Download A 16-Year-Old Female with Anemia and a Dropping Platelet

Case Challenge
A 16-Year-Old Female with Anemia
and a Dropping Platelet Count
Ugoeze Otome, MD; and Lisa Giordano, MD
A
16-year-old African-American
female was referred for anemia
and a dropping platelet count.
Ferrous sulfate 325 mg orally three times
per day had been initiated 3 days earlier.
She gave a history of menorrhagia, headache, fatigue, and shortness of breath, intermittently, for 3 months. Her medical
history was significant for anemia 2 years
earlier, for which she was placed on oral
iron but she was non-compliant. She denied any recent illness. Her gynecology/
obstetric history was notable for heavy
menstruation since menarche at 14. Her
usual menstrual pattern consisted of menses every 20 days, lasting 7 days with approximately five heavily soaked pads per
day and cramping on the first day. She also
had two episodes of light bleeding lasting about 2 days in between her last two
menstrual periods. She denied other systemic bleeding symptoms. Medications at
presentation included acetaminophen or
Ugoeze Otome, MD, is a general pediatrician,
Potomac Valley Family Medicine,
Moorefield,
WV. Lisa Giordano, MD, is Section Head of Pediatric Oncology, Division of Pediatric Hematology/
Oncology, John H. Stroger Jr. Hospital of Cook
County.
Address correspondence to Lisa Giordano
MD, Division of Pediatric Hematology/Oncology,
John H. Stroger Jr. Hospital of Cook County, 1900
West Polk Street, 11th Floor Pediatrics, Chicago,
IL 60612; email: [email protected].
Disclosure: The authors have no relevant financial relationships to disclose.
doi: 10.3928/00904481-20140825-05
354
ibuprofen for occasional headaches. There
was no history of bleeding disorder or malignancy in the family. The patient’s mother also was diagnosed with anemia and was
being treated with iron tablets.
On examination, she was well appearing without distress. She had a temperature 98.8°F, heart rate of 131, respiratory
rate of 24, blood pressure of 120/55 lying down and 101/61 sitting, with a body
mass index of 27 kg/m2. Examination was
significant for pallor, a flow murmur, and
active heavy menstrual bleeding. There
was no jaundice, lymphadenopathy, or organomegaly. Stigmata of polycystic ovarian syndrome, such as hirsutism and acne,
were absent and there were no other abnormal findings.
Prior to initiation of oral iron 3 days before presentation, hemoglobin was 5.0 g/
dL, mean corpuscular volume (MCV) was
63.9 fL, platelet count was 71 x 103/mm3,
and white blood cell (WBC) count was 3.7
x 103/mm3 with a normal differential. Serum ferritin level was 2.4 ng/mL.
Admission lab results included a negative urine pregnancy test, hemoglobin of
5.3 g/dL, MCV of 63.6 fL, red cell distribution width of 33.5%, platelet count
of 27 x 103/mm3, WBC of 5.4 x 103/mm3
with a normal differential, and a reticulocyte count of 2.3% (see Table 1). Blood
Figure 1. The patient’s peripheral blood smear after blood transfusion.
type was O positive with a negative direct
and indirect antiglobulin (Coombs) test.
Serum creatinine was 0.6 mg/dL, total
bilirubin 0.4 mg/dL, and lactate dehydrogenase 157 IU/L. Antinuclear antibody
was negative and von Willebrand profile
was normal. Hemoglobin electrophoresis
revealed only low hemoglobin A2 level.
Vitamin B12 and folic acid levels were
normal. Analysis of the peripheral blood
smear post-transfusion revealed two red
blood cell populations with hypochromic
microcytic erythrocytes, no schistocytes
or blasts, and reduced platelets (Figure 1).
Bone marrow studies revealed hypercellular trilineage hematopoiesis without increased blasts or stainable iron (Figure 2).
For diagnosis, see page 355
Editor’s note: Each month, this department features a discussion of an unusual diagnosis. A description and images are presented, followed by the diagnosis and an explanation of how the diagnosis was determined. As always, your comments are welcome
via email at [email protected].
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Case Challenge
Diagnosis:
Thrombocytopenia Due to
Severe Iron-Deficiency Anemia
The patient received two units of leuko-reduced packed red blood cells upon
admission (day 4 of oral iron therapy),
which resulted in an increase in the hemoglobin to 7.5 g/dL. The platelet count
increased to 33 x 103/mm3 then to 36 x
103/mm3 on the same day after transfusion of red cells (Table 1). Platelet
transfusions were not administered at
any time. The patient was evaluated by
the gynecology service for menorrhagia.
A pelvic ultrasound showed a thickened
endometrial echotexture. A clinical diagnosis of dysfunctional uterine bleeding
was made as the etiology for her menorrhagia, and therapy was initiated with
oral contraceptives with one active tablet
daily and instructions not to take the placebo tablets to prevent further bleeding.
The patient was continued on ferrous
sulfate and oral contraceptive therapy.
She was discharged home and was followed closely in the outpatient hematology clinic.
Ultimately, severe iron-deficiency
anemia (IDA) secondary to dysfunctional uterine bleeding was confirmed, iron
therapy was continued, and the patient’s
hemoglobin and platelet count normalized (Table 2).
DISCUSSION
Thrombocytopenia is a rare complication of severe IDA. Our patient’s
case was especially unusual because the
platelet count continued to drop during
the first few days of iron therapy. This
observation raised the possibility of an
alternative diagnosis, and a bone marrow
examination and further investigations
were performed. The differential diagnosis of anemia and thrombocytopenia
in this patient at presentation included
leukemia, which was ruled out by bone
PEDIATRIC ANNALS • Vol. 43, No. 9, 2014
B
A
Figure 2. (A) The patient’s bone marrow iron stain, which revealed no stainable iron. (B) A control bone
marrow iron stain (note the bluish discoloration).
TABLE 1.
Hematologic Parameters Prior to and During Admission
Day 1 Pretreatment
Day 1 on
treatment
Day 3 on
treatment
Day 4* on
treatment
Day 4† on
treatment
Hgb (g/dL)
5
5.5
5.3
5.9
7.5
MCV (fL)
63.9
64
63.6
67.7
70.4
RDW (%)
26.5
26.2
33.5
37.5
37.1
Platelets (x 10 /mm )
71
43
27
33
36
WBC (x 103/mm3)
3.7
4.3
5.4
8.6
8.4
Reticulocyte count
(%)
0.2
ND
2.3
ND
ND
3
3
*After first red blood cell transfusion.
†After second red blood cell transfusion and discharge day.
Hgb = hemoglobin; MCV = mean corpuscular volume; ND = not done; RDW = red cell distribution width; WBC = white blood
cell.
marrow exam); autoimmune hemolytic
anemia and immune thrombocytopenic
purpura (ie, Evan’s syndrome), which
was eliminated by the negative direct
antiglobulin (Coombs) test and lack of
evidence of hemolysis; and systemic
lupus erythematosus, which was ruled
out by the negative antinuclear antibody
result. Hemoglobinopathy was ruled
out by hemoglobin electrophoresis. The
low hemoglobin A2 was consistent with
IDA. Aplastic anemia was eliminated
by the hypercellular bone marrow, and
hemolytic uremic syndrome/thrombotic
thrombocytopenic purpura was ruled
out with a normal serum creatinine and
lactate dehydrogenase, and a lack of
schistocytes on the peripheral smear. An
important potential etiology of menor-
rhagia (von Willebrand disease) was
eventually ruled out by a normal von
Willebrand profile.
The mechanism of thrombocytopenia
associated with severe IDA is unknown.
Suggested mechanisms in the literature
include the existence of one or more irondependent cellular processes critical to
the late stages of thrombopoiesis that can
be altered during severe iron depletion.1-4
Also discussed is the stem cell competition/stem cell steal phenomenon based on
evidence in animals that megakaryocytic
and erythroid cell lineages share a common progenitor cell.2 Therefore, in IDA,
an increase in erythroid precursors may
result in a decreased number of megakaryocytes. However, this hypothesis was
dismissed by Perlman et al.2 as they noted
355
Case Challenge
TABLE 2.
Hematologic Parameters During the Course of Ferrous Sulfate Therapy
Day 1 Pretreatment
Day 1 on
Treatment
Day 3 on
Treatment
Day 4* on
Treatment
Day 4† on
Treatment
Day 11 on Day 23 on Day 44 on Day 74 on
Treatment Treatment Treatment Treatment
Hgb (g/dL)
5
5.5
5.3
5.9
7.5
9.5
11.1
12.4
13
MCV (fL)
63.9
64
63.6
67.7
70.4
75
76.9
82
82.7
RDW (%)
26.5
26.2
33.5
37.5
37.1
39.7
33
26.1
15.5
Platelets (x 103/mm3)
71
43
27
33
36
696
393
183
181
3
WBC (x 10 /mm
3.7
4.3
5.4
8.6
8.4
9.6
5.7
5.4
5.1
Reticulocyte count (%)
0.2
ND
2.3
ND
ND
6.1
1.5
0.5
0.7
3)
*After first red blood cell transfusion.
†After second red blood cell transfusion and discharge day.
Hgb = hemoglobin; MCV = mean corpuscular volume; ND = not done; RDW = red cell distribution width; WBC = white blood cell.
erythroid hyperplasia in two of three patients with IDA and an increase in megakaryocytes in all three patients with IDA
who had a bone marrow examination.
Our patient showed both erythroid hyperplasia and increased megakaryocytes
on her bone marrow examination as well.
Deficiencies of vitamin B12 or folic acid
superimposed on severe IDA may cause
thrombocytopenia; however, our patient
had normal vitamin B12 and folic acid
levels. Given the level of fortification of
most food products in the United States,
it is highly uncommon to see these vitamin deficiencies unless the patient is on
a very restrictive diet.
Another possibility is the effect of
erythropoietin (Epo), which has been
shown to be initially increased secondary to hypoxic stimuli in the setting of
356
severe anemia. Reports on the effect of
Epo on thrombopoiesis5-7 document that
an increased level of Epo in moderate
IDA can stimulate megakaryopoiesis,
whereas high levels of Epo may be associated with thrombocytopenia in severe
IDA. Although Epo therapy often results
in an increased platelet count initially,
higher Epo doses have been shown to
be associated with thrombocytopenia
in humans and rats with chronic renal
failure.5 Further study is necessary to
elucidate the mechanism of thrombocytopenia in severe IDA.
REFERENCES
1.Gross S, Keefer V, Newman AJ. The platelets in iron deficiency anemia. I. The response to oral and parenteral iron. Pediatrics.
1964;34:315-322.
2. Perlman MK, Schwab JG, Nachman JB, Ru-
bin CM. Thrombocytopenia in children with
severe iron deficiency anemia. J Pediatr Hematol Oncol. 2002;24:380-384.
3.Karpatkin S, Garg SK, Freedman ML. Role
of iron as a regulator of thrombopoiesis. Am J
Med. 1974;57(4):521-525.
4.Gupta MK, Joseph G. Severe thrombocytopenia associated with iron deficiency. Hosp
Physician. 2001;54:49-51. http://www.turnerwhite.com/pdf/hp_aug01_iron.pdf. Accessed
August 10, 2014.
5.Kadikoylu G, Yavasoglu I, Bolaman Z, Senturk T. Platelet parameters in women with
iron deficiency anemia. J Natl Med Assoc.
2006;98(3):398-402.
6.Loo M, Beguin Y. The effect of recombinant
human erythropoietin on platelet counts is
strongly modulated by the adequacy of iron
supply. Blood. 1999;93(10):3286-3293.
7. Beguin Y. Erythropoietin and platelet production. Haematologica. 1999;84:541-547.
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