1
Q
What are the two broad categories of red blood cell disorders?
A
- erythrocytosis- increased RBC mass
2. anemia- decreased RBC mass
2
Q
What are the three basic pathophysiological processes that lead to anemia?
A
- blood loss
- decreased RBC production
- increased RBC destruction/consumption
3
Q
What is the main cause of acute blood loss that causes anemia?
The main chronic blood loss causes?
A
Acute: trauma
Chronic:
- GI lesions
- GU/ gynecologic in the
4
Q
What are the 4 major causes of hereditary intravascular hemolysis?
A
- membrane abnormalities (spherocytosis, elliptocytosis)
- Enzyme deficiencies- G6PD, glutathione synthase
- Hb synthesis mutations - hemoglobinopathies (sickle cell, HbC HbE)
- Deficient Hb synthesis- thallasemia
5
Q
What are the major causes of acquired intravascular hemolysis?
A
paroxysmal nocturnal hemoglobinuria
6
Q
What are the 3 major causes of extrinsic (extravascular) hemolyis?
A
- Antibody mediated (auto/allo Ab)
- Mechanical trauma to RBC- microangiopathic hemolytic anemia (TTP, HUS, DIC)
- Infections (malaria)
7
Q
What are the 5 major causes of impaired RBC production?
A
- Disturbed proliferation/differentiation of stem cells (aplastic anemia, pure RBC anemia)
- Defective DNA synthesis (B12, folate)
- Defective Hb synthesis: iron, sideroblastic, thalassemia
- Marrow replacement: neoplasm, MDS
- Marrow infiltration: myelophthisic anemoa
8
Q
What are the four major ways the body compensates for tissue hypoxia due to anemia?
A
- Increased CO and pulmonary function
- shunting blood to vital organs (pallor)
- increase RBC production (Epo from kidney, Iron from macrophage stores)
- increase 2.3 DPG to release O2 easier to tissue
9
Q
What laboratory studies are done first when H&P suggests anemia?
A
- CBC with reticulocyte count
2. morphologic examination of peripheral blood
10
Q
What does the CBC give you information about?
A
- RBC count
- RBC indices
- WBC count
- platelet count
11
Q
What is the most imortant piece of information in the CBC for assessing overall oxygen-carrying capability?
A
Hb concentration
12
Q
What are MCV, MCHC, and RDW? What does each tell you about the anemia?
A
MCV= mean cell (corpuscular) volume can tell you if the RBC are microcytic, normocytic or macrocytic
MCHC= mean cell Hb concentration which can tell you if the cell is hypochromatic (central pallor >1/3 cell size) or hyperchromatic (central pallor < 1/3 cell size)
RDW= RBC distribution of width. Tells you if the cells are anisocytotic (Fe deficiency) or non-anisocytotic (anemia of chronic disease)
13
Q
What anemia is associated with a high red blood cell count?
A
Thalassemia- probably because globulin is not synthesized –> low Hb.
Body attempts compensation, and you get lots of RBC each with less Hb concentration
14
Q
What are reticulocytes? Where are they made and what is their typical life cycle?
A
They are the first anucleate cell that is a RBC precursor. It is the final stage before becoming a mature RBC.
They begin maturation in the marrow (3days)
Then circulate in the peripheral marrow for 1 day before becoming RBC
15
Q
What special stain is used to test for the presence of reticulocytes?
A
new methylene blue to visualize the reticular basophilic matrix of rRNA
16
Q
What percent of peripheral blood cells should be reticulocytes?
What happens to the number of reticulocytes in the blood following acute blood loss?
A
0.5-1.5%
If there is anemia due to blood loss, reticulocyte count should increase and be apparent in peripheral blood 2-3 days after the onset of blood loss
17
Q
In what anemic situations would the reticulocyte count elevate?
In what situations would the reticulocyte cound decrease?
A
Increase: 1. 2-3 days after blood loss 2. RBC loss/destruction via hemolysis Decrease: Abnormal/decreased bone marrow RBC production
18
Q
How do you calculate a corrected reticulocyte count? Why must you correct the count?
A
CRC= Patient’s count x (Hct/45)
The count needs to be corrected b/c reticulocyte count is a percentage and in anemic patients RBC count is depleted. This can give an inflated reticulocyte count.
19
Q
Reticulocytes are released into the peripheral blood at an _____________stage of development during anemia.
The stage at which the reticulocyte leaves is dependent on ______________________.
A
Earlier stage (ex. after 1 day of maturation in the marrow instead of the normal 3)
The stage at which it leaves is dependent on the degree of anemia (patient’s Hct)
20
Q
What is the reticulocyte production index?
What should RPI be if the patient is NOT anemic?
A
The stage at which the reticulocyte leaves the marrow.
It is CRC/Maturation Time Factor
If the patient is not anemic, RPI is between 1 and 2%
21
Q
If the patient is anemic, RPI less than what would indicate an inadequate bone marrow response?
What RPI indicates an adequate bone marrow response in an anemic patient?
A
Less than 2% RPI would indicate an inadequate bone marrow response to correct the anemiaO
RPI greater than 3% indicates an adequate response
22
Q
On the Giemsa-Wright stain of the peripheral blood what do the following correlate with?
- size of the RBC
- chromicity
- variability in size
- amount of RBC polychromasia
A
- MCV
- MCHC
- RDW
- reticulocyte count
23
Q
What are follow-up tests you can do after examining blood smear and CBC?
A
- Fe indices
- Plasma, UCB, haptoglobulin = hemolytic
- Serum B12, folate, homocysteine, MMA= megaloblastic
24
Q
Describe the anemia associated with acute blood loss.
A
It is a rapid decrease in intravascular whole blood. At first, there will be nothing remarkable on CBC because that measures % and everything decreases by relatively the same concentration.
When extravascular (tissue) fluid tries to replenish the decreased vascular supply or therapeutic volume is replaced, anemia and cytopenia will be recognized.
25
Describe the MCV and MCHC associated with acute blood loss.
| What would the reticulocyte count show?
normocytic and normochromic.
| The reticulocytes will be normal for 2-3 days at which point there will be a compensatory increase
26
Describe anemia associated with chronic blood loss.
The bone marrow will increase RBC production and compensate for the blood loss.
Over time, iron is used faster than it can be taken in, and an Fe-deficient anemia will develop.
27
If there is Fe deficiency in an elderly individual, what should it be regarded as "unless proven otherwise"?
Right-sided colon cancer causing chronic blood loss--> Fe deficiency
28
What are the three main ways anemia by decreased production occur?
1. Decreased proliferation
2. Decreased maturation
3. Secondary to inflammation--> ACD
29
What regulates RBC production?
Where is it produced?
What does it act on?
Erythropoietin (Epo) is produced by the kidney in response to low O2 (tissue hypoxia) and goes to the blood marrow to cause erythroid progenitor cells to proliferate and mature
30
What happens to RNA, nuclei, cytoplasmic Hb and cytoplasmic organelles as the RBC progenitors mature in the bone marrow?
What does this do to the color?
RNA decreases, nuclei shrink and are extruded, Hb increases and organelles decrease.
Color change is from blue to red.
31
On Wright-Giemsa stained peripheral blood, the earlier reticulocytes appear ________. The percentage of these cells can give information about the number of reticulocytes, however, for a true count a special stain (_____________) will stain the _____________________ creating the reticulated appearance in the cells.,
Polychromatic (magenta)
New methylene blue
rRNA
32
Describe the MCV, MCHC and reticulocyte count associated with proliferation defects.
normocytic and normochromic with decreased reticulocyte count
Proliferation defects arise from absolute decrease in RBC precursors
33
What 3 pathological states are associated with proliferation defects?
1. Renal failure (make less Epo)
2. Aplastic anemia (stem cell defects)
3. myelophthisic anemia (bone marrow replaced by non-hematopoietic tissue)
34
Why does renal failure cause proliferation defects of RBC?
the kidneys no longer make adequate epo
35
What is aplastic anemia? Why does it cause proliferation defects?
What would the bone marrow and blood smear look like?
It is a congenital or acquired defect in RBC stem cells leading to a failure to produce all hematopoietic lineages.
Bone marrow becomes hypocellular, and peripheral blood smear is pancytopenic.
36
What is myelophthisic anemia?
What is a characteristic cell you would see on a peripheral blood stain?
What does the reticulocyte count look like?
When bone marrow is replaced by non-hematopoietic tissue.
The body shifts production of RBC to other organs like the spleen and liver which do not have regulation so they release immature granulocytes and RBC to the peripheral blood.
You will see teardrop cells with myelophthisic anemia.
Reticulocyte count is elevated (a differentiating factor from the other proliferative defect anemias; renal failure and anaplastic anemia)
37
What are four examples of things that could cause myelophthisic anemia?
Leukemia
Metastatic carcinoma
Myelofibrosis
Storage disease of macrophages
38
What is meant by "maturation defects"?
What would you see in the bone marrow?
What would the peripheral blood smear show?
It is when there is adequate erythroblastic proliferation but the cells cant proceed all the way to maturity. ("ineffective erythropoiesis")
Marrow would be hypercellular with RBC precursors.
Peripheral blood would show a lack of mature RBC
39
What are 4 examples of conditions that would cause ineffective erythropoiesis?
1. Fe deficiency
2. Folate deficiency
3. B12 deficiency
4. Myelodysplastic disorder
40
What would the MCV, MCHC and RDW be for Fe deficient anemia?
microcytic and hypochromic due to the lack of iron to make Hb.
Microcytic- the cells undergo another division to make the cell smaller to make the concentration of Hb per cell larger
Hypochromia because despite the extra division, there is still too little Hb for the cell
RDW shows anisocytosis (large variation in size) and poikilocytosis (variable shape)
41
Describe the process by which Fe deficient anemia occurs.
Fe deficiency occurs when iron loss exceed iron intake.
1. Body attempts compensation by mobilizing iron stores (ferritin) and increasing Fe absorption
2. If the imbalance continues, serum Fe is decreased and plasma transferrin increases
3. Finally when the ferritin stores and plasma Fe are used up, anemia will occur
42
Describe the peripheral blood RBC count and reticulocyte count for iron deficiency.
RBC count is low bc you need iron to make functional RBC.
| Reticulocyte count is low
43
What is the gold standard for diagnosis of Fe deficiency?
Prussian blue stain on the bone marrow aspirate
44
Describe what you would see on a blood smear for Fe deficiency.
What would you see in the marrow?
Smear:
microcytic, hypochromic, anisocytotic, poikilocytotic RBCs with low RBC count and low reticulocyte count.
Marrow:
erythroid precursor hyperplasia (mild)
45
What are the major causes of megaloblastic anemia?
Folate deficiency
B12 deficiency
Toxins/Medications
MDS
46
Deficiency of folate OR B12 leads to impaired ___________ with relatively intact ______________.
Impaired nuclear maturation (because they are cofactors for dTMP for DNA synthesis)
Intact cytoplasmic maturation
47
Describe the MCV, RDW, and reticulocyte count for a B12/folate deficiency.
Macrocytic cells with a very high distribution width and low reticulocyte count
May also see leukocytopenia and thrombocytopenia
48
What are the two cells seen on a peripheral blood smear that would warrant further testing for folate or B12 deficiency?
What 5 other abnormal cells are seen on the smear?
1. Macro-ovalocytes
2. Hypersegmented neutrophils (6 or more lobes)
Other cells:
1. tear-drop cells
2. nucleated RBCs
3. basophilic stippling (precipitated RNA)
4. RBC fragments (secondary to hemolysis)
5. lack of polychromasia
49
What serum markers will be elevated with megaloblastic anemia? Why?
lactate dehydrogenase and bilirubin because they are markers associated with hemolysis of cells.
Megaloblastic anemia is associated with ineffective erythropoiesis and extensive intramedullary deaths of RBCs . (causing the serum increase in LDH and UCB)
50
What 5 additional tests are analyzed if you suspect megaloblastic anemia?
1. serum B12
2. serum folate
3. serum Methylmalonic acid
4. serum homocysteine
5. RBC folate
51
Serum cobalamin is fairly sensitive and specific for B12 deficiency. What situations could give it a false decrease in B12?
1. Pregnancy
2. HIV
3. Folate deficiency
52
What is the problem with testing serum folate? Compare that to testing with RBC folate.
Serum folate fluctuates with diet and hemolysis. RBC folate has less short-term fluctuation but can be deceptively low in B12 deficiency
53
If cobalamin deficiency is associated with a falsely low RBC folate, what happens to the serum folate to let you know that it is in fact a B12 deficiency?
serum folate is elevated
54
What 2 tests are used to confirm the diagnosis of B12 or folate deficiency?
Serum homocysteine is elevated in B12 or folate deficiency.
| Serum MMA is normal in folate deficiency but elevated in B12 deficiency
55
What is seen in the bone marrow of someone with a B12 or folate deficiency?
left shift- hypercellularity of immature cells with megaloblastic precursors
56
How can MDS be differentiated from folate/B12 deficiency?
They both share features of megaloblastic anemia on peripheral blood smear and marrow.
Megaloblastic: hypersegmented neutrophils, giant band neutrophils, metamelanocytes
MDS: hypo-segmented neutrophils, hypogranulated granulocytes
57
What is anemia of chronic disease?
When does it develop?
What is the process by which it causes anemia?
anemia associated with inflammatory states like infection or malignancy.
It develops 1-2 months after the onset of the underlying disease.
```
Cytokines are released that:
1. decrease iron absorption
2. sequester Fe in macrophages
3. decrease erythropoietin production
(the body thinks a bacterial invader is there so it is sequestering the Fe so the bacteria can't use it, even though there is not something there)
```
58
What is the profile for ACD in iron tests?
1. decreased serum Fe
2. Increased Fe store in ferritin
3. decreased Fe-binding capacity
59
What would bone marrow observation reveal about ACD?
1. normal number of RBC precursors
| 2. Increased Fe stores with decreased sideroblastic Fe
60
What is the MCV and MCHC for ACD?
80% are normocytic and normochromic
| 20% are microcytic and hypochromic (most prevalent form of microcytic anemia in tertiary care centers)
61
What lab evidence would support the findings for hemolytic anemia?
Signs that show bone marrow compensation:
1. Increased marrow RBC precursors
2. Peripheral blood reticulocytosis
Signs of hemolysis:
1. increased LDH, serum UCB, urobilirubin
2. decreased haptoglobin
62
What are intrinsic RBC defects associated with hemolytic anemia?
1. inherited abnormalilites in Hb, membrane, or enzymatic machinery
2. PIG-A genetic defect in paroxysmal nocturnal hemoglobinuria
63
Describe Paroxysmal Nocturnal Hemoglobinuria.
PNH is a genetic defect in PIG-A gene that leads to dysfunctional GPI anchors on the RBC membrane.
GPI anchors CD55 (decay-accelerating factor) and CD59 (membrane inhibitor of reactive lysis)
Loss of these molecules will cause hemolysis in acidotic environments (associated with sleep)
64
What causes sickle cell disease?
a mutation where valine is substituted for glutamic acid on the B-globulin protein.
This creates HbS.
Disease occurs most commonly in homozygous HbSS but can also be seen in compound heterozygotes (HbSC or HbS/B-thallasemia)
65
What causes morbidity in sickle cell disease?
abnormal polymerization of deoxygenated HbS which can cause hemolysis and microvascular occlusion -->
1. pain crisis
2. acute chest syndrome
3. renal dysfunction
4. retinal pathology
5. priapism -(erect penis cant return to flaccid)
6. Asplenia (due to repeated occlusions)
66
Describe the blood smear of sickle cell disease.
Normocytic and normochromic with anisocytosis
1. sickle cells
2. blister cells
3. spherocytes
4. nucleated RBC, target cells, Howell-Jolly bodies, pappenheimer bodies (all associated with asplenia)
67
What would cause aplastic crisis in a sickle cell disease patient?
parvovirus B19 infection
68
What are ancillary tests for diagnosis of sickle cell disease?
1. sickle solubility test= + in all sickle cell disease forms
2. Hb studies= sickle cell disease will have predominance of HbS with variable HbF and NO HbA
69
What is thalassemia?
A group of disorders that are characterized by a decreased production of normal globin chains (a or b).
This leads to excess of the other chains which can form tetramers and cause RBC damage --> hemolysis
70
What is the MCV and MCHC for thalassemias?
microcytic and hypochromic
71
Describe the genes for a and b globins.
| What type of mutation usually causes a-thalassemia? What mutations cause b-thalassemia?
there are 2a genes (4 alleles) and 1b genes (2 alleles)
| Mutations to a are usually deletions and mutations to b are usually point mutations in regulatory regions
72
Describe the presentation of:
1. one deletion a-thalassemia
2. two deletion a-thalassemia
3. heterozygous b-thalassemia
4. 3 or 4 deletion a-thalassemia
5. homozygous or compound b-thalassemia
1. silent clinically and hematologically
2. mild anemia, little clinical presentation
3. mild anemia, little clinical presentation
4. moderate to severe anemia
5. moderate to severe anemia
73
Describe the presentation of a mild thalassemia. What other disorders would it be a differential with?
Mild thalassemia is microcytic with mild anisocytosis and poikilocytosis (target cells, stippling)
It needs to be differentiated from:
1. ACD
2. Fe deficiency
74
Describe severe thalassemia blood smears,
```
bizarre anisocytosis with:
target cells
teardrop cells
schistocytes
nucleated RBC
```
75
What is the most commonly inherited hemolytic anemia?
| What is the defect that leads to the anemia?
Hereditary spherocytosis- several different mutations that lead to defective interactions between the RBC membrane and cytoskeleton can cause this.
The defects cause vesiculation and fragility of the membrane that is progressively lost during circulation.
76
Why do RBC with damaged membranes take on a sphere shape?
The osmolarity is higher inside the RBC and so fluid will enter making it a sphere. The cell is rigid now and cannot pass through the splenic cords and thus are removed (causing spherocytosis anemia)
77
Describe the peripheral blood smear and CBC data for hereditary spherocytosis.
Normocytic and hyperchromic with a predominance of spherocytes.
78
What two disorders are spherocytes seen in the peripheral smear?
What test can prove the presence of spherocytes?
What test would differentiate these two disorders?
1. Hereditary spherocytosis
2. Warm antibody immunohemolytic anemia
Both will be positive for the osmotic fragility test
DAT will differentiate the two with WAIA being positive and hereditary spherocytosis being negative
79
What are the major intrinsic defects that can cause increased consumption/destruction of RBC?
1. PNH
2. Sickle Cell Disease
3. Thalassemia
4. Hereditary spherocytosis
5. G6PD deficiency
80
How does G6PD deficiency cause destruction of RBCs?
G6PD is an enzyme that generates NADPH to reduce glutathionine. Glutathionine protects RBCs from oxidative stress.
G6PD deficiency will cause anemia in the presence of oxidative stress.
81
What would you see on a peripheral blood smear for G6PD deficiency under oxidative stress?
1. Heinz bodies (inclusion bodies of precipitated denatured Hb)
2. Bite cells from the spleen trying to remove the Heinz bodies
* *due to the acute nature, reticulocytes may not have time to elevate which is a normal feature of RBC consumption/destruction anemias
82
What tests can be done for G6PD deficiency?
1. Fluorescence screening "spot test"
2. Quantitative spectrophotometry test
3. Stain for Heinz bodies
83
What are examples of extrinsic defects that can cause RBC destruction/consumption anemias?
1. Immunohemolytic anemia
2. Microangiopathic anemias
3. Parasitic infestation
4. trauma
84
In warm Ab immunohemolytic anemia, what occurs?
IgG antibodies coat the RBC and are opsonized and taken to the spleen to be phagocytosed.
During phagocytosis little pieces of membrane are removed and spherocytes are formed.
85
In cold type immunohemolytic anemia, what occurs?
IgM antibodies attack the RBC which results in RBC aggregation instead of the spherocytes you would see with warm immunohemolytic anemia.
86
Warm immunohemolytic anemia uses _____ antibodies and results in ___________.
Cold immunohemolytic anemia uses _____ antibodies and results in _________________.
Warm- IgG- spherocytes
| Cold- IgM- aggregates of RBCs
87
What is the hallmark of anemias associated with mechanical trauma or microangiopathic anemia?
Large number of blood cell fragments (shistocytes)
| aka helmut cells
88
Microangiopathic anemia is seen commonly in what three situations?
DIC, Hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP)
Fundamentals 3- Heme
flashcards
Decks in class (19)
# Cards
-
Tumor Classification and Growth44
-
Neoplasia172
-
Radiation Oncology50
-
Clinical Presentation of a Patient with Cancer58
-
Anticancer Drugs98
-
Anemia88
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The Bleeding Patient72
-
Pathology of Blood Groups36
-
Blood Component Therapy73
-
Clinical Evaluation of Anemia47
-
Lymphocytic Neoplasia81
-
Myeloid Neoplasm78
-
Clinical and Therapeutic Aspects of Leukemia and Lymphoma40
-
Anti-Anemia Drugs38
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Anticoagulants37
-
Autopsy Pathology26
-
Sudden Unexplained Infant Death12
-
Clinical Medical Genetics56
-
Genetic Disorders151
