Hematology Exam 7 (Anemias, Iron kinetics) Flashcards
List the 3 iron compartments in the body and how much iron is held in each
Functional - 80% (hgb, myoglobin, enzymes)
Storage - 20% (ferritin and hemosiderin)
Transport - <1% (transferrin)
List the steps of the iron cycle to include what form of iron is in each stage
Iron ingested as heme
Absorbed through enterocytes of intestine as ferrous form
Can then be stored or transported to plasma for use
Must be in ferric form for transport in blood
Function of ferroportin
transports ferrous iron from enterocyte into blood
Function of hepcidin
protein made by hepatocytes that binds to and INACTIVATES FERROPORTIN
Function of hephaestin
protein that oxidizes iron turning ferrous iron (Fe2+) into ferric iron (Fe3+) for transport in the blood
Function of transferrin
Binds ferric iron for transport in the blood (iron transporter)
Function of erythroferrone
Used in the second mechanism for iron regulation - increased EPO will cause erythroferrone to be secreted which decreases hepcidin production to increase iron absorption in the intestine
Function of ferritin
What is apoferritin?
the major storage protein for iron
Apoferritin = ferritin not yet bound to iron
Function of hemosiderin
Partially degraded ferritin; another storage form of iron (iron is less available in this form)
Function of haptoglobin
binds hemoglobin released from degraded RBCs
Function of hemopexin
Binds heme released from degraded RBCs
How does decreased iron stores affect hepcidin, ferroportin, and iron absorption?
Decreased iron stores = decreased hepcidin = activated ferroportion = increased iron absorption
How is iron homeostasis maintained?
Changes in hepcidin production
How does increased iron stores affect hepcidin, ferroportin, and iron absorption?
Increased iron stores = increased hepcidin = inactivated ferroportin = decreased iron absorption
What is the serum iron test measuring and how?
Measures iron that had been bound to transferrin - iron released from transferrin by acid and measured spectrophotometrically
How does menstruation, lactation, and pregnancy, and growing children affect iron needs?
Increases iron needs
What is the TIBC test measuring and how?
This test is an indirect measure of transferrin. It measures how much iron could be bound if excess iron is added
What Is the formula for the TSAT test? What is it measuring?
This is calculated by Serum iron/TIBC x 100 to get the % transferrin saturation. It measures how much transferrin in your body is actually bound to iron
What is the prussian blue test measuring and how?
This test assesses body iron stores by staining tissues - dark blue granules present indicate iron stores (ferritin)
What is serum ferritin test measuring and how?
Immunoassay that indicates the levels of ferritin in your serum. Low ferritin levels = iron deficiency of some sort
These levels correlate with prussian blue results
What is the sTfR test measuring? What do results indicate?
Amount of soluble transferrin receptors on cell membranes - increased sTfR with decreased iron indicates an iron deficiency
What is the hemoglobin content of reticulocytes test measuring and what do results indicate?
Measures hemoglobin content of reticulocytes - decreased when iron available for erythropoiesis is restricted
What is the ZPP test?
This is when zinc binds protoporphyrin IX instead of iron - will be increased when iron is not available
sTfR/log ferritin levels and HGB content of retics for True Iron Deficiency (Thomas Plot)
True Iron deficiency (lower right quadrant) has increased sTfR/log ferritin and decreased HGB content of retics
sTfR/log ferritin levels and HGB content of retics for Normal Iron Status (Thomas Plot)
Normal iron status (upper left quadrant) has normal HGB content of retics and normal sTfR/log ferritin
sTfR/log ferritin levels and HGB content of retics for Latent Iron Deficiency (Thomas Plot)
Latent Iron Deficiency (upper right quadrant) has increased sTfR/log ferritin and normal HGB content of retics
sTfR/log ferritin levels and HGB content of retics for Functional Iron Deficiency (Thomas Plot)
functional iron deficiency (lower left quadrant) has normal sTfR/log ferritin and decreased retic HGB
Define anemia
A decrease in oxygen carrying capacity of the blood due to decreased RBC count, HGB, and/or HCT levels
What is the normal HCT range for newborns? Men? Females and children?
Newborns: 48-66%
Men: 40-54%
Females and children: 35-49%
What Is the normal HGB range for newborns? Men? Females and children?
Newborns: 16.5-21.5
Men: 13.5-18
Females and children: 12-15
What is the normal RBC count for newborns? Men? Females and children?
Newborns: 4.1-6.1
Men: 4.2-6
Females: 3.8-5.2
What is the difference between insufficient erythropoiesis and ineffective erythropoiesis?
Insufficient = decreased number of RBC precursors/decreased RBC production (decreased production)
Ineffective = defective RBC precursors produced (increased desruction)
What is the calculation for MCV and normal range?
HCT x 10/RBC count
Normal range = 80-100 fL
What is the calculation for MCH and normal range?
HGB x 10/RBC count
Normal range = 26-32 pg
What is the calculation for MCHC and normal range?
HGB x 100/HCT
Normal range = 32-36 g/dL
What is the purpose of the reticulocyte count?
Assesses the bone marrow’s ability to increase erythropoiesis to compensate for anemia
What is the purpose of the corrected reticulocyte count?
Corrects for the degree of anemia based on patient’s HCT
What is the purpose of the reticulocyte production index (RPI)?
calculated to correct for a low HCT and the presence of shift reticulocytes (immature retics) that may falsely elevate the retic count
What is the normal reticulocyte count for adults vs newborns?
Adults: 0.5-2.5%
Newborns: 1.5-6.0%
What information can the peripheral smear provide in the assessment of anemia?
It is the only way to determine poikilocytosis and RBC inclusions
What information can the bone marrow exam provide in the assessment of anemia?
Can see abnormal cellularity, evidence of ineffective erythropoiesis, lack of iron staining, and presence of tumor cells/fibrosis
What is a microcytic anemia and an example?
Anemias with MCV <80, small RBCs
Example: iron deficiency anemia
What is a macrocytic anemia and an example?
Anemias with MCV >100, large RBCs
Ex. megaloblastic anemias
What is a normocytic anemia and an example?
Anemias with MCV 80-100
Ex. Hemolytic anemia/aplastic anemia/blood loss anything due to decreased RBC production
What is the most common cause of IDA?
Excessive blood loss
List 4 causes of IDA and an example of each
Inadequate intake - diet
Increased need - childhood/pregnancy
Impaired absorption - celiac disease
Chronic blood loss - chronic hemorrhage
Stage 1 of IDA
Storage Iron Depletion - loss of storage iron so ferritin levels drop but RBC production/development is normal. This stage is considered “latent iron deficiency”
Stage 2 of IDA (what is it called, what lab values are increased/decreased)
Transport Iron Depletion - there is exhaustion of storage pool at this point.
Increased: TIBC, FEP, sTfRs
Decreased: retic HGB (onset of iron restricted erythropoiesis), iron, ferritin, prussian blue stain shows NO stored iron
Still considered latent iron deficiency because anemia is still not evident
Stage 3 of IDA
Functional iron depletion, Iron deficiency anemia.
Increased: FEP, sTfRs, TIBC
Decreased: H&H, storage and transport iron, HGB of retics
RBCs are microcytic and hypochromic now
First stage where anemia is evident
What group of people are at the highest risk for developing IDA?
Menstruating women, pregnant/nursing women, and growing children
What is an example of SCREENING tests for IDA and what would the values look like for a patient with IDA
CBC and peripheral smear - a patient with IDA would have anisocytosis (increased RDW = first sign), microcytosis, hypochromia
What is one of the first signs of a developing IDA?
Increased RDW (anisocytosis)
What are examples of DIAGNOSTIC tests for IDA and what would the values look like for a patient with IDA?
Iron studies such as TIBC (low), transferrin saturation (low), serum ferritin (low) and reticulocyte parameters (decreased retic count = diminished erythropoiesis)
What are examples of SPECIALIZED tests for IDA and what would the values look like for a patient with IDA?
FEP (increased), ZPP(increased), sTfRs(increased), BM exam will be hyperplastic and have a decreased M:E ratio
What is the central feature of ACI?
Sideropenia (low serum iron) despite abundant iron stores AKA functional iron deficiency
Causes of ACI
Impaired ferrokinetics
Impaired erythropoeisis
Shortened RBC lifespan
Population most affected by ACI
Hospitalized patients due to inflammatory conditions
What is the most important contributor to ACI?
Impaired ferrokinetics
What type of anemia is considered functional iron deficiency and why?
ACI - because iron stores are present but cannot be used because hepcidin levels are increased during inflammation which leads to decreased iron release from macrophage
What are the two acute phase reactants that are increased in ACI, causing functional iron deficiency?
Lactoferrin and hepcidin
Notable lab values in ACI
Normocytic, normochromic
Decreased iron
Decreased TIBC
Ferritin falsely increased (acute phase reactant)
Prussian blue stain shows abundant iron stores
NORMAL sTfR
IDA vs ACI lab values
IDA has increased sTfRs, ACI has normal sTfRs
What is the hallmark finding in sideroblastic anemias?
Ringed sideroblasts
What is sideroblastic anemia?
Anemia resulting from interference of production of protoporphyrin
What is an example of an acquired form of sideroblastic anemia? Lab results?
Lead poisoning which interferes with protoporphyrin synthesis.
Basophilic stippling is a classic finding in the peripheral smear, accumulated ALA in urine and increased FEP/ZPP
What is an example of a hereditary form of sideroblastic anemia?
Porphyrias - impaired heme synthesis with the accumulation of porphyrin and its precursors
What is hereditary hemochromatosis?
Mutations in genes (HFE gene) controlling proteins involved in iron kinetics leading to continually absorbed iron even when stores are full
What is hemochromatosis also called? Why?
Bronzed diabetes because it causes jaundice and diabetes
Lab diagnosis of hereditary hemochromatosis
Abnormal liver function tests
Increased TSAT, ferritin, and iron
Iron Study Values for IDA
(Iron, ferritin, TIBC, TSAT, sTfRs, FEP/ZPP, Prussian Blue)
Iron: decreased
Ferritin: decreased
TIBC: increased
TSAT: decreased
sTfRs: increased
FEP/ZPP: increased
Prussian Blue: no stained iron
Iron Study Values for ACI
(Iron, ferritin, TIBC, TSAT, sTfRs, FEP/ZPP, Prussian Blue)
Iron: decreased
Ferritin: increased
TIBC: normal/decreased
TSAT: normal/decreased
sTfRs: normal/decreased
FEP/ZPP: increased
Prussian Blue: normal/increased
Iron Study Values for HH
(Iron, ferritin, TIBC, TSAT, sTfRs, FEP/ZPP, Prussian Blue)
Iron: increased
Ferritin: increased
TIBC: normal/decreased
TSAT: increased
sTfRs: normal/decreased
FEP/ZPP: normal
Prussian Blue: increased stained iron
Iron Study Values for sideroblastic anemia
(Iron, ferritin, TIBC, TSAT, sTfRs, FEP/ZPP, Prussian Blue)
Iron: increased
Ferritin: increased
TIBC: normal/decreased
TSAT: increased
sTfRs: normal/decreased
FEP/ZPP: N/A
Prussian Blue: ringed sideroblasts present
What is the etiology/underlying cause of megaloblastic anemias? What are the 2 deficiencies leading to these anemias?
Impaired DNA synthesis because of decreased cell divisions –> leads to large cells
B12 and Folate deficiencies
How do B12 and Folate deficiencies lead to megaloblastic anemias?
Impaired nucleotide production for DNA synthesis, decreased thymidine availability, leads to ineffective erythropoiesis
Another name for B12
Cobalamin
What does no B12 lead to the buildup of?
MMA and homocysteine
Describe nuclear to cytoplasmic asynchrony. Why is this seen in megaloblastic anemias?
Nucleus is not maturing as fast as the cytoplasm. This is seen in megaloblastic anemias because there is impaired DNA synthesis (found in the nucleus) so it does not mature as fast as the cytoplasm, which has RNA in it.
Clinical presentations of B12 deficiency vs Folate deficiency
B12: neurologic symptoms that take years to develop
Folate: can lead to neural tube defects such as spina bifida in pregnancies, takes a few months to develop
Causes of B12 and Folate deficiency
Inadequate intake (B12 found in meats and dairy while folate found in vegetables, beans, cereal, fruit)
Impaired absorption
What is b12 bound to in normal absorption?
Intrinsic factor
What is pernicious anemia and how does it lead to megaloblastic anemia?
autoimmune disorder caused by impaired absorption of VITAMIN B12 due to an intrinsic factor deficiency
List notable lab findings of megaloblastic anemias
Macrocytosis, decreased H&H, oval macrocytes, MCV >120 fL, hypersegmented neutrophils
How can macrocytic nonmegaloblastic anemias be differentiated from a megaloblastic anemia?
Macrocytic anemias are not due to impaired DNA synthesis
MCV rarely exceeds 120 fL
Lack oval macrocytes and hypersegmented neutrophils
May be normal (newborns) or due to pathological condition (liver disease, alcoholism, BM failure)
