Hematology and Bleeding Disorders

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.
What this smear demonstrate?

• Note the poikilocytosis and microcytosis and
  hypochromia in this peripheral blood smear.

7
Questions

1. 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. 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

• 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?

1. 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.
2. 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.
3. 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.
4. Persons who can still absorb cobalamin can be
   treated for deficiency with oral replacement
   therapy consisting of 2 mg of crystalline B12 per
   day.
5. 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.
6. 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

20
(No Transcript)
21
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
questionsYou have 80 seconds to answer each
question
34

• 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

200
159
158
157
156
155
154
153
152
151
150
149
148
147
146
145
144
143
142
141
140
139
138
137
136
135
134
133
132
131
130
129
128
127
126
125
124
123
122
121
120
119
118
117
116
115
114
113
112
111
110
109
108
107
106
105
104
103
102
101
100
059
058
057
056
055
054
053
052
051
050
049
048
047
046
045
044
043
042
041
040
039
038
037
036
035
034
033
032
031
030
029
028
027
026
025
024
023
022
021
020
019
018
017
016
015
014
013
012
011
010
009
008
007
006
005
004
003
002
001
End
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
200
159
158
157
156
155
154
153
152
151
150
149
148
147
146
145
144
143
142
141
140
139
138
137
136
135
134
133
132
131
130
129
128
127
126
125
124
123
122
121
120
119
118
117
116
115
114
113
112
111
110
109
108
107
106
105
104
103
102
101
100
059
058
057
056
055
054
053
052
051
050
049
048
047
046
045
044
043
042
041
040
039
038
037
036
035
034
033
032
031
030
029
028
027
026
025
024
023
022
021
020
019
018
017
016
015
014
013
012
011
010
009
008
007
006
005
004
003
002
001
End
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
200
159
158
157
156
155
154
153
152
151
150
149
148
147
146
145
144
143
142
141
140
139
138
137
136
135
134
133
132
131
130
129
128
127
126
125
124
123
122
121
120
119
118
117
116
115
114
113
112
111
110
109
108
107
106
105
104
103
102
101
100
059
058
057
056
055
054
053
052
051
050
049
048
047
046
045
044
043
042
041
040
039
038
037
036
035
034
033
032
031
030
029
028
027
026
025
024
023
022
021
020
019
018
017
016
015
014
013
012
011
010
009
008
007
006
005
004
003
002
001
End
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
200
159
158
157
156
155
154
153
152
151
150
149
148
147
146
145
144
143
142
141
140
139
138
137
136
135
134
133
132
131
130
129
128
127
126
125
124
123
122
121
120
119
118
117
116
115
114
113
112
111
110
109
108
107
106
105
104
103
102
101
100
059
058
057
056
055
054
053
052
051
050
049
048
047
046
045
044
043
042
041
040
039
038
037
036
035
034
033
032
031
030
029
028
027
026
025
024
023
022
021
020
019
018
017
016
015
014
013
012
011
010
009
008
007
006
005
004
003
002
001
End
38
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
200
159
158
157
156
155
154
153
152
151
150
149
148
147
146
145
144
143
142
141
140
139
138
137
136
135
134
133
132
131
130
129
128
127
126
125
124
123
122
121
120
119
118
117
116
115
114
113
112
111
110
109
108
107
106
105
104
103
102
101
100
059
058
057
056
055
054
053
052
051
050
049
048
047
046
045
044
043
042
041
040
039
038
037
036
035
034
033
032
031
030
029
028
027
026
025
024
023
022
021
020
019
018
017
016
015
014
013
012
011
010
009
008
007
006
005
004
003
002
001
End