1. Exam 3
review

2. Three Ways to Get Anemic
Lose blood
Destroy too much blood
Extracorpuscular reasons
Intracorpuscular reasons
Make too little blood
Too few building blocks
Too few erythroblasts
Not enough room
balance between destroying (rbcs normally last about 4 months) and making new ones.

3. We went through 10 anemias (11 if you count warm and cold autoimmune hemolytic anemia separately). The next 11 slides are representative slides for each anemia, one slide per anemia. You might use them to jog your memory to see how much you remember about each type.

4. You see retics in anemia of blood loss, but only after a few days
You see retics in anemia of blood loss, but only after a few days. You see them, too, in any hemolytic process (assuming the bone marrow is intact and able to kick out new red cells).
Reticulocytes

5. Red cells snagged on fibrin strand

6. IgG coats red cells.
Warm AIHA

7. IgM and complement coat red cells.
Cold AIHA

8. What causes the weird shape?
Sickle cell anemia

9. Hemoglobin chain developmentα β γ δ
Patients with alpha thalassemia are missing _____ chains, and patients with beta thal are missing ____ chains.
birth
Hgb F = α2γ2
Hgb A2 = α2δ2
Hgb A = α2β2
Hemoglobin chain development

10. z
Abnormal spectrin leads to loss of surface area. Spleen eats spheres.

11. G6PD deficiency: Heinz bodies
What’s in a Heinz body?
G6PD deficiency: Heinz bodies

12. Iron-deficiency anemia

13. Megaloblastic anemia

14. Empty bone marrow in aplastic anemia

15. Which of the following red cell indices tells you
how much hemoglobin is in an average red cell?
A. RBC
B. Hgb
C. MCHC
D. Hct (hematocrit)
E. MCV
Answer: C. MCHC.
The word for this is “chromasia” - cells are either “normochromic” or “hypochromic.”

16. Complete Blood Count (CBC)
MCV
MCHC
microcytic
normocytic
macrocytic
hypochromic
normochromic

17. What does it mean if a patient’s red cells have a
lot of poikilocytosis?
A. They vary a lot in size
B. They have Heinz bodies
C. They vary a lot in shape
D. They have a lot of hemoglobin
E. They are very immature
Answer: C. They vary a lot in shape.

18. Additional Red Blood Cell Properties
Size variation
Shape
anisocytosis
poikilocytosis

19. Which anemia is characterized by the presence of these cells,
called schistocytes?
A. Microangiopathic hemolytic anemia
B. G6PD deficiency
C. Thalassemia
D. Sickle cell anemia
The answer is A., MAHA.

20. Which anemia is characterized by these inclusions, called Heinz
bodies?
A. Microangiopathic hemolytic anemia
B. G6PD deficiency
C. Thalassemia
D. Sickle cell anemia
The answer is B., G6PD deficiency.

21. What is the defect in this disorder?
A. A point mutation in a beta chain gene
B. A translocation between chromosomes 9 and 22
C. Absence of one or more beta chain genes
D. A membrane defect that renders the cells fragile and non pliable
The answer is A., a point mutation in a beta chain gene.
B would be CML, C refers to thalassemia, and D describes hereditary spherocytosis.

22. A. Iron-deficiency anemia B. Megaloblastic anemia
What is the diagnosis?
A. Iron-deficiency anemia
B. Megaloblastic anemia
C. Hereditary spherocytosis
D. Warm autoimmune hemolytic anemia
E. G6PD deficiency
The answer is B., megaloblastic anemia.
There is a hypersegmented neutrophil present, which is characteristic of megaloblastic anemia. These probably occur as a result of the differing maturation rates of the nucleus and cytoplasm in this anemia. Why they become hypersegmented, who knows.

23. Your healthy, 15-year-old brother was found to have an
abnormality on his blood smear during a routine sports physical for
school. His indices are as follows:
The most likely diagnosis is:
A. Iron-deficiency anemia
B. Thalassemia
C. Megaloblastic anemia
D. Aplastic anemia
E. Acute myeloid leukemia
RBC 7.0 x 1012/L ( ) WBC 10 x 109/L (4-11) Plt 300 x 109/L ( )
Hgb 10 g/dL (12-16) MCV 75 fL(80-100)
The answer is B, thalassemia.
In thalassemia, the MCV is decreased (cells are microcytic) and the RBC is increased.
A is incorrect because in IDA, you would not have an increased RBC (it would be decreased).
C is incorrect because megaloblastic anemia is a macrocytic anemia
D is incorrect because in aplastic anemia, there is a pancytopenia (RBC, WBC and plt are decreased)
E is incorrect because in AML, you’d expect an increased WBC (with lots of blasts), a decreased RBC and a decreased plt.

24. Mature neutrophilia
What’s this called?

25. What’s wrong with this cell? What’s wrong with the patient?
It’s a neutrophil with toxic granulation. Means the patient has an infection. Also, there’s a Dohle body if you look closely.
What’s wrong with this cell?
What’s wrong with the patient?

26. What do these things signify?
Dohle bodies; signify infection (bacterial infection).
What do these things signify?

27. Immature neutrophilia, or left shift.
What’s this called?

28. Leukoerythroblastotic reaction
What is this called?

29. What kind of cell is this?
This a Downey lymphocyte, a special type of reactive lymphocyte. The patient probably has infectious mono - but he/she could have another viral disease too.
What kind of cell is this?
What is most likely wrong with this patient?

30. How would you tell which one is benign?
You could be pretty sure that the one on the right is CML (two basophils in one field! Unheard of! Except in CML). But to really be sure, best thing would be to do cytogenetics to look for the Philadelphia chromosome. Or you could do pcr to look for the mutated bcr-abl gene (formed by the fusion of chromosomes 9 and 22).
How would you tell which one is benign?

31. How could you tell which one was malignant?
You could make a good guess based on the patient’s age (mature benign lymphocytoses happen in kids, for the most part, and CLL happens only in adults). To really find out, you’d have to do flow. If the cells all marked as B cells, and they had CD5 too, then it would be CLL. If the cells were a mixture of B cells and T cells, then it would be a benign process.
How could you tell which one was malignant?

32. Hematologic Malignancies
Leukemias
Acute leukemias
Chronic leukemias
Lymphomas
Hodgkin lymphoma
Non-Hodgkin lymphoma
Plasma cell disorders
Multiple myeloma

33. Hematologic Malignancies
Leukemias
Acute leukemias
Chronic leukemias

34. Hematologic Malignancies
Leukemias
Acute leukemias

36. Acute lymphoblastic leukemia Acute myeloid leukemia

37. Acute leukemia: bone marrow biopsy

39. What is this cell?
It’s a blast of unknown origin. Could be myeloid or lymphoid.

40. It’s a myeloblast. It has to be: it has Auer rods in it.
What is this cell?

41. If this patient has an acute leukemia, what kind is it, most likely?
Probably an AML with a monocytic component - either an M5 (A or B) or an M4.
If this patient has an acute leukemia, what kind is it, most likely?

42. Hematologic Malignancies
Leukemias
Acute leukemias
Chronic leukemias

44. What’s the translocation in this leukemia?
t(9;22) - it’s CML. THREE basophils in one field…plus a neutrophilic leukocytosis with a left shift, maybe one blast but basicallly just a ton of maturing neutrophils.
What’s the translocation in this leukemia?

45. Chronic myelofibrosis
Chronic myelofibrosis. Technically, you couldn’t tell for sure if this was all you had - because there are other things that can make a marrow fibrotic. Some of the other myeloproliferative disorders can end up with a fibrotic marrow. Metastatic carcinoma can do that too. But since we’re talking about leukemias, and since we didn’t get into great detail about all the possible permutations of the different myeloproliferative disorders, it would be safe to say that this is probably chronic myelofibrosis.
What’s this disorder?

46. What disorder is likely in this patient?
Probably chronic myelofibrosis, given our lecture topics! Other things can give you teardrop red cells too (like having a big spleen, or having a fibrotic marrow for other reasons) - so in a real patient, you would not jump to the conclusion that he/she has chronic myelofibrosis based only on this smear.
What disorder is likely in this patient?

48. CLL/SLL.
This 65 year old male is asymptomatic. On a routine CBC he was found to have a WBC of 60,000. His blood smear is shown here. The cells are CD19 positive and CD5 postive. What’s the diagnosis?

49. Hematologic Malignancies
Leukemias
Acute leukemias
Chronic leukemias
Lymphomas
Non-Hodgkin lymphoma
Hodgkin lymphoma

50. Which germinal center is benign?
The one on the left. Those are tingible body macrophages. And if you could look at the cells down there on a higher power, you’d see they’re all different (some big, some little) and there’s mitotic activity - just what you’d expect in a nice germinal center. The nodule on the right is probably not even a germinal center - it’s a round nodule of lymphoma cells. There’s no mantle zone, and no tingible body macrophages. You’d have to see more of the lymph node in real life, of course.
Which germinal center is benign?

51. Mycosis fungoides/Sezary syndrome
Mycosis fungoides/Sezary syndrome. MF (for short) is a T-cell leukemia/lymphoma that loves to go to the skin (many T-cell neoplasms do!). The cells are very convoluted - “cerebriform” is the buzzword you should connect with this disease. Patients get patches, then plaques, then nodules.
This skin biopsy is from a 65 year old male with red skin nodules and cerebriform cells in his blood. What is the diagnosis?

52. ALL B-lineage ALL T-lineage ALL (= B-lymphoblastic lymphoma)
(= T-lymphoblastic lymphoma)

53. What’s the translocation?
t(8;14). This is Burkitt lymphoma (or B-cell ALL). You can tell because of the starry sky pattern! The sky is the tumor cells, and the stars are tingible body macrophages. Wait, didn’t you say there are tingible body macrophages in benign germinal
centers? Why yes, I did. How astute of you. It is true that there are tingible body macrophages in BOTH Burkitt lymphoma and benign germinal centers. That’s because the job of a tingible body macrophage is to clean up debris (that’s the “tingible body” - stainable material - part). So in Burkitt lymphoma, the tingible body macrophages are cleaning up the debris from this rapidly turning over tumor. In benign germinal centers, the tingible body macrophages are cleaning up the debris from the normal, highly-proliferating cells of the germinal center.
So how am I supposed to tell the difference between Burkitt lymphoma and benign germinal centers, then, you might well ask. Here’s how: in Burkitt lymphoma, you have sheets of bad leukemia cells (that’s the sky in the above photo). The cells are diffusely spread out over the whole lymph node (or bone marrow section, as above); they are dark blue, and tightly packed, and they all look very similar. That’s very different from the way normal benign germinal centers look. Germinal centers are part of secondary follicles - so they are pale round nodules that contain cells which look very different from each other…and they have a surrounding darker-staining mantle zone of small, mature lymphocytes (see slide 40).
What’s the translocation?

54. Name the cell and the disease.
Reed-Sternberg cell; Hodgkin lymphoma.
Name the cell and the disease.

55. Hodgkin lymphoma spreads in a contiguous fashion, which makes it easier to treat than non-Hodgkin lymphoma (which skips around).
Hodgkin lymphoma

56. Multiple Myeloma

57. Rouleaux (red cells stacking on top of each other because there’s so much immunoglobulin in the blood that the normal repellant force between the red cells is disrupted)
Multiple Myeloma

58. Serum protein electrophoresis
Immunoglobulins migrate to the gamma region. Nice gentle curve because in normal blood, there are all different kinds (so they migrate to slightly different places on the gel).
Serum protein electrophoresis

59. Serum protein electrophoresis
Big monoclonal gammopathy. Also, normal immunoglobulins are decreased.
Serum protein electrophoresis

60. Pro-Clotting
clot
Three steps to making a clot: blood vessel constriction, platelet plug, fibrin formation.

61. Platelet activation

62. clot Intrinsic Extrinsic Xa prothrombin thrombin fibrinogen fibrin
exposed TF XI
XIa TF
VIIa IX
IXa
VII
VIII
VIIIa X V Va Xa
Yikes.
prothrombin
thrombin
clot
fibrinogen
fibrin

63. SINtrinsic
SEXtrinsic TF
VII IX
VIII X V
thrombin
fibrin
clot

64. Anti-Clotting
fibrinogen
fibrin
clot
FDPs
plasminogen
plasmin
t-PA

65. clot Intrinsic Extrinsic Xa prothrombin thrombin fibrinogen fibrin
TFPI
thrombin
exposed TF XI
XIa
ATIII TF
VIIa IX
IXa
VII
VIII
VIIIa
protein C X V Va Xa
prothrombin
thrombin
clot
fibrinogen
fibrin

68. In DIC you get both bleeding and clotting.
Thrombosis
Hemorrhage

69. TTP (due to deficiency of ADAMTS 13, which means that von Willebrand factor multimers remain large, which isn’t good because platelets love to stick to the huge multimers).

70. Hemolytic Uremic Syndrome
Things you must know
MAHA and thrombocytopenia
Most are related to E. coli infection
Toxin damages endothelium
Treat supportively

71. Idiopathic Thrombocytopenic Purpura
Things you must know
Antiplatelet antibodies coat platelets
Splenic macrophages eat platelets
Diagnosis of exclusion
Steroids or splenectomy

72. clot Intrinsic Extrinsic X thrombin fibrin TF VII IX VIII VIIIa V Va
protein C
In factor V Leiden, the patient’s factor V can’t be turned off (the activated form can’t be cleaved by protein C!). So the patient is at risk for thrombosis.
fibrin
clot