1. History 1: 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. No other organomegaly.
CBC RBC 5.25 x 10[12]/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 10[9]/L,
N 24 %, L (shown) 73%,
M 0, E 3% , B 0
PLT 333 x 10[9]/L
Question1
What morphologic alterations are seen in this blood smear field?

2. Answer 1
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
Question 2
What further laboratory studies, if any, are indicated?

3. Question 3: What is the most likely diagnosis?
Answer 2
Further Laboratory Studies:
Heterophil antibody screen: positive
Question 3: What is the most likely diagnosis?

4. Answer 3
Diagnosis: Infectious mononucleosis
Clinical Course:
Three weeks later, the patient's symptoms had abated, and
his WBC count was 7.6 x 10[9]/L, with 56% lymphocytes

5. History 2: 70 year old female
History 2: 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 RBC 3.71 x 10[12]/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 10[9]/L
N 82 %, L 13%
M 1%, E 4%, B 0
PLT 383 x 10[9]/L
Question 1
What morphologic alterations are seen in this blood smear field?

6. Answer 1
Morphologic Alterations 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
Question 2
What further laboratory studies, if any, are indicated?

7. Answer 2
Further Laboratory Studies
Iron studies were performed, and results were:
serum ferritin <10 ng/mL (RI 12-86)
serum iron 24 µg/dL (RI )
TIBC 729 µg/dL (RI ) saturation 3 % (RI 20-55)
Question 3 What is the most likely diagnosis?

8. Answer 3: Diagnosis Iron deficiency anemia
Clinical Course
Diagnostic procedures included upper GI endoscopy, colonoscopy,
and small bowel biopsy. All were negative.
The patient received packed RBC transfusions and was started on iron therapy.
The etiology of her iron deficiency anemia could not be determined,
but it was most likely nutritional.

9. History 3: 51 year old male. Seen by 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 extending from the left costal margin to just above the iliac crest. No other organomegaly.
CBC RBC 3.36 x 10[12]/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 10[9]/L
N 14 %
L 15 %
Abnormal cells 71% (shown)
PLT 59 x 10[9]/L
Question 1
What morphologic alterations are seen in this blood smear field?

10. Answer 1
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: Thrombocytopenia
Question 2: What further laboratory studies, if any, are indicated?

11. Answer 2
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: CD19: (35%), CD20: (35%), CD22: (31%),
CD 103: (36%), CD5: (1%).
Question 3 What is the most likely diagnosis?

12. Answer 3 Diagnosis Hairy cell leukemia
Clinical Course The patient was treated with appropriate therapeutic agents and responded well.

13. History 5: 34 year old female
History 5: 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 RBC 2.38 x 10[12]/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 10[9]/L,
N 78 % L 14%
M 8%, E 0, B 0
PLT 14 x 10[9]/L
Question 1 What morphologic alterations are seen in this blood smear field?

14. Answer 1
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: Thrombocytopenia
Question 2 What further laboratory studies, if any, are indicated?

15. Answer 2: Further Laboratory Studies
Coagulation:
PT 12.2 sec (RI ),
PTT 29.2 sec (RI 23-34)
TT 22.9 sec (RI 13-18),
Fibrinogen 0.43 g/dL (RI )
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 )
Bilirubin Conj. 0.5 mg/dL (RI )
Total 2.8 mg/dL (RI )
Haptoglobin <5 mg/dL (RI )
Urinalysis: Large amount of blood present
Protein positive (100 mg/dL)
Question 3 What is the most likely diagnosis?

16. Answer 3
Diagnosis Thrombotic thrombocytopenic purpura (TTP)
Clinical Course
Plasma exchange was commenced promptly after admission.
Initially, she became more acutely ill, and developed neurologic symptoms (combative and irritable, with fluctuating levels of consciousness).
She was continued on plasma exchange and given other appropriate therapy.
Over the next several days, her physical and mental status improved,
signs of hemolysis diminished, and her PLT count gradually increased.
She was discharged to be followed in Hematology Clinic.

17. History 8: 34 year old male. Seen for treatment of superficial skin wounds resulting from a shotgun accident while grouse hunting. Family physician noted slight pallor, jaundice, and scleral icterus. History of cholecystectomy five years prior to admission. At that time the patient was told he had Gilbert's syndrome. He stated he had always had "low blood," and that his father and paternal grandfather both had "liver ailments."
Physical Exam: Somewhat pale yellowish skin with scattered small surface wounds-mostly over the face, scalp and upper extremities. Moderate scleral icterus. Spleen palpable 3 cm below the left costal margin.
CBC: RBC 3.93 x 10[12]/L
HGB 11.3 g/dL HCT 33.1 % MCV 84.1 fL MCH 28.8 pg MCHC 34.4 g/dL RDW 18.7
WBC 5.0 x 10[9]/L
N 53 % , L 31%, M 8%, E 6%, B 2%
PLT 362 x 10[9]/L
Question 1
What morphologic alterations are seen in this blood smear field?

18. Answer 1
Morphologic Alterations Results of the blood smear exam were:
RBC morphology: normochromic 2+ polychromasia 2+ anisocytosis 2+ spherocytes 1+ echinocytes
WBC morphology: Within normal limits (one lymphocyte shown here)
PLT morphology: Within normal limit
Question 2 What further laboratory studies, if any, are indicated?

19. Answer 2
Further Laboratory Studies Hematology:
Reticulocytes 14.3 % Absolute 562 x 10[6]/L
Osmotic fragility (unincubated) Initial hemolysis 0.65% NaCL
Complete hemolysis 0.40% NaCL Control: Initial 0.50%;
Complete 0.20% Osmotic fragility (incubated) Initial hemolysis 0.85% NaCL
Complete hemolysis 0.60% NaCL Control: Initial 0.60%; Complete 0.20%
Chemistry:
Bilirubin Conj. 0.5 mg/dL (RI )
Total 5.8 mg/dL (RI )
Question 3 What is the most likely diagnosis?

20. Diagnosis Hereditary spherocytosis
Answer 3
Diagnosis Hereditary spherocytosis
Clinical Course
The patient was referred to a hematologist to evaluate the
advisibility of a splenectomy

21. History 14; 37 year old male. Lifelong history of a seizure disorder, treated since age two. At a routine check with his neurologist, he complained of fatigue, exertional dyspnea, and lightheadedness over the past 2-3 months. He appeared pale, but otherwise his physical exam was within normal limits. He was found to have a decreased hemoglobin, and was referred to Hematology Clinic.
CBC RBC 1.26 x 10[12]/L
HGB 5.7 g/dL
HCT 16.3 %
MCV 130 fL MCH 45.2 pg
MCHC 34.9 g/dL RDW 18.1
WBC 6.2 x 10[9]/L
N 73 %, L 21%, M 1%,
E 4%, B 1%
PLT 219 x 10[9]/L
Question 1
What morphologic alterations are seen in this blood smear field?

22. Answer 1
Morphologic Alterations Results of the blood smear exam were:
RBC morphology: Normochromic 3+ macrocytosis 3+ anisocytosis Numerous oval macrocytes Occ teardrop cells and fragments
WBC morphology: Many neutrophils show nuclear hypersegmentation
PLT morphology: Within normal limits
Question 2
What further laboratory studies, if any, are indicated?

23. Answer 2 Further Laboratory Studies
Bone marrow biopsy Aspirate : Erythroid hyperplasia with megaloblastic maturation. Large polychromatic and orthochromatic megaloblasts show nuclear karyorrhexis and other dyserythropoietic changes. Multiple Howell Jolly bodies are seen in both megaloblasts and oval macrocytes. Neutrophils show premature nuclear segmentation, with giant metamyelocytes and band forms.
Sections:Appear hypercellular
Chemistry:
Serum folate <1.0 µg/L (RI )
RBC folate 131 µg/L (RI )
Serum B ng/L (RI )
Question 3
What is the most likely diagnosis?

24. Answer 3
Diagnosis Megaloblastic anemia due to folate deficiency
Clinical Course
The patient was given large doses of folic acid, and within 6 days his reticulocyte count was 15.2%.
One month later, his hemoglobin was 12.7 g/dL, MCV was 92 fL, and his blood smear morphology was normal.
The anticonvulsant drug he had been taking is known to interfere with folate metabolism. In addition, the patient had been trying to lose weight, and over the past few months his diet had consisted mainly of TV dinners, with little or no fresh vegetables or fruits.
A nutritional consult was arranged, and he was instructed to add folic acid to his daily medications.
Note: Patients with folic acid deficiency occasionally show decreased levels of vitamin B12. Because of the patient's history and lack of typical neurologic symptoms, concurrent pernicious anemia was considered very unlikely.

25. History 24: 8 month old male brought to emergency room
History 24: 8 month old male brought to emergency room. In good health until 24 hours prior to admission, when parents noted fever, progressive lethargy, and dark red urine. Product of normal pregnancy and uncomplicated delivery. Diet had consisted mainly of breast milk and formula, with some fruits and vegetables added recently. Parents were both from Egypt. No known family history of anemia, jaundice, gallstones, or splenectomy.
Physical Exam: Lethargic, pale infant with jaundiced skin and scleral icterus. Moderate splenomegaly and hepatomegaly. Temperature of 102°F.
CBC: RBC 1.28 x 10[12]/L
HGB 4.5 g/dL HCT 11.4 %
MCV 89.1 fLMCH 35.2 pg
MCHC 39.4 g/dL
WBC 27.8 x 10[9]/L
N seg 65 % N myelo 1 L 31
M 3 E 0 B 0 NRBC/100 WBC 2
PLT 425 x 10[9]/L
Question 1 What morphologic
alterations are seen in this blood smear field?

26. Answer 1
Morphologic Alterations: Results of the blood smear exam were:
RBC morphology: Normochromic 2+ polychromasia 3+ irregularly shaped spherocytes 2+ fragments 1+ echinocytes Many of the spherocytes have a clear "veil" or "blister" of membrane on the edge of the cell. RBC fragments include helmet and "bite" cell forms.
WBC morphology: Reactive neutrophils with toxic granulation.
PLT morphology: Within normal limits .
Question 2
What further laboratory studies, if any, are indicated?

27. Answer 2
Further Laboratory Studies
Chemistry:
Serum was grossly hemolysed.
Bilirubin Conj. 1.0 mg/dL (RI )
Total 6.7 mg/dL (RI )
Haptoglobin <5 mg/dL (RI )
Urinalysis:
Urine was grossly red.
Blood 3+
Protein 3+
Biochemical Genetics:
RBC enzymes: G6PD 0.8 IU/10[11]RBC equiv. (RI )
Pyruvate kinase levels within normal limits
Question 3 What is the most likely diagnosis?

28. Answer 3
Diagnosis
Glucose-6-phosphate dehydrogenase (G6PD) deficiency
Clinical Course
The patient was admitted and transfused with packed RBCs. On the following day, his hemoglobin was 10.7 g/dL. His condition stabilized and his hematuria cleared. He recovered rapidly. Other laboratory parameters returned to normal levels and there was no further evidence of hemolysis. Note: G6PD is an enzyme that protects erythrocyte hemoglobin from oxidation and subsequent denaturation. Individuals with a deficiency of this enzyme are susceptible to hemolytic episodes following oxidant stress to their red cells. In the Mediterranean type of G6PD deficiency, acute hemolysis can be initiated by the ingestion of fava beans. Questioning of the parents disclosed that one of the vegetables that had been added to the infant's diet—on the day before admission was fava beans. The patient was discharged, and the parents were provided with a list of foods, medications, and other substances that should be avoided by persons with G6PD deficiency.

29. History 30: 18 year old male student from Nigeria
History 30: 18 year old male student from Nigeria. Came to the emergency room with symptoms of fever, shaking chills, nausea, and generalized malaise; occurring intermittently over the past five days.
Physical Exam: Fever of 103.3°F. Tachycardia with a heart rate of 122. Otherwise within normal limits.
CBC RBC 5.85 x 10[12]/L
HGB 13.3 g/dL
HCT 41.8 %
MCV 71.5 fL, MCH 22.7 pg
MCHC 31.8 g/dL, RDW 12.1
WBC 6.2 x 10[9]/L
N 89 % L 8 M 2 E 1 B 0
PLT 102 x 10[9]/L
Question 1
What morphologic alterations are seen in this blood smear field?

30. Answer 1
Morphologic Alterations Results of the blood smear exam were:
RBC morphology: Normochromic Numerous red cells contain intraerythrocytic organisms.
Infected RBCs are enlarged; some are oval shaped, others appear somewhat "fimbriated." Doubly infected cells are present, and several morphologic stages can be found, including ring forms, mature schizonts, and gametocytes.
WBC morphology: Within normal limits (one lymphocyte shown here)
PLT morphology: Within normal limits.
Question 2
What further laboratory studies, if any, are indicated?

31. Answer 2
Further Laboratory Studies
Biochemical Genetics:
RBC enzyme: G6PD 11.7 U/g Hgb (RI )
Question 3
What is the most likely diagnosis?

32. Answer 3
Diagnosis: Malaria Upon further questioning, the patient stated that he had arrived in the Saudi Arabia from Nigeria approximately six months prior to this visit. Shortly after his arrival, he had experienced a similar illness that was diagnosed as malaria.
Medication was prescribed, but once he felt better he did not continue to take it. Based on the blood smear morphology, the periodic pattern of his fever and chills, and his travel history, the causative organism was identified as Plasmodium ovale.
Clinical Course
The patient was hydrated with normal saline, and started on appropriate
Treatment for the erythrocytic stages of malaria. Several days later he began a second course of therapy to eliminate the exoerythrocytic
(hepatic) forms of the organism. He completed the course of therapy, and on subsequent visits was asymptomatic.
Note: On the basis of his low MCV, his relatively high RBC count,
and his ethnic background, it is likely that this patient also has alpha thalassemia trait.