Hemepath - Anemias Part I (General And Hypchromic, Microcytic Anemia)

Front 1

Reticulocytes still retain some cytoplasmic __, and persists for about __ hours

Back 1

cytoplasmic RNA persist for about 24 hours

Front 2

acanthocytes

Back 2

due to altered cell membrane lipids
- abetalipoproteinemia (mutation in apoB gene - not apoB-48 (chylomicrons) or apoB-100 (LDL, IDL, VLDL)
- fat malabsorption with fat-soluble vitamin difficiencies, notably vit E (neurologic/vision abn); note: vit D, although fat-soluble, is not marked affected because its absorption is not dependent on chylomicrons)
- retinitis pigmentosa
- acanthocytosis (red cell memebrane abn)

Front 3

basophilic stippling

Back 3

Due to precipitated ribosomes (RNA)

Coarse stippling:
- lead
- thalassemia

Fine stippling:
- many anemias (nonspecific)

Front 4

Bit cell

Back 4

degmacyte
- due to Heinz body pitting by spleen
- G6PD deficiency, drug-induced oxidant hemolysis

Front 5

Burr cell

Back 5

ecchinocyte or crenated cell
- preserved central pallor, contrast with loss of central pallor in acanthocytes

- usually artifact
- uremia
- bleeding ulcers
- gastric carcinoma

Front 6

Howell-Jolly bodies

Back 6

usually single nuclear remnant

- postsplenectomy
- hemolytic anemia
- megaloblastic anemia

Front 7

macrocytes

Back 7

>8.5 micrometer

- increase erythropoiesis
- oval macrocytes in megaloblastic anemia
- round macrocytes in liver disease

Front 8

ovalocyte

Back 8

elliptocyte
- hereditary elliptocytosis

Front 9

Pappenheimer bodies

Back 9

iron-containing mitochondrial remnant ro siderosome

- sideroblastic anemia
- post splenectomy

Front 10

Rouleaux

Back 10

paraprotein
artifact

Front 11

schistocytes

Back 11

2 to 3 pointed ends
- MAHA (DIC, TTP)
- prosthetic valve
- severe burns

Front 12

sickle cell

Back 12

drepanocyte
- not seen in S trait!!

Front 13

spherocyte

Back 13

no central pallor
- herediatry spherocytosis
- immune-mediated hemolysis
- transfusion
- artifact

Front 14

stomatocyte

Back 14

hereditary stomatocytosis
immune-mediated hemolysis

Front 15

target cell

Back 15

codocyte
- liver disease
- postsplenectomy
- thalassemia
- HbC disease
- iron deficiency

Front 16

teardrop cell

Back 16

dacrocyte
- myelofibrosis
- myelophthisic anemia

Front 17

PB smear in a patient with combined folate and iron def

Back 17

- masked macrocytosis

Front 18

Ferritin level consistent with iron deficiency in men and women

Back 18

men <22ng/ml
women <10ng/ml

Front 19

% transferrin saturation consistent with iron deficiency

Back 19

<9% (low)

Front 20

In iron deficiency, the serum soluble transferrin receptor levels will be __

Back 20

high

Front 21

Patient with macrocytic anemia, reticulocytosis, and no evidence fo occult blood loss, what next __

Back 21

look at PB smear and order a DAT
- DAT negative - probably a non-autoimmune hemolytic anemia

- DAT positive with spherocytes on smear supports and AIHA

Front 22

Anemia can be relative or absolute!

Back 22

Relative anemia - due to increased plasma volume with a normal RBC mass

Absolute anemia - decreased RBC mass

Rule out relative anemia first!!
- pregnancy, excessive hydration, macroglobulinemia

Note: dehydration (decrease plasma volume) can mask an absolute decrease in RBC mass

Front 23

Anemias due to vitamin deficiencies tend to have a __ RDW

Back 23

high (in general; treatment effect, other diagnoses...)

Front 24

Common cause of mild macrocytosis with a normal RDW

Back 24

direct toxic effects alcohol

Front 25

Patient with macrocytic anemia with nml RDW and
megaloblastic bone marrow changes present only in the erythroid line; what additional testing should be considered

Back 25

- cytogenetics to evaulate for myelodysplasia
- thyroid function tests too!

Front 26

3 most common causes of microcytic anemia

Back 26

- iron def
- thal
- anemia of chronic disease

Front 27

The RDW in thalassemia tends to be __

Back 27

lower than expected, based on the degree of anemia; also, there is a erythrocytosis

Front 28

Patient with normo- or hypoproliferative reticulocyte counts with a normocytic normochronic anemia, general need a __

Back 28

PB smear and probably bone marrow exam

Front 29

DDX for patient with a NCNC anemia without high retic repsonse and the following:
- leukoerythroblastosis
- abn WBCs
- rouleuax
- no abn cells

Back 29

leukoerythroblastosis
- suspect myelophthisic process
- BM exam to eval for space occupying process (metastatic tumor, lymphoma, myelofibrosis)
- in children suspect infection

abn WBCs
- suspect leukemia, lymphoma
- BM exam

rouleuax
- suspect myeloma
- SPEP, UPEP, radiographs, BM exam

no abn cells
- suspect anemia of chronic disease or sideroblastic anemia
- BM exam
- rule out underly disease
- iron studies

Front 30

NCNC anemia with high retic response, a __ would be useful

Back 30

DAT
- AIHA
vs
- Coombs-negative anemia

Front 31

Reticulocyte count; PB smear is stained with __

Back 31

brilliant cresyl blue or methylene blue

Front 32

Reticulocytes must have at least __ dots of stainable reticulin material

Back 32

two
- more immautre forms have multiple dots and small networks or skeins of bluish staining material

Front 33

the number of reticulocytes should be compared with the ___

Back 33

expected number to be released in a paitent without anemia

corrected reticulocyte count = (%retic x HCT)/45

Reticulocyte production index (RPI)
- correction of the retic count for immature reticulocytes; in severe anemia with brisk retic response, retic are released into circulation earlier and thus can persist 2-3 days (instead of typical 24hrs)

RPI = CRC/correction factor

RPI < 2 (hypoproliferative anemia)
RPI>3 (hyperproliferative anemia) or appropriate response

Front 34

Low EPO (liver or renal disease) could give a RPI corrected retic count that suggest __

Back 34

bone marrow failure to respond

Front 35

Anemia is __ in lead poisoning

Back 35

uncommon, despite interference with heme sythesis

- lead interferes with multiple enzyme steps in heme synthesis, most importantly it ihibits delta-ALA dehydratase and ferrochelatase leading to accumulation of heme intermediates (protoporphyrin) and decreased RBC survival

Front 36

Mechanism leading to basophilic stippling a/w lead poisoning

Back 36

Lead ihibits pyrimidine 5'-nucleotidase, an enzyme that normally digests residual RNA in RBCs

Front 37

Fate of residual RNA in reticulocytes, as the mature

Back 37

pyrimidine 5'-nucleotidase digests residual RNA

Front 38

hypochromic, microcytic anemia could be due to ___ (mechanism)

Back 38

HCMiC anemia
- insufficient iron (most common)
- abn iron utilization
- abn in heme synthesis (sideroblastic anemias)
- hereditary abn in globin protein synthesis (thalassemias)

Front 39

Sideroblatic anemias

Back 39

- disorders of heme synthesis

Include:
- Hereditary (X-linked or autosomal)
- Acquired idiopathic (myelodysplasia)
- Acquired toxic (lead, drugs, alcohol)

Front 40

Anemia of chronic diseae is most often a ___ anemia

Back 40

NCNC, but can be HCMiC anemia

- defective iron cycling between macrophages and erythroid precursors; iron is trapped in macrophages

Front 41

Iron is trapped in __ in anemia of chronic diseae and in ___ in sideroblastic anemias

Back 41

AOCD - iron trapped in macrophages

Sideroblastic anemias - iron trapped in erythroid mitochondria and is not available for heme synthesis (despite being in the erythroid precursor)

Front 42

Siderotic granules seen in ringed sideroblast are a result of __ (basic mechanism)

Back 42

- defective heme synthesis
- iron is trapped in erythroid mitochondria
- in erythroid precursors, the mitochondria are normally perinuclear
- in sideroblastic anemia, the abnormal iron deposition leads to mitochondrial swelling
- iron stain shows ringed sideroblasts

Front 43

new onset HCMiC anemia in an elderly patient - DDX

Back 43

- iron def anemia due to blood loss
- AOCD
- acquired sideroblastic anemia (idiopathic such as MDS, or toxic - alcohol, drug)

Front 44

HCMiC anemia in an infant or child - DDX

Back 44

iron def
thalassemia

Front 45

Red cell count in thalassemia may be __

Back 45

normal or high

Front 46

HCMiC anemia with high RDW (DDX)

Back 46

- iron def
- sideroblastic anemia could have high RDW too

Front 47

Serum soluble transferrin receptor is useful in that it is ___

Back 47

a measurement of iron stores that is NOT altered by inflammatory states

Front 48

Free erythrocyte protorphyrin (FEP) could be helpful in the eval of HCMiC in distinguishing __ from ___

Back 48

increased in iron deficiency and lead poisoning, but normal in thalassemia

Front 49

HCMiC anemia and target cells (DDX)

Back 49

- hemoglobinopathies (HbC, thal)
- liver disease
- iron deficiency (but probably not predominant cell morphology)

Front 50

HCMiC anemia and basophilic stippling (DDX)

Back 50

- thalassemia
- lead toxicity

Front 51

Iron stores in BM biopsy/aspirate in HCMiC anemia

Back 51

- iron def: absent iron
- thal: increased iron
- sideroblastic: increased ringed sideroblasts

Front 52

In acquired siderblastic anemia, the RDW will show __

Back 52

- dimorphic RBC population (characteristic of acquired form)

Front 53

Bone marrow iron staining will show __ in anemia of chronic disease

Back 53

- decreased siderocyte iron staining
- increased RE cell iron staining

Front 54

In anemia of chronic disease, the serum iron, TIBC, and transferrin percent saturation , serum soluble transferrin receptor, and BM storage iron are __

Back 54

serum iron: low
TIBC: low
% sat: low
soluble tfn-R: normal
BM iron: increased in reticuloendothelial cells (macrophages) and decreased in siderocytes

Front 55

Free erythrocyte protoporphyrin is a good screening test to __

Back 55

separate iron deficiency and thalassemia minor

Front 56

BM findings in sideroblastic anemia (required)

Back 56

- increased ringed sideroblasts
- increased reticuloendothelial iron

Front 57

Increased BM reticuloendothelial iron is increased in thalassemia due to __

Back 57

ineffective erythropoiesis

Front 58

Serum iron measures ___

TIBC is a measure of ___

% transferrine saturation is calculated by __

Back 58

serum iron = measure of transferrin-bound iron (note: iron is transported in plasma in the ferric state Fe3+)

TIBC is a measure of total transferrin (increased tfn in iron deficiency)

% tfn saturation = serum iron/TIBC x 100

Front 59

serum iron quantitation assay

TIBC assay

Back 59

- serum acidifyed to release iron from transferrin
- iron is reduced to ferrous state Fe2+
- protein is precipitated out leaving iron in filtrate
- iron measured spectrophotometrically after reaction with a chromogen

TIBC
- add excess iron to sample to completely saturate all transferrin
- remove unbound iron
- then measure iron as in serum iron assay above

- alternative method: measure transferrin via immunodiffusion

Front 60

normal transferrin saturation is about

Back 60

30%
(20-50%)

Front 61

Transferrin saturation levels typical of iron deficiency vs AOCD

Back 61

Low in both conditions and overlap, but in general

iron def: <16%

AOCD: >16%

Front 62

TIBC in iron def is __ and __ in AOCD

Back 62

iron def: TIBC increased (increased serum transferrin)

microcytic AOCD: TIBC is nml or decreased

Front 63

In sideroblastic anemia, serum iron is __

Back 63

increased

Front 64

Serum iron in AOCD is ___

Back 64

increased

Front 65

Serum samples for iron studies should be drawn in the ___

Back 65

morning
- serum iron has diurnal variation (highest in morning)

Front 66

before drawning a sample for iron studies, oral iron therapy should be withdrawn at least __

Back 66

24hours

Front 67

Bone marrow core biopsy, iron staining may be falsely low due to __

Back 67

decalcification

Front 68

the stainable form of iron store is __

Back 68

hemosiderin

Front 69

normal BM iron staining

Back 69

Normal: see iron granules in every third to fourth oil immersion field

Decreased: none seen

Increased: see iron granules in every oil immersion field and in chunks

Front 70

Normal percentage of sideroblasts in BM

Back 70

20-40% of erythroid precursors are iron-containing sideroblasts

- in sideroblastic anemia, its ringed siderblasts that are increased

Front 71

Ringed sideroblasts is a sideroblast in which __

Back 71

perinuclear iron granules surround at least 2/3 of the nucleus

Front 72

Parental iron, can be in the form of __ or ___

Back 72

Iron dextran or RBC transfusion

iron dextran causes plasma iron levels to be elevated for several weeks, unlike oral iron therapy which elevates it for 24 hours

Front 73

Ferritin is __

Back 73

a storage form of iron (apoferritin + iron)

largest store of ferritin is in the liver (its hemosiderin that we see with Prussian blue stain)

Ferritin usually reflects body iron store; it is affected by inflammatory states

Front 74

sideroblastic anemia is a type of iron __ state

Back 74

iron overload state, iron is not being utilized appropriately and with resulting anemia

Front 75

High serum ferritin (DDX)

Back 75

- inflammatory state
- hemosiderosis
- sideroblastic anemia

Front 76

Iron def, AOCD, sideroblastic anemia, thalassemia; the TIBC is increased in which one(s)?

Back 76

iron def only!!

in all other states, the marrow iron stores are increased

Front 77

Serum soluble transferrin receptor levels can high in __

Back 77

iron def (useful)

But also, it can be high in other conditions, regardless of iron stores:
- hematologic malignancies
- condidtions with increased effective or ineffective erythropoiesis (hemolytic anemia, hemoglobinopathies, def of vitB12 or folate)

Front 78

Free erythrocyte protoporphyrin is elevated when there is an abnormality in __

Back 78

incorporation of iron into heme durig heme synthesis

- iron def
- lead toxicity and other sideroblastic anemia (iron trapped in mitochondria)
- AOCD (iron trapped in macrophages)

In abnormalities of globin synthesis (thalassemia), FEP is normal!!

Front 79

Free erythrocyte protoporphyrin levels in lead toxicity are typically __

Back 79

markedly high (>1000 ug/dL)

Front 80

microcytic anemia with erythrocytosis, normal RDW, and targets, which test should be recommended

Back 80

- iron studies (R/O iron def)
- FEP
- quantitate HbA2 levels and/or possibly Hb electrophoresis

Front 81

Sideroblastic anemia (other than acquire idiopathic forms - MDS) may respond to __ therapy

Back 81

pyridoxine therapy
- many drugs causing toxic acquired sideroblastic anemia are pyridoxine antagonists