1. Hematology and Bleeding Disorders
Lab and MCQs

2. OBJECTIVES: to be able to:
Correlate the results on a CBC laboratory report with the evaluation of a peripheral blood smear.
Identify and distinguish lymphocytes, monocytes, granulocytes, eosinophils, basophils, platelets, and red blood cells.
Understand the differences and the uses of automated and manual differential white blood cell counts.
Distinguish between normochromic and hypochromic red blood cells and understand what hypochromasia means.
Distinguish between normocytic, microcytic, and macrocytic red blood cells and know their significance.
Identify spherocytes and indicate what they mean.
Know what a reticulocyte is, what a reticulocyte count means, and what polychromasia means.

3. CASE 1 Normal peripheral blood smear
A normal complete blood count (CBC) and normal peripheral blood smear are shown.

4. A normal peripheral blood smear is seen here with a normal segmented neutrophil and a lymphocyte.

5. Case 2
History:
A 72-year-old man has had increasing fatigue for the past 5 months. On physical examination there no abnormal findings. Laboratory studies include a CBC with peripheral blood smear.
What this CBC demonstrate?
A CBC demonstrates microcytosis and hypochromia.

6. Peripheral blood smear.
Poikilocytes are abnormally shaped red blood cells
What this smear demonstrate?
Note the poikilocytosis and microcytosis and hypochromia in this peripheral blood smear.

7. Questions How to estimate the red blood cell size?
A normal red blood cell is 2/3 the size of a small lymphocyte, or about the size of (or slightly smaller than) the lymphocyte nucleus. This man's peripheral blood smear shows red blood cells with hypochromasia and microcytosis

8. What is the diagnosis from these findings?
Hypochromic microcytic anemia (from probable iron deficiency).

9. Which of the following tests would be most useful to determine the etiology of this patient's findings? A. Hemoglobin electrophoresis B. Reticulocyte count C. Stool for occult blood D. Vitamin B12 assay E. Bone marrow biopsy
Answer: C This patient most likely has a blood loss anemia, and a colon cancer is a likely source in an older man. Laboratory testing consistent with iron deficiency anemia would include a low serum ferritin and low serum iron with low % saturation.

10. What therapy would you offer this man?
If the anemia from iron deficiency is severe and symptomatic, then transfusion therapy is indicated as immediate intervention to treat the anemia, not the underlying iron deficiency.
For most persons with iron deficiency, the anemia is mild to moderate and can be treated with oral iron therapy. Up to 300 mg per day of ferrous sulfate (20% elemental iron, or 60 mg) for an adult for a period of 6 to 12 months is a standard dose. Oral iron should be taken on an empty stomach, since foods may inhibit iron absorption. Up to 20% of patients may develop abdominal pain, nausea, vomiting, or constipation. Ferrous iron is mainly absorbed in the duodenum and jejunum where the mucosal cells oxidize it to ferric iron that is bound to ferritin. The iron stored in ferritin is slowly released and bound to plasma transferrin for transport to tissues.
Parenteral iron administration may be considered in patients who are unable to tolerate oral iron, who need acute therapy, or who have ongoing iron requirements from persistent blood loss, usually gastrointestinal loss. Intravenous iron dextran has a potential serious complication--anaphylaxis--and must be monitored closely.

11. Excessive iron can be toxic
Excessive iron can be toxic. Iron that is not bound to plasma transferrin can catalyze the formation of free radicals that can cause mitochondrial injury, lipid peroxidation, increased capillary permeability, vasodilation, and intestinal, renal, hepatic, myocardial, and pulmonary toxicity.
Ingestion of 60 mg of elemental iron per kg of body weight can cause systemic toxicity. Generally, this is a greater problem for small children.
The first signs of iron toxicity include vomiting and bloody diarrhea. Systemic effects include lethargy, hypotension, and metabolic acidosis.
Severe iron poisoning can produce seizures, coma, pulmonary edema, vascular collapse, and liver injury with icterus, elevated liver enzymes, increased prothrombin time, and hyperammonemia.

12. CASE 3
History:
A 48-year-old man has become progressively more fatigued at the end of the day. This has been going on for the past 6 months. In the past month he has noted paresthesias with numbness in his hands and feet. On physical examination he has decreased vibration and position sensation in both hands and feet. Laboratory studies include a CBC with peripheral blood smear.

13. What this CBC demonstrate?
A CBC demonstrates megaloblastic changes.

14. Describe his peripheral blood smear findings
His peripheral blood smear shows red blood cells displaying macro-ovalocytosis and neutrophils with hypersegmentation.

15. What is the diagnosis from these findings?
This is a macrocytic (megaloblastic) anemia. The neurologic findings suggest vitamin B12 deficiency (pernicious anemia).

16. A. Hemoglobin electrophoresis B. Reticulocyte count
Which of the following tests would be most useful to determine the etiology for these findings?
A. Hemoglobin electrophoresis
B. Reticulocyte count
C. Stool for occult blood
D. Vitamin B12 assay
E. Bone marrow biopsy
Answer: D Macrocytic anemia could also be caused by a folate deficiency, but the neurologic findings would not be present.

17. How do you explain his neurologic findings?
The B12 deficiency leads to a subacute combined degeneration of the spinal cord (posterior and lateral columns).

18. How do treat his condition?
Most diets contain sufficient cobalamin, which is stored in the liver to provide a buffer against short-term dietary deficiencies. Lacto-ovo-vegetarian diets have minimal cobalamin.
Cobalamin is released from food such as meat products by the action of acid and pepsin in the stomach, and this process is less efficient in the elderly.
Persons with chronic problems absorbing B12 can be given parenteral therapy in the form of intramuscular cyanocobalamin, typically 1000 micrograms of cobalamin per week for 2 months and then 1000 micrograms of cyanocobalamin intramuscularly every month thereafter.
Persons who can still absorb cobalamin can be treated for deficiency with oral replacement therapy consisting of 2 mg of crystalline B12 per day.
Folate deficiency is treated with an oral dose of 1 mg per day. Malabsorbtion may require higher doses of up to 5 mg per day.
Drugs that inhibit DNA synthesis (some chemotherapeutic agents such as hydroxyurea or 5-fluorouracil) and drugs that are folate antagonists such as methotrextate can produce megaloblastic anemia.

19. CASE 4
History:
A 30-year-old woman has the onset of fever, abdominal pain, nausea over the past day. On physical examination her vital signs include temperature 38 C, pulse 102/minute, respirations 20/minute, and blood pressure 95/50 mm Hg. She has scleral icterus. Her spleen tip is palpable, but there is no lymphadenopathy or hepatomegaly. She has Hgb 11.1 g/dL, Hct 28.8%, MCV 77 fL, platelet count 273,400/microliter, and WBC count 8900/microliter. The direct and indirect Coombs tests are negative. A month ago, a CBC showed the following findings:

21. A peripheral blood smear is shown here
A peripheral blood smear is shown here. Compare the size of the RBC's to the lymphocyte nucleus. Describe her peripheral blood findings
The RBC morphology shows small cells that lack central pallor (spherocytes).

22. Polychromasia correlates with reticulocytes
Nucleated red blood cells indicate a significant degree of haemolysis.

23. What is the diagnosis from these findings?
Hereditary spherocytosis.

24. Which of the following is the most likely genetic inheritance pattern for her condition?
A. Autosomal dominant, European ancestry
B. X-linked, Asian ancestry
C. Autosomal recessive, Middle Eastern ancestry
D. Autosomal recessive, West African ancestry
E. Sporadic occurrence
Answer: A

25. Which of the following is most likely to initiate an aplastic crisis in this patient?
A. Quinacrine
B. Parvovirus infection
C. Decreased oxygen tension
D. Exposure to cold
E. Transfusion
Answer: B Parvovirus (sometimes called 'fifth disease') infects RBC precursors and can lead to a temporary shutdown in RBC production. In a person whose marrow is already working at increased production (such as persons with RBC membrane disorders and persons with hemoglobinopathies such as sickle cell anemia), the effect of parvovirus infection is more dramatic than in persons with normal erythropoiesis.

26. How do you explain the appearance of her RBCs?
Hereditary spherocytosis results from mutations in spectrin and/or ankyrin gene.
Spectrin is a cytokeletal membrane protein that aids in maintaining the RBC shape.
This destabilizes the RBC membrane and makes the RBC less deformable and less able to pass through the splenic sinusoids, making it more likely to be trapped or damaged.
The marrow responds by increasing RBC production and releasing more reticulocytes.

27. CASE 5
History:
A 20-year-old African-American man comes to the emergency room because of the sudden onset of severe abdominal pain. On physical examination he has diffuse, severe abdominal tenderness. Bowel sounds are absent. His sclerae appear icteric. A plain film radiograph of the abdomen shows no free air, only dilated loops of bowel. Laboratory studies include a CBC that shows Hgb 4.8 g/dL, Hct 12.8%, MCV 80 fL, platelet count 205,000/microliter, and WBC count 9800/microliter with differential count showing 70 segs, 7 bands, 22 lymphs, and 3 monos, with 12 NRBC's (nucleated red blood cells) per 100 WBC's.

28. Note the shape of the RBC's in this peripheral blood smear.

29. What does the peripheral blood smear show?
Examination of the peripheral smear shows marked poikilocytosis and anisocytosis with numerous sickled erythrocytes.

30. What is the diagnosis from these findings?
Sickle cell anemia (Hgb SS).

31. 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
Answer: A

32. A "crisis" in this patient is most likely to be initiated by which of the following?
A. Quinacrine ingestion
B. Adenovirus infection
C. Decreased oxygen tension
D. Exposure to cold
E. Transfusion therapy
Answer: C This is why people with Hgb SS disease do not live at high elevation.

33. Please, take your pen and answer on the following questions You have 80 seconds to answer each question

34. Q1: A 26-year-old man has the sudden onset of severe abdominal pain
Q1: A 26-year-old man has the sudden onset of severe abdominal pain. On physical examination he is afebrile. He has no lymphadenopathy or splenomegaly. He has right upper quadrant tenderness. His peripheral blood smear is shown here. Which of the following conditions is he most likely to have?
A Epstein-Barr virus infection
B Chronic atrophic gastritis
C Pigmented gallstones
D Hepatitis A infection
E An esophageal web
Pigmented
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35. Q2. A 79-year-old woman has become increasingly lethargic for the past 6 months. On physical examination she is afebrile. Her peripheral blood smear is shown here. Which of the following findings reported on a CBC is most likely to be present in this woman?
A Platelet count of 540,000/microliter
B Mean corpuscular volume of 72 femtoliters
C Hematocrit of 55%
D Mean corpuscular hemoglobin concentration of 36.5 picograms/microliter
E Red cell distribution
width of 9.8%
MCV 72
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36. Q3: A 63-year-old woman has had malaise and nausea for the past 14 months. On physical examination her stool is negative for occult blood. An upper GI endoscopy is performed and reveals loss of gastric rugal folds. Microscopic examination of a gastric biopsy reveals mucosal atrophy. Her Hgb is 7.9 g/dL. Which of the following laboratory findings is most likely to be present in this woman?
A Decreased serum ferritin
B Increased reticulocyte count
C Decreased serum folate
D Increased neutrophil segmentation
E Decreased red cell MCV
Segmentation
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37. Q4: A 30-year-old woman has the sudden onset of fever, abdominal pain, tachycardia, and nausea. On physical examination her vital signs include T 37.9 C, P 90/minute, RR 18/minute, and BP 100/60 mm Hg. Her conjunctivae are icteric. The spleen tip is palpable. Laboratory studies shows Hgb 9.0 g/dL, Hct 27.3%, MCV 99 fL, platelet count 209,500/microliter, and WBC count 6840/microliter. Her reticulocyte count is 0.1%. On microscopic examination of her peripheral blood smear, the RBC's are small and lack central pallor. Which of the following most likely initiated this woman's acute illness?
A Quinacrine use
B Parvovirus infection
C Decreased oxygen tension
D Exposure to cold
E Transfusion therapy
Parvovirus
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38. Q5: A A 72-year-old man has been feeling tired for the past 8 months
Q5: A A 72-year-old man has been feeling tired for the past 8 months. On physical examination there are no abnormal findings. Laboratory studies show Hgb 10.4 g/dL, Hct 30.3%, MCV 72 fL, platelet count 239,000/uL, and WBC count 7500/uL with automated differential count of 70.1% grans, 18.8% lymphs, and 11.1% monos. His total bilirubin is 1.0 mg/dL. Which of the following morphologic findings is most likely to be seen on his peripheral blood smear?
A Fragmentation
B Many nucleated forms
C Microcytosis and hypochromasia
D Spherocytosis
E Howell-Jolly bodies
Microcytosis
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