DRAFT Flashcards
(1054 cards)
1
Q
– continuous, regulated process of blood cell production that includes cell renewal, proliferation, differentiation, and maturation.
A
Hematopoiesis
2
Q
Hematopoiesis Types:
A
Primitive hematopoiesis Definitive hematopoiesis
3
Q
Site of hematopoiesis:
A
ribs
sternum
skull
scapula
vertebrae
pelvic bones
proximal ends of the long bones
4
Q
Yolk sac
A
Mesoblastic phase
5
Q
Liver (main), spleen
A
Hepatic phase
6
Q
Bone marrow
A
Myeloid phase
7
Q
Gower I, Gower II, Portland
A
Mesoblastic phase
8
Q
Hb F (major), Hb A1, Hb A2
A
Hepatic phase
9
Q
Hb A1 (major), Hb A2, Hb F
A
Myeloid phase
10
Q
Primitive erythroblasts
A
Mesoblastic phase
11
Q
Erythroblasts Granulocytes Monocytes Megakaryocytes
A
Hepatic phase
12
Q
All blood cells
A
Myeloid phase
13
Q
Start: 19-20th day
End: 8-12th week
A
Mesoblastic phase
14
Q
Start: 5th to 7th week
End: 1st to 2nd week (after birth)
A
Hepatic phase
15
Q
Start: 5th month of gestation *Lifetime
A
Myeloid phase
16
Q
the spleen, liver, and the lymph nodes revert back to produce immature blood cells in certain abnormal conditions where the bone marrow cannot produce sufficient number of hematopoietic cells
A
extramedullary hematopoiesis
17
Q
are frequently noted on physical examination
A
✓ Hepatomegaly and splenomegaly
18
Q
Hematopoietic hormones
A
▪ Erythropoietin
▪ Thrombopoietin
19
Q
− produced by the kidneys (90%) and the liver (10%)
A
▪ Erythropoietin
20
Q
prevents the apoptosis of erythroid precursors
A
▪ Erythropoietin
21
Q
Stimulates Hb synthesis
A
▪ Erythropoietin
22
Q
Serves as differentiation factor causing the CFU-E to differentiate into pronormoblasts
A
▪ Erythropoietin
23
Q
− Also known as mpL kit ligand
A
▪ Thrombopoietin
24
Q
− Synthesized by the liver
A
▪ Thrombopoietin
25
Note: the primary source of erythropoietin among the newborns is the
liver
26
Adult Hematopoietic tissue
▪ Bone marrow ▪ Liver ▪ Spleen
27
− hematopoietically active marrow
Red marrow
28
− consists of developing blood cells and their progenitors
Red marrow
29
− hematopoietically inactive
Yellow marrow
30
− composed primarily of adipocytes
Yellow marrow
31
− under physiologic stress, it will revert back to active marrow
Yellow marrow
32
: the process of replacing the active marrow by adipocytes
Retrogression
33
- the primary site of hematopoiesis during the hepatic phase of hematopoiesis
▪ Liver
34
Responsible for splenic culling/pitting of RBCs
▪ Spleen
35
Removes senescent RBCs Stores
▪ Spleen
36
1/3 of platelets
▪ Spleen
37
▪ Refers to RBC production
Erythropoiesis
38
Erythropoiesis
▪ Occurs in distinct anatomical sites called erythropoietic islands where each island consists of a macrophage surrounded by a cluster of erythroblasts
(suckling pig phenomenon)
39
− a condition where oxygen content decreases within the tissues
▪ Tissue hypoxia
40
− primary stimulus for the production of RBCs
▪ Tissue hypoxia
41
− produces a dramatic increase in the production of EPO
▪ Tissue hypoxia
42
Erythroblastic
Proerythroblast
Basophilic erythroblast
Polychromatophilic erythroblast
Orthochromic erythroblast
Polychromatophilic erythrocyte/Reticulocyte
Erythrocyte
43
Rubriblastic
Rubriblast
Prorubricyte
Rubricyte
Metarubricyte
Polychromatophilic erythrocyte/Reticulocyte
Erythrocyte
44
Normoblastic
Pronormoblast
Basophilic normoblast
Polychromatophilic normoblast
Orthochromic normoblast
Polychromatophilic erythrocyte/Reticulocyte
Erythrocyte
45
RBC Maturation Series:
46
▪ Earliest recognizable RBC precursor
Pronormoblast
47
▪ Fine and uniform chromatin pattern
Pronormoblast
48
▪ It takes approximately 3 days for the pronormoblast to develop into orthochromic normoblast
Pronormoblast
49
▪ Nuclear chromatin becomes more clumped
Basophilic normoblast
50
▪ Last stage with nucleolus (last stage of RNA synthesis)
Basophilic normoblast
51
▪ Note: Hb is produced in this stage but not detected in light microscopy but in EM (Rodak)
Basophilic normoblast
52
▪ Hb production begins during this stage
Polychromatophilic normoblast
53
▪ Characterized by muddy, light gray appearance of cell due to variable amounts of pink coloration mixed w/ basophilia
Polychromatophilic normoblast
54
▪ Last stage capable of mitosis
Polychromatophilic normoblast
55
▪ Nucleus is tightly condensed and described as pyknotic
Orthochromic normoblast
56
▪ Last stage w/ nucleus
Orthochromic normoblast
57
▪ Part of this stage occurs in the bone marrow (2 days), and the later part of this stage takes place in the circulation (1 day)
Polychromatophilic erythrocyte
58
▪ Anucleate
Polychromatophilic erythrocyte
59
▪ When stained with supravital stain = reticulocyte
Polychromatophilic erythrocyte
60
▪ Last stage capable of Hb synthesis
Polychromatophilic erythrocyte
61
Earliest recognizable precursor
Pronormoblast/Proerythroblast/Rubriblast
62
Last stage capable of mitosis
Polychromatophilic normoblast/Polychromatophilic erythroblast/Rubricyte
63
Last stage with a nucleolus
Basophilic normoblast/Prorubricyte
64
Last stage with nucleus
Orthochromic normoblast/Metarubricyte
65
Last stage that can synthesize hemoglobin
Reticulocyte
66
Caused by increased number of reticulocytes that are prematurely released from the bone marrow under the stimulus of EPO because of certain conditions (e.g., hypoxia, acute bleeding)
Stress or shift retics
67
An elevated reticulocyte count accompanied w/ a shortened RBC survival
Polychromatophilia/Reticulocytosis
68
▪ Anaerobic glycolysis
Embden-Meyerhof pathway
69
▪ Supplies 90-95% ATP
Embden-Meyerhof pathway
70
▪ G6PD and glutathione are generated in this pathway
Hexose Monophosphate Shunt
71
▪ Purpose: prevents oxidative denaturation of hemoglobin
Hexose Monophosphate Shunt
72
▪ Maintains the iron present in the Hb in a functional reduced state (Ferrous iron) for oxygen transport
Methemoglobin Reductase pathway
73
▪ Generates 2,3-DPG
Rapoport-Luebering shunt
74
▪ Alcohol intoxication
Acanthocyte Thorny cells Spur cell Spike cell
75
▪ PK deficiency
Acanthocyte Thorny cells Spur cell Spike cell
76
▪ Congenital abetalipoproteinemia (neuroacanthocytosis)
Acanthocyte Thorny cells Spur cell Spike cell
77
▪ Severe liver disease (spur cell anemia)
Acanthocyte Thorny cells Spur cell Spike cell
78
▪ Vitamin E deficiency
Acanthocyte Thorny cells Spur cell Spike cell
79
▪ Lipid metabolism disorder
Acanthocyte Thorny cells Spur cell Spike cell
80
▪ Hereditary stomatocytosis
Stomatocytes Mouth cell
81
▪ Electrolyte imbalance
Stomatocytes Mouth cell
82
▪ Liver disease, alcoholism
Stomatocytes Mouth cell
83
▪ Rh null syndrome
Stomatocytes Mouth cell
84
▪ Hydroxyurea therapy
Stomatocytes Mouth cell
85
▪ Hemoglobinopathies (Hb CC, Hb SS, Hb SC)
Target cells Codocyte Mexican hat cell Platycyte Leptocyte Greek helmet cell Bull’s eye cell
86
▪ Liver disease (flattened surface)
Target cells Codocyte Mexican hat cell Platycyte Leptocyte Greek helmet cell Bull’s eye cell
87
▪ MDS
Ovalocytes/Elliptocytes Egg shape
88
▪ Thalassemia
Ovalocytes/Elliptocytes Egg shape
89
▪ Megaloblastic process
Ovalocytes/Elliptocytes Egg shape
90
▪ IDA
Ovalocytes/Elliptocytes Pencil shape
91
▪ Hereditary elliptocytosis
Ovalocytes/Elliptocytes Pencil shape
92
▪ Idiopathic myelofibrosis
Ovalocytes/Elliptocytes Pencil shape
93
▪ associated with hemolytic process
Spherocytes Bronze cell
94
▪ ABO HDN
Spherocytes Bronze cell
95
▪ Immune hemolytic anemia
Spherocytes Bronze cell
96
▪ Hereditary spherocytosis
Spherocytes Bronze cell
97
▪ Severe burns
Spherocytes Bronze cell
98
▪ Others: normal aging process, storage phenomenon
Spherocytes Bronze cell
99
▪ Artifact
Echinocytes (Evenly distributed uniformly sized blunt)
100
▪ Seen in old specimen
Echinocytes (Evenly distributed uniformly sized blunt)
101
▪ Associated w/ renal insufficiency
Burr cells (Irregularly sized and unevenly spaced spicules)
102
▪ Dehydration
Burr cells (Irregularly sized and unevenly spaced spicules)
103
▪ Azotemia
Burr cells (Irregularly sized and unevenly spaced spicules)
104
▪ Hallmark of hemolytic anemia
Schistocytes Schizocytes Helmet cells Triangular cells Keratocytes
105
▪ MAHA (DIC, TTP, HUS)
Schistocytes Schizocytes Helmet cells Triangular cells Keratocytes
106
▪ Exposure of RBCs to heat or mechanical trauma
Schistocytes Schizocytes Helmet cells Triangular cells Keratocytes
107
▪ Prosthetic heart valve
Schistocytes Schizocytes Helmet cells Triangular cells Keratocytes
108
▪ Clostridial infection
Schistocytes Schizocytes Helmet cells Triangular cells Keratocytes
109
▪ Removal of Heinz bodies
Keratocytes Bite cell Degmacyte Horned cell
110
▪ Seen in G6PD deficiency
Keratocytes Bite cell Degmacyte Horned cell
111
▪ Overt hemolysis
Semilunar bodies
112
▪ Associated with malaria
Semilunar bodies
113
▪ Myelofibrosis w/ myeloid metaplasia
Teardrop cells Dacryocytes
114
▪ Myelophthisic anemia
Teardrop cells Dacryocytes
115
▪ Pernicious anemia
Teardrop cells Dacryocytes
116
▪ Beta-Thalassemia
Teardrop cells Dacryocytes
117
▪ Hypersplenism
Teardrop cells Dacryocytes
118
▪ Severe burns
Pyropoikilocytes
119
▪ Hereditary pyropoikilocytosis
Pyropoikilocytes
120
▪ Sickle cell anemia
Drepanocyte Sickle cell
121
▪ Hb SC disease
Drepanocyte Sickle cell
122
▪ Hb C disease
Folded cell Biscuit cell
123
▪ Hb SC disease
Folded cell Biscuit cell
124
Small round reddish-blue fragments of nucleus
Howell-Jolly bodies
125
(+) Feulgen stain
Howell-Jolly bodies
126
DNA
Howell-Jolly bodies
127
Accelerated or abnormal erythropoiesis
Megaloblastic anemia
Alcoholism
Howell-Jolly bodies
128
Reddish violet, thin ringlike, figure of eight, loop-shaped appearance
Cabot rings
129
Mitotic spindle
Cabot rings
130
Megaloblastic anemia
Lead poisoning
Homozygous thalassemia
Severe anemia
Cabot rings
131
Small faint basophilic coccoid bodies near the periphery of RBCs
Pappenheimer bodies (Wright’s stain)
Siderotic granules (Prussian blue)
132
Iron
Pappenheimer bodies (Wright’s stain)
Siderotic granules (Prussian blue)
133
Refractory anemia
Sideroblastic anemia
Iron overload (hemosiderosis, hemochromatosis)
Thalassemia
Hemoglobinopathies
Pappenheimer bodies (Wright’s stain)
Siderotic granules (Prussian blue)
134
Multiple, uniform, evenly distributed dark blue granules
Basophilic stippling
135
RNA
Basophilic stippling
136
▪ Megaloblastic anemia
▪ Thalassemia
▪ Hemoglobinopathies
▪ Alcoholism
▪ Pyrimidine-5nucleotidase deficiency
Basophilic stippling Fine
137
▪ Lead poisoning
Basophilic stippling Coarse
138
Single or multiple purplish inclusions on the RBC periphery
Heinz bodies
139
Supravital stains: CV, BCB
Heinz bodies
140
Precipitated Hb
Heinz bodies
141
G6PD deficiency (favism)
Naphthalene ball ingestion
Hemoglobinopathies
Thalassemia major
Sulfonamides
Hb Koln and Hb Zurich
Post-splenectomy
Heinz bodies
142
Small-greenish blue
Hb H inclusions
143
“Pitted gold ball appearance”
Hb H inclusions
144
Supravital stain: BCB
Hb H inclusions
145
Fingerlike or quartz like crystal of dense Hb protruding from the RBC membrane
Hb SC crystal
146
Hexagonal crystal of dense Hb
Hb C crystal
147
Also known as hemozoin/hematin
Malarial inclusions
148
Plasmodium spp.
Malarial inclusions
149
Malaria
Malarial inclusions
150
Resembles maltese cross/tetrads
Babesia inclusion
151
Babesia spp.
Babesia inclusion
152
Babesiosis/Piroplasmosis
Babesia inclusion
153
− Macrophage-mediated hemolysis
Extravascular hemolysis
154
− Occurs in the spleen
Extravascular hemolysis
155
− 90% of RBCs are destroyed
Extravascular hemolysis
156
− Mechanical hemolysis
Intravascular hemolysis
157
− Occurs within the lumen of blood vessels
Intravascular hemolysis
158
− Extremely damaged cells are being destroyed within the circulation before they reach the liver or the spleen
Intravascular hemolysis
159
− 10% of RBCs are destroyed
Intravascular hemolysis
160
− Removal of senescent and damaged red blood cells in the spleen
▪ Splenic culling
161
▪− Removal of RBC inclusion bodies in the spleen
Splenic pitting
162
NOTE: when red blood cells are destroyed, only the [?]are recycled for reuse
iron and globin chains
163
▪ Function: to transport oxygen to the tissue and carbon dioxide from tissues to the lungs
Hemoglobin
164
Hemoglobin Composition:
4 heme
4 globin
165
– consists of protoporphyrin IX and ferrous iron
4 heme
166
– consists of 2 identical pairs of unlike polypeptide chains
4 globin
167
✓ every heme group is capable of carrying [?] of oxygen, therefore each Hb molecule is able to transport [?] of oxygen
1 mole
4 moles
168
✓ 1 gram Hb = can carry [?] of oxygen
1.34 mL
169
✓ 1 gram Hb = can carry [?] of iron
3.47 mg
170
✓ there are 4 pyrrole rings for every [?] of iron
1 molecule
171
: occurs in the mitochondria
▪ Heme synthesis
172
: occurs in the ribosomes
▪ Globin synthesis
173
Alpha
141
174
Zeta
Beta
Gamma
Delta
Epsilon
146
175
Alpha
Zeta
Ch 16
176
Beta
Gamma
Delta
Epsilon
Ch 11
177
2 alpha, 2 beta
A1
178
>95%
A1
179
Predominant Hb among the adults
A1
180
2 alpha, 2 delta
A2
181
<3%
A2
182
2 alpha, 2 gamma
F
183
1-2%
F
184
Predominant Hb during the hepatic phase
F
185
Major Hb of newborn
F
186
Embryonal hemoglobin
187
2 zeta, 2 epsilon
Gower I
188
2 alpha, 2 epsilon
Gower II
189
2 zeta, 2 gamma
Portland
190
Cherry red
Carboxyhemoglobin
191
Chocolate brown
Methemoglobin
192
Mauve lavender
Sulfhemoglobin
193
Reversible
Carboxyhemoglobin Methemoglobin
194
Not Reversible
Sulfhemoglobin
195
Hb bounded with CO
Carboxyhemoglobin
196
Hb that contains iron in oxidized or ferric state (Fe3+)
Methemoglobin
197
Hb bounded with sulfur
Sulfhemoglobin
198
The affinity of hemoglobin to CO is 200 times greater than oxygen
Carboxyhemoglobin
199
Cannot transport oxygen
Methemoglobin
200
Once formed, it will stay in the RBC during its entire 120day lifespan
Sulfhemoglobin
201
Associated with C. perfringens infection
Sulfhemoglobin
202
Formation is caused by oxidizing drugs (acetanilid, phenacetin, and sulfonamides)
Sulfhemoglobin
203
▪ Graphically describe the relationship between oxygen content and partial pressure of oxygen
Oxygen Dissociation Curve
204
▪ Shape of the curve:
sigmoid (affected by 2,3-DPG and oxygen)
205
(Hb won’t let go its oxygen)
Increase in oxygen affinity – hemoglobin has increased affinity for oxygen
206
(Hb releases oxygen)
Decrease in oxygen affinity – hemoglobin has decreased affinity for oxygen
207
– increased oxygen affinity
▪ Shift to the left
208
– decreased oxygen affinity
▪ Shift to the right
209
– hemoglobin’s affinity for oxygen is influenced by pH
▪ Bohr effect
210
– hemoglobin’s affinity for oxygen is influenced by carbon dioxide
▪ Haldane effect
211
Carbon Dioxide
Increased:
Decreased:
shift to the R ; shift to the L
212
pH
Increased:
Decreased:
shift to the L ; shift to the R
213
2,3-DPG
Increased:
Decreased:
shift to the R ; shift to the L
214
Exercise
Increased:
shift to the R (due to lactic acid)
215
Temperature
Increased:
Decreased:
shift to the R ; shift to the L
216
Hb F:
shift to the L
217
Hb Chesapeake:
shift to the L
218
Hb Kansas:
shift to the R
219
▪ Together with protoporphrin IX, [?] is important for the synthesis of heme
iron
220
– functional, absorbable form in the intestine
▪ Ferrous iron
221
▪ Normal adult iron level – approximately [?] (60% in the circulation; 40% in the storage form)
400 mg
222
▪ Storage form of iron
o – short-term storage form of iron
o – long-term storage form of iron
Ferritin
Hemosiderin
223
o Also known as siderophilin
▪ Transferrin
224
o Transport protein of iron
▪ Transferrin
225
o Produced by the liver
▪ Hepcidin
226
o Negative regulator of intestinal iron absorption
▪ Hepcidin
227
o Suppresses the release of iron from macrophage
▪ Hepcidin
228
o Plays an important role in anemia of chronic inflammation
▪ Hepcidin
229
▪ Storage site of iron in the body
o Liver (major) o Bone marrow o Spleen
230
▪ Main function: primary defense against foreign invaders such as bacteria, viruses and other foreign antigens
White blood cells
231
White blood cells Compartments in the body:
bone marrow, peripheral blood, tissues
232
: most valuable and reliable criterion for deciding whether a cell is mature or immature
Nuclear chromatin pattern
233
According to granularity
234
According to segmentation
235
According to function
236
Granulocytes
Neutrophil Basophil Eosinophil
237
Agranulocytes
Monocyte Lymphocyte
238
Polymorphonuclear cells
Neutrophil Basophil Eosinophil
239
Mononuclear cells
Monocyte Lymphocyte
240
Phagocytes
Neutrophil Monocyte Eosinophil
241
Immunocytes
Lymphocyte
242
▪ Earliest recognizable blast
Myeloblast
243
▪ No visible granules
Myeloblast
244
▪ The nucleus is made up of a smooth, delicate, uniformly distributed chromatin pattern (lacy chromatin pattern)
Myeloblast
245
▪ First appearance of primary granules (azurophilic/non-specific granules)
Promyelocyte
246
▪ Appearance of secondary or specific granules
Myelocyte
247
▪ Dawn of neutrophilia
Myelocyte
248
▪ Also known as Juvenile cells
Metamyelocyte
249
▪ Appearance of tertiary granules
Metamyelocyte
250
▪ Nucleus: kidney bean or peanut shaped
Metamyelocyte
251
▪ Indentation of the nucleus: <50% of the width of the nucleus
Metamyelocyte
252
▪ Also known as Stab cell/Staff cell
Band cell
253
▪ Appearance of secretory granules
Band cell
254
▪ Nucleus: sausage-shaped
Band cell
255
▪ Indentation of the nucleus: >50% of the width of the nucleus
Band cell
256
▪ First immature WBC to be released in the circulation
Band cell
257
▪ Youngest cell in the granulocytic series to normally appear in the peripheral blood
Band cell
258
▪ Most common WBC in normal peripheral blood
Neutrophil
259
Neutrophil Two forms in the peripheral blood:
Segmenters and Bands
260
Neutrophil Lifespan:
o 9-10 days (Steininger)
o 5 days (Brown)
261
o Tissue neutrophil
Ferrata cell
262
o Associated with subacute bacterial endocarditis
Ferrata cell
263
: o Described as drumstick
▪ Barr body
264
o Described as drumstick
▪ Barr body
265
o Represents the second X chromosome in females and may be seen in 2-3% of the neutrophils in females
▪ Barr body
266
Pools of neutrophils in the Bone marrow:
Mitotic/Proliferating pool
Storage/Maturation pool
267
− Myeloblasts, Promyelocytes, Myelocytes
Mitotic/Proliferating pool
268
− Cells undergoing cell division
Mitotic/Proliferating pool
269
− Metamyelocytes, Bands, Segmented neutrophils
Storage/Maturation pool
270
− Cells no longer undergoing cell division but progressively maturing
Storage/Maturation pool
271
o Pools of neutrophils in the circulation:
Circulating pool (50%)
Marginating pool (50%)
272
Azurophilic/nonspecific granules
Primary granules
273
Produced by Promyelocytes
Primary granules
274
Primary granules:
▪ MPO
▪ Cathepsins
▪ Acid beta-glycerophosphatase
▪ Defensins
▪ Elastase
▪ Proteinase-3
275
Specific granules
Secondary granules
276
Produced by Myelocyte
Secondary granules
277
Secondary granules:
▪ Lactoferrin
▪ Collagenase
▪ Gelatinase
▪ beta-2 microglobulin
▪ Lipocalin
278
Produced by metamyelocyte
Tertiary granules
279
▪ Gelatinase
▪ Collagenase
▪ Lysozyme
▪ Acetyltransferase
▪ Beta-2 microglobulin
Tertiary granules
280
Also known as secretory vesicles
Secretory granules
281
Produced by Band cell
Secretory granules
282
Secretory granules:
▪ ALP
▪ Vesicle-associated membrane-2
▪ CD13, CD10, CD14, CD16, CD18
283
▪ Plays a major role in defense against parasitic invasion and in hypersensitivity reaction
Eosinophil
284
▪ Eosinophil Important products:
MBP and Charcot-Leyden crystals
285
– an arginine-rich protein that plays an important role in the eosinophil’s ability to damage parasites
▪ Major Basic Protein
286
: − Hexagonal pyramidal crystals
▪ Charcot-Leyden crystals
287
− Found in the nasal mucus of patients with allergic asthma, pleural fluid of patients w/ pulmonary eosinophilic infiltrates, and stool of patients w/ parasitic infections
▪ Charcot-Leyden crystals
288
▪ Mediator of Immediate hypersensitivity reaction
Basophil
289
cells have specific receptor for IgE
▪ Basophils and mast
290
▪ Basophils Important products:
Histamine and Heparin
291
Main function: phagocytosis
▪ Monocyte
292
Slightly immature cells whose ultimate goal is to enter the tissues and mature into macrophages
▪ Monocyte
293
Size: 15-20 um
▪ Monocyte
294
o Chromatin pattern: lacelike
Monocyte
295
o Nucleus: horseshoe or tulip shape
Monocyte
296
o Cytoplasm: blue-gray with fine azure granules often referred to as azure dust or a ground glass appearance
Monocyte
297
▪ Monocyte Maturation series:
monoblast → promonocyte → monocyte → macrophage
298
o There is no storage pool in the bone marrow
Monocyte
299
o Proliferation in the bone marrow: 55 hours
Monocyte
300
spends about 12 hours in the peripheral blood before going to the tissues
Monocyte
301
o The marginal pool in the peripheral blood is 3.5 times greater than the circulating pool
Monocyte
302
▪ Main function: immune response
Lymphocyte
303
▪ Serves as a “marker cell” for estimating the size of surrounding cells
Lymphocyte
304
– most small lymphocytes
▪ T-lymphocytes
305
– most large lymphocytes
▪ B-lymphocytes
306
– third population of lymphocytes
▪ NK cells
307
▪ Lifespan: several months to years
Lymphocyte
308
▪ Mononuclear cells with round or oval and smooth or irregular margins
Plasma cells
309
▪ The eccentrically located nucleus is composed of blocks of heterochromatin resembling a tortoise shell
Plasma cells
310
▪ Nucleus exhibits a cartwheel pattern
Plasma cells
311
▪ The area next to the nucleus containing the Golgi apparatus is unstained (Hof)
Plasma cells
312
: located on the cytoplasm that may contain round, discrete globules that appear paleclue, or occasionally red which contains immunoglobulins
▪ Russel bodies
313
– cluster of Russel bodies
▪ Morula cell/grape cell/Mott cells
314
Associated with increased RBC count, hemoglobin, hematocrit
Polycythemia
315
May be classified as relative or absolute
Polycythemia
316
NOTE: A hematocrit value of [?] in men and [?] in
women is often diagnostic of Polycythemia
>52%
>50%
317
Refers to true increase in red cell mass
ABSOLUTE POLYCYTHEMIA
318
– due to bone marrow defect
▪ Primary Polycythemia
319
Refers to true increase in red cell mass
ABSOLUTE POLYCYTHEMIA
320
– due to kidney defect
▪ Secondary Polycythemia
321
▪ Chronic myeloproliferative disorder
Absolute Primary Polycythemia
322
▪ Due to mutation of JAK2 gene
Absolute Primary Polycythemia
323
▪ Pancytosis: absolute increased in RBC, WBC, platelets Absolute
Absolute Primary Polycythemia
324
▪ Panhyperplasia: the bone marrow is hypercellular showing an overall increase
Absolute Primary Polycythemia
325
Characterized by hyperviscous blood (due to increased RBCs)
Absolute Primary Polycythemia
326
▪ Prone to IDA (therapeutic phlebotomy)
Absolute Primary Polycythemia
327
▪ Hallmark of PV:
plethora
328
Absolute Primary Polycythemia Clinical features:
▪ ESR is decreased
▪ EPO is decreased
▪ LAP is increased
▪ Dacryocyte in PBS is a common finding
329
▪ Due to increased level of EPO
Absolute Secondary Polycythemia
330
▪ Residence at high altitudes
Absolute Secondary Polycythemia
331
▪ Chronic pulmonary disease
▪
Absolute Secondary Polycythemia
332
CHF
Absolute Secondary Polycythemia
333
▪ Heavy smoking
Absolute Secondary Polycythemia
334
▪ Methemoglobinemia
Absolute Secondary Polycythemia
335
▪ Tumor of the kidneys
Absolute Secondary Polycythemia
336
▪ Due to decrease in the fluid (plasma) portion of the blood that gives the appearance of an increased red cell mass in relation to total blood volume rather than a true increase in red cell mass
RELATIVE POLYCYTHEMIA
337
▪ NOT a hematologic disorder
RELATIVE POLYCYTHEMIA
338
▪ Actual number of RBC in the blood is not increased, but the number of cells per unit volume of blood is increased
RELATIVE POLYCYTHEMIA
339
1. Dehydration secondary to diarrhea, vomiting, excessive sweating, burns, anaphylaxis, and diuretics
RELATIVE POLYCYTHEMIA
340
2. Anxiety and stress
RELATIVE POLYCYTHEMIA
341
3. Tobacco smoking
RELATIVE POLYCYTHEMIA
342
4. Gaisbock’s syndrome
RELATIVE POLYCYTHEMIA
343
− also known as Spurious polycythemia or Stress syndrome
Gaisbock’s syndrome
344
− Associated with smoking, CVD, hypertension, and diuretic therapy
Gaisbock’s syndrome
345
A decrease in red blood cells, hemoglobin, and hematocrit below the reference range for healthy individuals of the same age, sex, and race, under similar environmental conditions
Anemia
346
Mechanisms of Anemia
A. Due to Production B. Due to Destruction
347
A. Due to Production
▪ Ineffective erythropoiesis
▪ Insufficient erythropoiesis
348
B. Due to Destruction
▪ Intrinsic defects in the RBC membrane, enzyme, or hemoglobin
▪ Extrinsic causes such as antibody-mediated process, mechanical fragmentation, or infectionrelated
349
Test for Accelerated RBC destruction
1. Lactate dehydrogenase
2. Indirect bilirubin
3. Chromium Radioisotope: the reference method for RBC survival studies by ICSH
350
Laboratory Diagnosis of Anemia
1. CBC and RBC indices
2. Reticulocyte count
3. Peripheral Blood Smear Examination
4. Bone Marrow Examination
5. H/H
351
– serves as an important tool to assess the bone marrow’s ability to increase RBC production in response to anemia
2. Reticulocyte count
352
– indicated for a patient with an unexplained anemia, fever of unknown origin, or suspected hematologic malignancy
4. Bone Marrow Examination
353
– widely used tests for anemia
5. H/H
354
▪ A condition in which there is a peripheral blood pancytopenia
Aplastic Anemia
355
▪ Pancytopenia: dec RBC, WBC, Platelets, Reticulocytes
Aplastic Anemia
356
▪ Lymphocytes are the predominant cell in the peripheral blood (less affected)
Aplastic Anemia
357
Clinical Features:
▪ Bleeding
▪ Infection
▪ Anemia
▪ No splenomegaly
▪ No lymphadenopathy
Aplastic Anemia
358
▪ Genetic defect
Aplastic Anemia
359
▪ Ionizing radiation
Aplastic Anemia
360
▪ Chemicals
Aplastic Anemia
361
▪ Parvovirus B19
Aplastic Anemia
362
▪ Benzene
Aplastic Anemia
363
▪ Chloramphenicol (most common cause)
Aplastic Anemia
364
▪ Trinitrotoluene
Aplastic Anemia
365
▪ Arsenic
Aplastic Anemia
366
▪ Fanconi Anemia
Hereditary Aplastic Anemia
367
▪ Diamond-Blackfan anemia
Hereditary Aplastic Anemia
368
▪ Chronic Kidney Disease
Acquired Aplastic Anemia
369
▪ Myelophthisic anemia
Acquired Aplastic Anemia
370
▪ Also known as Congenital Aplastic Anemia
Fanconi Anemia
371
▪ Autosomal recessive
Fanconi Anemia
372
▪ Pancytopenia
Fanconi Anemia
373
▪ Normocytic anemia
Fanconi Anemia
374
▪ Low birth weight (<2,500 gram)
Fanconi Anemia
375
▪ Skin hyperpigmentation (café au lait spots)
Fanconi Anemia
376
▪ Short stature
Fanconi Anemia
377
▪ Renal malformations
Fanconi Anemia
378
▪ Microcephaly
Fanconi Anemia
379
▪ Mental retardation
Fanconi Anemia
380
▪ Hypogonadism
Fanconi Anemia
381
▪ Strabismus
Fanconi Anemia
382
▪ Also known as Congenital Pure Red Cell Aplasia
Diamond-Blackfan Anemia
383
▪ Defective/reduced CFU-E
Diamond-Blackfan Anemia
384
▪ Caused by a mutation in RPS19 gene; idiopathic (Steininger)
Diamond-Blackfan Anemia
385
▪ Normocytic anemia w/ normal leukocyte and platelet count and a marked decrease in marrow erythroblasts
Diamond-Blackfan Anemia
386
▪ Also known as leucoerythroblastic anemia
Myelophthisic Anemia
387
▪ Common finding in patients with carcinoma
Myelophthisic Anemia
388
▪ Results when the bone marrow is replaced by abnormal cells such as metastatic tumor cells, leukemic cells, fibroblasts, and inflammatory cells (found in miliary TB and fungal infections)
Myelophthisic Anemia
389
= invasion of abnormal cell
▪ Myelophthisis
390
Myelophthisic Anemia Lab Picture:
▪ Normocytic anemia
391
▪ Normocytic anemia
▪ Reticulocyte, Teardrop cells, nRBCs, immature myeloid cells in the peripheral blood, presence of abnormal cells in the bone marrow Anemia of Chronic Kidney Disease
▪ Anemia is due to inadequate production of EPO by the kidneys
▪ EPO, presence of Burr cells (Uremia)
Myelophthisic Anemia
392
▪ dec Reticulocyte, Teardrop cells, nRBCs, immature myeloid cells in the peripheral blood, presence of abnormal cells in the bone marrow
Myelophthisic Anemia
393
▪ Anemia is due to inadequate production of EPO by the kidneys
Anemia of Chronic Kidney Disease
394
▪ dec EPO, presence of Burr cells (Uremia)
Anemia of Chronic Kidney Disease
395
▪ Impaired DNA synthesis affects all rapidly dividing cells of the body, including the skin, GIT, and bone marrow
ANEMIA OF ABNORMAL NUCLEAR DEVELOPMENT
396
▪ Vitamin B12 and Folate are essential in DNA synthesis
ANEMIA OF ABNORMAL NUCLEAR DEVELOPMENT
397
▪ Deficiencies of either vitamin impair DNA replication, halt cell division, and increase apoptosis, which results in ineffective erythropoiesis and megaloblastic morphology
ANEMIA OF ABNORMAL NUCLEAR DEVELOPMENT
398
▪ Dietary source: meat
Vitamin B12 Deficiency
399
▪ The liver stores adequate amount of Vitamin B12 for several years if no more is ingested
Vitamin B12 Deficiency
400
: forms a protective complex with Vitamin B12 that is transported down the GIT
▪ Intrinsic factor
401
▪ Vitamin B12 is maximally absorbed in the
ileum
402
Vitamin B12 Deficiency Causes:
▪ Inadequate intake
▪ Increased need
▪ Impaired absorption
403
▪ Autoimmune disorder characterized by impaired absorption of vitamin B12 due to lack of IF
Pernicious Anemia
404
▪ Most common form of Vitamin B12 deficiency
Pernicious Anemia
405
▪ More common in people with blood type A
Pernicious Anemia
406
▪ The organism has the ability to split vitamin B12 from IF, rendering the vitamin unavailable for host absorption
D. latum infection
407
▪ Portions of the intestines becomes stenotic as a result of surgery or inflammation
Blind loop syndrome
408
▪ These sites can become overgrown with intestinal bacteria that compete effectively with the host for available vitamin B12
Blind loop syndrome
409
▪ Causes Vitamin B12 malabsorption
Imerslund-Grasbeck syndrome
410
▪ Not related to IF deficiency/defect
Imerslund-Grasbeck syndrome
411
▪ Defect in cubilin/amnionless receptor (Henry’s)
Imerslund-Grasbeck syndrome
412
▪ Provides a measure of body’s ability to secrete viable IF and absorb orally administered 57Co-labeled B12 in the ileum
Schilling Test (Classical Test)
413
Schilling Test (Classical Test) Specimen requirement
▪ Fasting specimen
▪ A 24-hour urine collection is begun immediately upon administration of the labeled B12 by mouth Interpretation
414
Schilling Test (Classical Test)
Phase 1 (radiolabeled B12 w/o IF)
▪ >7% of labeled B12 is excreted =
▪ <7% of labeled B12 is excreted =
Dietary B12 deficiency
Proceed to Phase 2
415
Schilling Test (Classical Test)
Phase 2 (radiolabeled B12 w/IF)
▪ >7% of labeled B12 is excreted =
▪ <7% of labeled B12 is excreted =
Pernicious anemia
Malabsorption syndrome (Tropical Sprue, D. latum, Blind Loop syndrome)
416
Sources of Folate:
green leafy vegetables
417
▪ Inadequate intake
Folate Deficiency
418
▪ Increased need
Folate Deficiency
419
▪ Impaired absorption
Folate Deficiency
420
▪ Excessive loss due to renal dialysis
Folate Deficiency
421
▪ Alcohol (alcohol interferes with folate metabolism)
Folate Deficiency
422
▪ Lacks hypersegmented neutrophil and oval macrocytes in the peripheral blood and megaloblasts in the bone marrow
Macrocytic Non-Megaloblastic Anemia
423
Macrocytic Non-Megaloblastic Anemia ▪ Physiologic cause:
newborn
424
Macrocytic Non-Megaloblastic Anemia ▪ Pathologic cause:
liver disease, chronic alcoholism, bone marrow failure
425
CBC Folate deficiency Vitamin B12 deficiency
Pancytopenia ([?]RBC, WBC, Platelet count)
[?] MCV, MCH
[?] RDW
[?] Reticulocyte count
Dec
Inc
Inc
Dec
426
PBS examination Folate deficiency Vitamin B12 deficiency:
Macroovalocytosis
Teardrop cells
nRBCs
Hypersegmented neutrophils
427
Bone marrow examination Folate deficiency Vitamin B12 deficiency:
Presence of megaloblasts
Inc M:E ratio
Hypercellular bone marrow
428
(+) anti-parietal cells, anti-IF
Vitamin B12 deficiency
429
Achlorhydria
Vitamin B12 deficiency
430
(+) D. latum eggs
Vitamin B12 deficiency
431
Gastric analysis NORMAL
Folate deficiency
432
Anemia of Iron and Heme Metabolism Mechanisms:
1. Deficiency of[?]
2. Defective release of[?] from macrophages (Anemia of Chronic Inflammation)
3. Defective utilization of[?] within the erythroblast (SDA, lead poisoning)
raw material (e.g., iron)
stored iron
iron
433
Tests used to differentiate iron metabolism disorders:
1. Serum Ferritin
2. Serum Iron
3. FEP
4. TIBC
5. Transferrin saturation
6. Zinc Erythrocyte Porphyrin
434
▪ Reflects the body’s tissue iron stores
Serum Ferritin
435
▪ A good indicator of iron storage status
Serum Ferritin
436
▪ First laboratory test to become abnormal when iron stores begin to decrease
Serum Ferritin
437
▪ Decreased only in IDA
Serum Ferritin
438
▪ Helpful in cases where the diagnosis is not obvious from other laboratory tests
Serum Iron
439
▪ Normally, red cells produced slightly more protoporphyrin than is needed
FEP
440
▪ However, when iron is deficient, protoporphyrin levels builds up in RBCs than the normal level
FEP
441
▪ Indirect measurement of transferrin concentration
TIBC
442
▪ Measures the binding site
TIBC
443
▪ (dec Anemia of chronic inflammation; inc IDA)
TIBC
444
▪ Obtained through the measurements of serum iron and TIBC
Transferrin saturation
445
%Transferrin saturation =
serum iron/TIBC x 100
446
▪ Measures unused protoporphyrin
Zinc Erythrocyte Porphyrin Test
447
▪ Increased in IDA, Lead poisoning, and Porphyria
Zinc Erythrocyte Porphyrin Test
448
▪ Most common form of anemia
Iron Deficiency Anemia
449
▪ The individual may not exhibit signs or symptoms until the appearance of Frank anemia
Iron Deficiency Anemia
450
▪ Microcytic, hypochromic anemia
Iron Deficiency Anemia
451
Iron Deficiency Anemia
▪ [?] Iron
▪ [?] TIBC and FEP
▪ Normal Reticulocyte count
▪ [?] Reticulocytes after iron therapy
Dec
Inc
Inc
452
Iron Deficiency Anemia Causes
Inadequate intake
Increased body demand (pregnancy, growing children)
Impaired absorption
Chronic blood loss due to infection (Hookworm infection)
Marching anemia: develops when RBCs are hemolyzed by footpounding trauma and iron is lost (hemoglobinuria is a common finding)
453
Chronic blood loss due to infection (?)
Hookworm infection
454
Chronic blood loss due to infection (?)
Hookworm infection
455
: develops when RBCs are hemolyzed by footpounding trauma and iron is lost (hemoglobinuria is a common finding)
Marching anemia
456
Stages of iron loss
▪ Stage 1 – progressive loss of storage iron
▪ Stage 2 – exhaustion of the storage pool of iron
▪ Stage 3 – Frank anemia (storage pool and circulatory iron is depleted)
457
Stages of iron loss
▪ Stage 1 – progressive loss of storage iron
▪ Stage 2 – exhaustion of the storage pool of iron
▪ Stage 3 – Frank anemia (storage pool and circulatory iron is depleted)
458
– progressive loss of storage iron
▪ Stage 1
459
– exhaustion of the storage pool of iron
▪ Stage 2
460
– exhaustion of the storage pool of iron
▪ Stage 2
461
– Frank anemia (storage pool and circulatory iron is depleted)
▪ Stage 3
462
▪ Glossitis
Iron Deficiency Anemia
463
▪ Glossitis
Iron Deficiency Anemia
464
▪ Angular cheilosis
Iron Deficiency Anemia
465
– inflamed cracks at the corner of the mouth
Angular cheilosis
466
– inflamed cracks at the corner of the mouth
Angular cheilosis
467
▪ Koilonychia
Iron Deficiency Anemia
468
▪ Koilonychia
Iron Deficiency Anemia
469
– spooning of the fingernails
Koilonychia
470
▪ Pica
Iron Deficiency Anemia
471
▪ Pagophagia
Iron Deficiency Anemia
472
▪ Decreased: RBC count, H/H, MCV, MCH, MCHC
Iron Deficiency Anemia
473
▪ Increased RDW (anisocytosis)
Iron Deficiency Anemia
474
▪ Increased RDW (anisocytosis)
Iron Deficiency Anemia
475
are iron-containing normoblasts found in a normal bone marrow
Sideroblastic Anemia ▪ Sideroblasts
476
▪ The iron deposits are identified using Prussian blue stain, and the resulting abnormal cells are identified as ringed sideroblasts
Sideroblastic Anemia
477
▪ Caused by: defective iron loading (accumulation of erythroid precursor in the mitochondria) due to deficiency of ALA synthetase
Sideroblastic Anemia
478
Sideroblastic Anemia Hereditary:
▪ Hereditary Sideroblastic Anemia
479
Sideroblastic Anemia Acquired:
▪ Refractory Anemia w/ Ringed Sideroblasts
▪ Idiopathic Acquired Sideroblastic Anemia
▪ Primary Idiopathic Sideroblastic Anemia
▪ Secondary Sideroblastic Anemia
480
▪ Severe anemia (Hct = <20%)
Hereditary Sideroblastic Anemia
481
▪ Dimorphic population of RBCs:
✓ Normocytic, normochromic
✓ Microcytic, hypochromic
Hereditary Sideroblastic Anemia
482
▪ (+) Target cells and basophilic stippling
Hereditary Sideroblastic Anemia
483
▪ inc iron and % transferrin saturation
Hereditary Sideroblastic Anemia
484
▪ More common SDA
Primary Idiopathic SDA
485
▪ Moderate anemia (Hct = 25-30%)
Primary Idiopathic SDA
486
▪ (+) normocytes and macrocytes w/ few microcytes
Primary Idiopathic SDA
487
▪ Erythroid hyperplasia w/ ringed sideroblasts in all stages of development
Primary Idiopathic SDA
488
▪ Due to toxins and drugs that interfere w/ heme synthesis
Secondary SDA
489
▪ Alcoholism, lead poisoning, TB drugs, and chloramphenicol
Secondary SDA
490
▪ Second most common anemia
Anemia of Chronic Inflammation
491
▪ Associated with infections, inflammatory, or malignant diseases of more than 1 or 2 months of duration
Anemia of Chronic Inflammation
492
▪ Most common anemia among hospitalized patients
Anemia of Chronic Inflammation
493
▪ Iron appears to be trapped in macrophages; therefore iron is not made available for reutilization in normoblasts
Anemia of Chronic Inflammation
494
▪ The anemia is often corrected when the primary disease is resolved
Anemia of Chronic Inflammation
495
▪ dec Transferrin (due to being a negative APR)
Anemia of Chronic Inflammation
496
▪ Tuberculosis
Anemia of Chronic Inflammation
497
▪ Lung abscess
Anemia of Chronic Inflammation
498
▪ Bacterial endocarditis
Anemia of Chronic Inflammation
499
▪ Neoplasms
Anemia of Chronic Inflammation
500
▪ RA
Anemia of Chronic Inflammation
501
▪ Rheumatic fever
Anemia of Chronic Inflammation
502
▪ SLE
Anemia of Chronic Inflammation
503
▪ Chronic liver disease
Anemia of Chronic Inflammation
504
▪ Hormone produced by the liver to regulate body iron levels particularly absorption of iron in the intestine and release of iron from macrophages
Hepcidin
505
▪ Iron-binding protein in the granules of the neutrophils
Lactoferrin
506
▪ Prevents phagocytized bacteria from using intracellular iron
Lactoferrin
507
▪ During infection and inflammation, inflammation is released into the plasma
Lactoferrin
508
▪ Binds iron
Ferritin
509
▪ Because developing RBCs do not have a ferritin receptor, this iron is unavailable for incorporation into hemoglobin
Ferritin
510
▪ Because developing RBCs do not have a ferritin receptor, this iron is unavailable for incorporation into hemoglobin
Ferritin
511
▪ A form of acquired porphyria and acquired Sideroblastic Anemia
Lead Poisoning
512
▪ Children may be exposed to lead secondary to ingestion of leadcontaining paint
Lead Poisoning
513
▪ Also associated with the use of improperly glazed pottery for cooking or eating
Lead Poisoning
514
▪ Similar to Sideroblastic anemia (lead inhibits several enzymes needed in heme biosynthesis)
Lead Poisoning
515
▪ Anemia, when present in lead poisoning, is most often normocytic and normochromic; however, with a chronic exposure to lead, a microcytic hypochromic clinical picture may be seen
Lead Poisoning
516
▪ (+) Coarse basophilic stippling
Lead Poisoning
517
Inherited disorder of defective heme synthesis
Porphyria
518
Accumulation of porphyrin precursors
Porphyria
519
Rare autosomal recessive disorder common in males
Hemochromatosis
520
Abnormal iron deposition in the tissues causing “bronze skin pigmentation”
Hemochromatosis
521
Associated with Bronze diabetes
Hemochromatosis
522
Normal H/H
Inc Iron and transferrin saturation
Dec Transferrin
Hemochromatosis
523
Caused by qualitative structural abnormalities of the globin chains that result from alteration of genetic sequence
Hemoglobinopathies
524
Quantitative defect/reduction in globin chain synthesis
Thalassemia
525
High incidence in Mediterranean descent
Thalassemia
526
= sickle cell anemia
▪ Homozygous SS
527
= sickle cell trait
▪ Heterozygous SS
528
▪ Autosomal codominant
Sickle Cell Anemia
529
▪ When fully oxygenated, hemoglobin S is fully soluble (reversible)
Sickle Cell Anemia
530
▪ Sickling occurs when oxygen decreases at the tissue level
Sickle Cell Anemia
531
▪ Provides resistance against P. falciparum
Sickle Cell Anemia
532
▪ When oxygen is released from the molecule, a conformational change occurs, which results in polymerization of Hb molecule leading to the formation of tactoids or crystals which causes the cells to become rigid
Sickle Cell Anemia
533
Any situation that produces excessive deoxygenation of the RBC may cause painful sickle cell crises (e.g., infection, dehydration, strenuous exercise, obstetric delivery and high altitudes)
Sickle cell crises
534
▪ Occur when rigid sickle cells increase the blood viscosity
Vaso occlusive crises
535
▪ Occur when rigid sickle cells increase the blood viscosity
Vaso occlusive crises
536
▪ Associated with the development of microthrombi, vascular occlusions, and microinfarction in the joints and extremities as well as in the major organs, which can cause organ failure
Vaso occlusive crises
537
▪ Associated with the development of microthrombi, vascular occlusions, and microinfarction in the joints and extremities as well as in the major organs, which can cause organ failure
Vaso occlusive crises
538
▪ Primary cause of death of patients with sickle cell anemia
Infectious crises
539
▪ Causative agent: S. pneumoniae (common in children) ▪
Infectious crises
540
▪ Also known as dactylitis
Hand-Foot syndrome
541
▪ First sites affected by decreased blood flow are the small bones of hands and feet
Hand-Foot syndrome
542
▪ Normocytic, normochromic anemia
Sickle Cell Anemia
543
▪ (+) Sickle cell, Target cell, Ovalocyte, Schistocyte, Polychromasia, nRBC
Sickle Cell Anemia
544
Sickle Cell Anemia
▪ [?] RDW
▪ [?] OFT, ESR
▪ [?] M:E ratio
Inc
Dec
Inc
545
occurs when sickle cells become trapped in the splenic microcirculation.
Splenic sequestration
546
▪ The spleen enlarges as more cells are trapped leading to [?] which may cause shock and death
hypovolemia
547
▪ 2nd most common Hb variant
Hemoglobin C
548
▪ tends to crystallize when dehydrated
Hemoglobin CC
549
▪ Note: the cells most vulnerable to intracellular crystallization are[?] because they tend to lose water as they age
older RBCs
550
▪ in MCHC
▪ Normocytic, normochromic anemia
▪ (+) Target cell, Spherocyte
▪ (+) Hb CC or SC crystal
Hemoglobin C disease
551
▪ in MCHC
▪ Normocytic, normochromic anemia
▪ (+) Target cell, Spherocyte
▪ (+) Hb CC or SC crystal
Hemoglobin C disease
552
▪ Caused by deletion of all four alpha globin genes (--/--) resulting in the production of hemoglobin Barts (γ4)
Bart’s Hydrops Fetalis
553
▪ has high affinity for oxygen
Bart’s Hydrops Fetalis
554
▪ The disorder is lethal; infants are usually stillborn or die within hours of birth
Bart’s Hydrops Fetalis
555
▪ Hb Barts has high affinity for oxygen
Bart’s Hydrops Fetalis
556
▪ Hb Barts has high affinity for oxygen
Bart’s Hydrops Fetalis
557
▪ The disorder is lethal; infants are usually stillborn or die within hours of birth
Bart’s Hydrops Fetalis
558
▪ Caused by deletion of 3 out of 4 alpha globin genes (--/-a)
Hb H Disease
559
▪ This disorder results from the decreased synthesis of alpha chains and the resultant formation of the unstable hemoglobin, Hb H (β4)
Hb H Disease
560
Hb H Disease ▪ At birth =
Inc Hb Barts (due to the presence of gamma globin chains)
561
▪ Also known as alpha thalassemia trait
Alpha Thalassemia minor
562
Hb H Disease ▪ Adult =
Inc Hb H (due to availability of beta globin and replaces Barts Hb
563
▪ Caused by deletion of 2 out of 4 alpha globin genes
Alpha Thalassemia minor
564
▪ Caused by deletion of 2 out of 4 alpha globin genes
Alpha Thalassemia minor
565
▪ Heterozygous a0 (--/aa)
▪ Homozygous a+ (a-/a-)
Alpha Thalassemia minor
566
▪ Also known as heterozygous alpha thalassemia
Silent carrier
567
▪ Caused by deletion of 1 out of 4 alpha globin genes (-a/aa)
Silent carrier
568
▪ Benign, and often discovered only during family studies
Silent carrier
569
Results to reduced production of beta globin chains → excess production of alpha chain (unstable)
Beta Thalassemia
570
▪ Also known as Cooley’s anemia/Mediterranean anemia
Thalassemia major
571
▪ Beta globin chain synthesis is impaired
Thalassemia major
572
▪ inc Hb A2
Thalassemia major
573
Marked skeletal deformities with frontal bossing, cheek bone and jaw protrusion
Beta Thalassemia
574
Characterized by increased levels of Hb F in adults in the absence of the usual hematologic features of thalassemia
Hereditary Persistence of Hemoglobin F
575
1st most common Enzymopathies
G6PD Deficiency
576
Most common RBC enzymopathy
G6PD Deficiency
577
Produced in: HMP
G6PD Deficiency
578
Triggers of hemolysis: antimalarial drugs, fava beans
G6PD Deficiency
579
Classical finding: Heinz bodies
G6PD Deficiency
580
2nd most common Enzymopathies
PK Deficiency
581
Produced: EMP
PK Deficiency
582
can lead to hemolytic anemia
PK deficiency
583
Deficiency 3rd most common Enzymopathies
Pyrimidine-5-nucleotidase
584
Substitution of glutamic acid to lysine at 6th position of the β-chain
Hemoglobin C
585
Substitution of glutamic acid to lysine at 26th position of the β -chain
Hemoglobin E
586
Substitution of asparagine to threonine at 102nd position of the β-chain
Hemoglobin Kansas
587
Substitution of glutamic acid to lysine at 121st position of the β-chain
Hemoglobin O-Arab
588
Also known as D-Punjab Substitution of glutamic acid to glycine at 121st position of the β-chain
Hemoglobin D-Los Angeles
589
Also known as C-Georgetown
Hemoglobin C-Harlem
590
Caused by two amino acid substitutions
Hemoglobin C-Harlem
591
Substitution of glutamic acid to valine at 6th position and aspartic acid to asparagine at 73rd position of the β-chain
Hemoglobin C-Harlem
592
Substitution of asparagine to lysine at 68th position of the alpha chain
Hemoglobin G-Philadelphia
593
Substitution of arginine to leucine at 92nd position of the alpha chain
Hemoglobin Chesapeake
594
Addition of 31 amino acids in the alpha chain
Hemoglobin Constant Spring
595
Amino acid deletion
Hemoglobin Gun Hill
596
Unstable hemoglobin
Hemoglobin Koln
597
Protein 4.1 and Spectrin deficiency
Hereditary Spherocytosis
598
(+) Autohemolysis test
Hereditary Spherocytosis
599
Inc OFT
Hereditary Spherocytosis
600
Protein 4.1 deficiency
Hereditary Elliptocytosis
601
Spectrin deficiency
Hereditary Pyropoikilocytosis
602
Commonly seen in burn patients
Hereditary Pyropoikilocytosis
603
Band 3 deficiency
Southeast Asian Ovalocytosis
604
Hemolytic anemia with dehydrated red blood cells
Hereditary Xerocytosis
605
(+) stomatocytes, target cells, macrocytes
Hereditary Xerocytosis
606
Also known as hydrocytosis
Hereditary Stomatocytosis
607
Characterized by neurologic impairment and acanthocytes on the PBS
Neuroacanthocytosis
608
Also known as hereditary acanthocytosis
Abetalipoproteinemia (Bassen-Kornzweig Syndrome)
609
Due to absence of β-lipoprotein
Abetalipoproteinemia (Bassen-Kornzweig Syndrome)
610
Characterized by malabsorption of fat, retinitis pigmentosa, neurologic damage and acanthocytosis
Abetalipoproteinemia (Bassen-Kornzweig Syndrome)
611
Characterized by chorea, hyperkinesia, cognitive impairment, and neuropsychiatric symptoms
Chorea Acanthocytosis
612
Due to KX gene mutation
McLeod syndrome
613
– precursor for the production of Kell antigen
Kx substance
614
▪ Also known as Marchiafava-Micheli syndrome
Paroxysmal Nocturnal Hemoglobinuria
615
▪ Hemoglobinuria occurs at night when blood pH falls (acidic)
Paroxysmal Nocturnal Hemoglobinuria
616
▪ Complication of PNH may progress to aplastic anemia
Paroxysmal Nocturnal Hemoglobinuria
617
▪ Cause: stem cell mutation that results in circulating blood cells that lack CD55 and CD59
Paroxysmal Nocturnal Hemoglobinuria
618
Paroxysmal Nocturnal Hemoglobinuria
▪ = DAF
▪ = MIRL
CD55
CD59
619
are complement-inhibiting regulator proteins
▪ CD55 and CD59
620
Paroxysmal Nocturnal Hemoglobinuria ▪ Screening test:
Sugar water test or sucrose hemolysis test
621
Paroxysmal Nocturnal Hemoglobinuria ▪ Confirmatory test:
Acidified Serum Test (Ham’s test)
622
▪ Dec LAP
Paroxysmal Nocturnal Hemoglobinuria
623
Due to severe liver disease that develop a hemolytic anemia with acanthocyte
Spur cell anemia
624
A disease of small blood vessels
Microangiopathic Hemolytic Anemia
625
Can be a complication of one of several conditions in which there is a disturbance of the microvascular environment (DIC, TTP, HUS)
Microangiopathic Hemolytic Anemia
626
▪ When there is extensive damage to vessel endothelium or exposure to compounds to initiate clotting (thromboplastic substances that encourage coagulation), DIC may follow
DIC
627
▪ As a direct result of fibrin deposition along and across the vessel lumen, RBCs can be fragmented or destroyed as they are pushed through the vessel by the action of blood pressure and rapidly flowing circulation
DIC
628
▪ (+) Schistocyte
DIC
629
▪ (+) D-dimer
DIC
630
▪ Also known as Moschkovitz syndrome
TTP
631
▪ Due to ADAMTS13 deficiency
TTP
632
▪ Most common in children
HUS
633
▪ Involves acute intravascular hemolysis and renal failure
HUS
634
▪ Causative agent: E. coli O157:H7
HUS
635
▪ EHEC produces Shiga-like toxin
HUS
636
▪ (+) Shistocytes, Burr cells, polychromasia
HUS
637
▪ Inc BUN, Creatinine
HUS
638
Autoimmune Hemolytic Anemia
WAIHA
CAIHA
PCH
639
Alloimmune Hemolytic Anemia
HDN
HTR
DIHA
640
Caused by Autoanti-P (biphasic hemolysin)
Paroxysmal Cold Hemoglobinuria
641
Paroxysmal Cold Hemoglobinuria Diagnostic test:
Donath-Landsteiner Test
642
Infection
Leishmaniasis Malaria Babesiosis B. bacilliformis
643
Also known as Chronic Myeloproliferative Disorders
MYELOPROLIFERATIVE DISORDERS
644
Splenomegaly is a common finding (extramedullary hematopoiesis)
MYELOPROLIFERATIVE DISORDERS
645
Examples:
Polycythemia vera
Essential Thrombocythemia
Primary Myelofibrosis
CML
MYELOPROLIFERATIVE DISORDERS
646
▪ Also known as Primary Thrombocytosis, Idiopathic Thrombocytosis
Essential Thrombocythemia
647
▪ Characterized by a thrombocytosis of 1000 x 109/L with spontaneous aggregation of functionally abnormal platelets
Essential Thrombocythemia
648
▪ Must be differentiated from secondary or reactive thrombocytosis
Essential Thrombocythemia
649
▪ Due to mutation of JAK2 gene
Essential Thrombocythemia
650
▪ Markedly increased platelet count
Essential Thrombocythemia
651
▪ Bone marrow examination: megakaryocytes stick together (Glued together appearance)
Essential Thrombocythemia
652
▪ Characterized by fibrosis and granulocytic hyperplasia of the bone marrow, with granulocytic and megakaryocytic proliferation in the liver and spleen
Primary Myelofibrosis Description
653
▪ Hepatomegaly and splenomegaly are common (extramedullary hematopoiesis)
Primary Myelofibrosis
654
▪ Due to mutation of JAK2 gene
Primary Myelofibrosis
655
▪ Normocytic, normochromic anemia
Primary Myelofibrosis
656
▪ Inc Reticulocyte count
▪ Inc WBC
Primary Myelofibrosis
657
▪ PBS: Teardrop cell, Polychromatophilia, NRBC
Primary Myelofibrosis
658
▪ Bone marrow examination: “dry tap” → presence of fibrotic tissues
Primary Myelofibrosis
659
▪ A stem cell disorder affecting the granulocytic, monocytic, erythrocytic, and megakaryocytic cell lines
Chronic Myelogenous Leukemia
660
▪ Common in adults (between ages of 30 and 50)
Chronic Myelogenous Leukemia
661
▪ A WBC count of 50,000-300,000/uL is often diagnostic of CML
Chronic Myelogenous Leukemia
662
▪ Cause: translocation between the long arms of chromosome 9 and 22
Chronic Myelogenous Leukemia
663
▪ Philadelphia chromosome: indicates good prognosis
Chronic Myelogenous Leukemia
664
▪ Must be differentiated from Leukemoid reaction using LAP test
Chronic Myelogenous Leukemia
665
▪ Inc RBC, WBC, and Platelet count
Chronic Myelogenous Leukemia
666
▪ BM Examination: hypercellular bone marrow
Chronic Myelogenous Leukemia
667
▪ Inc M:E ratio ▪ Inc LAP
Chronic Myelogenous Leukemia
668
Formerly known as Refractory anemia
Myelodysplastic Syndrome
669
Caused by proliferation of abnormal stem cells
Myelodysplastic Syndrome
670
Poikilocytosis, Basophilic stippling, Howell-Jolly bodies, and Siderocytes
Myelodysplastic Syndrome
671
French-American-British Classification of MDS
1. RARS 2. RAEB-t 3. RAEB 4. CMML
672
An abnormal, uncontrolled proliferation and accumulation of one or more of the hematopoietic cells
Leukemia
673
A disease of the blood forming tissues and the bone marrow
Leukemia
674
Classification of Leukemia
Based on duration of the untreated disease
Based on number of WBC present
Based on WBC type involved
675
Based on duration of the untreated disease
▪ Acute leukemia:
▪ Subacute leukemia:
▪ Chronic leukemia:
several days to 6 months
2 to 6 months
1-2 years
676
Based on number of WBC present
▪ Leukemic leukemia:
▪ Subleukemic leukemia:
▪ Aleukemic leukemia:
>15,000/uL
<15,000/uL w/ immature WBCs
<15,000/uL
677
Based on WBC type involved
▪ Acute leukemia:
▪ Chronic leukemia:
predominance of blasts
predominance of mature WBCs
678
Small cell, homogenous
L1
679
Most common acute leukemia in children
L1
680
Best prognosis
L1
681
Large cell, heterogenous
L2
682
Burkitt type
L3
683
Large lymphocytes w/ basophilic cytoplasm and numerous vacuoles
L3
684
Poor prognosis
L3
685
Acute myeloblastic leukemia, minimally differentiated
M0
686
Acute myeloblastic leukemia without maturation
M1
687
Acute myeloblastic leukemia with maturation
M2
688
Acute promyelocytic leukemia
M3
689
Characterized by the presence of bowtie/butterfly appearance of nucleus
M3
690
DIC is common
M3
691
(+) FSP
(+) Faggot cells
PT and APTT: prolonged
Dec Fibrinogen
M3
692
Acute myelomonocytic leukemia
M4
693
Also known as Naegeli monocytic leukemia
M4
694
Acute monocytic leukemia
M5
695
Also known as Schilling leukemia
M5
696
: ▪ Poorly differentiated leukemia
M5a
697
▪ Nucleus: lacy chromatin w/ nucleoli
M5a
698
▪ Well differentiated leukemia
M5b
699
▪ Nucleus: cerebriform shape with nucleoli
M5b
700
▪ Presence of all stages of monocytes in the peripheral blood
M5b
701
Erythroleukemia
M6
702
Also known as Di Guglielmo’s syndrome
M6
703
Predominance of myeloblasts and erythroblasts in the peripheral blood
M6
704
Acute megakaryocytic leukemia
M7
705
Predominance of megakaryocytes
M7
706
(+) PAS, ACP, platelet peroxidase
M7
707
M1, M2, M3, M4
MPO
SBB
Specific esterase (Naphthyl AS-D chloroacetate)
708
M1, M2, M3, M4
MPO
SBB
Specific esterase (Naphthyl AS-D chloroacetate)
709
M4, M5, M6
Nonspecific esterase (Naphthyl Acetate and Butyrate)
710
M5, M6, M7
PAS
711
ALL: +
AML: -
Terminal deoxynucleotidyl transferase
PAS
Oil Red O
712
ALL: -
AML: +
MPO
SBB
713
Most affected lymphocytes are B-cells
Chronic Lymphocytic Leukemia
714
Characterized by fragile lymphocytes
Chronic Lymphocytic Leukemia
715
Smudge cells (formed during film preparation, thumbprint appearance)
Chronic Lymphocytic Leukemia
716
(+) PAS
Chronic Lymphocytic Leukemia
717
▪ A stem cell disorder affecting the granulocytic, monocytic, erythrocytic, and megakaryocytic cell lines
Chronic Myelocytic Leukemia
718
▪ Common in adults (between ages of 30 and 50)
Chronic Myelocytic Leukemia
719
▪ A WBC count of 50,000-300,000/uL is often diagnostic of CML
Chronic Myelocytic Leukemia
720
▪ Cause: translocation between the long arms of chromosome 9 and 22
Chronic Myelocytic Leukemia
721
▪ Philadelphia chromosome: indicates good prognosis
Chronic Myelocytic Leukemia
722
▪ Must be differentiated from Leukemoid reaction using LAP test
Chronic Myelocytic Leukemia
723
▪ Inc RBC, WBC, and Platelet count
▪ BM Examination: hypercellular bone marrow
▪ Inc M:E ratio
▪ Dec LAP
▪ Chronic Myelocytic Leukemia
724
▪ (+) Basket cells
Chronic Myelocytic Leukemia
725
= nuclear remnants of granulocytic cells w/ netlike chromatin pattern
Basket cells
726
= nuclear remnants of granulocytic cells w/ netlike chromatin pattern
Basket cells
727
= nuclear remnants of granulocytic cells w/ netlike chromatin pattern
Basket cells
728
Also known as Leukemic Reticuloendotheliosis
Hairy Cell Leukemia
729
: lymphocyte w/ hairlike projections around the outer border
Hairy cell
730
(+) TRAP
HCL
731
A group of malignant tumors of the lymphoid tissue
Lymphoma
732
Usually, blood and bone marrow are not involved
Lymphoma
733
Lymphoma Classification:
Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, Miscellaneous lymphoma
734
Starts in one lymph node group and spreads in a predictable fashion to adjacent lymph nodes (unifocal)
Hodgkin’s Lymphoma
735
Hodgkin’s Lymphoma Definitive diagnostic test:
Lymph node biopsy
736
= classifies the different types of Hodgkin’s lymphoma
▪ Rye Classification
737
= used to formulate the treatment plan
▪ Ann Arbor staging system
738
Types of Hodgkin’s Lymphoma:
a. Nodular lymphocyte-predominant Hodgkin lymphoma
b. Classical Hodgkin lymphoma
739
-predominant Hodgkin lymphoma
a. Nodular lymphocyte
740
− presence of popcorn cell
a. Nodular lymphocyte
741
Classical Hodgkin lymphoma − types:
✓ Lymphocytic predominant (best prognosis)
✓ Lymphocyte depleted (worst prognosis)
✓ Mixed cellularity
✓ Nodular sclerosis (most common type)
742
− presence of Reed-Sternberg cell
b. Classical Hodgkin lymphoma
743
Spreads in a much less predictable way
Non-Hodgkin’s Lymphoma
744
Classified under Rappaport system (replaced by NCI)
Non-Hodgkin’s Lymphoma
745
Non-Hodgkin’s Lymphoma Types:
✓ Well differentiated lymphocytic lymphoma
✓ Poorly-differentiated lymphocytic lymphoma
✓ Histiocytic lymphoma
✓ Mixed histiocytic-lymphocytic lymphoma
746
▪ Caused by neoplastic T-cells that migrate into the skin
Mycosis fungoides
747
▪ Affects primarily the T-cells
Mycosis fungoides
748
▪ Classic symptoms: pruritus
Mycosis fungoides
749
▪ Pautrier's microabscesses = cluster of lymphocytes in the epidermis
Mycosis fungoides
750
▪ NOTE: fungal infection is not present
Mycosis fungoides
751
▪ Leukemic phase of mycosis fungoides
Sezary syndrome
752
▪ (+) Sezary cells
Sezary syndrome
753
▪ Prognosis is worst at this stage
Sezary syndrome
754
▪ Also known as Kahler’s disease
Multiple Myeloma
755
▪ Caused by excessive production of IgG
Multiple Myeloma
756
▪ The homogenous protein synthesized by the abnormal clone may be complete immunoglobulins or light chains (kappa and lambda)
Multiple Myeloma
757
▪ The homogenous protein synthesized by the abnormal clone may be complete immunoglobulins or light chains (kappa and lambda)
Multiple Myeloma
758
▪ Idiopathic
Multiple Myeloma
759
▪ Clonal proliferation begins in the bone marrow and multiple tumors appear as patchy infiltrates in skeletal structures producing osteoporosis and lytic bone disease
Multiple Myeloma
760
▪ As the neoplastic mass grows, pathologic bone fractures and vertebral collapse may occur
Multiple Myeloma
761
▪ (+) Bence Jones proteins in urine
Multiple Myeloma
762
▪ PBS: Rouleaux formation, Dutcher bodies, Russell bodies
Multiple Myeloma
763
▪ Caused by excessive production of IgM
Waldenstrom’s Macroglobulinemia
764
▪ Monoclonal IgM may exhibit cryoglobulin activity demonstrated by precipitation or gel formation during refrigeration at 4’C and dissolve when heated
Waldenstrom’s Macroglobulinemia
765
▪ May result to renal damage caused by deposition of IgM complexes
Waldenstrom’s Macroglobulinemia
766
▪ Characterized by a WBC count of greater than 50,000/uL
Leukemoid Reaction
767
▪ Resembles CML
Leukemoid Reaction
768
Leukemoid Reaction ▪ Differential test:
LAP score
769
▪ Inc LAP
Leukemoid Reaction
770
▪ Also known as Leukoerythroblastic anemia
Leukoerythroblastic Reaction
771
▪ (+) NRBCs and immature neutrophils in peripheral blood smear
Leukoerythroblastic Reaction
772
▪ Caused by space-occupying disturbances of the bone marrow
Leukoerythroblastic Reaction
773
▪ Caused by space-occupying disturbances of the bone marrow
Leukoerythroblastic Reaction
774
Causes:
▪ Myelofibrosis w/ myeloid metaplasia
▪ Metastatic carcinoma
▪ Leukemia
▪ Multiple myeloma
▪ Gaucher disease
Leukoerythroblastic Reaction
775
▪ Hyposegmented neutrophils (bilobed)
Pelger-Huet anomaly
776
▪ The bilobed nuclei are commonly described as “pince-nez spectacles” or peanut or dumbbell shape
Pelger-Huet anomaly
777
Pelger-Huet anomaly
▪ Homozygous =
▪ Heterozygous =
round nucleus
pince-nez nucleus (more common)
778
▪ Also known as hereditary hypersegmentation of neutrophils
Undritz anomaly
779
▪ Characterized by leukopenia, thrombocytopenia, giant platelets, and presence of gray-blue spindle-shaped inclusions in the cytoplasm of granulocytes and monocytes
May-Hegglin anomaly
780
▪ NOTE: the cytoplasmic inclusion resembles Dohle bodies
May-Hegglin anomaly
781
▪ Characterized by the presence of abnormally large azurophilic granules resembling severe toxic granulation in the cytoplasm of granulocyte, lymphocyte and monocyte
Alder-Reilly anomaly
782
▪ Associated with mucopolysaccharidoses
Alder-Reilly anomaly
783
▪ Random movement of phagocytes is normal, but chemotaxis (directional motility) is impaired
Job’s syndrome
784
▪ As a result, bacteria have more time to multiply in the tissues
Job’s syndrome
785
▪ Both random and directed movement of the phagocytes are impaired
Lazy Leukocyte syndrome
786
▪ Presence of giant cytoplasmic granules in the phagocytes and lymphocytes
Chediak Higashi anomaly
787
▪ Inability of phagocytes to produce superoxide and ROS
Chronic Granulomatous Disease
788
▪ Due to NADPH oxidase
Chronic Granulomatous Disease
789
▪ Diagnostic test: (-) NBT dye test
Chronic Granulomatous Disease
790
▪ Also known as Alius-Grignaschi Anomaly
Myeloperoxidase deficiency
791
Most common form of neutrophil abnormality
Myeloperoxidase deficiency
792
▪ Function abnormality is not severe
Myeloperoxidase deficiency
793
Neutrophil that contains a large spherical body in its cytoplasm ; SLE
LE cell
794
Formed during LE cell preparation (May be confused with LE cell) ; Unknown
Tart cell
795
Crumpled tissue paper appearance
796
Macrophage with swollen cytoplasm composed of numerous small, uniform lipid droplets ; Niemann-Pick disease
Foam cell
797
Abnormal plasma cell with immunoglobulin trapped in endoplasmic reticulum ; Plasma cell myeloma
Morula cell
798
Nuclear remnants of granulocytic cells with netlike chromatin pattern Formed during blood film preparation ; CML
Basket cell
799
Nuclear remnants of lymphocytes Formed during blood film preparation Thumbprint appearance ; CLL
Smudge cell
800
Large lymphoid cells with a bilobed nucleus with prominent eosinophilic nucleoli and abundant cytoplasm (owl’s eye appearance) ; Hodgkin’s lymphoma
Reed-Sternberg cell
801
Large lymphoid cells with abundant cytoplasm and vesicular multilobed nuclei ; Nodular Lymphocyte ; Predominant-Hodgkin’s lymphoma
Popcorn cell
802
Plasma cell with abundant cytoplasm with a reddish tinge of ribosomal protein ; IgA myeloma
Flame cell
803
Lymphocyte with hairlike projections around the outer border ; HCL
Hairy cell
804
Contains bundles of Auer rods in the cytoplasm ; AML M3/APL
Faggot cell
805
Also known as Reactive lymphocytes, atypical lymphocytes, stress lymphocytes, virocytes, variant lymphocytes, transformed lymphocytes ; Non-malignant reactive disorders
Downey cells
806
✓ Type 1 –
Turk’s cell (also known as plasmacytoid lymphocyte, Turk’s irritation cell)
807
✓ Type 2 –
Infectious mononucleosis cell (Flared skirt appearance)
808
✓ Type 3 –
Transformed/Reticular lymphocytes
809
▪ Pale blue, round or elongated bodies
Dohle bodies
810
▪ Consists of rRNA
Dohle bodies
811
▪ Found in neutrophils
Dohle bodies
812
▪ Associated with pregnancy, infection, poisoning, burn and surgery
Dohle bodies
813
▪ Resembles May-Hegglin bodies
Dohle bodies
814
▪ Larger than Dohle bodies
May-Hegglin bodies
815
▪ Consists of mRNA
May-Hegglin bodies
816
▪ Found in granulocytes and monocytes
May-Hegglin bodies
817
▪ Heavy, coarse, blue-black granulation of the leukocytes
Alder-Reilly bodies
818
▪ Resembles toxic granules
Alder-Reilly bodies
819
▪ Associated with Hurler’s and Hunter’s syndrome and Alder-Reilly Anomaly
Alder-Reilly bodies
820
▪ Dark blue-black cytoplasmic granules in the neutrophil
Toxic granules
821
▪ Composed of primary granules
Toxic granules
822
▪ Associated with severe infection
Toxic granules
823
▪ Results when the degenerating cytoplasm begins to acquire holes or as the result of active phagocytosis
Vacuolation
824
▪ Associated with infection
Vacuolation
825
▪ Rod-like bodies representing aggregated primary granules that stain a reddish purple
Auer rods
826
▪ Associated with AML
Auer rods
827
▪ Stimulates vasodilation
Prostacyclin (PGI2)
Adenosine
828
Reduces blood flow rate
Prostacyclin (PGI2)
Adenosine
829
Inhibits platelet activation
Prostacyclin (PGI2)
830
Anticoagulant
Prostacyclin (PGI2)
Thrombomodulin
Heparan sulfate
831
Fibrinolytic
Thrombomodulin
tPA
832
Coagulation
von Willebrand factor
833
▪ Endothelial receptor for thrombin
Thrombomodulin
834
▪ Binds and inactivates thrombin and enhances anticoagulant and fibrinolytic action of Protein C
Thrombomodulin
835
▪ Coats the endothelial cell surface and weakly enhances the activity of antithrombin-III
Heparan sulfate
836
▪ Converts plasminogen to plasmin which plays an important role in fibrinolysis
tPA
837
▪ NOTE: released only on appropriate stimulus, such as vessel injury, to prevent excessive clot formation at the site of tissue injury
tPA
838
tPA ▪ NOTE: released only on appropriate stimulus, such as vessel injury, to prevent excessive clot formation at the site of tissue injury
839
▪ Secreted by endothelium
von Willebrand factor
840
▪ Required for platelet adhesion
von Willebrand factor
841
✓ Synthesized by endothelial cells, and megakaryocytes
von Willebrand Factor
842
✓ Stored in endothelial cells (Weibel-Palade bodies) and platelets
von Willebrand Factor
843
: entire molecule as it circulates in the plasma
✓ VIII/vWF
844
– portion of molecule responsible for binding to endothelium and supporting normal platelet adhesion and function
✓ VIII:vWF
845
– portion of molecule participating in intrinsic pathway
✓ VIII:C
846
✓ Labile factors:
V and VIII
847
✓ Activated by cold temperature:
VII and XI
848
✓ Fibrinogen is the most abundant clotting factor with a normal value of
200-400 mg/dL
849
✓ Serine protease:
II, X, VII, IX, XII, XI, and PK
850
✓ Prothrombinase:
Xa-Va
851
Intrinsic Tenase:
VIII-IX
852
Extrinsic Tenase:
VII-III-IV
853
: central regulatory component of coagulation (can inhibit or accelerate coagulation)
Thrombin (IIa)
854
▪ Extrinsic pathway:
III and VII
855
▪ Intrinsic pathway:
XII, XI, IX, VIII
856
▪ Common pathway:
I, II, V, X
857
▪ Fibrinogen group:
I, V, VIII, XIII
858
▪ Prothrombin group (Vitamin K dependent):
II, VII, IX, X
859
▪ Contact group:
XI, XII, PK, HMWK
860
▪ A transmembrane receptor for Factor VIIa
Tissue factor (thromboplastin)
861
= mixture of tissue factor and phospholipid
▪ Tissue thromboplastin
862
▪ Found on extravascular cells such as fibroblasts and smooth muscle cells (not found in endothelial cells under normal conditions)
Tissue factor (thromboplastin)
863
▪ High levels are found in brain, lung, heart, kidneys, and testes
Tissue factor (thromboplastin)
864
▪ Produced by B. fragilis and E. coli
Vitamin K
865
▪ Found in green leafy vegetables
Vitamin K
866
▪ Catalyzes an essential post-translational modification of the prothrombin group proteins
Vitamin K
867
▪ Vitamin K dependent factors:
o II, VII, IX, X
o Protein C, S, Z
868
▪ Participates in platelet adhesion and transports Factor VIII
von Willebrand Factor
869
▪ Large multimeric glycoprotein
von Willebrand Factor
870
▪ Composed of multiple subunits of 240,000 Da each
von Willebrand Factor
871
▪ The subunits are produced by endothelial cells and megakaryocytes, where they combine to form multimers that range from 600,000 to 20,000,000 Da
von Willebrand Factor
872
▪ Once released into the plasma, they are normally degraded into small-multimers by vWF-cleaving protease called ADAMTS13 (a disintegrin-like metalloprotease with a thrombospondin type 1 motif, member 13)
von Willebrand Factor
873
= associated with abnormally large vWF
▪ TTP
874
= associated with abnormally large vWF
▪ TTP
875
▪ Required for the assembly of coagulation complexes
Calcium
876
▪ Expressed by vascular endothelial cells
Thrombomodulin
877
▪ Cofactor of thrombin
Thrombomodulin
878
= activates Protein C
▪ Thrombomodulin + Thrombin
879
: a coagulation inhibitory protein, and thrombin activatable fibrinolysis inhibitor (TAFI)
▪ Protein C
880
▪ Once thrombin is bound to thrombomodulin, it loses its procoagulant ability to activate factors V and VII, and through the activation of Protein C, leads to the destruction of factors V and VII, thus suppressing further generation of thrombin
Thrombomodulin
881
▪ Considered as the key protease of coagulation pathway
Thrombin
882
▪ Primary function is to cleave fibrinopeptidases A and B from the alpha and beta chains of fibrinogen molecule, triggering spontaneous polymerization
Thrombin
883
✓ Activates cofactors V, VIII, and IX
Thrombin
884
✓ Activates factor XIII
Thrombin
885
✓ Initiates platelet aggregation
Thrombin
886
✓ Activates TAFI to suppress fibrinolysis
Thrombin
887
Principal regulator of tissue factor pathway
Tissue factor pathway inhibitor
888
→ Protein C → Activated Protein C
Thrombin + Thrombomodulin
889
→ inactivates factor Va and VIIIa
Protein S
890
Antithrombin and other serine protease inhibitors (Serpins)
Antithrombin
Heparin cofactor II
Protein Z-dependent protease inhibitor (ZPI)
Protein C inhibitor
a1-antitrypsin
a2-macroglobulin
a-2-antiplasmin
PAI-1
891
Inhibits thrombin
Antithrombin III
892
Synthesized by the liver
Antithrombin III
893
SERPIN
Antithrombin III
Heparin cofactor II
894
Inactivates thrombin
Heparin cofactor II
895
Potent inhibitor of factor Xa
Protein Z-dependent protease inhibitor (ZPI)
896
Final stage of coagulation
Fibrinolysis
897
Dependent on plasmin
Fibrinolysis
898
Destroys fibrinogen, fibrin, factor V, and factor VIII
Plasmin
899
Not normally present in the blood in an active form
Plasmin
900
Zymogen of plasmin
Plasminogen
901
Normally present in the plasma
Plasminogen
902
Homologous to Lp (a)
Plasminogen
903
Released in vivo by endothelial cell damage
Tissue plasminogen activator
904
Activates plasminogen
Tissue plasminogen activator
905
Activates plasmin
Urokinase plasminogen activator
906
May be administered to a patient to activate plasminogen
Urokinase plasminogen activator
907
Activates plasminogen
Streptokinase
908
Early degradation products:
FDP/FSP
X, Y
909
Late degradation products:
FDP/FSP
D (D-dimer) and E
910
Indicates fibrin degradation products
D-dimer
911
Marker of thrombosis and fibrinolysis
D-dimer
912
Produced by digestion of either fibrin or fibrinogen by plasmin
Fragment X, Y, E
913
o Purplish red, pinpoint hemorrhagic spots caused by loss of capillary ability to withstand normal blood pressure and trauma
▪ Petechiae
914
o Size: <3 mm
▪ Petechiae
915
o Produced by hemorrhage of blood into small areas of skin, mucous membrane, and other tissues
▪ Purpura
916
▪ o Size: <1 cm
Purpura
917
o Form of purpura in which blood escapes into large areas of the skin or mucous membrane but not into deep tissues
▪ Ecchymosis
918
o Size: >3 cm
▪ Ecchymosis
919
▪ Autosomal Dominant
Ehlers-Danlos Syndrome
Hereditary hemorrhagic telangiectasia
Gray Platelet Syndrome
920
▪ Characterized by hyperextensible joints and hyperelastic skin
Ehlers-Danlos Syndrome
921
▪ Autosomal Recessive
Pseudoxanthoma elasticum
Bernard-Soulier Syndrome
Glanzmann’s Thrombasthenia
Hermansky-Pudlak Syndrome
Chediak-Higashi Anomaly
Thrombocytopenia w/ absent Radii
922
▪ The connective tissue elastic fibers in small arteries are calcified and structurally abnormal
Pseudoxanthoma elasticum
923
▪ Also known as Rendu-Osler-Weber syndrome
Hereditary hemorrhagic telangiectasia
924
▪ Characterized by vascular malformations and skin lesions called telangiectasias
Hereditary hemorrhagic telangiectasia
925
▪ Also known as Kasabach-Merritt syndrome
Congenital hemangiomathrombocytopenia syndrome
926
▪ Associated with tumors composed of vessels that commonly swell and bleed at the surface
Congenital hemangiomathrombocytopenia syndrome
927
▪ Formation of fibrin clots, platelet consumption, and RBC destruction secondary to vascular obstruction occur at the site of tumor
Congenital hemangiomathrombocytopenia syndrome
928
▪ Also known as Scurvy
Vitamin C deficiency
929
▪ Vitamin C is required for the formation of intact structure of the vascular basement membrane
Vitamin C deficiency
930
▪ Gingival bleeding and hemorrhage into subcutaneous tissues and muscles are common finding
Vitamin C deficiency
931
▪ Acquired and chronic disorder of the elderly causing abnormalities in connective tissues
Senile Purpura
932
▪ The aging process brings about a degeneration of collagen, elastin, and subcutaneous fat
Senile Purpura
933
▪ Common in elderly men
Senile Purpura
934
▪ Purpura associated with abdominal pain secondary to GIT bleeding
Henoch-Schonlein Purpura
935
▪ Abdominal and joint pain related to allergic purpura
Henoch-Schonlein Purpura
936
▪ Common in children
Henoch-Schonlein Purpura
937
▪ Caused by lack of expression of Gp Ib/IX complex on the platelet surface
Bernard-Soulier Syndrome
938
▪ Characterized by large platelets
Bernard-Soulier Syndrome
939
Lab Findings:
▪ Giant platelets
▪ BT: Prolonged
▪ Platelet Aggregation studies: Ristocetin is abnormal
Bernard-Soulier Syndrome
940
▪ Lacks vWF
von Willebrand Disease
941
Lab Findings:
▪ APTT, BT, TT, CT = Prolonged
▪ Platelet Aggregation studies: Ristocetin is abnormal
▪ Treatment of choice: cryoprecipitate, DDAVP
von Willebrand Disease
942
▪ Lacks Gp IIb-IIIa
Glanzmann’s Thrombasthenia
943
▪ Clot Retraction: Abnormal
Glanzmann’s Thrombasthenia
944
▪ BT: Prolonged
Glanzmann’s Thrombasthenia
945
▪ Platelet aggregation studies: ADP, Collagen, and Epinephrine are abnormal
Glanzmann’s Thrombasthenia
946
▪ Lacks alpha granules
Gray Platelet Syndrome
947
▪ Giant platelets
Gray Platelet Syndrome
948
▪ Platelets are gray or blue-gray
Gray Platelet Syndrome
949
▪ Lacks dense granules
Hermansky-Pudlak Syndrome
950
▪ Triad of oculocutaneous albinism, bleeding tendency associated with abnormal platelet function, and accumulation of ceroid-like pigment in macrophages
Hermansky-Pudlak Syndrome
951
▪ Lacks dense granules
Chediak-Higashi Anomaly
952
▪ Characterized by albinism, recurrent infection, and giant lysosomes
Chediak-Higashi Anomaly
953
▪ Decreased delta granules
Wiskott-Aldrich Syndrome
954
▪ Platelets are small
Wiskott-Aldrich Syndrome
955
▪ Triad of thrombocytopenia, recurrent infection and eczema
Wiskott-Aldrich Syndrome
956
▪ X-linked recessive
Wiskott-Aldrich Syndrome
957
▪ Platelets have structural defects in delta granules
Thrombocytopenia w/ absent Radii
958
▪ Characterized by congenital absence of the radial bones
Thrombocytopenia w/ absent Radii
959
inhibits the synthesis of cyclooxygenase
Aspirin
960
inhibits platelet aggregation
Aspirin
961
most common acquired platelet disorder
Aspirin
962
▪ Autoimmune disorder
ITP
963
▪ Develops after transfusion of platelet containing blood products
PTP
964
▪ Also known as Moschowitz syndrome
TTP
965
▪ Characterized by triad of microangiopathic hemolytic anemia, thrombocytopenia, and neurologic abnormalities
TTP
966
▪ Due to ADAMTS13 deficiency
TTP
967
− Inherited TTP − Severe
Upshaw-Schulman Syndrome
968
− Caused by mutation in the ADAMTS13 gene
Upshaw-Schulman Syndrome
969
− Caused by autoantibodies
Idiopathic TTP
970
− triggered by infections, pregnancy, surgery, trauma, inflammation, and disseminated malignancy
Secondary TTP
971
− Trimethoprim, Ticlopidine, Quinine drugs
Secondary TTP
972
▪ Resembles TTP
HUS
973
▪ Common in children
HUS
974
▪ Due to E. coli infection
HUS
975
▪ Similar to TTP
DIC
976
▪ Thrombi are primarily composed of platelets and fibrinogen
DIC
977
▪ (+) D-dimer
DIC
978
▪ Due to massive blood transfusion (effect is temporary)
Dilutional
979
▪ Rationale: stored blood contains platelets whose viability is severely impaired by the effects of storage and temperature. Under these conditions, the damaged platelets are rapidly sequestered by the RES of the patient resulting to thrombocytopenia
Dilutional
980
Due to uncontrolled proliferation of platelets (e.g., PV, ET)
Primary Thrombocytosis
981
Splenectomy
Secondary Thrombocytosis (Reactive)
982
▪ Do not demonstrate clinical bleeding
PK deficiency
983
▪ May be vulnerable to thrombotic tendencies
PK deficiency
984
▪ Prolonged APTT
PK deficiency
HMWK deficiency
Factor XII deficiency
Factor XI deficiency
Factor VIII deficiency
985
▪ Prolonged APTT, PT, Stypven time
Factor X deficiency
986
▪ Prolonged APTT and PT
Factor IX deficiency
Factor V deficiency
Factor II deficiency
Factor I deficiency
987
▪ 5M Urea: Abnormal
Factor XIII deficiency
988
▪ Do not manifest bleeding disorder
Factor XII deficiency
989
▪ May be vulnerable to thrombosis
Factor XII deficiency
990
Confirmatory test: Factor XII assay
Factor XII deficiency
991
▪ Hemophilia C
Factor XI deficiency
992
▪ Also known as Hemophilia B, Christmas Disease, Rosenthal syndrome
Factor IX deficiency
993
▪ Also known as Hemophilia A or Classic hemophilia or Royal disease
Factor VIII deficiency
994
▪ X-linked disorder (males are affected)
Factor VIII deficiency
995
▪ Also known as Owren’s disease or Parahemophilia
Factor V deficiency
996
▪ Screening test for primary hemostasis
Bleeding Time
997
▪ Principle: the time it takes for a standard wound to stop bleeding
Bleeding Time
998
▪ NV: 2 to 4 minutes
Bleeding Time
999
– earlobe was punctured (not accurate, obsolete)
▪ Duke’s method
1000
– uses blood pressure cuff (40 mmHg)
▪ Ivy method
1001
– standardization of wound
▪ Mielke
1002
▪ For primary hemostasis
Whole Blood Clotting Time
1003
▪ Principle: when venous blood is put into a foreign surface, it will form a solid clot
Whole Blood Clotting Time
1004
▪ Lee and White method
Whole Blood Clotting Time
1005
NV: 5-15 minutes
Whole Blood Clotting Time
1006
Uses 75 x 100 mm test tube
Whole Blood Clotting Time
1007
Visual detection of fibrin clot formation
▪ Tilt tube method
1008
▪ Also known as Capillary Fragility Test ; Used to measure capillary fragility
Tourniquet Test
1009
(+) result: formation of petechiae
Tourniquet Test ▪
1010
Tourniquet Test ▪ Grading:
1+ =
2+ =
3+ =
4+ =
few petechiae on the anterior part of the forearm
many petechiae on the anterior part of the forearm
multiple petechiae over the whole arm and back of the arm
confluent petechiae on the arm and back of the hand
1011
▪ For platelet aggregation in vitro
Platelet aggregometry
1012
▪ Reagents used: ADP, Collagen, Epinephrine, Ristocetin
Platelet aggregometry
1013
▪ For extrinsic and common pathway
Prothrombin Time
1014
▪ Used to monitor oral anticoagulants (Warfarin, Coumadin, Coumarin)
Prothrombin Time
1015
prolonged if fibrinogen level is <80 mg/dL
Prothrombin Time
1016
▪ PT reagent:
Thromboplastin (rabbit brain or lung tissue)
Calcium chloride (CaCl2)
1017
Calculation made to standardize PT ; It is based on ratio of patient’s PT and normal mean PT
ISI – assigned by the manufacturer
Prothrombin Time ▪ INR
1018
▪ NV: 10-14 seconds
Prothrombin Time
1019
▪ For intrinsic and common pathway
Activated Partial Thromboplastin Time
1020
▪ Used to monitor heparin therapy
Activated Partial Thromboplastin Time
1021
▪ APTT Reagent:
Platelet substitute (phospholipid)
Activator (Kaolin, Celite, Silica, Ellagic acid)
1022
▪ NV: 20-45 seconds
Activated Partial Thromboplastin Time
1023
▪ Also known as Russell’s viper venom time
Stypven Time
1024
▪ For common pathway
Stypven Time
1025
Stypven Time ▪ Reagent:
Russell’s viper venom is obtained from the snake Vipera russelli
1026
▪ For fibrinogen
Thrombin Time
1027
▪ NOTE: affected by heparin therapy
Thrombin Time
1028
▪ Sensitive test in detecting heparin inhibition
Thrombin Time
1029
▪ Prolonged Thrombin time is noted when fibrinogen level is below
75 to 100 mg/dL
1030
▪ For fibrinogen
Reptilase Time
1031
▪ NOTE: NOT affected by heparin therapy
Reptilase Time
1032
is an enzyme found in the venom of Bothrops atrox snake
▪ Reptilase
1033
▪ Also known as Plasma Clotting Time
Plasma Recalcification Time
1034
▪ For intrinsic pathway
Plasma Recalcification Time
1035
▪ For Factor XIII
Duckert’s test
1036
▪ Reagent: 5M Urea and 1% Monochloroacetic acid
Duckert’s test
1037
▪ (+) Factor XIII deficiency: the clot is dissolved in the presence of 5M Urea
Duckert’s test
1038
▪ NOTE: a clot that has not stabilized by Factor XIII is soluble to 5M Urea
Duckert’s test
1039
▪ Screening test for DIC
Fibrinosticon
1040
▪ The presence of crosslinked D-dimer indicates that a stable fibrin clot has been lysed
Fibrinosticon
1041
▪ Screening test for DIC
Ethanol Gelation Test
1042
▪ Used to detect fibrin monomers in the plasma
Ethanol Gelation Test
1043
▪ Used to differentiate DIC from primary fibrinolysis
Ethanol Gelation Test
1044
Principle: ▪ During the process of DIC, the level of fibrin monomer (product of fibrinogen conversion to fibrin) in the blood increases
Ethanol Gelation Test
1045
▪ NaOH is added in the plasma to increase the pH to 7.70 (if pH is below 7.70, this will cause precipitation of fibrinogen instead of fibrin monomer)
Ethanol Gelation Test
1046
▪ Ethyl alcohol will cause precipitation of any fibrin monomers
Ethanol Gelation Test
1047
▪ Used to detect the presence of fibrin monomers
Protamine Sulfate
1048
▪ NOTE: normally, there should be no fibrin monomers present in the plasma
Protamine Sulfate
1049
▪ Screening test for fibrinolytic activity
Euglobulin clot lysis time
1050
▪ Clot lysis in less than 1 hour indicates abnormal fibrinolytic activity
Euglobulin clot lysis time
1051
▪ Used for the detection of lupus anticoagulant
Platelet neutralization test
1052
▪ Also known as Mixing studies
Substitution Test
1053
Used to identify specific factor deficiency
▪ Substitution Test
1054
▪ A specific factor deficiency may be identified by mixing correction reagents with a patient’s plasma and then performing PT and APTT (1:1 dilution)
Substitution Test
