Hematology: Case Studies

Front 1

CASE 1: A 30-old-male of Afro-American descent was treated at the Howard University hospital complaining of extreme tiredness after exercise, occasional dizziness, and shortness of breath. On one occasion he actually fainted on the job.

1. What valuable information can be extracted from this?

Back 1

1. The clinical symptoms of extreme tiredness often suggest the presence of an anemia , but there is not enough information to make an assumption of the specific anemia present.

Front 2

CASE 1 cont.

Initial Laboratory Profile:

WBC 10.0X10 9/L (4.8-19)mm3
MCV 79 fl.( 78-96)
RBC 5. 0X10 12/L (4.2-5.4)
MCH 24 pg (27-31)
Hb 13. 9gm/ dL (12-16)
MCHC 34 %(32-36)
Hct 40 % (37-47)
Plt 150X10 9/L (150-450) N

2. What does the evaluation of these routine lab results show?

Back 2

2. The hemoglobin(Hb), hematocrit (Hct), and the Red Cell count (RBC) are all below the acceptable reference ranges for the age and sex of the patient, but the hemoglobin is commonly used as the indicator of anemia. A reduced hemoglobin value always suggest Anemia.

Front 3

CASE 1 cont:

Additional Lab Results:

Peripheral smear morphology shows: microcytic, hypochromic erythrocytes, poikilocytosis, occasional target and banana shaped cells. The white blood cells(WBC’s) had fairly normal morphology, and the platelet distribution was slightly increased.

3. Is this smear abnormal and which are the specific abnormalities?

4. What additional testing should be done to make proper identification of the anemia?

Back 3

3. The erythrocytes(hypochromic/ microcytic, targets . The banana shaped cells are commonly found in anemia caused by the deficiency of dietary iron. Iron Deficiency Anemia-IDA

4. The following tests are commonly used to differentiate between the microcytic, hypochromic anemia:
Serum Iron Serum Ferritin
Total Iron Binding Ferritin % Saturation
Capacity (TIBC) Bone Marrow Iron Stores

Front 4

CASE 1 cont:

Patient Test Results

Serum Iron Decreased
TIBC Increased
% Saturation Decreased
Iron Stores Decreased

5. What is the correct specific anemia presented here?

Back 4

5. Iron Deficiency Anemia -IDA

Front 5

CASE 1 Discussion:

Back 5

Iron deficiency anemia is one of the most frequently encounters anemia. This anemia may result from nutritional deficiency, abnormal absorption of iron , increased demand or excessive bone marrow loss. Among all of these nutritional deficiency appears to be the most frequent cause of Iron Deficiency Anemia (IDA).

Front 6

CASE 2: A 26-year-old American female was treated for excessive joint pains, swollen ankles and fever over a period of years with analgesics and other pain therapy. Her physical examination revealed signs of inflammation, splenomegaly, and some bacterial infection.

Initial Laboratory Profile:

WBC 15.5x 10 9/L (4.8-10.8)N
MCV 91fl (80-96)N
RBC 3.5 X1012/L (4.2- 5.5) N
MCH 29. 8 pg ( 27-32)N
Hb 10. 5gm/dl ( 12-16) N
MCHC 32. 4% ( 32-36)N
Hct 31.6 % (37-47) N
Sed Rate 30/ mm/hr (0-20)N

1. What category of anemia is suggested here?

Back 6

1. The RBC parameters (Hct, Hb) indicate the presence of anemia, and the MCV suggests a normocytic, normochromic anemia . The MCV is mostly a measure of erythrocyte size. This situation occurs in a specific group of disorders caused by poor utilization of iron.

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CASE 2 cont:

Additional Lab Results:

Peripheral smear shows normocytic/normochromic, sl. poikilocytosis, and occasional target cells. Some erythrocytes show inclusions in clusters.
•Differential: Seg Neut. 80% Lymphs 10%
•Monos 6% Eos 3%
•Baso 1%

2. What are the inclusions in the erythrocytes?

Back 7

2. These are iron deposits seen usually in bunches or clusters and visible on Wright stain also.

Front 8

CASE 2 cont:

3. What would you expect to find on a bone marrow iron stain?

4. What is serum iron and TIBC values for this group of anemia?

Back 8

3. The bone marrow (iron stain) should show increased iron storage in 30-50% of the normoblasts (multiple dark inclusions) sideroblasts.


4. The Serum Iron and TIBC values can be normal or increased.

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CASE 2 cont:

5. This anemia is most likely called what?

Back 9

5. Chronic Disorder Anemia (CDA)

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CASE 2 Discussion:

Back 10

Anemia of chronic disorders is produced by blockage of iron release from the storage areas (macrophage) and availability to be used in the synthesis of heme in the hemoglobin molecule. Current concept suggest a deficiency of an enzyme essential the iron transfer process. This anemia is usually associated with chronic conditions, eg. rheumatoid arthritis, chronic liver disease, rheumatic fever, lupus erythematous, and other related to the inflammatory response.

Front 11

CASE 3: A 24-year-old female on her first visit to her physician complained of weakness and being continually tired. She also stated that she had lost an appreciable amount of weight . There was no family history of anemia, but evidence was produced that she had abused the use of alcohol by consuming several quarts weekly, and neglected having a normal diet for several years.

Initial Laboratory Profile
RBC 3.0 X 10 12/L ( 4.2-4.5) N MCV 92 fl (78-96) N
WBC 9.7 X 10 9/ L ( 4.8-10.8) N MCH 30.9 (27-32) N
Hct 26.9 % ( 37-47) N MCHC 33.5 ( 32-36) N
Hb 9.0 gm/dL ( 12-14) N RDW 15.0 (11.5-14.5) N

1. What is the category of this anemia?

Back 11

1. The MCV suggests a normocytic/ normochromic anemia, which includes the hemolytic anemias.

Front 12

CASE 3 cont:

Additional Lab Results:

Differential
Seg Neutrophil 71% Lymphs 5%
Bands 5% Monos 11% Lymphs 5 % Eos 3%
Peripheral blood morphology shows hypochromic/ microcytic and normochromic/ normocytic RBC with basophilic stippling in some erythrocytes.

2. Explain the discrepancy suggested here?

Back 12

2. The hematocrit and hemoglobin suggest iron deficiency anemia, the MCV suggests a hemolytic anemia, but the dimorphism found in the erythrocytes and the basophilic stippling are indicative of a Iron deficiency Anemia associated with increased iron storage.

Front 13

CASE 3 cont:

Additional Lab Results:

This smear represents the bone marrow iron content:

3. Which morphological features are significant in the diagnosis of this anemia?

Back 13

3. The presence of increased iron stores, sideroblasts and ringed sideroblasts.

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CASE 3 cont:

4. What are the expected values for the following chemistry tests?. Serum Iron? TIBC? Serum transferrin? Serum B12?

Back 14

•Serum Iron Increased
•TIBC Normal/decreased
•Serum Transferrin Increased
•Serum Folate Normal

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CASE 3 cont:

5. What is the etiology of this anemia?

Back 15

5. This anemia is caused by poor utilization of iron associated with defective heme synthesis.

Front 16

CASE 3 cont:

6. What is the diagnosis of this anemia?

Back 16

6. Sideroblastic Anemia

Front 17

CASE 3 Discussion:

Back 17

Sideroblastic anemia is generally produced by the deficiency of the enzyme delta-ALA synthetase enzyme which causes accumulation of nonferritin iron around the nucleus of the immature erythroblast ( metarubricyte stage) cell. This forms the ringed sideroblast which a diagnostic feature of this anemia

Front 18

CASE 4: 23 year old male.

Over the past week noted increasing fatigue, sore throat, earaches, headaches, and episodic fever and chills. Unable to run his customary 25 miles per week.

Physical Exam:

Erythematous throat and tonsils.
Swollen cervical lymph nodes.

CBC
(with microscopic differential)

RBC 5.25 x 1012/L
HGB 15.4 g/dL
HCT 46.1 %
MCV 87.9 fL
MCH 29.3 pg
MCHC 33.4 g/dL
RDW 12.2

WBC 12.9 x 109/L
N 24 %
L (shown) 73
M 0
E 3
B 0

PLT 333 x 109/L

Morphologic Alterations

Results of the blood smear exam were:

RBC morphology:
Normocytic, normochromic

WBC morphology:
Most of the lymphocytes are reactive. They are large cells with a smudged chromatin pattern and abundant cytoplasm with radial and/or peripheral basophilia. Some of the larger cells have finer chromatin and nucleoli.


PLT morphology:
Within normal limits

1. What further laboratory studies, if any, are indicated?

Back 18

Further Laboratory Studies

Heterophil antibody screen: positive

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CASE 4 cont:

2. What is the most likely diagnosis?

Back 19

Infectious mononucleosis

Front 20

CASE 5: 70 year old female.

Symptoms of dyspnea on exertion, easy fatigability, and lassitude for past 2 to 3 months.

Denied hemoptysis, GI, or vaginal bleeding. Claimed diet was good, but appetite varied.

Physical Exam:
Other than pallor, no significant physical findings were noted. Occult blood was negative.

CBC
(with microscopic differential)

RBC 3.71 x 1012/L
HGB 5.9 g/dL
HCT 20.9 %
MCV 56.2 fL
MCH 15.9 pg
MCHC 28.3 g/dL
RDW 20.2

WBC 5.9 x 109/L
N 82 %
L 13
M 1
E 4
B 0

PLT 383 x 109/L

Results of the blood smear exam were:

RBC morphology:
2+ hypochromasia
3+ microcytosis
2+ anisocytosis
2+ elliptocytes and target cells
occ teardrops and fragments

WBC morphology:
Within normal limits
(one lymphocyte shown here)

PLT morphology:
Within normal limits

1. What further laboratory studies, if any, are indicated?

Back 20

Further Laboratory Studies

Iron studies were performed, and results were:

serum ferritin <10 ng/mL
(RI 12-86)
serum iron 24 µg/dL
(RI 65-175)
TIBC 729 µg/dL
(RI 250-410)
saturation 3 %
(RI 20-55)

Front 21

CASE 5 cont:

2. What is the most likely diagnosis?

Back 21

Iron deficiency anemia

Front 22

CASE 6: 51 year old male.

Seen by local physician for routine preoperative exam prior to dental surgery. Found to have low hemoglobin and a large left upper quadrant mass.

Physical Exam
Marked splenomegaly (subsequently confirmed by CT scan) extending from the left costal margin to just above the iliac crest.
No other organomegaly.

CBC
(with microscopic differential)

RBC 3.36 x 1012/L
HGB 10.9 g/dL
HCT 31.2 %
MCV 92.8 fL
MCH 32.4 pg
MCHC 34.9 g/dL

WBC 9.3 x 109/L
N 14 %
L 15
abnormal cells 71
(shown)

PLT 59 x 109/L

Morphologic Alterations

Results of the blood smear exam were:

RBC morphology:
Normocytic, normochromic

WBC morphology:
The abnormal cells have round or indented nuclei with a fairly coarse chromatin pattern. They have variable amounts of grainy blue-gray cytoplasm with irregular ragged borders and numerous projections.


PLT morphology:
Within normal limits

1. What further laboratory studies, if any, are indicated?

Back 22

Further Laboratory Studies

Bone marrow biopsy:

Aspirate:
Marrow was difficult to obtain. A small amount of fluid was aspirated, and the differential showed 78.1% abnormal cells similar to those in the blood.


Sections:
Hypocellular with a diffuse loosely structured infiltrate of mononuclear cells. Increased areas of fibrosis.


Cytochemistry:

Tartrate resistant acid phosphatase (TRAP) stain of abnormal cells: positive

Immunophenotyping:

Not done.

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CASE 6 cont:

2. What is the most likely diagnosis?

Back 23

Hairy cell leukemia

Front 24

CASE 7: 25 year old male.

Recurrent upper respiratory infections with fever, nausea, and submandibular swelling for several months prior to admission.

Noted that cuts on his hands did not heal well.

Physical Exam
Submandibular adenopathy.
No other organomegaly.

CBC
(with microscopic differential)

RBC 2.70 x 1012/L
HGB 9.9 g/dL
HCT 28.7 %
MCV 106.3 fL
MCH 36.9 pg
MCHC 34.8 g/dL

WBC 7.9 x 109/L
N 4 %
L 16
M 1
E 0
B 0
abnormal cells 79
(shown)

PLT 50 x 109/L

Morphologic Alterations

Results of the blood smear exam were:

RBC morphology:
Normochromic
1+ polychromasia
1+ macrocytosis

WBC morphology:
The abnormal cells are medium-sized blasts. The nuclei are often irregular in shape, and some have invaginations or deep clefts. Most have a fine chromatin pattern and one or more prominent nucleoli. The cytoplasm is basophilic, and thin Auer rods are seen.


PLT morphology:
Within normal limits

1. What further laboratory studies, if any, are indicated?

Back 24

Further Laboratory Studies

Bone marrow biopsy:

Aspirate:
The differential showed 93.6% blasts similar to those in the blood. Dyserythropoiesis was not seen in the red cell precursors.


Sections:
Markedly hypercellular.


Cytochemistry:

Myeloperoxidase: positive
Sudan black B: positive
Non-specific esterase: negative

Immunophenotyping:

Not done.

Cytogenetics:

Not done.

Front 25

CASE 6 cont:

2. What is the most likely diagnosis?

Back 25

Acute myeloblastic leukemia
(AML) FAB M1

Front 26

CASE 7: 34 year old female.

Two day history of ecchymoses, petechiae, and hematuria.

She had noted headaches, nausea, and increasing dysphoria over the past week.

Physical Exam
Mild scleral icterus.
Scattered ecchymoses and petechiae.
Appeared anxious and agitated.

CBC
(with microscopic differential)

RBC 2.38 x 1012/L
HGB 6.6 g/dL
HCT 18.4 %
MCV 77.5 fL
MCH 27.7 pg
MCHC 35.8 g/dL
RDW 23.8

WBC 16.9 x 109/L
N 78 %
L 14
M 8
E 0
B 0

PLT 14 x 109/L

Morphologic Alterations

Results of the blood smear exam were:

RBC morphology:
normochromic
2+ polychromasia
3+ anisocytosis
3+ fragments
2+ spherocytes


WBC morphology:
Within normal limits
(one lymphocyte shown here)


PLT morphology:
Within normal limits

1. What further laboratory studies, if any, are indicated?

Back 26

Further Laboratory Studies

Coagulation:

PT 12.2 sec (RI 11.0-13.5)
PTT 29.2 sec (RI 23-34)
TT 22.9 sec (RI 13-18)
Fibrinogen 0.43 g/dL (RI 0.17-0.37)
FDP 80 µg/mL (RI 0-10)
D dimer 2320 ng/mL (RI 0-420)
Chemistry:

BUN 41 mg/dL (RI 9-23)
Creatinine 0.8 mg/dL (RI 0.3-1.0)
Bilirubin
Conj. 0.5 mg/dL (RI 0.0-0.3)
Total 2.8 mg/dL (RI 0.0-1.3)
Haptoglobin <5 mg/dL (RI 50-150)
Urinalysis:

Large amount of blood present
Protein positive (100 mg/dL)

Front 27

CASE 7 cont:

What is the most likely diagnosis?

Back 27

Thrombotic thrombocytopenic purpura (TTP)

Front 28

CASE 8: 6 year old male.

Well until 3 weeks prior to admission.

Developed upper respiratory symptoms, persistent headaches, bone pain, and easy bruising.

Physical Exam
Adenopathy: submandibular, axillary, and cervical. Hepatosplenomegaly. Petechiae and bruises on trunk and limbs.

CBC
(with microscopic differential)

RBC 3.34 x 1012/L
HGB 9.0 g/dL
HCT 27.2 %
MCV 82.0 fL
MCH 27.2 pg
MCHC 33.4 g/dL
RDW 13.9

WBC 92.4 x 109/L
N 4 %
L 8
M 1
E 0
B 1
abnormal cells 86
(shown)

PLT 18 x 109/L

Morphologic Alterations

Results of the blood smear exam were:

RBC morphology:
Normocytic, normochromic

WBC morphology:
The abnormal cells are small to medium-sized blasts. They have a relatively fine chromatin pattern, one or more indistinct nucleoli, and scanty basophilic cytoplasm. Occasional cells show nuclear clefts.


PLT morphology:
Within normal limits

1. What further laboratory studies, if any, are indicated?

Back 28

Further Laboratory Studies

Bone marrow biopsy:

Aspirate:
The differential showed 89.1% blasts similar to those in the blood.


Sections:
Markedly hypercellular.


Cytochemistry:

Myeloperoxidase negative
Sudan black B negative
PAS positive
(intensely staining clumps in
cytoplasm)
Immunophenotyping:

TdT positive
B precursor markers positive
T precursor markers negative
Myelomonocytic markers negative
Cytogenetics:

46, XY. No numerical or structural abnormalities found.

Cerebrospinal fluid analysis:

Clear, colorless CSF
Glucose 62 mg/dL (RI 50-80)
Protein 25 mg/dL (RI 20-60)
RBC 85 x 106/L
WBC 2 x 106/L
Gram stain negative
Culture negative

Front 29

CASE 8 cont:

2. What is the most likely diagnosis?

Back 29

B precursor ALL (acute lymphoblastic leukemia), FAB L1

Front 30

CASE 9: 72 year old male.

Symptoms of itching, rash, skin discomfort, and malaise increasing over several months.

Physical Exam
Generalized erythroderma. Skin appeared leathery, cracked, and peeling.

Bilateral epitrochlear and inguinal adenopathy.

CBC
(with microscopic differential)

RBC 4.80 x 1012/L
HGB 14.2 g/dL
HCT 42.4 %
MCV 88.3 fL
MCH 29.7 pg
MCHC 33.6 g/dL

WBC 10.8 x 109/L
N 35 %
L 13
M 8
E 4
B 0
abnormal cells 40
(shown)

PLT 158 x 109/L

Morphologic Alterations

Results of the blood smear exam were:

RBC morphology:
normocytic, normochromic

WBC morphology:
The abnormal cells have convoluted cerebriform nuclei. The cytoplasm is basophilic, and occasionally contains small vacuoles. Both small and large cell types are seen.


PLT morphology:
Within normal limits

1. What further laboratory studies, if any, are indicated?

Back 30

Further Laboratory Studies

Cytochemistry:

PAS: many of the abnormal cells show punctate PAS positivity around the nuclei.

Immunophenotyping:

Elevated CD3 and CD4 positivity consistent with helper T cell phenotype.

Front 31

CASE 9 cont:

2. What is the most likely diagnosis?

Back 31

Sezary syndrome

(Confirmed by skin and lymph node biopsy.)

Front 32

CASE 10: 30 year old male.

Almost 4 years prior to admission, he was diagnosed with a malignant brain tumor. It was removed surgically and he received chemotherapy.

After about three years, the tumor recurred. He was treated with radiation, and chemotherapy was resumed. During a clinic visit he was found to have a fever of 101°F, WBC of 1.0 x 109/L, and ANC (absolute neutrophil count) of 0 (zero).

He was admitted to the hospital and started on IV antobiotics and daily G-CSF injections. This CBC is from the sixth day of growth factor therapy.

Back 32

CASE 9: CBC & Diff

CBC
(with microscopic differential)

RBC 3.17 x 1012/L
HGB 10.4 g/dL
HCT 30.0 %
MCV 94.7 fL
MCH 32.9 pg
MCHC 34.7 g/dL
RDW 11.9

WBC 23.9 x 109/L
N seg 52 %
N band 13
N meta 8
N myelo 8
N pro 4
Myeloblast 1
L 8
M 3
E 3

PLT 103 x 109/L

Front 33

CASE 9 cont:

Morphologic Alterations

Results of the blood smear exam were:

RBC morphology:
normocytic, normochromic
1+ polychromasia

WBC morphology:
Both mature and immature stages of neutrophils have intense azurophilic granulation. Some bands and segmented forms contain Dohle bodies. Some have bubbly, vacuolated cytoplasm. Neutrophil nuclei are deeply stained, and nuclear projections are seen. Some promyelocytes are extremely large.


PLT morphology:
Within normal limits

1. What further laboratory studies, if any, are indicated?

Back 33

Answer:

Further Laboratory Studies

None

Front 34

CASE 9 cont:

2. What is the most likely diagnosis?

Back 34

Answer:

Shift to the left and reactive changes in neutrophils consistent with response to G-CSF or GM-CSF therapy.

Front 35

CASE 10: 33 year old female.

Immigrated to the United States from Laos four years prior to admission. History obtained through an interpreter.

Multiple transfusions and splenectomy two years prior to admission. Reason and/or diagnosis unclear to patient.

Presented with flu-like symptoms of fever, malaise, epigastric discomfort and nonproductive cough.

Back 35

CASE 10: CBC & Diff

CBC
(with microscopic differential)

RBC 4.15 x 1012/L
HGB 8.1 g/dL
HCT 28.6 %
MCV 68.9 fL
MCH 19.5 pg
MCHC 28.2 g/dL
RDW 22.3

WBC (corrected) 8.0 x 109/L
N 51 %
L 36
M 7
E 4
B 2

NRBC/100 WBC 83

PLT 540 x 109/L

Front 36

CASE 10 cont:

Morphologic Alterations

Results of the blood smear exam were:

RBC morphology:
3+ hypochromasia
1+ polychromasia
2+ anisocytosis
3+ target cells
occ spherocytes and fragments
Howell Jolly bodies present


WBC morphology:
Within normal limits


PLT morphology:
Within normal limits

1. What further laboratory studies, if any, are indicated?

Back 36

Answer:

Further Laboratory Studies

Hemoglobin electrophoresis:

Hemoglobin E 80 %
Hemoglobin F 5 %
Other hemoglobins* 15 %

*Identified as hemoglobin A2,
hemoglobin Barts and a
hemoglobin H mutant.
Iron studies:
Serum ferritin 3234 ng/mL
(RI 12-86)
Serum iron 140 µg/dL
(RI 65-175)
TIBC 152 µg/dL
(RI 250-410)
Saturation 92 %
(RI 20-55)

Front 37

CASE 10 cont:

2. What is the most likely diagnosis?

Back 37

Answer:

Homozygous hemoglobin E disease and alpha thalassemia