Hematopathology Schoenwald Flashcards
1
Q
What are three mechanisms of anemia?
A
- Blood loss(acute or chronic
- Decreased production of RBC
- Increased destruction of RBC (hemolysis)
2
Q
This acquired defect of anemia occurs when complement-regulating proteins CD55 and CD59 are deficient and red cells are more prone to lysis by complement
A
PNH (Paroxysmal nocturnal hemoglobinuria)
3
Q
Acquired defect in the gene for phosphatidylinositol class A (PIG-A) goes with which anemia type?
A
PNH (Paroxysmal nocturnal hemoglobinuria)
4
Q
What are clinical signs of PNH (Paroxysmal nocturnal hemoglobinuria)?
A
episodic hemoglobinuria, 1st morning urine
5
Q
Disturbance of stem cells is in what type of anemia
A
aplastic
6
Q
Which two types of anemia have defective heme production?
A
IDA & thalassemia
7
Q
Which two types of anemia have defective DNA production?
A
Vitamin B12 & folate deficiency
8
Q
Which type of anemia has destruction of bone marrow?
A
Metastatic tumor
9
Q
Where does extravascular removal of RBC from circulation happen?
A
Phagocytic systems of liver and spleen
10
Q
Where does intravascular removal of RBC from circulation happen?
A
Destruction of RBC inside the vessel
11
Q
Complications of extravascular removal of RBC from circulation?
A
• Hemosiderin deposition in organs
• Jaundice and gallstones
– Result from elevated unconjugated bilirubin associated with
hemolysis
12
Q
Complications of intravascular removal of RBC from circulation?
A
- Acute tubular necrosis due to hemoglobinemia
* Jaundice,gallstones can occur due to increased unconjugated bilirubin
13
Q
What are lab findings in hemolysis of RBCs?
A
- Low RBC
- H/H low
- Low K+
- Increased LDH
- Decreased haptoglobin
14
Q
Spherocytes
A
hereditary spherocytosis and immune hemolysis
15
Q
Schistocytes
A
TTP and HUS
16
Q
Target cells
A
hemaglobinopathies
17
Q
Teardrops
A
myelofibrosis
18
Q
Sickle Cells
A
sickle cell, thalessemia minor with sickle cell
19
Q
Rouleaux
A
“stacking of coins” due to increased globins or decreased albumin (multiple myeloma)
20
Q
What does an increased reticulocyte count mean?
A
• bone marrow intact and able to produce RBC
– Acute blood loss or hemolysis
21
Q
What does a decreased reticulocyte count mean?
A
primary bone marrow disorder or deficiency in building blocks-iron, b12 or folate
22
Q
Microcytic anemias (name 3)
A
- Iron Deficiency
- Thalassemia
- Late stage anemia of chronic disease
23
Q
What are a few causes of IDA?
A
- In US, most likely due to GI blood loss or menstrual blood loss
- Outside of US-poor nutrition
- Malabsorption or increased demand(pregnancy)
24
Q
What labs would you expect for IDA?
- Ferritin
- Serum Iron
- Iron Stores in Bone Marrow
- TIBC
- RDW
- Transferrin
A
- Dec Ferritin
- Dec Serum Iron
- Dec Iron Stores in Bone Marrow
- Inc TIBC
- Inc RDW
- Dec Transferrin (ratio of serum iron to TIBC normal>20%, in iron deficiency <10%
25
Deficient production of hemoglobin due to mutation or complete loss of globin chain is what anemia?
Thalassemias
26
Tell me whats going on with the alpha and beta globulin chain in thalassemias
There are 4 copies of the alpha globulin chain and 2 copies of beta globulin.
27
Alpha or beta thalassemia?
Due to complete loss of one or more of the 4 copies of the alpha globulin chain gene
Alpha
28
Alpha or beta thalassemia?
Malfunction of gene due to mutation which result in complete loss of the hemoglobin protein
Beta
29
Loss of one copy of gene
silent (carrier)
30
Loss of 2 copies
alpha thalassemia trait
| asymptomatic but MCV low
31
Loss of 3 copies
HbH disease (marked anemia)
32
Loss of 4 copies
hydrops fetalis (stillborn)
33
Mediterranean descent
Beta thalassemia
34
Alpha or beta thalassemia?
Alpha chains are insoluble and result in intravascular hemolysis and ineffective erythropoiesis
Beta
35
This type of beta thalassemia is usually onset after 6 months of age due to loss of Hgb F and transition to Hgb A
Beta thalassemia MAJOR
36
Which is more problematic, beta thal major or minor?
MAJOR (develop skeletal deformities due to bone marrow expansion) and may not live past 20-30s
Require blood transfusions
MINOR doesn't require transfusions and people just have disproportionate hgb (10) and MCV (55)
37
Labs of Thalassemia?
* MCV
* hgb
* Anisocytosis shows
* Poikilocytosis shows
* Decreased MCV
* Decreased hgb
* Anisocytosis (microcytes)
* Poikilocytosis (targets)
38
Anemia that occurs in background of chronic disease
| – Lung carcinoma, Hodgkin lymphoma, rheumatoid arthritis, infection-TB
Anemia of chronic dz
39
• Cannot transfer iron from phagocytic cells to
erythroid precursors
• Through TNF and interferons erythropoietin is decreased
• Hepcidin is stimulated
– Hepcidin-protein that is key regulator of the entry of iron into circulation
– impairs release of iron from storage
Anemia of chronic dz
40
Labs of anemia of chronic dz
- storage iron
- serum iron
- TIBC
- ferritin
- inc storage iron
- dec serum iron
- dec TIBC
- inc ferritin
41
B12 is needed for regeneration of __________ so giving folate will correct a b12 anemia
tetrahydrofolate
Unfortunately doesn't correct neuro findings
42
* Impaired DNA synthesis involving all bone marrow precursors, not just RBC
* Impairment of DNA slows nuclear maturation but not cytoplasmic
Vitamin B12 def (macrocytic anemia)
43
B12 deficiency causes elevated levels ________ and _________
homocysteine and methyl-malonic acid (MMA)
44
What are some complications of B12 def?
* Anemia, thrombocytopenia and leukopenia
* Ineffective erythropoiesis
* Neurologic deficiencies
45
Pernicious anemia
B12 def
46
– Condition is due to antibodies against parietal cells or blocking antibodies or antibody against B12-IF complex
– Autoimmune gastritis, loss of parietal cells causes loss of intrinsic factor
Pernicious anemia
47
Diphyllobathrium latum
Pernicious anemia cause
infection –fish tapeworm
48
Hypersegmented neutrophils on CBC
Vit B12 def
49
How do you distinguish B12 def from folate def?
– Folate deficiency does not cause neurologic
deficits
– Often due to dietary deficiency(US)
• alcoholism
– Folate deficiency is not associated with pernicious anemia
50
Anemia due to absence of RBC in bone marrow and likely due to suppression of stem cell function
aplastic anemia
51
Which anemia can convert to leukemia?
aplastic anemia
52
What type of anemia has the following?
– Increased RBC destruction (intravascular or extravascular
– Increased erythropoiesis
– Increased iron deposition in tissues-spleen and
liver
– Some cases have pigment gallstones (from increase in bilirubin
Hemolytic anemia
53
What are signs of intravascular hemolytic anemia on labs?
- Haptoglobin
- Billirubin
- LDH
- urine
* Decreased haptoglobin
* Increased unconjugated(indirect) bilirubin
* Increased LDH-markedly
* Positive urine hemosiderin and urine hemoglobin (brown urine)
54
What are signs of extravascular hemolytic anemia on labs?
- Haptoglobin
- Billirubin
- LDH
- urine
• Normal to slightly decreased haptoglobin (not as marked as with
intravascular)
• Increased unconjugated (indirect)bilirubin-usually more than intravascular
• Normal to slightly increased LDH
• Negative urine hemosiderin and urine hemoglobin
55
What is the mechanism of increased unconjugated bilirubin in hemolysis?
RBC contain billirubin, rbc phagocytosed by macrophage, bilirubin breakdown and separation by macrophage, unconjugated billirubin binds with albumin and goes into liver, unconjugated converts to conjugated which is then excreted out by urine and GI tract
56
Explain why haptoglobin decreases in hemolytic anemia?
Large release of free hgb by rbc breakdown causes haptoglobin to quickly bind to it. The liver is unable to rapidly compensate for this so it ultimately decreases
57
What are examples of congenital hemolytic anemia?
- Enzyme def (G6P)
- Defects of cytoskeleton (spherocytosis)
- Hemoglobinopathies (sickle cell, thalassemias)
58
What are examples of acquired hemolytic anemia?
- Antibody induced (autoimmunue process)
| - Mechanical (mechanical heart valve)
59
In this test, antibodies causing hemolysis are on the surface of the RBC. What antibody is involved causing agglutination of cells?
Direct Coombs, IgG
60
In this test, antibodies causing hemolysis are in the plasma but not on the RBC surface so the antibody reacts when an antibody added
Indirect Coombs
61
– RBC transfusion reactions-ABO or other blood
type incompatibility
– Ertyhroblastosis fetalis-RH incompatibility
These are examples of what?
Isohemagglutinin
62
– Warm autoimmune anemia
– Cold autoimmune anemia
Are examples of what?
Autoimmune
63
___________ transfusion rxn is IgM mediated, involves intravascular hemolysis, hemoglobinemia leading to acute renal failure and high mortality rate, and Anti A and Anti B IgM naturally occurring
ABO transfusion rxn
64
What blood type is the universal donor?
O
65
What blood type is the universal recipent?
AB
66
Blood type O has _________ antigens present and _________ antibodies present
No, anti A and anti B
67
A type blood has _____ antigen present and ______ antibodies present
A, anti B
68
Blood type AB has _________ antigens present and _________ antibodies present
AB, none
69
__________ transfusion rxn is IgG mediated, involves extravascular hemolysis- antibody binds to RBC then complex is removed by spleen, usually require previous exposure to non ABO antigen (example Rh factor), and can cause jaundice
Non ABO transfusion rxn
70
Maternal antibody against a fetal red blood cell antigen and Rh factor (made up of DCE ag) D potential for most potent reaction is what disease?
Erythroblastosis Fetalis
71
If the mom is Rh factor (D) -, 1st child D+= exposure is the child okay? What about the second child?
* Mom Rh factor(D) negative, 1st child D+=exposure , child okay
* Second child D+= erythroblastosis fetalis due to IgG present in mom, able to cross placenta and bind to fetal RBC=hemolysis
72
What is the presentation of Erythroblastosis Fetalis
Fetal hemolytic anemia
- hydrops fetalis
- kernicertus (mental retardation/death)
73
In Erythroblastosis Fetalis is direct coombs + or -?
positive direct coombs
74
You give this to moms with Rh- and when do you give it?
Rhogam (anti D antibody) and during pregnancy and at birth
75
Warm or Cold autoimmune anemia?
* IgG vs self antigen reaction at 37 C acts as opsonin
* RBC removed by phagocytosis
* Extravascular hemolysis
* Present with anemia, jaundice,+/-splenomegaly
Warm
76
In warm autoimmune anemia, direct coombs is _________ and there is an elevated _________ count
positive, reticulocyte
77
Whats the cause of warm autoimmune anemia
• Primary-60% idiopathic
• Secondary-drugs, Bcell neoplasm, lupus
– Penicillin, methyldopa, immune complex formation with drugs
78
Warm or cold hemolytic anemia?
IgM binds to RBC at 300 with complement, at 370 IgM releases, cleaves C3b>opsonin
Cold
79
In cold autoimmune anemia, direct coombs is _________ and there are _________ present
Negative, spherocytes
80
What is this describing?
* Defect in cytoskeleton of RBC
* Mutation of gene of one of the proteins responsible for cytoskeleton matrix
* RBC not as flexible and becomes trapped in spleen
Hereditary spherocytosis
81
Labs for spherocytosis: direct coombs ________, ________ osmotic fragility test (cell cannot swell in hypotonic solution), ________ unconjugated bili
negative, increased, increased
82
Homozygous sickle cell means?
all HbS anemia, present with siclkle cell
83
Heterozygous sickle cell means?
50% Hbs trait, half sickle cell
84
Sickle cell is “sticky” hemoglobin due to _______ substitution for _________ in Beta globin chain
Valine, glutamic acid
85
This is describing what?
• X linked recessive
• Most common enzyme deficiency to cause hemolysis
• Prevalent in Middle East and African descent
• RBC unable to regenerate glutathione-normally
helps to reduce oxidized substances
• Source of oxidants
– Antimalarial (primiquine), sulfonamides, aspirin, nitrofurantoin, viral hepatitis and fava beans
G6P Deficiency enzyme
86
This disease shows Heinz bodies and bite cells
G6P Deficiency enzyme
87
Examples of what disease?
Increased number of RBC
• Clinical findings=red faces, headaches, hgb>60%
Polycythemia
88
Relative polycythemia
Hemoconcentration
89
Primary polycythemia
Polycythmia rubra vera-proliferation of RBC
90
Secondary polycythemia
Lung dx, cyanotic heart dx, erythropoietin producing tumors
