Pathology: RBC Flashcards
1
Q
What is in a complete blood count (CBC)?
10
A
WBC count, RBC count, [Hb], Hematocrit (Hct), Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH), Mean Corpuscular Hemoglobin Concentration (MCHC), Red cell Distribution Width (RDW), Platelet count, Mean Platelet Volume (MPV)
2
Q
Define: WBC count, RBC count, Hct
A
WBC Count: nucleated cells in blood’
RBC Count: absolute number per microliter (mm3)
# of RBC cells in a sample
Hematocrit (Hct): packed red cell volume
3
Q
Define: MCV, MCH, MCHC
A
Mean Corpuscular Volume (MCV): average size of all RBCs
MCH: average amount of hemoglobin per RBC
MCHC: % per red blood cell
useful if spherocytes in peripheral blood
4
Q
What is a CBC with differential?
A
Percentage of each WBC found in the peripheral blood
- Wright/Giemsa stained peripheral blood smear used
5
Q
What is found in the CBC w/ differential using an AUTOMATED counter?
A
In addition to CBC the automated counter gives % and absolute # of:
- neutrophils
- eosinophils
- basophils
- lymphocytes
- monocytes
6
Q
A MANUAL counter is used to find what in a CBC w/ diff?
A
Automated doesn’t separate immature neutrophils, use manual to find:
- bands
- metamyelocytes
- myelocytes
- promyelocytes
- blasts
7
Q
What you’ll find in a peripheral blood smear
A
platelets - little small dots
neutrophils - multi-lobed nucleus; mediate killing for bacteria and fungi
lymphocyte
basophils
8
Q
More interesting things found in peripheral blood smear
A
**eosinophils - fighting parasites, allergies, asthma, etc… (he likes this one so make sure you know how it looks like)
neutrophilic band - immature neutrophil; if there’s a lot, maybe an infection occurring (“Left Shift”); granules present
monocytes - will have vacuoles present (different from neutrophil band which has granules)
9
Q
What is Anisocytosis?
A
variability in RBC size
10
Q
What is Poikilocytosis?
A
variability in RBC shape
11
Q
What is a Spherocyte?
A
round cells
12
Q
What is a Dacrocyte?
A
tear-drop cells
13
Q
What is an Elliptocyte?
A
oblong cells
14
Q
What is Polychromasia?
A
immature RBCs
15
Q
What is a Blast?
A
primitive multipotent cells
e.g found in leukemia
16
Q
In Hematopoiesis, what is the pluripotent stem cell?
A
CD34+
17
Q
CD34+ pluripotent stem cell divides into:
A
Granulocyte-Monocyte lineage
Lymphoid lineage
18
Q
What is under the Granulocyte-Monocyte lineage?
A
Myeloid lineage:
- Erythrocytes (RBCs)
- Granulocytes (Neutrophils, Eosinophils and Basophils)
- Megakaryocytes (platelets)
Monocytes
19
Q
What is under the Lymphoid lineage?
A
Lymphoid cells in Thymus Gland:
CD3+ T-Lymphocytes:
-CD 4+ Helper T cells
-CD8+ Cytotoxic T cells
Lymphoid cells in “Bursa Equivalent”
B-Lymphocytes
20
Q
Define Anemia?
A
Reduction of [RBC] below normal limits
-decreased [Hb] (
21
Q
Is anemia symptomatic or asymptomatic?
A
Both!
symptoms include: fatigue, dyspnea
22
Q
What are the two types of anemia?
A
increased destruction or loss of blood cells: blood loss
hemolytic anemias
problems in the production of blood cells:
decreased hematopoiesis
23
Q
Anemia of blood loss: What is involved in acute blood loss?
A
NO TIME FOR COMPENSATION
- Hemorrhage
- May lead to Hypovolemic Shock
- Loss of total blood volume more important than acute loss of hemoglobin
- CBC is usually INITIALLY NORMAL
- (CBC) Hemoglobin drops over time and also when IVF are given (dilutional effect)
24
Q
Anemia of blood loss: What is involved in chronic blood loss?
A
Body CAN COMPENSATE if able to
- Usually GI tract or uterine bleeding
- (e.g. elderly diverticulosis, menopause) - Causes anemia ONLY if blood loss greater than the capacity of bone marrow to replace lost RBCs
- Intrinsic bone marrow diseases OR nutritional deficiencies:
- Vitamin B12, Folate, Iron, Pyridoxine, Protein imbalance
25
Differential Dx for Anemia of decreased hematopoiesis
Iron Deficiency** - leading cause (not enough heme being made)
Vitamin B12 Deficiency
Folic Acid/Folate Deficiency
Anemia of Chronic Disease
Anemia of Bone Marrow Stem Cell Failure
-Primary failure (of bone marrow)
-Secondary failure from malignancy (causing bone marrow to be deficient)
26
Microcytic/Hypochromatic Anemia: slide contains:
Neutrophilic bands
neutrophils
hypochromatic cells (Fe deficiency until proven otherwise)
microcytic cells (can tell bc normal RBC is a little bit smaller than a lymphocyte)
Normal RBC might mean anemic pt received blood transplant
27
MIcrocytic anemia
small RBC
28
Hypochromic anemia
pale RBC
29
What is the gold standard for evaluating blood problems?
Bone marrow biopsy
30
Is a bone marrow biopsy necessary?
Not usually
Only if >= 2 cell lines are decreased on a lab result (e.g. RBC, WBC, Plt)
31
What kind of procedure is a bone marrow biopsy?
outpatient that last < 1 hr
not as bad as most ppl think
32
What can be found in a bone marrow aspirate slide?
made from liquid part of bone marrow
Very immature cells
Huge nucleus
33
What can be found in a bone marrow stain?
if there are only a few cells --> bone marrow isn't healthy
same for too many cells
34
What is the most common etiology of microcytic/hypochromic anemia?
Iron Deficiency (a type of anemia of diminished erythropoiesis)
35
Iron loss from chronic bleeding:
```
Menstrual blood loss (reproductive age women)
GI bleeding (age >50 in man or woman)
```
36
What are the other etiologies of microcytic/hypochromic?
- Thalassemia
- Hemoglobinopathy
- Anemia of Chronic Disease
- Sideroblastic Anemia
37
What is the most common nutritional disorder throughout the world?
Iron deficiency
38
Where are Fe2+ found in the body?
- 80% of Fe2+ found in Hb
| - 20% found in myoglobin, cytochromes, catalase, others
39
Name the two Fe storage pool
Ferritin and Hemosiderin
40
What is Ferritin?
Protein-Fe complex found mostly in liver, spleen, bone marrow and skeletal muscle
41
What is Hemosiderin?
Brown pigment in macrophages
42
What is the histologic stain for Fe?
PRUSSIAN BLUE
Darker blue spots mean that there is a concentration of Fe in that area
43
What are the lab test for Fe?
Serum Fe: concentration on transferrin (transfers iron in the body)
Serum Ferritin: proportionate to total body Fe stores
Total Iron-Binding Capacity: amount or iron carried by blood
--INDIRECT measure of transferrin
Transferrin Saturation: iron/TIBC x 100
44
```
What are results for Iron Deficiency anemia?
Serum Fe:
Serum Ferritin:
Serum TIBC:
Transferrin Saturation:
```
Serum Fe: DECREASED
Serum Ferritin: DECREASED
Serum TIBC: INCREASED
Transferrin Saturation: LOW
45
If you have microcytic anemia + esophageal webs, what's your dx?
Plummer-Vinson Syndrome:
Microcytic, Hypochromic Anemia, Atrophic Glossitis and Esophageal Webs (Upper GI)
46
What type of anemia is Megaloblastic Anemia?
and
Name the two deficiency
Vitamin Deficiencies
Vitamin B12 Deficiency
Folic acid/Folate Deficiency
47
What is Megaloblastic anemia?
Macrocytic
| Results from inhibition of DNA synthesis during red blood cell production
48
What does Vit B12/Cobalamin require for absorption and where is it absorbed?
INTRINSIC FACTOR
It's secreted by PARIETAL CELLS IN STOMACH
INTRINSIC FACTOR/VITAMIN B12 complex is absorbed in the terminal ileum (last 100cm)
49
What are some problems that impair Vit B12 absorption?
Crohn's Disease
stomach ca
just not enough B12
50
What two conditions lead to Folic Acid/Folate Deficiency?
Alcoholism (Usually a nutritional problem)
| Pregnancy (supplementation necessary to avoid neural tube defects)
51
What causes Vit B12 deficiency?
Nutritional deficiency
GI tract malabsorption:
-Surgical rearrangement
-Autoimmune (pernicious anemia--> attack on parietal cells)
-Parasitic infections (fish tapeworm --> eats all the B12)
52
What are some characteristics of Vit B12 deficiency?
Megaloblastic anemia
hypersegmented neutrophils --> nucleus inapporpriately develops
Neuropathy (irreversible)
53
What causes Anemia of Chronic Disease?
Chronic inflammatory diseases may impair the production of erythrocytes in myeloid bone marrow
54
What are the 3 Major Categories of Inflammatory Diseases that cause Anemia of Chronic Disease?
Chronic Infectious Diseases: osteomyelitis, bacterial endocarditis, lung abscess
Chronic Autoimmune Disorders: collagen vascular diseases, inflammatory bowel disease
Malignant Neoplasms
55
Anemia of Chronic Disease:
| Defect of iron incorporation into Hb molecules during erythropoiesis:
Problem in mobilizing Fe from storage pool
56
```
What are results are seen in Anemia of Chronic Disease?
Serum Fe:
Serum Ferritin:
Serum TIBC:
Transferrin Saturation:
```
```
Serum Fe: DECREASED/NORMAL
Serum Ferritin: NORMAL/INCREASED (inflammation - during acute inflammatory phase ferrtin will go up)
**Serum TIBC: DECREASED**
-limited ability to "grab up" Fe
Transferrin Saturation: NORMAL
```
** used to distinguish btwn this and Fe deficiency anemia
57
What is Pancytopenia?
An abnormal reduction in the number of erythroid (RBCs), myeloid granulocytes (WBCs), and megakaryocytes (platelets) in the blood
58
What is Aplastic anemia?
Pancytopenia due to the body's bone marrow not making enough new blood cells
59
Etiologies of Aplastic anemia?
Mostly drug and chemical exposures: idiosyncratic
| Autoimmune
60
How do you treat aplastic anemia?
Recovery doesn’t always occur –> bone marrow transplant
61
What are the characteristics of idiopathic aplastic anemia?
Mechanism of stem cell failure poorly understood
May occur at any age and no gender preference
- HYPOCELLULAR BONE MARROW
- ALMOST NO MATURING MYELOID CELLS—JUST SCATTERED LYMPHOCYTES AND PLASMA CELLS
62
What is Fanconi's anemia and what anemia does it fall under?
Autosomal recessive disease of defects in DNA repair leading to stem cell failure
Aplastic Anemia
63
What is PNH (paroxysmal nocturnal hemoglobinuria)?
Abnormal stem cell produces RBCs that are deficient in proteins attached by Glycosyl phosphatidyl inositol (GPI) anchor
- Loss of CD55/CD59
64
How do you treat PNH (paroxysmal nocturnal hemoglobinuria)?
Eculizumab is treatment
65
A rare form of bone marrow failure leading to erythroid aplasia only
Pure Red Cell Aplasia
- granulopoiesis and thrombopoiesis aren't effected
Type of Aplastic anemia
66
What disease is associated with Aplastic anemia?
Mostly idiopathic but...
| THYMOMAS of anterior mediastinum
67
What is Myelophthisic Anemia?
(Overcrowding inside bone marrow)
Bone Marrow space replaced by other components
-Neoplasm
-Fibrosis
68
What is seen on slides for Myelophthisic Anemia?
Target cells and Dacrocytes
69
Differential Dx of Myelophthisic Anemia?
- Metastatic carcinoma
- Myelofibrosis with myeloid metaplasia,
- Plasma cell myeloma
- Malignant lymphoma
- Osteosclerosis
70
What are the two types of organ failure associated with anemia of diminished erythropoiesis?
Chronic Renal Failure:
- Lack of erythropoietin production
- Often proportional to degree of renal failure
Diffuse liver disease:
- end-stage liver cirrhosis
- Infections (usually viral hepatitis)
- Toxins (acetaminophen, mushrooms)
71
What is hemolytic anemia?
Condition in which red blood cells are destroyed and removed from the bloodstream before their normal lifespan is over.
72
What are schistocytes?
Fragmented RBC cuased by physical damage to the circulating cell
on slides looks like "dented helmets"
seen in hemolytic anemia
73
Increased destruction of RBCs is...
Hemolysis
RBC usually live for 120 days
74
What are the causes of Hemolytic anemia?
- Mechanical Injury (valves)
- Autoimmune complement fixation on surface membrane
- Exogenous toxic Factors
- RBC membrane abnormalities
- Enzyme abnormalities
75
Clinical characteristics of intravascular hemolysis?
```
Anemia symptoms (fatigue, dyspnea)
Jaundice (destruction of Hb-->bilirubin)
```
76
What is Intravascular hemolysis?
When something is wrong with the RBC itself
77
How do the lab results look like for Intravascular hemolysis?
```
DECREASED Hb
DECREASED haptoglobin (binds Hb to prevent toxicity)
INCREASED LDH (lactate dehydrogenase)
INCREASED Reticulocytes (immature RBCs)
```
78
What is extravascular hemolysis?
RBC is "chewed up" in organ
| e.g Liver, spleen --> sinusoidal organs
79
Clinical characteristics of Extravascular hemolysis?
- Anemia (fatigue, dyspnea)
- Sometimes hepatomegaly, splenomegaly
- Less hemoglobinuria
- Fewer laboratory abnormalities
- Other comorbidities
80
Intrinsic causes of hemolytic anemia
- Defects in RBC membranes: hereditary
- Defects in Hb production: sickle-cell, thalassemia
- Defective RBC metabolism: G6PD deficiency, pyruvate kinase deficiency
81
Extrinsic causes of hemolytic anemia
- Infections (mycoplasma pneumonia)
- Autoimmune (SLE, RA, Hodgkin’s disease, CLL, PNH, HUS, TTP)
- Hypersplenism
- Toxins (lead, heavy metals)
- Trauma
- -Defective heart valves
- -“March hemoglobinuria”
82
What is Hereditary Spherocytosis?
Inherited disorder of erythrocytes
Abnormal membranes and shape of RBCs
-Mutated Spectrin (most common), ankyrin, band 3 protein, or protein 4.2
Seen most commonly in Northern European descendants (1 in 5,000)
-Usually autosomal dominant
83
What is a spherocyte?
- RBC with little of no central pallor.
- No longer biconcave.
- Smallest possible surface area-to-volume ratio.
- Less deformable
- -therefore more likely to be sequestered in splenic sinusoids
- Premature destruction
84
What is the gold standard lab test and result for Hereditary Spherocytosis?
Osmotic fragility
Abnormally increased
85
What are the clinic characteristics of Hereditary Spherocytosis?
- Anemia
- Splenomegaly
- Jaundice
Severity differs among pts
86
What is Hemolytic Crisis and what condition is it associated with?
Sudden onset of massive hemolysis, fever, abdominal pain, jaundice, low blood pressure, shock
Hereditary Spherocytosis
87
What is Hereditary Spherocytosis: Aplastic Crisis?
- Temporary suppression (shut down) of bone marrow production
- Worsening of anemia
- Later: Disappearance of reticulocytes from peripheral blood
88
What is Aplastic Crisis associated with?
Parvovirus Infection
89
What is Polychromasia and which condition does it appear in the lecture?
disorder where there is an abnormally high number of RBC found in the bloodstream as a result of being PREMATURELY released from the bone marrow during blood formation
- sign of immature RBC --> Reticulocytes are increased
has purple specs --> nuclear material
90
Is Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD deficiency) an intrinsic or extrinsic defect?
Intrinsic defect of hemolytic anemia usually caused by infection and drug exposure
- Anti-malarial
- Sulfa-drugs
91
What does G6PD do?
Key enzyme in the hexose monophosphate shunt (HMP) --> HMP produces NADPH needed for glutathione reductase
--NADPH removes reactive oxygen species from RBCs
92
What does G6PD deficiency do?
```
Causes oxidation of globin chains which leads to DENATURED HEMOGLOBIN (Heinz bodies)
and
after 2-3 days of oxidative stress
- acute intravascular hemolysis
- decreased hemoglobin
```
93
In what population does G6PD deficiency affect?
Deficiency is present in ~ 10% of African-Americans or those of Mediterannean ancestry
- Autosomal recessive inheritance
- Variable phenotypic expression of the disease
94
Heinz Bodies cause ...
splenic macrophages to “bite” out section of RBC membrane
| - ultimately leading to formation of spherocytes
95
Hemolytic Anemia: Intrinsic defects
What is Hemoglobinopathies?
Structural abnormalities in alpha or beta hemoglobin
| - Most common in beta-globin chain
96
What are the two clinically significant Hemoglobinopathies?
Thalassemia, Sickle-cell Anemia
97
What and where is the mutation for Sickle Cell Disease and Trait?
Glutamate --> Valine substitution at position #6 of b-globin chain.
Autosomal Recessive
98
What group of people do Sickle Cell Disease mostly affect?
Predominant in African-American population
| - Confers resistance to malaria (if heterozygous)
99
Heterozygous Sickle Cell Trait or Disease
Trait
| < 50% of hemoglobin is hemoglobin S
100
Homozygous Sickle Cell Trait or Disease
Disease
| > 50% of hemoglobin is hemoglobin S
101
In Sickle Cell anemia HbS undergoes ..., in ... condition?
polyermerization... low oxygen tension (ie. Denver)
102
HbS polyererization does what exactly in low O2 tension?
Converts normal hemoglobin from freely flowing liquid to viscous gel
- causes RBC membrane to undergo “Sickle” malformation
At first reversible but later irreversible
103
When does Chronic Hemolytic Anemia occur in relation to sickle cell?
Presence of irreversibly sickled RBCs
104
Irreversible sickled RBCs also results in what?
Occlusion of small blood vessels resulting in ischemic tissue damage
- this is why pt are in pain
- "gumming up" of vessels
105
When does the first sickling episode begin?
occurs in homozygote after “SWITCH” from producing normal hemoglobin F to attempting to produce normal hemoglobin A1 (but this can't be made)
- at about 5-6 months after birth
106
What facilitates sickling?
Dehydration and acid pH
| - high altitiudes
107
What occurs in Sickle Cell Disease and Trait?
- Elevated peripheral destruction of RBCs
- Average RBC survival in peripheral blood directly proportional to number of sickled RBCs
- - approximately 20 days
- Hyperplastic Bone Marrow with Erythroid Hyperplasia with extramedullary hematopoiesis
- - splenomegaly --> trying to get rid of sickle cells, it autoinfarcts
108
Clinical features of Sickle cell Disease and trait?
- Splenomegaly in early course of disease in children
- Erythrostasis in spleen results in repeated infarction of spleen: “AUTO-SPLENECTOMY”
- Infarction secondary to RBC occlusion often in bone, brain, kidney, liver and retina -- vaso-occulsive complication
- Chronic cutaneous leg ulcers in adults
- Pigment calculi (gallstones) in gallbladder
- Hyperbilirubinemia during active hemolysis
109
Which two bacterial infections are the most common etiology of DEATH in CHILDREN with HOMOZYGOUS sickle cell anemia?
Streptococcus pneumoniae
Haemophilus influenzae
Both are encapsulated
110
What is Sickle cell crisis associated with?
Associated with infection, dehydration and acidosis (favor sickling)
Associated with severe pain
111
What organs are involved in Vaso- occlusive episdoes?
bones, lungs, liver, brain spleen and penis
Priapism in male patients secondary to vascular engorgement of penis
112
What is involved in aplastic crisis in relation to sickle cell?
and
what infection is usually associated?
temporary cessation of bone marrow cell production --> it stops working
often associated with PARVOVIRUS INFECTION
113
what is Sequestration Crisis?
and
what clinical conditions are seen in CHILDREN still with spleen?
sequestration of most of blood volume in spleen
- leads to SPLENOMEGALY, HYPOGLYCEMIA and SHOCK in severe cases only in children who still have spleen
114
What is the definitive Dx for sickle cell
```
HEMOGLOBIN ELECTROPHORESIS
or
fetal DNA analysis
or
metabisulfite screening test
```
115
Sickel cell:
| What does chronic hypoxia lead to?
impairment of growth and chronic organ damage to spleen, heart and lungs
116
at what age do Homozygous Sickle cell disease usually live up to?
30s or 40s but many die in first three years of life secondary to bacterial infections
117
What condition can develop in pt with sickle cell secondary to Salmonella infection?
Osteomyelitits
118
What is Thalassemias?
ABNORMALLY DECREASED RATE OF PRODUCTION OF 1 or more GLOBIN CHAINS in a Hb tetramer
119
What is a-Thalassemias?
and
Seen in what population?
decreased rate of production of a-globin chains allow excess production of beta, gamma and delta-globin chains
a-Thalassemias are DELETIONS of genes coding for a-globin chains
Usually seen in patients of Asian descent
120
What is b-Thalassemias?
and
Seen in what population?
decreased rate of production of beta-globin chains allows for excess production in alpha-globin chain
Usually seen in patients of African/Mediterranean descent
121
What is seen in a Hb structure?
Tetrameric protein:
| 2 alpha globin chains, 2 beta chains, heme for each chain, Fe2+ for each heme
122
How many beta globin GENEs and alpha globin GENEs are there in a chain?
2 beta globin genes
4 alpha globin genes
123
in patients with Sickle cell which globin chain is increased?
gamma
| bc alpha and beta is abnormal
124
What is the globin changes over time?
gestational age: alpha majority, gamma
fetal age: make more beta, alpha is consistent throughout
postnatal age: alpha and beta dominate
125
Describe the mech. of disease of Thalassemia?
Excess a, b, g, or d chains precipitate out as tetrameric complexes (a4, b4, g4, or d4) -->
Lead to RBC membrane damage and early apoptotic necrosis
INEFFECTIVE ERYTHROPOIESIS within bone marrow and decreased RBC survival in peripheral blood
126
What is b-Thalassemia Major?
beta-0: if homozygous (both beta genes are reduced/absent), essentially no beta-globin chain production
- not making enough beta
127
What is b-Thalassemia Minor?
beta-+: if homozygous or heterozygous (1 bete gene is missing or dsyfxnal) will still be some beta-globin chain production
- you're making enough just less than normal
128
Which Thalassemia show up clinically?
b-Thalassemia Major
b-Thalassemia Minor is clinically silent
-decrease Hb, slight anemia
129
what are some characteristics of b-Thalassemia Minor?
- Usually low normal hemoglobin level or slight anemia
- RBC count often elevated BUT low MCV (small RBCs)
- Provides some protection against malaria
130
what are some characteristics of b-Thalassemia Major?
- Essentially no Hemoglobin A1 production
- Increase in Hemoglobin F
- Variable levels of Hemoglobin A2
131
What is seen on skull xray for Thalassemia?
"crew cut" appearance in severe Thalassemia
-in young pts, bone marrow will go into spasms and skull bones will go though hematopoeisis
132
What are the clinical findings of 1 deletion alpha chain gene ?
Silent Carrier, no physical abnormality
133
2 deletion alpha chain gene?
a-Thalassemia Trait, like Beta-Thalassemia Minor
134
3 deletion alpha chain gene?
Hemoglobin H (tetramer of beta chains) Disease, severe disease
135
4 deletion alpha chain gene?
Hydrops Fetalis, incompatible with life—death in utero,
Presence of hemoglobin Barts (tetramer of gamma chains)
High oxygen affinity prevents oxygen delivery to tissues
136
What is a target cell?
Aka: Codocytes - abnormal red blood cells with a bullseye appearance in hematology.
Usually seen in defective globin chain synthesis, (eg. hemoglobinopathies, thalassemia)
137
Which defect is autoimmune hemolytic anemia (AIHA)?
Extrinsic defect
Warm (most common) vs Cold
138
What do you find in the presence of Ig on teh surface of RBCs?
- Autoantibodies
| - Coomb’s positive (Direct anti-globulin test)
139
why is direct coomb's test done?
It finds antibodies attached to your red blood cells.
| -The antibodies may be those your body made because of disease or those you get in a blood transfusion.
140
What is a Direct Coomb's Test?
Test done on a sample of red blood cells from the body. It detects antibodies that are already attached to red blood cells.
141
What is an Indirect Coomb's Test?
Test done on a sample of the liquid part of the blood (serum). It detects antibodies that are present in the bloodstream and could bind to certain red blood cells, leading to problems if blood mixing occurs.
- used more in transfusion
142
What is Coomb's reagent?
antihuman antibodies
143
How does Direct Coomb's work?
- blood sample taken from AIHA pt
- after pts washed RBCs are incubated with antihuman Ab then RBC agglutinate
- antihuman Ab form links btwn RBC by binding to the Ab already on the RBC
144
How does Indirect Coomb's work?
- get recipient's serum containing Ab (Ig's)
- Add donor's blood sample to the serum
- recipient's Ig's form ab-antigen complex with donor's RBC
- Coomb's Ab (antihuman Ig) add to the solution
- agglutination fo RBC bc human Ig's are attached to RBC
145
what is the primary cause of Warm AIHA?
60% of cases are idiopathic
40% are secondary to drugs or other disease
146
Which auto-Abs dominate on a RBC in warm AIHA?
IgG (rarely IgA)
147
what is the primary cause of Warm AIHA?
60% of cases are idiopathic
40% are secondary to drugs or other disease
148
Which auto-Abs dominate on a RBC?
IgG (rarely IgA)
149
In warm AHIA, hemolysis is ... ?
extravascular (removal of opsonized RBC's in spleen)
- transforms normally biconcave RBCs into spherocytes
- splenomegaly results over time
150
Dx of AHIA?
osmotic fragility
151
What are the 3 immunologic mechanisms for warm AIHA?
Hapten Model
Immune-Complex Model
Autoantibody Model
152
what is Hapten Model?
Drug combines with RBC membrane to form a new Ag to which Ab binds
- related to LARGE DOSES of antibiotics
153
What is Immune-Complex Model?
Drug binds to plasma protein and DRUG-PROTEIN COMPLEX serves as Ag for Ab binding
- Ag-Ab complex is non-specifically attached to RBC membrane
154
what is Autoantibody Model?
Drug somehow causes the production of Abs against INTRINSIC RBC Ags
155
Which defect is Cold Agglutinin Immune Hemolytic Anemia?
Extrinsic
IgM auto-antibodies bind to RBCs
- IgM is pentameric and binds best at low temps
- Exacerbated in winter months in northern climates
156
How do the symptoms occur?
- agglutination of RBCs with fixation of complement in distal parts of the body where temp < 30C
- hemolysis occurs when RBCs return to 37C
- IgM is released from RBCs BUT complement is still on RBC
- which makes them more susceptible to phagocytosis in spleen and/or liver --> vas. obstruct, raynauds
157
What are the clinical symptoms of cold AIHA?
vascular obstruction
| Raynaud's Phenomenon
158
How do the symptoms occur?
- agglutination of RBCs with fixation of complement in distal parts of the body where temp < 30C
- hemolysis occurs
- IgM is released from RBCs BUT complement is still on RBC
- which makes them more susceptible to phagocytosis in spleen and/or liver --> vas. obstruct, raynauds
159
Does Cold AIHA require specialized colleciton and analysis?
YES
160
Trauma to RBCs is a ... defect?
and
what does it lead to?
Extrinsic
Fragmentation of RBCs with trauma may lead to INTRAVASCULAR HEMOLYSIS
161
Mechanism of autoantibody production in cold AIHA is ...
...poorly understood
162
Trauma to RBCs is a ... defect?
and
what does it lead to?
Extrinsic
Fragmentation of RBCs with trauma may lead to INTRAVASCULAR HEMOLYSIS
163
In PNH, what does the GPI protein do?
GPI proteins normally inactivate complement
**Abnormal RBCs are sensitive to lysis from endogenous complement**
Paroxysmal Noctural Hemoglobinuria (PNH):
Glycosyl phosphatidyl inositol (GPI)
164
Differential Dx of Trauma to RBCs?
-Heart Valve Prostheses Defect
-Deposition of FIBRIN in Microvasculature
=TTP, HUS, DIC, malignancy, hypertension, renal cortical necrosis, SLE, metastatic adenocarcinoma
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In PNH, what does the GPI protein do?
GPI proteins normally inactivate complement
Paroxysmal Noctural Hemoglobinuria (PNH):
Glycosyl phosphatidyl inositol (GPI)
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Which sequellae of PNH has ~ 50% fatal rate?
Hypercoagulable State with repeated episodes of venous thrombosis involving hepatic, portal or cerebral veins
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What are the complications of PNH?
Hemosiderinuria leads to Iron Deficiency anemia --> lead to pancytopenia
pancytopenia: An abnormal reduction in the number of RBC, WBC, plt
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What is a possible outcome of PNH?
Hypercoagulable State with repeated episodes of venous thrombosis involving hepatic, portal or cerebral veins
Fatal in ~ 50% of cases
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What are other possible outcome of PNH?
- Infections related to granulocyte (neutrophil) dysfunction or granulocytopenia may also occur
- Clonal abnormality related to other stem cell disorders (aplastic anemia/acute leukemia)
- Usually chronic disease with median survival of 10 years if untreated
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What other disease are associated with hemolysis?
HELLP – pregnant women
HUS – bacterial infections - E. coli O157:H7
TTP – thrombotic thrombocytopenic purpura
- Defect or auto-antibodies to ADAMTS13
