1. A 21 year old man presented with pancytopenia with a Hb of 5.0, WBC of 2.6, neutrophils of 1.1, and platelets of 45. His MCV was elevated at 104. 2. Initial tests such as B12, folate, ferritin, LFTs and virology were normal. A bone marrow aspirate and trephine was performed. 3. The bone marrow aspirate and trephine revealed findings consistent with aplastic anemia, explaining the patient's pancytopenia. Further investigation is needed to determine the underlying cause of the aplastic anemia.

1. CASE 1
• History:
– A 72 year old male has the findings shown
below on a CBC.

2. Slide 2.1
A CBC demonstrates microcytosis and hypochromia.

3. Slide 2.2
Note the poikilocytosis and microcytosis and hypochromia
in this peripheral blood smear.

4. Questions
1. What is the diagnosis from these findings?
2. Which of the following tests would be most useful to
determine the etiology:
A. Hemoglobin electrophoresis
B. Reticulocyte count
C. Stool for occult blood
D. Vitamin B12 assay
E. Bone marrow biopsy

5. CASE 1:
1. What is the diagnosis from these findings?
Hypochromic microcytic anemia (from probable iron deficiency).
Answer: C
This patient most likely has a blood loss anemia, and a colon
cancer is a likely source in an older male. Laboratory testing
consistent with iron deficiency anemia would include a low
serum ferritin and low serum iron with low % saturation.

6. CASE 2
• History:
– A 48 year old male has become progressively
more fatigued at the end of the day. This has
been going on for months. In the past month
he has noted paresthesias with numbness in
his hands. A CBC demonstrates the findings
shown below..

7. Slide 3.1
A CBC demonstrates megaloblastic changes.
A peripheral blood smear (the slide is representative of this
condition) shows red blood cells displaying macro-
ovalocytosis and neutrophils with hypersegmentation

8. Slide 3.2
A peripheral blood smear demonstrates megaloblastic
changes. Describe the appearance of the neutrophil.

9. Questions
1. What is the diagnosis from these findings?
2. Which of the following tests would be most useful to determine the
etiology:
A. Hemoglobin electrophoresis
B. Reticulocyte count
C. Stool for occult blood
D. Vitamin B12 assay
E. Bone marrow biopsy
3. How do you explain the neurologic findings?

10. CASE 2
1. This is a macrocytic (megaloblastic) anemia.
The neurologic findings suggest vitamin B12 deficiency
(pernicious anemia).
2- Answer: D Macrocytic anemia could also be caused by a folate
deficiency, but the neurologic findings would not be present.
3.The B12 deficiency leads to a subacute combined degeneration
of the spinal cord (posterior and lateral columns).

11. CASE 3
• History:
– A 30 year old female has sudden onset of
fever, abdominal pain, tachycardia, nausea,
and jaundice. She is anemic, with Hgb 11.1
g/dL, Hct 28.8%, and MCV 77 fL. The WBC
count is normal, and she has marked
reticulocytosis. RBC morphology shows small
cells that lack central pallor. Physical
examination reveals a palpable spleen tip. A
month ago, a CBC showed the following
findings:

12. Slide 4.1
A CBC is shown here characteristic for this condition.

13. Slide 4.2
A peripheral blood smear is shown here. Compare the
size of the RBC's to the lymphocyte nucleus.

14. Questions
1.What is the diagnosis from these findings?
2.. An aplastic crisis in this patient could be initiated by:
A. Quinacrine
B. Parvovirus infection
C. Decreased oxygen tension
D. Exposure to cold
E. Transfusion

15. CASE 3
1. Hereditary spherocytosis.
2- B. Parvovirus infection
(sometimes called "fifth disease") infects RBC precursors.

16. CASE 4
• History:
– A 29 year old female with a diagnosis of acute
promyelocytic leukemia develops petechiae and
ecchymoses at multiple sites. She becomes
progressively more hypotensive before losing
consciousness. A CBC shows Hgb 8.7 g/dL, Hct
24.5%, MCV 85 fL, platelets 17,000/microliter, and
WBC count 8700/microliter.
– The peripheral blood smear demonstrates many
fragmented RBC's.
– Demonstrate schistocytes.

17. Slide 5.1
Note the fragmented RBC's in this peripheral blood
smear.

18. Questions
1. What is the diagnosis from these findings?
2. Which of the following tests would be most useful to
diagnose this condition in this patient with acute
promyelocytic leukemia:
A. Hemoglobin electrophoresis
B. Reticulocyte count
C. Coagulation tests
D. Vitamin B12 assay
E. Bone marrow biopsy

19. CASE 4
1. Microangiopathic hemolytic anemia, in this case disseminated
intravascular coagulation (DIC). Note: this slide does not show the
leukemia, only DIC.
2. Gram-negative sepsis with endotoxemia, disasters that release tissue
thromboblastic substances (obstetric complications such as abruptio
placenta, major trauma, malignancies), and promyelocytic leukemia.
3.
C. Coagulation tests
Answer: C The D-dimer test would be the most specific.

20. 75-year-old female reported the following over the last
month :
- Slight increase in confusion
- Loss of energy
PMH:
HTN, Osteoarthritis, Osteoporosis,GERD
Medications:
Ibuprofen, Lisinopril, Omeprazole, Alendronate,
Calcium w/D
Case 5

21. Labs:
Hemoglobin (Hb) 10.8 mg/dL; MCV 80
Serum Creatinin 1.4 mg/dL; BUN 12 mmol/L
s.Iron decreased - TIBC decreased
What laboratory test(s) can confirm your diagnosis?
A) Peripheral Blood Smear
B) GFR
C) Reticulocyte count
D) Iron/TIBC
E) B12 level
Case 5

22. What treatment approach is most appropriate?
A) Stop Ibuprofen
B) Start B12 500 mcg tablet daily
C) Stop Lisinopril
D)Start Ferrous Sulfate 325 mg tablet daily
E) Start Erythropoetin injections
Case 5

23. 67-year-old female with Rheumatic heart disease comes
to your office complaining of chronic fatigue and
shortness of breath upon exertion and tongue redness
and fissuring.
Physical examination suggested signs of jaundice and
Systolic ejection murmur. WBC 4.5 x109; HGB 10.0 g/dL
;HCT 31 %; MCV 90 fl; PLT 255 x 109/L
What test(s) would you order next? Why?
A)Hemaccult of stool
B)Ferritin
C)Peripheral smear
D)Serum Electrophoresis
E)Colonoscopy
Case 6

24. A peripheral blood smear showed numerous
fragmented erythrocytes.
LDH was elevated at 316 IU/l
haptoglobin was less than 7.3 mg/dl,
Total and un-conjugated hyperbilirubinemia and
hemosiderinuria was evident.
What is your Diagnosis?
Case 6

25. Hemolytic anemia due
to red blood cell trauma
and intravascular hemolysis
(Macroangiopathic hemolytic anemia)
Case 6

26. CASE 7
• History:
– This 15 year old female was sent home from
summer camp because of weakness,
lassitude, and sore throat. As her family
physician, you found that on physical
examination she had an inflamed pharynx,
enlarged tonsils, several enlarged and slightly
tender lymph nodes in the neck, a palpable
spleen, and a tender palpable liver edge.

27. Slide 3.1
This peripheral smear demonstrates atypical lymphocytes.

28. Laboratory studies:
– CBC showed
– Hgb 14.9 g/dl,
– WBC 12.5 X 109/L,
– and platelet count 282 X 109/L

29. Questions:
1. What is the predominant white blood cell
type?
2. What is your diagnosis in this case?
3. What is the differential diagnosis?
4. What other laboratory test may be
helpful in arriving at a specific diagnosis?

30. CASE 7
1. The predominant cell is a lymphocyte. There is an
absolute lymphocytosis with many atypical
lymphocytes
2. The diagnosis is infectious mononucleosis.
3. The differential diagnosis includes various viral
infections including hepatitis and
cytomegalovirus,mumps.
4. A serologic test for infectious mononucleosis would
confirm the diagnosis in most cases.

31. Case 8
• 34 year old African American woman who has
been known to have a mild microcytic anemia,
which was picked up some years ago on
routine blood work. She is entirely
asymptomatic. She has been prescribed iron
several times over the years without a
response.
• What data would you like to review?

32. Case 8
• Labs:
– HCT 31-34%
– Hgb 10.6-10.9gm/dL
– PLT 232-312K/mm3
– WBC 6500-8000/mm3 with a normal differential
– MCV 72-74 cubic microns
• What is in your differential diagnosis?

33. Case 8
• Differential Diagnosis:
– Iron deficiency anemia
• Noncompliance, inadequate dosing, incorrect
formulation.
– Beta thalassemia
– Alpha thalassemia
– Anemia of chronic disease
– Sideroblastic anemia
– Lead
• What additional lab tests would you like to
order?

34. Case 8
• Iron studies are normal.
• Chemistries, liver function tests, thyroid
studies are normal.
• No history of lead exposure.
• You ask to see a peripheral blood smear and
one other study. What is it?

35. Case 8

36. Case 8
• You also request a hemoglobin
electrophoresis.
– Hgb A = 97.5%
– Hgb A2 = 2.1%
– Hgb F = 0.6%
• What is your diagnosis of exclusion?

37. Case 8
• Alpha thalassemia with a double gene
deletion.
– No treatment is necessary.
– Anemia is not progressive.
– No other systemic problems.
– Often mistaken for iron deficiency and treated
with iron or for anemia of chronic disease.

38. Case 9
• You are asked to see a 43 year old previously
healthy woman who presented to the ER
complaining of fevers, weakness, and bleeding
from her gums.
• Her only significant past history is a recently
resolved viral syndrome. Her family notes she
has been somewhat confused over the last 24
hours.

39. Case 9
• The ER attending notes:
– The patient to be ill appearing
– T 38.3, HR 123, BP 126/76, RR 26
– Dried blood in the nares and mouth
– Petechiae on lower extremities
– Patient slightly confused.
• Before you arrive in the ER she has a seizure.

40. Case 9
• Labs:
– WBC 5600/mm3, normal differential
– HCT 16.3%
– Hgb 5.3 gm/dL
– Platelets 21,000/mm3
– PT 11 sec
– PTT 29 sec

41. Case 9
• Labs:
– Creatinine 2.0 mg/dL
– LDH 3000 U/L
– Bili 3.2 mg/dL, mostly indirect
– Reticulocyte count 6.2%
– Haptoglobin <10mg/dL
– Urine: 2+ hemoglobin, neg RBC

42. Case 9

43. Case 9
• What is your differential diagnosis based on
the history, physical, labs and blood smear?
• What else could give you a similar blood
smear?

44. Case 9
• You diagnosis TTP based on the classic pentad
and consistent blood smear:
– Microangiopathic hemolytic anemia
– Thrombocytopenia
– Fever
– Renal Failure
– MS changes
• What is the first line treatment of TTP?

45. Case 9
• You begin daily plasma exchange procedures
using FFP as your replacement fluid. Her
mental status improves by the next day. Her
platelet count normalizes and LDH decreases
over the next week.Her anemia slowly
improves as does her renal failure. She is
weaned off plasma exchange and has a single
relapse, which responds to similar therapy.

46. Case 10
• A 67 year old woman with a history of IDDM
and treated hypothyroidism is referred to you
for evaluation of anemia. Her complaints
leading to this diagnosis included weakness,
fatigue, weight loss, and mild numbness in her
feet bilaterally.
• Physical exam was essentially normal except
for mild loss of proprioception in her feet
bilaterally.

47. Case 10
Current Labs: 2 years ago:
How do you interpret these values?

48. Case 10
*Hypersegmented neutrophil, macroovalocytes

49. Case 10
• What tests or procedures do you want to
perform to further evaluate this patient?

50. Case 10
• You diagnose B12 deficiency and prescribe
B12 injections 1000ug weekly x4 then 1000ug
a month indefinitely.
• In 1 month the patient feels remarkably better
and her blood counts have all improved.

51. Case study.
• 21 year man
• Presented with pancytopenia
• Hb 5.0 WBC 2.6,neutrophils 1.1, platelets 45,
MCV 104.
• B12/folate/ferritin were normal.
• Main symptom tiredness
• Examination was unremarkable.

52. Investigations.
• C B C
• Reticulocyte count
• Blood film.
• B12/folate.
• Liver function tests.
• Virology
• Bone marrow aspirate & trephine
• PNH screen.

53. Marrow trephine