had
been discharged with a prescription for oxycodone. His condition did
not respond to the pain medicine; his pain remained uncontrollable.
Medical History: The patient has had multiple sickle cell crises since
childhood and is a former smoker. He denied alcohol consumption or
illegal drug use.
Physical Examination Findings: The patient had normal vital signs.
No splenomegaly was present.
Family History: Both parents carry sickle cell thalassemia.
Principal Laboratory Findings: Table 1, Table 2, and Image 1.
Keywords: sickle cell anemia, S/ß0 thalassemia, hemoglobinopathy,
hemoglobin S, sickling disorders, sickle cell crisis
Questions
1. What are the most striking clinical and laboratory
findings for this patient?
2. What is sickle cell anemia, and what are the expected
laboratory findings for this condition?
3. What is S/ß0 thalassemia, and how can it be
differentiated from sickle cell anemia?
Abbreviations
SCC, sickle cell crisis; NRBCs, nucleated red blood cells; HbSS, sickle
cell hemoglobin; RBCs, red blood cells; GTG, valine; GAG, glutamic
acid; HbF, hemoglobin F; HbA 2, hemoglobin A 2; HbA, hemoglobin
A; WBC, white blood cell; MCV, mean corpuscular volume; MCH,
mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin
concentration; HbSC, hemoglobin SC; HbS, hemoglobin S; thal,
thalassemia; HPFH, hereditary persistence of fetal hemoglobin.
Department of Biology, University of North Florida, Gainesville, FL
Department of Laboratory Medicine and Pathology, Mayo Clinic,
Jacksonville, FL
1
2
*To whom correspondence should be addressed.
[email protected]
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4. What is the prevalence for sickle cell anemia and S/ß0
thalassemia?
5. What is the most likely diagnosis for this patient?
6. What is the recommended treatment and management
of the disease of this patient?
Possible Answers
1. Recurring sickle cell crises and absence of
splenomegaly are striking clinical findings. The most
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Case Studies
Table 1. Complete Blood Counta
Cell Type
Cell Count
Reference Value
WBC
RBC
Hemoglobin
Hematocrit
Platelet
MCV
MCH
MCHC
Neutrophil
Lymphocyte
Monocyte
Eosinophil
Basophil
Metamyelocyte
Myelocyte
nRBC
9.4 × 103/µL
2.9 × 106/µL
5.7 g/dL
17.6%
519 × 103/µL
60.7 fL
19.7 pg
32.4 g/dL
76%
11%
4%
6%
1%
1%
1%
319
4.0-10.5 × 103/µL
4.7-6.0 × 106/µL
13.5-18.0 g/dL
42%-52%
150-450 × 103/µL
78-100 fL
27-31 pg
32-36 g/dL
44.4%-70.9%
17.8%-41.5%
4.7%-14.8%
0.8%-7.2%
0-2.2%
0-2%
0-2%
0-1
WBC, white blood cell; RBC, red blood cell; MCV,
mean corpuscular volume; MCH, mean corpuscular hemoglobin; MCHC, mean
corpuscular hemoglobin concentration; NRBC, nucleated red blood cells.
a
The patient is a 37-year-old man of half African and half Italian ethnicity.
Table 2. Degree of Presence of Certain Cell
Types and Diseasesa
Condition/Cell Type
Degree Present
Anisocytosis
Poikilocytosis
Microcytes
Macrocytes
Polychromia
Hypochromia
Target cells
Howell-Jolly bodies
Drepanocytes
Oval macrocytes
Marked
Moderate
Marked
Moderate
Slight
Moderate
Moderate
Present
Moderate
Moderate
The patient is a 37-year-old man of half African and half Italian ethnicity.
a
Table 3. Prevalence of Sickling Disorders in
African Americansa
Variant
Percentage
HbSS
HbSC
HbS/thal
HbS/HPFH
45.2
36.7
17.0
1.1
HbSS, sickle cell hemoglobin; HbSC, hemoglobin SC; HbS, hemoglobin S; thal,
thalassemia; HPFH, hereditary persistence of fetal hemoglobin.
a
Derived from McPherson et al.1
striking laboratory findings are an elevated count of
nucleated red blood cells (NRBCs; Table 1), along
with marked anisocytosis and moderate poikilocytosis
(drepanocytes and target cells) in the peripheral blood
smear from the patient (Table 2). The patient had anemia,
and his RBCs were microcytic and hypochromic.
2. Sickle cell anemia, also known as sickle cell hemoglobin
(HbSS) disease or homozygous SS disease, is an inherited
autosomal recessive disorder resulting in qualitative
mutation of the hemoglobin structure in red blood cells
(RBCs). The mutation of normal hemoglobin A (α 2ß2)
to hemoglobin S (α 2ß2 6 Val) is caused by the amino acid
substitution of valine (GTG) for glutamic acid (GAG) on the
sixth position of the ß chain. The sickling process occurs
under deoxygenated conditions in which hemoglobin S
polymerizes, forming aggregates called tactoids that give
the resulting product a rigid structure. Nearly half of all
patients with sickle cell anemia experience vaso-occulsive
crisis (abdominal and joint/bone pain accompanied by
fever) caused by masses of sickle cells trapped in the
blood vessels due to decreased deformability of RBCs
from tactoid formation.1 Sickle cell anemia has several
characteristic laboratory findings. The peripheral blood
e80 Lab Medicine Summer 2015 | Volume 46, Number 3
smear results demonstrate normocytic, normochromic
RBCs, the presence of nucleated RBCs (NRBCs),
polychromasia, sickle cells, target cells, Howell-Jolly
bodies, and Pappenheimer bodies. Neutrophilia and
thrombocytosis may also be observed. The expected
hemoglobin electrophoresis results in blood specimens
from patients with sickle cell anemia show the following
values: 80% sickle cell hemoglobin (HbSS), 1% to 20%
hemoglobin F (HbF), 2% to 4.5% hemoglobin A 2 (HbA 2),
and absence of hemoglobin A (HbA) if the patient has not
recently received a transfusion.1
3. S/ß0 thalassemia results from the absence of ß-chain
production that cause red blood cell (RBC) instability due
to excess α chains, leading to abnormal erythropoiesis.
S/ß0 thalassemia can be differentiated from sickle cell
anemia based on RBC morphologic characteristics and
hemoglobin electrophoresis results. S/ß0 thalassemia is
characterized by microcytic, hypochromic RBCs, along
with the presence of target cells and fewer sickle cells.
The expected results of hemoglobin electrophoresis in
patients with S/ß0 thalassemia are as follows: 75% to 90%
sickle cell hemoglobin (HbSS), 5% to 20% hemoglobin F
(HbF), 4% to 6% hemoglobin A 2 (HbA 2) (although in some
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Case Studies
Table 4. Differentiation of Sickle cell Anemia and S/β0 Thalassemia
Clinical manifestation
RBC morphology
Hemoglobin electrophoresis
A2
F
A
S
Sickle cell Anemia
Our Patienta
S/β0 Thalassemia
No splenomegaly
Normocytic
Normochromic
2%-4.5%
1%-20%
0%
80%
No splenomegaly
Microcytic
Hypochromic
6.80%
1.90%
0%
91.3%
Splenomegaly
Microcytic
Hypochromic
4%-6%
5%-20%
0%
75%-90%
A 37-year-old man of half African and half Italian ethnicity.
a
Image 1
Wright-Giemsa stained peripheral blood smear from our patient, a
37-year-old man of half African and half Italian ethnicity, illustrating anisocytosis, thrombocytosis, and poikilocytosis. Note the
abnormal poikilocytes, including target and sickle cells (original
magnification, 1000x).
cases, this cell count can be significantly elevated), and
0% hemoglobin A (HbA).1
S/ß0 thalassemia most closely match the results from our
patient, especially hemoglobin S.
4. As of 2007, sickle cell anemia is the most prevalent
sickling disorder in African Americans (Table 3).
6. Supportive care is used to manage the symptoms
associated with sickle cell disease. Blood transfusions are
given to correct low hemoglobin levels, as needed. Other
more permanent solutions include allogeneic bone marrow
transplantation and gene therapy. The only currently
available curative therapy is allogeneic hematopoietic
stem cell transplantation, which allows patients to become
transfusion independent.3
S/ß0 thalassemia is most common in ethnic Mediterranean
populations. It is usually mild in individuals of African
descent but it causes severe disease similar to sickle
cell anemia for individuals of Italian, Turkish, and Greek
descent.1 Second, patients of Mediterranean ancestry
have a higher incidence of thalassemia trait than those of
African descent because they tend to have ß0 thalassemia
instead of ß-plus thalassemia.2 S/ß0 thalassemia is an
autosomal recessive disorder that can be inherited from
parents who carry sickle cell thalassemia.
5. The most likely diagnosis for our patient is S/ß0
thalassemia. This hematological disorder is diagnosed
by laboratory findings (Table 4) and is characterized by
the presence of splenomegaly as well as red blood cell
(RBC) morphologic characteristics in peripheral blood.
The expected results of hemoglobin electrophoresis for
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References
1. McPherson RA, Pincus MR. Henry’s Clinical Diagnosis and
Management by Laboratory Methods. 21st edn. Philadephia:
Saunders Elsevier. 2007;520-530.
2. Advani P. Beta Thalassemia Differential Diagnoses. Medscape Web
site. Available at: http://emedicine.medscape.com/article/206490differential. Accessed on: August 24, 2015.
3. Beta-thalassemia. Online Mendelian Interitance of Man (OMIM) Web
site. Available at: http://omim.org/entry/613985. Accessed on: August
24, 2015.
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