MTAP W3 (Hematology W14: General=Anemia) Flashcards
derived from the greek word ‘ANAIMIA’= without blood
anemia
decrease in number of RBCs or amount of hemoglobin in the RBCs= decreased oxygen delivery and subsequent tissue -
hypoxia
anemia is considered to be present if the HGB and HCT is below the lower limit of the -% reference interval
95%
RBC parameters: HGB AND HCT are affected by the individual’s -
- age
- gender
- geographical location
anemia arises from decrease oxygen carrying capacity of blood
it can arise if there is:
1. INSUFFICIENT hemoglobin
2. hemoglobin is NONFUNCTIONAL
which is the more frequent cause?
insufficient hemoglobin
reduction from baseline value in total number of RBCs; hgb and rbc mass/hct
anemia
normal or increased total red cell mass may occur with PREGNANCY, MACROGLOBULINEMIA, SPLENOMEGALY
dilutional anemia
pag may PMS=delusional
QUANTITATIVE CHANGES IN RBCs
-decreased RBCs
-decreased oxygen carrying capacity of blood
anemia
QUANTITATIVE CHANGES IN RBCs
-too many RBC in circulation
-increased PCV
-hypervolemia
-hyperviscosity
polycythemia vera/ erythrocytosis
used as a screening test to evaluate if px has HEMOLYTIC ANEMIA
reticulocyte count
normal value of hgb in women
12-15 g/dL
normal value of hgb in men
13.5-18 g/dL
anemia: typical of hypoproliferation
normocytic, normochromic
CLASSIFICATION OF ANEMIA
Iron deficiency
Thalassemia
Sideroblastic anemia
low MCV, low MCHC
microcytic, hypochromic
CLASSIFICATION OF ANEMIA
Iron deficiency
Thalassemia
Sideroblastic anemia
low MCV, low MCHC
microcytic, hypochromic
CLASSIFICATION OF ANEMIA
Iron deficiency
Thalassemia
Sideroblastic anemia
low MCV, low MCHC
microcytic, hypochromic
CLASSIFICATION OF ANEMIA
Bone marrow disorder
Anemia of chronic disorders
Autoimmune disease
normal MCV, normal MCHC
normocytic, normochromic
CLASSIFICATION OF ANEMIA
Vitamin B12 deficiency
Folate deficiency
Excessive alcohol ingestion
Hypothyroidism
high MCV, normal MCHC
macrocytic, normochromic
MECHANISM OF ANEMIA
term used for marrow erythroid proliferative activity
erythropoiesis
MECHANISM OF ANEMIA
- erythropoiesis: DEFECTIVE progenitor cells, DESTROYED in the BM before maturation
ineffective erythropoiesis
MECHANISM OF ANEMIA
- erythropoiesis: DECREASE in number of erythroid precursor cells in the BM, NOT DESTROYED
insufficient erythropoiesis
MECHANISM OF ANEMIA
diseases associated:
1. megaloblastic anemia
2. thalassemia
3. sideroblastic anemia
ineffective erythropoiesis
‘MTS’- ineffective medtechs?
MECHANISM OF ANEMIA
the peripheral blood HGB is low despite an increase in RBC precursors in the bone marrow
ineffective erythropoiesis
MECHANISM OF ANEMIA
diseases associated:
infection/ parvovirus B19
sarcoidosis
acute leukemia
insufficient erythropoiesis
CATEGORIES OF ANEMIA
- acute
- chronic
blood loss
CATEGORIES OF ANEMIA
- aplastic
- iron deficiency
- sideroblastic anemia
- anemia of chronic disease
- megaloblastic
impaired production
CATEGORIES OF ANEMIA
- inherited defects
- acquired disorders
hemolytic
CATEGORIES OF ANEMIA
Normal MCV
80-100fL
CATEGORIES OF ANEMIA
Normal MCHC
31-37g/dL
CATEGORIES OF ANEMIA
MORPHOLOGICAL CLASSIFICATION
high MCV
macrocytic
CATEGORIES OF ANEMIA
MORPHOLOGICAL CLASSIFICATION
low MCV
microcytic
CATEGORIES OF ANEMIA
MORPHOLOGICAL CLASSIFICATION
high MCHC
hyperchromic
CATEGORIES OF ANEMIA
MORPHOLOGICAL CLASSIFICATION
low MCHC
hypochromic
CATEGORIES OF ANEMIA
- CLASSIFICATION
caused by pathophysiological mechanism responsible for the RBC deficit
-decreased erythrocyte production
-increased erythrocyte loss
etiologic classification
MORPHOLOGICAL CLASSIFICATION
- bleeding
- hypoproliferation of hematopoietic stem cells
normocytic normochromic anemia
MORPHOLOGICAL CLASSIFICATION
1.IDA
2. sideroblastic anemia
microcytic hypochromic anemia
MORPHOLOGICAL CLASSIFICATION
- megaloblastic anemia
macrocytic normochromic anemia
2 approach for classification of anemia
- reticulocyte count
- MCV
signs and symptoms: NOT seen in ANEMIA
- prone to infection
- ruby complexion
the most important indices is the -
MCV
the least important indices is the -
MCH
tool to assess bone marrow ability to increase RBC production in response to anemia
reticulocyte count
laboratory procedures used to diagnose anemia
- HGB
- PLT
- WBC
- OFT
- bilirubin
- haptoglobin
‘ha-bi phow’
plasma protein that binds free hemoglobin
haptoglobin
plasma protein that decreases in case of hemolytic anemia
haptoglobin
LABORATORY PROCEDURES USED TO DIAGNOSE ANEMIA
increased in hemolytic anemia during lysis, found inside the RBC
LDH test
LABORATORY PROCEDURES USED TO DIAGNOSE ANEMIA
reflects the body’s tissue major iron stores
serum ferritin
serum ferritin in male:
12-300ng/mL
serum ferritin in female:
12-150ng/mL
LABORATORY PROCEDURES USED TO DIAGNOSE ANEMIA
body’s ability to transport iron, measured to identify how much iron is being carried in the blood
TIBC/ total iron binding capacity
LABORATORY PROCEDURES USED TO DIAGNOSE ANEMIA
measures the total excretion of the breakdown products of heme
fecal urobilinogen
LABORATORY PROCEDURES USED TO DIAGNOSE ANEMIA
determine the amount of protoporphyrin not used for hgb synthesis
FPE/ free erythrocyte protoporphyrin
ZPP/ zinc protoporphyrin
LABORATORY PROCEDURES USED TO DIAGNOSE ANEMIA
measured by direct-fluorescene-hematofluorometer
FEP/ free erythrocyte protoporphyrin
ZPP/ zinc protoporphyrin
LABORATORY PROCEDURES USED TO DIAGNOSE ANEMIA
radioactive iron is injected IV
plasma iron turnover
LABORATORY PROCEDURES USED TO DIAGNOSE ANEMIA
PLASMA IRON TURNOVER
rate of disappearance from blood is -hrs
2-3hrs
LABORATORY PROCEDURES USED TO DIAGNOSE ANEMIA
PLASMA IRON TURNOVER
70-80% of the injected Fe appears within -days
10days
LABORATORY PROCEDURES USED TO DIAGNOSE ANEMIA
uses radioactive chromium
shorter life span= faster disappearance
red cell life span
INCREASED RBC CONCENTRATION
HCT: higher than -L/L in male
> 0.52 L/L, 52%
normal value: 40-54%
INCREASED RBC CONCENTRATION
HCT: higher than -L/L in female
> 0.50 L/L, 50%
normal value: 35-49%
are young RBCs that lack a nucleus but still contain RESIDUAL RNA
reticulocytes
2 days in BM
1 day PB
the adult reference range for reticulocyte -
0.5-1.5%
the newborn reference range for reticulocyte -
1.5-5.8%
PERIPHERAL BLOOD FILM EXAMINATION
variation in shape is called
poikilocytosis
PERIPHERAL BLOOD FILM EXAMINATION
variation in size is called
anisocytosis
this serves as a quality control to verify results produced by automated analyzers
peripheral blood film examination
a process that determine the M:E ratio
bone marrow examination
‘slit-v’
sternum, lumbar,iliac,tibia,vertebrae
bone marrow samples can be obtained by - and -
aspiration and trephine biopsy
BONE MARROW EXAMINATION
- yields semi-liquid bone marrow
aspirate
BONE MARROW EXAMINATION
Aspirate=semi-liquid bone marrow
examined under a - microscope
and analyzed by (3)
light microscope
flow cytometry
chromosome analysis
PCR
BONE MARROW EXAMINATION
frequently obtained which yields a narrow
trephine biopsy
BONE MARROW EXAMINATION
trephine biopsy: examined microscopically with the aid of -
immunohistochemistry
RED CELL INDICES
-liter=1 fL
10-15
RED CELL INDICES
normal value of MCV
80-100fL
RED CELL INDICES
MCV formula
HCT % x10/RBC
RED CELL INDICES
average volume of the individual red blood cell
MCV
RED CELL INDICES
average weight of hgb of the individual red cell
MCH
RED CELL INDICES
normal value of MCH
27-32pg/ug
RED CELL INDICES
MCH formula
HGB x10/RBC
RED CELL INDICES
the percent of hgb in the average red cell
MCHC
RED CELL INDICES
MCHC formula
RED CELL INDICES
HGB x100/HCT%
MCV and ANEMIA CLASSIFICATION
is characterized by an MCV of less than 80fL with small RBCs (<6um)
microcytic anemia
characterized by an MCHC of less tahn 32g/dL and INCREASED central pallor in the RBCs may accompany microcytosis
hypochromia
MCV and ANEMIA CLASSIFICATION
is characterized by an MCV greater than 100fL with large RBCs (>8um)
can be megaloblastic or non megaloblastic
macrocytic anemia
MCV and ANEMIA CLASSIFICATION
caused by impaired synthesis of DNA such as Vit 12, B9/folate deficiency or myelodysplasia
megaloblasic anemia
the next test after reticulocyte count is - in classifying anemia
MCV
ARC->MCV
- Thalassemia
- Anemia of chronic inflammation
- Iron deficiency
- Lead poisoning
- Sideroblastic anemia
- CHronic inflammation?
- hemoglobin E
microcytic/ low MCV
ARC->MCV
- Aplastic anemia
- Anemia of renal disease
- Myelophthisic anemia
- Infection: parvovirus B19
- Anemia of chronic inflammation
normocytic/ normal MCV
ARC->MCV
- Myelodyplastic syndrome
- Aplastic anemia
- some Drugs
- Erythroleukemia
- Chronic liver disease
- Vitamin B12 deficiency
- Folate deficiency
MADEplastiC9-12
macrocytic/ high MCV
ARC: excessive RBC loss
HEMOLYSIS
-cause
immune hemolytic anemias
EXTRINSIC causes
ARC: excessive RBC loss
HEMOLYSIS
-hemolytic
1. TTP
2. HUS
3. DIC
MICROangiopathic hemolytic
can help determine the cause of an anemia when used in conjunction with MCV!
RDW
CLASSIFICATION OF ANEMIA BASED ON MCV AND RDW
MICROCYTIC/LOW MCV
1. Thalassemia
2. Anemia of chronic inflammation
3. Hb E disease
RDW normal/microcytic
‘TAE’
CLASSIFICATION OF ANEMIA BASED ON MCV AND RDW
MICROCYTIC/LOW MCV
1. Iron deficiency
2. Sickle cell thalassemia
RDW high/microcytic
‘IS’
CLASSIFICATION OF ANEMIA BASED ON MCV AND RDW
NORMOCYTIC/NORMAL MCV
1. Anemia of chronic inflammation
2. Anemia of renal disease
3. Acute hemorrhage
4. Hereditary spherocytosis
RDW normal/normocytic
CLASSIFICATION OF ANEMIA BASED ON MCV AND RDW
NORMOCYTIC/NORMAL MCV
1. Iron, folate, Vit b12 deficiency
2. sickle cell anemia
3. Hb SC disease
RDW high/normocytic
CLASSIFICATION OF ANEMIA BASED ON MCV AND RDW
MACROCYTIC/HIGHMCV
1. Aplastic anemia
2. Chronic liver disease
3. Alcoholism
RDW normal/macrocytic
CLASSIFICATION OF ANEMIA BASED ON MCV AND RDW
MACROCYTIC/HIGHMCV
1. folate, B12 deficiency
2. myelodyplastic syndrome
3. chemotherapy
4. cold agglutinin
5. chronic liver dx
RDW high/macrocytic
due to defective hemoglobin synthesis resulting to cytoplasmic maturation defect
microcytic/hypochromic anemia
MICROCYTIC/HYPOCHROMIC ANEMIA type
abnormalities of iron homeostasis (deficiency in metabolism)
defective heme synthesis
MICROCYTIC/HYPOCHROMIC ANEMIA
DEFECTIVE HEME SYNTHESIS
- anemia: commonly known as the IRON DEFICIENCY ANEMIA
sideropenic anemia
MICROCYTIC/HYPOCHROMIC ANEMIA
DEFECTIVE HEME SYNTHESIS
-anemia: adequate or excess iron but defective utilization. ANEMIA OF CHRONIC INFLAMMATION
sideroachrestic anemia
MICROCYTIC/HYPOCHROMIC ANEMIA
DEFECTIVE HEME SYNTHESIS
-anemia: defective porphyrin metabolism
sideroblastic anemia
MICROCYTIC/HYPOCHROMIC ANEMIA
defective - synthesis
1. sideropenic anemia
2. sideroachrestic anemia
3. sideroblastic anemia
defective HEME synthesis
MICROCYTIC/HYPOCHROMIC ANEMIA
defective - synthesis
results to thalassemia and hemiglobinopathies
defective GLOBIN synthesis
MICROCYTIC/HYPOCHROMIC ANEMIA
defective - synthesis
deletion or mutation of globin synthesis
defective GLOBIN synthesis
MICROCYTIC/HYPOCHROMIC ANEMIA
most common form of anemia
IDA
MICROCYTIC/HYPOCHROMIC ANEMIA
prevalent in infants and children, pregnancy, excessive menstrual flow, elderly with poor diets, malabsorption syndromes, chronic blood loss
IDA
MICROCYTIC/HYPOCHROMIC ANEMIA
clinical signs and symptoms:
1. glossitis
2. angular cheilosis
3. koilonychia
4. pica
IDA
MICROCYTIC/HYPOCHROMIC ANEMIA: IDA
sore tongue
glossitis
MICROCYTIC/HYPOCHROMIC ANEMIA: IDA
inflamed cracks at the corners of the mouth
angular chielosis
MICROCYTIC/HYPOCHROMIC ANEMIA: IDA
spooning of the fingernails, may be seen if the deficiency is long-standing
koilonychia
MICROCYTIC/HYPOCHROMIC ANEMIA: IDA
cravings for non food items such as dirt, clay, laundry starch
pica
major iron store in the body
ferritin
MICROCYTIC/HYPOCHROMIC ANEMIA: STAGES OF IDA
Stage -
storage depletion
stage 1
MICROCYTIC/HYPOCHROMIC ANEMIA: STAGES OF IDA
Stage -
transport depletion
stage 2
MICROCYTIC/HYPOCHROMIC ANEMIA: STAGES OF IDA
Stage -
functional depletion
stage 3
MICROCYTIC/HYPOCHROMIC ANEMIA: STAGES OF IDA
Stage -
HGB: normal
Serum iron: normal
TIBC: normal
ferritin: decreased
stage 1
MICROCYTIC/HYPOCHROMIC ANEMIA: STAGES OF IDA
Stage -
HGB: normal
Serum iron: decreased
TIBC: increased
ferritin: decreased
stage 2
MICROCYTIC/HYPOCHROMIC ANEMIA: STAGES OF IDA
Stage -
HGB: decreased
Serum iron: decreased
TIBC: increased
ferritin: decreased
stage 3
MICROCYTIC/HYPOCHROMIC ANEMIA
parasites associated with IDA (4)
- hookworms (necator, ancylostoma)
- T. trichiura
- S. mansoni
- S. haematobium
major protein that transport iron in the plasma
transferrin
MICROCYTIC/HYPOCHROMIC ANEMIA
beta globulin responsible for binding iron and its transport in the blood stream
transferrin
MICROCYTIC/HYPOCHROMIC ANEMIA
transferrin
1 gram can bind - mg of iron
1.25mg
MICROCYTIC/HYPOCHROMIC ANEMIA
refers to the total amount of iron that transferrin can carry, capacity of transferrin to bind iron
TIBC
MICROCYTIC/HYPOCHROMIC ANEMIA
an index of iron storage
% saturation
MICROCYTIC/HYPOCHROMIC ANEMIA
% saturation
calculated value: -
100x serum iron/TIBC
rough estimate of body iron content
ferritin
MICROCYTIC/HYPOCHROMIC ANEMIA
second most common type of anemia
anemia of chronic inflammation
MICROCYTIC/HYPOCHROMIC ANEMIA
Commonly associated with systemic diseases, including chronic
inflammatory conditions
- rheumatoid arthritis
- tuberculosis
- HIV
- malignancies
anemia of chronic inflammation
MICROCYTIC/HYPOCHROMIC ANEMIA
Due to inability to use available iron for hemoglobin production
anemia of chronic inflammation
MICROCYTIC/HYPOCHROMIC ANEMIA
Impaired release of storage iron associated with increased Acute
phase reactants such as Hepcidin, Ferritin and lactoferrin
anemia of chronic inflammation
MICROCYTIC/ HYPOCHROMIC ANEMIA
anemia of chronic inflammation
impaired release of APR such as: (3)
- hepcidin
- ferritin
- lactoferrin
MICROCYTIC/ HYPOCHROMIC ANEMIA
anemia of chronic inflammation
impaired release of APR such as: (3)
- hepcidin
- ferritin
- lactoferrin`
decreases release of iron from
stores
acute phase reactant / inflammation
hepcidin
- Hepcidin: Decreased Iron (because hepcidin stops iron to go outside)
increased
- Hepcidin: Increase Iron ( because iron will release)
decreased
MICROCYTIC/ HYPOCHROMIC ANEMIA
-Anemia
Caused by BLOCKS IN THE PROTOPORPHYRIN PATHWAY resulting in defective hemoglobin synthesis and iron overload
sideroblastic anemia
MICROCYTIC/ HYPOCHROMIC ANEMIA
-Anemia
Excess iron accumulates in the mitochondrial region of
the immature RBC in the BM and encircles the nucleus;
cells are called ringed sideroblasts (iron accumulates).
sideroblastic anemia
MICROCYTIC/ HYPOCHROMIC ANEMIA
Sideroblastic Anemia
EXCESS IRON ACCUMULATES in the mitochondrial region of
the immature RBC in the BM and encircles the nucleus;
cells are called -
ringed sideroblasts (iron accumulates)
MICROCYTIC/ HYPOCHROMIC ANEMIA
Sideroblastic Anemia
Excess iron accumulates in the mitochondrial region of
the mature RBC in circulation ; cells are called RINGED SIDEROCYTES; inclusions are -
(Pappenheimer bodies on Wright’s stained smears)
Sideroticgranules
MICROCYTIC/ HYPOCHROMIC ANEMIA
Sideroblastic Anemia
Siderocytes are best demonstrated using -
Perl’s Prussian blue stain
MICROCYTIC/ HYPOCHROMIC ANEMIA
Sideroblastic Anemia
- IRREVERSIBLE; causes of block is UNKNOWN OR IDIOPATHIC
primary
MICROCYTIC/ HYPOCHROMIC ANEMIA
Sideroblastic Anemia
- Dimorphic
- RARS
primary
MICROCYTIC/ HYPOCHROMIC ANEMIA
Sideroblastic Anemia
- REVERSIBLE; causes include alcohol, anti-TB drugs (RIFES), chloramphenicol
secondary
MICROCYTIC/ HYPOCHROMICANEMIA
is most often normocytic and
normochromic; however, with chronic exposure to lead, a microcytic,
hypochromic clinical picture may be seen
lead poisoning
MICROCYTIC/ HYPOCHROMICANEMIA
Multiple blocks in the protoporphyrin pathway that affect heme synthesis
lead poisoning
MICROCYTIC/ HYPOCHROMICANEMIA
Presence of many coarse Basophilic Stippling
lead poisoning
MICROCYTIC/ HYPOCHROMICANEMIA
lead poisoning will lead to acquired sideroblastic anemia and acquired
porphyria
lead poisoning
MICROCYTIC/ HYPOCHROMICANEMIA
It inhibits ferrochelatase and D-ALA synthase enzyme in
Heme/Protoporphyrin pathway
lead poisoning
MICROCYTIC/ HYPOCHROMICANEMIA
It inhibits ferrochelatase and D-ALA synthase enzyme in -
Heme/Protoporphyrin pathway
MICROCYTIC/ HYPOCHROMICANEMIA
ACUTE exposure to lead: -
normocytic, normochromic
MICROCYTIC/ HYPOCHROMICANEMIA
CHRONIC exposure to lead: -
microcytic, hypochromic
Serum iron and serum TIBC is -
inversely proportional
MICROCYTIC/ HYPOCHROMICANEMIA
DIFFERENTIAL DIAGNOSES
all are decreased
increased TIBC, ZPP
TZ
IDA
MICROCYTIC/ HYPOCHROMICANEMIA
DIFFERENTIAL DIAGNOSES
all are normal
increased iron, ferritin
IF
B-thalassemia
MICROCYTIC/ HYPOCHROMICANEMIA
DIFFERENTIAL DIAGNOSES
all are decreased
increased TIBC, ferritin
TF
anemia of chronic disease
MICROCYTIC/ HYPOCHROMICANEMIA
DIFFERENTIAL DIAGNOSES
all are increased except:
decrease TIBC
T
sideroblastic anemia
MACROCYTIC/ NORMOCHROMICANEMIA
It is characterized by an MCV greater than -fL w/ large RBC (greater
than 8 um diameter). Macrocytic anemias maybe megaloblastic or
non- megaloblastic.
100fL
MACROCYTIC/ NORMOCHROMICANEMIA
The most common causesof megaloblastic anemia are acquired,
although congenital forms exist. Deficiencies in -,-, or both account for the majority of cases
cobalamin (B12)
folate (B9)
Red blood cells in megaloblastic anemias have an abnormal nuclear
maturation and imbalance between nuclear and cytoplasmic maturation
MACROCYTIC/ NORMOCHROMICANEMIA
Refers to the abnormal marrow erythrocyte precursor seen in processes,
such as pernicious anemia, associated with altered DNA synthesis.
MACROCYTIC/ NORMOCHROMICANEMIA
CLASSIFICATION BASED ON MCV
MACROCYTIC/MCV
-
1. Aplastic anemia
2. Chronic liver disease
3. Alcoholism
nonmegaloblastic
CLASSIFICATION BASED ON MCV
MACROCYTIC/MCV
-
1. B12 deficiency
2. B9 deficiency
3. Myelodysplasia
4. Erythroleukemia
5. Drugs
megaloblastic
CLASSIFICATION BASED ON MCV
NORMOCYTIC/MCV
Reticulocytes: INCREASED= hemolytic anemia -
- membrane defects
- hemoglobinopathies
- enzyme deficiencies
intrinsic
CLASSIFICATION BASED ON MCV
MACROCYTIC/MCV
Reticulocytes: -
- aplastic anemia
- anemia of renal dx
- myelophthisic anemia
- infection; parvovirus B19
- anemia of chronic inflammation
normal or decreased
MACROCYTIC/ NORMOCHROMICANEMIA
disruption of cholesterol-to-phospholipid ratio
NO IMPAIRMENT of DNA synthesis
ROUND
NO HYPERSEGMENTED
non-megaloblastic anemia
MACROCYTIC/ NORMOCHROMICANEMIA
IMPAIRED DNA synthesis
OVAL
HYPERSEGMENTED
megaloblastic anemia
MACROCYTIC/ NORMOCHROMICANEMIA
- ANEMIA
- B12 deficiency
- B9 deficiency
- acute erythroleukemia
- myelodysplasia
- congenital dyserythropoietic anemia type 1 and 3
megaloblastic anemia
MACROCYTIC/ NORMOCHROMICANEMIA
Defective DNA synthesis causes abnormal nuclear maturation;
RNA synthesis is normal, so the cytoplasm is not affected. The
nucleus matures slower than the cytoplasm (Asynchronism)
megaloblastic anemia
MACROCYTIC/ NORMOCHROMICANEMIA
Laboratory picture of Pancytopenia,Oval macrocyte, Howell-jolly bodies, Hypersegmentedneutrophil
megaloblastic anemia
MACROCYTIC/ NORMOCHROMICANEMIA
defect in - affects cytoplasm
RNA
MACROCYTIC/ NORMOCHROMICANEMIA
defect in - affects nucleus
DNA
SCREENINGTEST USED TO DIAGNOSE MEGALOBLASTIC ANEMIA (5)
- CBC
- Reticulocyte count
- WBC differential
- bilirubin
- LDH
SCREENINGTEST USED TO DIAGNOSE MEGALOBLASTIC ANEMIA
macrocytes, pancytopenia
CBC
SCREENINGTEST USED TO DIAGNOSE MEGALOBLASTIC ANEMIA
Decreased: megaloblastic anemia
reticulocyte count
MACROCYTIC/ NORMOCHROMICANEMIA
VITAMIN B12 (COBALAMIN)DEFICIENCY
-anemia: –caused by deficiency of INTRINSIC FACTOR, Antibody to intrinsic factor or antibodies to parietal cells, autoimmune
disease.
pernicious anemia
MACROCYTIC/ NORMOCHROMICANEMIA
VITAMIN B12 (COBALAMIN)DEFICIENCY
parasite that causes cobalamin deficiency
D. latum
takes 3-6 years to develop because of high body stores
Clinical symptoms: Jaundice, weakness, glossitis,GIbleeding, numbness
and CNSPROBLEMS
pernicious anemia
Vitamin B12
intrinsic factor is needed for its proper absorption in the -
intrinsic factor is produced in the PARIETAL cells
ileum
regulates the folate synthesis (DNA)
Vitamin B12
MACROCYTIC/ NORMOCHROMICANEMIA
FOLIC ACIDDEFICIENCY
Associated with poor diet, pregnancy or chemotherapeutic anti
folic drugs such as -
METHOTREXATE
MACROCYTIC/ NORMOCHROMICANEMIA
Clinical symptoms: same with vitamin B12deficiency, except
NO CNSinvolvement
folic acid deficiency
other name of folic acid
Pteroylmonoglutamic acid
Vitamin B9/folic acid
absorbed in -
jejunum
MACROCYTIC/ NORMOCHROMICANEMIA
Acts asco-enzyme in the formation of thymidylate synthetase
FolicAcid (Pteroylmonoglutamic acid)
MACROCYTIC/ NORMOCHROMICANEMIA
Thymidylate synthetase –needed to produce thymidine (one of
the pyrimidine basesofDNA)
FolicAcid (Pteroylmonoglutamic acid)
MACROCYTIC/ NORMOCHROMICANEMIA
Dietary aspects: B-: meat
B12
MACROCYTIC/ NORMOCHROMICANEMIA
Dietary aspects: B-: vegetables
B9
CAUSESOFFOLICACIDDEFICIENCY
- is acondition that DAMAGES THE LINING OF THE SMALL INTESTINE and prevents it from absorbing parts of food that are important for staying healthy
Celiac disease
CAUSESOFFOLICACIDDEFICIENCY
- is a MALABSORPTION disease
commonly found in the tropical regions, marked with ABNORMAL FLATTENING OF THE VILLI AND INFLAMMATION of the lining of the SMALL INTESTINE
tropical sprue
MACROCYTIC/ NORMOCHROMICANEMIA
*Include Alcoholism, Liver disease, and conditions causes
accelerated erythropoiesis
* RBC are ROUND not oval
NON- MEGALOBLASTICANEMIA
MACROCYTIC/ NORMOCHROMICANEMIA
IMPORTANT FINDINGS IN
MEGALOBLASTIC ANEMIA (5)
- ineffective erythropoiesis and decreased retics,wbc,platelets
- hypersegmented neutrophils
- macroovalocytes
- howell-jolly bodies
anemia is characterized by an MCV in the range of 80 to 100 fL.
normocytic
- anemia
a DIMORPHIC POPULATION OF MICROCYTES AND MACROCYTES
that can yield a normal MCV
Normocytic-Normochromic
Anemia
NORMOCYTIC-NORMOCHROMIC ANEMIA
- anemia
Bone marrow failure causes PANCYTOPENIA (decrease of
blood cells).
aplastic anemia
NORMOCYTIC-NORMOCHROMIC ANEMIA
- anemia
poor prognosis with complications that
include bleeding, infection, and iron overload due to
frequent transfusion needs.
aplastic anemia
NORMOCYTIC-NORMOCHROMIC ANEMIA
- anemia
15-20% of cases
1.fanconi anemia
2. dyskeratosis congenita
3. shwachmann-bodian-diamond syndrome
INHERITED aplastic anemia
NORMOCYTIC-NORMOCHROMIC ANEMIA
- anemia
80-85% of cases
1.idiopathic
2. secondary
ACQUIRED aplastic anemia
NORMOCYTIC-NORMOCHROMIC ANEMIA
- anemia
most common aplastic anemia
ACQUIRED aplastic anemia
ANORMOCYTIC-NORMOCHROMIC ANEMIA
- ACQUIRED aplastic anemia
50-70%
DIAMOND BLACKFAN ANEMIA
idiopathic/ unknown cause
ANORMOCYTIC-NORMOCHROMIC ANEMIA
ACQUIRED aplastic anemia
10-75%
(exposure to drugs such as sulfonamides and
chloramphenicol) , chemicals (benzene), radiation or infection)
secondary
A NORMOCYTIC-NORMOCHROMIC ANEMIA
problem
-: microcytic
heme
A NORMOCYTIC-NORMOCHROMIC ANEMIA
problem
-: macrocytic
nucleus
A NORMOCYTIC-NORMOCHROMIC ANEMIA
- anemia
Autosomal recessive trait
Dwarfism, renal disease, mental retardation
A NORMOCYTIC-NORMOCHROMIC ANEMIA
- anemia
Strong association with malignancy development,
especially ACUTE LYMPHOBLASTIC LEUKEMIA
Genetic aplastic anemia
Fanconi anemia
Acquired aplastic anemia (secondary)
caused by:
Antibiotics: (2)
1.chloramphenicol
2. sulfonamides
Acquired aplastic anemia (secondary)
caused by:
Chemicals: (2)
- benzene
- herbicides
NORMOCYTIC-NORMOCHROMIC ANEMIA
About 30% of acquired aplastic anemias are due to drug exposure.
Acquired aplastic anemia (secondary)
NORMOCYTIC-NORMOCHROMIC ANEMIA
low RBCs, normal WBC and PLT
Diamond-Blackfan anemia
NORMOCYTIC-NORMOCHROMIC ANEMIA
-anemia
Hypoproliferative anemia caused by replacement of
bone marrow hematopoietic cells by malignant cells or
fibrotic tissue
myelophthisic (marrow replacement) anemia
NORMOCYTIC-NORMOCHROMIC ANEMIA
-anemia
Associated with cancers (breast, prostate, lung,
melanoma) with bone metastasis
myelophthisic (marrow replacement) anemia
NORMOCYTIC-NORMOCHROMIC ANEMIA
-anemia
Laboratory: Normocytic/normochromic anemia;
leucoerythroblastic blood picture (high WBC and high
immature RBC)
myelophthisic (marrow replacement) anemia
NORMOCYTIC-NORMOCHROMIC ANEMIA
-anemia
Characterized by a sudden loss of blood resulting
from trauma or other severe forms of injury
acute blood loss anemia
NORMOCYTIC-NORMOCHROMIC ANEMIA
-anemia
Clinical symptoms: Hypovolemia, rapid pulse, low
blood pressure, pallor
acute blood loss anemia
NORMOCYTIC-NORMOCHROMIC ANEMIA
-anemia
Initially normal reticulocyte count hemoglobin/ hematocrit; in a few hours, increase in platelet count
and LEUKOCYTOSIS with a LEFT SHIFT, drop in hemoglobin/
hematocrit and RBC
acute blood loss anemia
reticulocytosis in - days
3-5 days
NORMOCYTIC-NORMOCHROMIC ANEMIA
shift to the -: immature WBC
left
NORMOCYTIC-NORMOCHROMIC ANEMIA
shift to the -: hypersegmented cells
right
NORMOCYTIC-NORMOCHROMIC ANEMIA
- anemia
Characterized by a gradual, lLON-TERM loss of blood;
often caused by gastrointestinal bleeding
NORMOCYTIC-NORMOCHROMIC ANEMIA
- anemia
Initially normocytic/normochromic anemia that over time causes a DECREASE in hemoglobin/hematocrit;
gradual loss of iron causes microcytic/hypochromic anemia
NORMOCYTIC-NORMOCHROMIC ANEMIA
- anemia due to -
All cause a normocytic/normochromic anemia; usually hereditary
with INCREASE reticulocytosis due to accelerated destruction
hemolytic anemias due to intrinsic defects
NORMOCYTIC-NORMOCHROMIC ANEMIA
HEMOLYTIC ANEMIAS DUE TO INTRINSIC DEFECTS
- DEFECT
- Hereditary spherocytosis
- Hereditary elliptocytosis (ovalocytosis)
- Hereditary stomatocytosis
- Hereditary acanthocytosis (abetalipoproteinemia)
membrane defects
NORMOCYTIC-NORMOCHROMIC ANEMIA
HEMOLYTIC ANEMIAS DUE TO INTRINSIC DEFECTS
- DEFECT
- G6PD deficiency
- PK deficiency
- Paroxysmal nocturnal hemoglobinuria/ PNH
enzyme defects
one altered copy of a gene is enough to cause a disease
autosomal dominant= hereditary spherocytosis
NORMOCYTIC-NORMOCHROMIC ANEMIA
HEMOLYTIC ANEMIAS DUE TO INTRINSIC DEFECTS
MEMBRANE DEFECT
MOST COMMON membrane defect; autosomal dominant
hereditary spherocytosis
NORMOCYTIC-NORMOCHROMIC ANEMIA
HEMOLYTIC ANEMIAS DUE TO INTRINSIC DEFECTS
MEMBRANE DEFECT
characterized by splenomegaly, variable degree of anemia,
spherocytes on the peripheral blood smear
hereditary spherocytosis
NORMOCYTIC-NORMOCHROMIC ANEMIA
HEMOLYTIC ANEMIAS DUE TO INTRINSIC DEFECTS
MEMBRANE DEFECT
Increased permeability of the membrane to sodium
Results in loss of membrane fragments; erythrocytes have
DECREASED
surface area-to-volume ratio; rigid spherocytes culled/removed by
splenic macrophages
hereditary spherocytosis
NORMOCYTIC-NORMOCHROMIC ANEMIA
HEMOLYTIC ANEMIAS DUE TO INTRINSIC DEFECTS
MEMBRANE DEFECT
Laboratory:
1. MCHC may be >37 g/dL, increased
2. osmotic fragility
3. increased serum bilirubin
hereditary spherocytosis
NORMOCYTIC-NORMOCHROMIC ANEMIA
HEMOLYTIC ANEMIAS DUE TO INTRINSIC DEFECTS
MEMBRANE DEFECT
Autosomal dominant; most persons asymptomatic
due to normal erythrocyte life span; >25% ovalocytes
on the peripheral blood smear
hereditary ovalocytosis
NORMOCYTIC-NORMOCHROMIC ANEMIA
HEMOLYTIC ANEMIAS DUE TO INTRINSIC DEFECTS
MEMBRANE DEFECT
Membrane defect is caused by POLARIZATION OF CHOLESTEROL at the ends of the cell rather than around pallor area.
hereditary ovalocytosis
NORMOCYTIC-NORMOCHROMIC ANEMIA
HEMOLYTIC ANEMIAS DUE TO INTRINSIC DEFECTS
MEMBRANE DEFECT
Autosomal dominant; variable degree of anemia; up
to 50% stomatocytes on the blood smear.
Hereditary stomatocytosis
NORMOCYTIC-NORMOCHROMIC ANEMIA
HEMOLYTIC ANEMIAS DUE TO INTRINSIC DEFECTS
MEMBRANE DEFECT
Membrane defect due to abnormal permeability to
both SODIUM AND POTASSIUM; causes erythrocyte
swelling
Hereditary stomatocytosis
both altered copies of the gene are needed to cause the dx
autosomal recessive
NORMOCYTIC-NORMOCHROMIC ANEMIA
HEMOLYTIC ANEMIAS DUE TO INTRINSIC DEFECTS
MEMBRANE DEFECT
Autosomal recessive; mild anemia associated with
steatorrhea, neurological and retinal abnormalities; 50-
100% of erythrocytes are acanthocytes
Hereditary acanthocytosis (abetalipoproteinemia)
NORMOCYTIC-NORMOCHROMIC ANEMIA
HEMOLYTIC ANEMIAS DUE TO INTRINSIC DEFECTS
MEMBRANE DEFECT
Increased cholesterol:lecithin ratio in the membrane
due to abnormal plasma lipid concentrations;
absence of serum p-lipoprotein needed for lipid
transport
Hereditary acanthocytosis (abetalipoproteinemia)
NORMOCYTIC-NORMOCHROMIC ANEMIA
HEMOLYTIC ANEMIAS DUE TO INTRINSIC DEFECTS
ENZYME DEFECT
SEX-linked enzyme defect; most common enzyme deficiency in
the HEXOSE MONOPHOSPHATE SHUNT
G6PD (glucose-6-phosphate dehydrogenase) deficiency
NORMOCYTIC-NORMOCHROMIC ANEMIA
HEMOLYTIC ANEMIAS DUE TO INTRINSIC DEFECTS
ENZYME DEFECT
Reduced glutathione levels are not maintained because of
decreased NADPH generation.
G6PD (glucose-6-phosphate dehydrogenase) deficiency
NORMOCYTIC-NORMOCHROMIC ANEMIA
HEMOLYTIC ANEMIAS DUE TO INTRINSIC DEFECTS
ENZYME DEFECT
Results in oxidation of hemoglobin to methemoglobin (Fe3+);
denatures to form HEINZ BODIES
G6PD (glucose-6-phosphate dehydrogenase) deficiency
pathway that produces glutathione
hexose monophosphate shunt
NORMOCYTIC-NORMOCHROMIC ANEMIA
HEMOLYTIC ANEMIAS DUE TO INTRINSIC DEFECTS
ENZYME DEFECT
Autosomal recessive; most common enzyme deficiency
in EMBDEN-MEYERHOF PATHWAY
Pyruvate kinase (PK) deficiency
NORMOCYTIC-NORMOCHROMIC ANEMIA
HEMOLYTIC ANEMIAS DUE TO INTRINSIC DEFECTS
ENZYME DEFECT
Severe hemolytic anemia with reticulocytosis and
echinocytes
Pyruvate kinase (PK) deficiency
NORMOCYTIC-NORMOCHROMIC ANEMIA
HEMOLYTIC ANEMIAS DUE TO INTRINSIC DEFECTS
ENZYME DEFECT
An acquired membrane defect in which the red cell
membrane has an increased sensitivity for complement
binding as compared to normal erythrocytes
Paroxysmal nocturnal hemoglobinuria (PNH)
NORMOCYTIC-NORMOCHROMIC ANEMIA
HEMOLYTIC ANEMIAS DUE TO INTRINSIC DEFECTS
ENZYME DEFECT
decrease of cd55 and cd59
All cells are abnormally sensitive to lysis by complement
Paroxysmal nocturnal hemoglobinuria (PNH)
NORMOCYTIC-NORMOCHROMIC ANEMIA
HEMOLYTIC ANEMIAS DUE TO INTRINSIC DEFECTS
ENZYME DEFECT
Characterized by pancytopenia
uses Ham’s and sugar water test
Paroxysmal nocturnal hemoglobinuria (PNH)
Hams and sugar water test have been tradiotionally used in diagnosis of PNH the standard now used is - to detect CD 55, CD 59
flowcytometry
decreased CD59 means
MRL/ membrane inhibitor of reactive lysis
decreased CD55 means
DAF/ decay accelerating factor
NORMOCYTIC-NORMOCHROMIC ANEMIA
- anemia due to -
All cause a normocytic/normochromic anemia due to defects
extrinsic to the RBC. All are acquired disorders that cause
accelerated destruction with reticulocytosis.
Hemolytic Anemias Due to Extrinsic/Immune Defects
NORMOCYTIC-NORMOCHROMIC ANEMIA
HEMOLYTIC ANEMIA DUE TO - DEFECTS
- Warm autoimmune hemolytic anemia (WAIHA)
- Cold autoimmune hemolytic anemia (CAIHA or cold
hemagglutinin disease)
3.Paroxysmal cold hemoglobinuria (PCH) (extrinsic)
4.Hemolytic transfusion reaction - Hemolytic disease of the newborn (HDN)
hemolytic anemia due to extrinsic/immune defects
NORMOCYTIC-NORMOCHROMIC ANEMIA
HEMOLYTIC ANEMIA DUE TO - DEFECTS
Paroxysmal cold hemoglobinuria/PCH
extrinsic
NORMOCYTIC-NORMOCHROMIC ANEMIA
HEMOLYTIC ANEMIA DUE TO IMMUNE DEFECTS
- anemia
RBCs are coated with IgG and/or complement.
Macrophages may phagocytize these RBCs, or they may
remove the antibody or complement from the RBC’s
surface, causing membrane loss and spherocytes.
Warm autoimmune hemolytic anemia (WAIHA)
NORMOCYTIC-NORMOCHROMIC ANEMIA
HEMOLYTIC ANEMIA DUE TO IMMUNE DEFECTS
- anemia
60% of cases are IDIOPATHIC; other cases are secondary to
diseases that alter the immune response (e.g., chronic
lymphocytic leukemia, lymphoma); can also be drug
induced.
Warm autoimmune hemolytic anemia (WAIHA)
IgG and complement react to -c
WITH LYSIS
37c/BT
NORMOCYTIC-NORMOCHROMIC ANEMIA
HEMOLYTIC ANEMIA DUE TO IMMUNE DEFECTS
- anemia
Laboratory Findings
1. Spherocytes
2. MCHC may be >37 g/dL
3. Increased osmotic fragility, bilirubin, reticulocyte count
4. Occasional nRBCs present
5. Positive direct antiglobulin test (DAT) helpful in
differentiating from hereditary spherocytosis
Warm autoimmune hemolytic anemia (WAIHA)
DAT (direct antihuman globulin test)
(+)
WAIHA
DAT (direct antihuman globulin test)
(-)
HS
NORMOCYTIC-NORMOCHROMIC ANEMIA
HEMOLYTIC ANEMIA DUE TO IMMUNE DEFECTS
- anemia
RBCs are coated with IgM and complement at
temperatures below 37°C. RBCs are lysed by complement
or phagocytized by macrophages. Antibody is usually
anti-I but can be anti-i.
Cold autoimmune hemolytic anemia (CAIHA or cold
hemagglutinin disease)
NORMOCYTIC-NORMOCHROMIC ANEMIA
HEMOLYTIC ANEMIA DUE TO IMMUNE DEFECTS
- anemia
Can be idiopathic, or secondary to Mycoplasma
pneumoniae, lymphoma, or infectious mononucleosis
If antibody titer is high enough, sample must be warmed
to 37°C to obtain accurate RBC and indices results.
Cold autoimmune hemolytic anemia (CAIHA or cold
hemagglutinin disease)
NORMOCYTIC-NORMOCHROMIC ANEMIA
HEMOLYTIC ANEMIA DUE TO IMMUNE DEFECTS
- anemia
Laboratory Findings:
Seasonal symptoms
RBC clumping can be seen both macroscopically
and microscopically
MCHC >37 g/dL
Increased bilirubin and reticulocyte count
Positive DAT detects complement-coated RBCs
CAIHA
IgM and complement reacts at -c
NO LYSIS
4c/ ref temp
NORMOCYTIC-NORMOCHROMIC ANEMIA
HEMOLYTIC ANEMIA DUE TO IMMUNE DEFECTS
- anemia
An IgG biphasic Donath-Landsteiner antibody with
P specificity fixes complement to RBCs in the cold
(less than 20°C); the complement-coated RBCs lyse
when warmed to 37°C.
Paroxysmal cold hemoglobinuria (PCH)
NORMOCYTIC-NORMOCHROMIC ANEMIA
HEMOLYTIC ANEMIA DUE TO IMMUNE DEFECTS
- anemia
Laboratory Findings:
Variable anemia following hemolytic process
Increased bilirubin and plasma hemoglobin
Decreased haptoglobin
DAT may be positive
Donath-Landsteiner test positive
Paroxysmal cold hemoglobinuria (PCH)
