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72 Cards in this Set

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What are the components of a routine CBC?
Red Blood Cell Count (RBC)
Hct: measures RBC mass
HGB – main component of the RBC
RBC indices: these are calculated values of
Size of RBC
HGB content of RBC
Both of which are important in the evaluation of anemia
The Red cell indices include:
MCV – mean corpuscular volume
Mean corpuscular HGB concentration (MCHC)
Mean Corpuscular Hemoglobin (MCH)
White blood cell count (WBC)
Differential WBC - demonstrating specific patterns of the leukocyte cell lines
Platelet count: thrombocytes are needed for clotting and control of bleeding
Peripheral blood smear
Red Cell Distribution Width, indicates degree of variability & abnormal size
Mean Platelet Volume: index of platelet production
What is included in a hemogram?
RBC, WBC, HGB, Hct, Red blood cell indices, and platelet count
When ordering a CBC you should advize your patient to perform what pre-test tasks?
1. They should avoid stress if possible.
(Altered physiologic status influences and changes normal values (especially those related to the red blood cell)).

2. For a CBC with differential fasting is not necessary. Thus, dehydration or overhydration can dramatically alter values (i.e. large volumes of fluid (such as IV) can dilute blood and counts will appear lower than normal).

3. After the blood is drawn your patient will need to know some indications of potential problems/ complications. Advise your patient to watch for: Oozing around puncture site and/or hematoma formation. Also alert them to the fact that bruising at the puncture site is not uncommon, but inflammation is therefore explain to them about the signs of inflammation.
What do the tests of the red blood cell (erythrocyte) examine?
1. Cell size
2. Cell number
3. the amount of HGB
4. the rate of production
5. the percent composition in the blood
What must be taken into account when running an RBC?
In order to “run” a CBC with a RBC:
1. a 5ml sample of anti-coagulated venous blood is collected in a lavender topped tube (it contains the anticoagulant/preservative EDTA).
2. Important to note on the label for the tube: patient age, gender, and time of collection.
3. The patient’s arm is evaluated for the appropriate venipuncture site.
What are the normal reference ranges for an RBC-men and women?
Normal RBC Reference range:
Men: 4.2-5.4 X 10^6/mm3
Women: 3.6-5.0 X 10^6/mm3
What does a decreased RBC tell the physician? And can a diagnosis be obtained strictly from a decrease in RBC?
So, what does a decrease in the number of RBCs really tell us? Not much! Is it a production problem? Destruction problem? You will need to put it together with other parameters in order to interpret the exact clinical significance and diagnosis. For instance, anemia has numerous causes and can be multifactorial. One cannot jump to a diagnosis of anemia without further testing of the erythrocyte values.
What is Anemia? What are some causes of anemia?
Anemia is a condition in which there is a reduction in: the number of circulating erythrocytes, and/or the amount of HGB, and/or the volume of packed cells (Hct). Anemia is associated with:
1. Cell destruction
2. Blood loss
3. Dietary insufficiency of iron or certain vitamins
4. Production deficits
What are the 3 primary categories of causation for anemia:
1. Excessive blood loss (acutely such as a hemorrhage or chronically through low-volume loss)
2. Excessive blood cell destruction hemolysis
3. Deficient red blood cell production (ineffective hematopoiesis)

1. Production
2. Destruction and
3. Loss

PDL: What approch evaluates PDL?
What are the 2 major approaches of clinically classifying anemias:
1. the "kinetic" approach which involves evaluating production, destruction and loss of RBCs

2. The "morphologic" approach which groups anemia by red blood cell size.
-The morphologic approach uses a quickly available and cheap lab test as its starting point (the MCV)
What are the 4 red cell parameters?
1. RBC
2. RDW
3. MCV
4. Hemoglobin concentration
What is referred to as the red cell indices?
There are 4 red cell parameters (RBC, hemoglobin concentration, MCV and RDW) that are directly measured, allowing other values to be calculated. These calculated values are the RCI:
1. Hematocrit (Hct)
2. Mean corpuscular
3. Hemoglobin (MCH) and
4. mean corpuscular hemoglobin concentration (MCHC).
All of the values are then compared to standard ranges of normal that have been adjusted for age and sex.
What is refered to as a reticulocyte count? Which specific approach to classifying anemia does this fall under?
Using the reticulocyte count and the "kinetic" approach to anemia has become more common.

A reticulocyte count is a quantitative measure of the bone marrow’s production of new red blood cells. The reticulocyte production index is a calculation of the ratio between the level of anemia and the extent to which the reticulocyte count has risen in response.
Why use the reticulocyte count?
1. To help evaluate the bone marrow’s ability to produce red blood cells (RBCs)
2. To help distinguish between anemia related to blood loss or destruction versus anemia related to decreased RBC production
3. To help monitor bone marrow response and return of normal marrow function following chemotherapy treatment, bone marrow transplant, or post-treatment follow-up for iron deficiency anemia

Basically, to monitor production, DDX anemia, and evaluate post TX
What if RBC values are decreased, what are the potential DDX implications?
General list of diseases condition with associated anemia:

1. Hodgkin’s disease and other lymphomas
2. Multiple myeloma, 3. myeloproliferative disorders, leukemia
3. Acute and chronic hemorrhage
4. Lupus erythmatosus
5. Addison’s Dz
6. Rheumatic fever
7. Subacute endocarditis, chronic infection
8. Other
What are potential DDX that present with pimary eryhtrocytosis?
Primary erythrocytosis:

1. Polycythemia vera ( myeloproliferative disorder)
2. Erthythemic erythrocytosis (increased RBC production in the bone marrow)
What are potential DDX that present with secondary erythrocytosis?
Secondary erythrocytosis:

1. Renal disease
2. Extrarenal tumors
3. High altitude
4. Pulmonary disease
5. Cardiovascular disease
6. Alveolar hypoventilation
7. Hemoglobinopathies
8. Tobacco/carboxyhemoglobin
What are potential reletive increases in RBC, things which present as erythrocytosis?
Relative Increase:

1. Dehydration (vomiting, diarrhea)
2. Gaisbock syndrome (relative polycythemia with HTN but without splenomegaly)
While evaluating a CBC for abnormalities in the RBC results/values it is essential to understand that there can be interfering/confounding factors. Such as?
1. Posture: if in recumbent position the RBC is 5% lower; if patient is anemic count will be even lower
2. Dehydration: hemoconcentration may obscure significant anemia
3. Age
4. Falsely high counts may occur because of prolonged venous stasis during the venipuncture (tourniquet left on too long)

5. Stress – can cause a rise in RBCs
6. Altitude: the higher the altitude the greater the increase in RBC
7. Decreased oxygen content of the air stimulates an increase in RBCs

8. Pregnancy: there is a relative decrease in RBC when the body fluid increases in pregnancy, with the normal number of erythrocytes becoming more dilute

9. Many drugs will cause alterations in the number of RBCs and the RBC test values
10. The sample tube must be at least ¾ full or else the EDTA will cause alterations
This was a primary argument used in the OJ case!

11. Blood in the sample must not be clotted
What is the hematocrit?
Hematocrit literally means “to separate blood.” This test indirectly measures the red blood cell mass. The results of this test are expressed as the percentage of volume of packed RBCs in whole blood (packed cell volume – PCV). It is most useful in the assessment of anemia and polycythemia.
What are the normal ranges of hematocrit -men, women, children?
About 45% adults)...less in children.

Men: 42-52%
Women: 36-48%

Children:
6mos to 1 yr: 29-43%
1-6 yrs: 30-40%
6-16 yrs: 32-42%
16-18 yrs: 34-44%
1. What do decreased values of hematocrit indicate?
2. What DDX can present with a decreased hematocrit?
3. When is the hematocrit invalid?
Decreased Hct:
Decreased values are an indicator of anemia.

Anemia: condition in which there is a reduction in the PCV

An Hct of <30% indicates moderate to severe anemia

An Hct of <20% can lead to cardiac failure & death

Decreased values also seen:
1. Leukemias, lymphomas, Hodgkin’s Dz,
2. myeloproliferative disorders
3. Adrenal insufficiency
4. Hemolytic reaction

*Not reliable immediately after a transfusion or loss of blood:
donating blood
Transfusion
What if your patient presents with an increased hematocrit, what are the potential DDx and complications?
Increased Hct:

1. Erythrocytosis
2. Polycythemia vera
3. Shock, when there is hemoconcentration the Hct rises considerably

*Hct >60% is associated with spontaneous clotting of the blood
What are some interfering factors of a hematocrit count?
Interfering factors:

Interfering factors to be aware of when interpreting the hematocrit:

1. People living at high altitude have high Hct, High HGB, and RBC
2. Age and gender, Hct slightly lower in women vs. men
3. Severe dehydration may cause falsely elevated Hct
What are the normal reference ranges of HGB- Men and Women?
Normal Reference Range:

Men: 14.0-17.4 g/dL
Women: 12.0-16.0 g/dL
Panic value of Hgb is <5.0 g/dL, a condition that leads to heart failure and death
Severe hemoconcentration: a value of 20g/dL, this leads to clogging of the capillaries
What potential DDx are indicated with decreased HGB?
Potential conditions with decreased HBG include:

IDA
Thalassemia
Pernicious anemia
Hemoglobinopathies
Liver disease
Hypothyroidism
Hemorrhage – chronic or acute
Hemolytic anemias

A decrease in the amount of HGB is found in numerous anemic states. Thus, HGB must be evaluated along with the RBC and Hct in order to narrow down the exact mechanism/cause.
Hemolytic anemia includes conditions/causes such as?
1. Transfusion incompatibility
2. Reactions to chemicals or drugs
3. Reaction to infectious agents
4. Reactions to physical agents:
-Severe burns
-Artificial heart valves
5. Various systemic diseases
-Hodgkin’s disease
-Leukemias
-Lymphomas
-SLE
-Sarcoidosis
-Renal cortical necrosis
Increased numbers of HGB are seen in which conditions?
Increased HGB:

1. Polycythemia Vera
2. Congestive heart failure
3. Chronic obstructive pulmonary disease (COPD)
What are some interfering factors to the HGB?
Interfering factors
People that live at high altitudes have increased HGB values as well as increased Hct and RBC
Excessive fluid intake can cause decreased HGB
HGB is normally decrease in pregnancy as a result of plasma volume
Drugs that decrease HGB are NUMEROUS
Drugs that increase HGB include gentamicin & methyldopa
Explain the differences in polycythemia vera...reletive v. absolute, what are the clinical implications of PCV?
Clinic Implications of Polycythemia: Increased RBC, Hct, and/or HGB

First, it will be important to determine if the polycythemia is relative or absolute.

In relative Polycythemia the increase in the HBG, RBC, or Hct is caused by a decrease in the plasma volume such as from: dehydration or spurious erythrocytosis from stress or smoking.

There are 2 types of absolute polycythemia:

primary or secondary

Primary: Vera or erythemic erythrocytosis
Secondary: Appropriate vs. Inappropriate

Appropriate (secondary) polycythemia is an appropriate bone marrow response to certain physiologic conditions such as: high altitude, cardiopulmonary disorder, or an increased affinity for oxygen.

Inappropriate (secondary) polycythemia is an over production of red blood cells but the over production is not related to or necessary for increased delivery of oxygen to the tissues. Examples of this type of secondary polycythemia are: certain renal tumors, hepatoma, or cerebellar hemangioblastoma.
What are the different ways of classiying anemia?
Morphologically-MCV

Kinetically-production destruction and loss

Functionally-
hypopreoliferative anemia: anemia that is the result of inadequate production of erythrocytes and abnormal MCV. Examples, are myelo disorders like,
Marrow aplasia
Myelophthisic anemia
Anemia with blood dyscrasias
Anemia of chronic disease
Anemia of organ failure

maturation defect anemias: relates to the development/life span of the erythrocyte. Examples,
Cytoplasmic: hypochromic anemias
Nuclear: megaloblastic anemias (i.e. pernicious anemia)
Combined: myelodysplastic syndromes

Hyperproliferative anemias are a group of anemias that have decreased HGB or Hct despite an increased production of red blood cells (an increase in the RBC) This group includes:
Hemorrhagic: acute blood loss
Hemolytic: premature accelerate destruction of RBCs
Immune hemolysis
Primary membrane
Hemoglobinopathies
Toxic hemolysis
Hypersplenism
Enzymopathies
Parasitic Infectio

Dilution Anemias are just as the name sounds, relative to an increase in blood/plasma volume.
The best example of this occurs with pregnancy.
What tests or values make up the RED CELL indices?
1. MCV- It expresses the volume occupied by a single erythrocyte.
2. MCHC
3. MCH

These are values taken from the RBC which includes HCT, HGB, MCV
Define the red blood cell distribution width, or RDW? What the uses of RDW in conjunction with MCV?
It is a measure of the variation of red blood cell width that is reported as part of a standard CBC.

Certain disorders, however, cause a significant variation in cell size. Higher RDW values indicate greater variation in size.

It is mainly used to differentiate between IDA (in which RDW is elevated) and other microcytic anemias.
It may denote hereditary spherocytosis (normal RDW but decreased MCV)
An elevated RDW, i.e. red blood cells of unequal sizes, is known as anisocytosis.
What are the clinical implications of RDW?
Clinical Implications of the RDW:

The RDW is helpful in determining thalassemia (MCV and normal RDW) heterozygous from IDA (low MCV and high RDW). It is helpful in determining anemia of chronic disease (low-normal MCV and normal RDW) from early IDA (low-normal MCV and elevated RDW)

Increased RDW:
IDA
Vit B12 or folate deficiency
Homozygous thalassemia
Fragmentation of RBCs
Decreased RDW: no known causes

Important to note: A normal RDW occurs in anemias with homogenous red cell size: chronic disease, acute blood loss, aplastic anemia, HGB-E disease, Sickle cell
What are the factors which can interefere with MCV?
Factors that interfere with the MCV:

1. Mixed (bi-morphic) population of macrocytes and mircocytes can result in a normal MCV
2. Marked leukocytosis increases the MCV
3. Marked hyperglycemia increases the MCV
4. Cold agglutinins can increase MCV
Cold agglutinin disease is an autoimmune dz. characterized by the presence of high concentrations of circulating antibodies directed against red blood cells. It is a form of autoimmune hemolytic anemia, specifically one in which antibodies only bind red blood cells at low temperatures, typically 28-31°C.
What is the MCHC and define how it's calculated, not with an equation?
It measures the average concentration of HGB in the erythrocyte. It is most valuable in monitoring therapy for anemia because the 2 most accurate hematologic determinants are used in its calculation. It is the ratio of the weight of HGB to the volume of the erythrocyte
What are some interefering factors of MCHC?

What is the "cut off" range for MCHC to determine a lab error?
Interfering factors:

The MCHC can be Falsely elevated in the presence of:

1. Lipemia
2. Cold agglutinins
3. High heparin concentrations

IMPORTANT: The MCHC cannot be higher than 37 g/dL. If it is check for lab error!
Define MCH, how is it calculated, not by an equation?
Mean corpuscular Hemoglobin MCH
The MCH is a calculated value. It is the measure of the weight of HGB per red blood cell.
What are the clinical implications of MCH?
Clinical Implications:
Increased MCH is associated with Macrocytic anemias
Decreased MCH associated with microcytic anemias
What factors interfere with MCH?
Interfering factors:
Hyperlipidemia falsely elevates
WBC > 50000/mm3 falsely raises HGB therefore also MCH
High heparin concentrations falsely elevate
What are the tests utilized for the evaluation of hemolytic anemia?
1. Pyruvate kinase
2. Erythrocyte fragility
3. Glucose-6-Phosphate Dehydrogenase (G6PD)
4. Heinz Bodies – Glutathione Instability
5. 2,3 – Diphosphoglycerate (2,3-DPG)
What will definitive test results for hemolytic anemia indicate?
1. Injury to the RBC
2. Oxidative activity that interferes with normal HGB function
3. Increased RBC fragility
What is pyruvate kinase? How is it related to hemolysis?
PK is used in RBC metabolism. It is used in glycolysis and therefore ATP production. Without ATP the Na+/K+ pump is not operable and because of this NA+ will accumulate inside the cell and water will follow. The cell will then swell increaseing cell fragility. The PK test measures for a defecit.

PK deficiency is genetic disorder. It is characterized by lowered concentration of adenosine triphosphate (ATP) in the RBC. In turn the deficiency leads to a red blood cell membrane defect. The result is a non-spherocytic chronic hemolytic anemia; meaning the red blood cell has increased membrane fragility but the defect is not related to “spherocytosis.” PK deficiency is actually the most common and most important form of hemolytic anemia resulting from a deficiency in RBC glycolytic enzymes.
What is seen with decreased PK?
Decreased PK seen with:
1. Recessive non-spherocytic hemolytic anemia
2. Patients tolerate the anemia because they also have increase 2, 3-diphosphoglycerate
What is the Erythrocyte Fragility Test (Osmotic fragility)? How many times should it be ran?
Spherocytes of any origin are more susceptible than normal RBCs to hemolysis in dilute (hypotonic) saline and show increased osmotic fragility. Generally, fully expanded cells have increased osmotic fragility. Cells with higher surface area-to-volume ratios (thin cells, hypochromic cells) have decreased osmotic fragility. This test is performed “twice.” There is an initial test examining for increased erythrocyte fragility, and then a 24 hr incubation of the specimen and the sample is then re-tested.
What are the clinical implications of an increased osmotic (erythrocyte) fragility test?
Hemolytic anemia (acquire immune)
Hereditary spherocytosis
hemolytic disease of the newborn
Malaria
Severe PK deficiency
What are the clinical implications of a decreased osmotic fragility test?
IDA (macrocytic hypochromic)
Thalessemia
Asplenia
Liver disease (obstructive jaundice)
Reticulocytosis (increased immature red blood cells)
Hemoglobinopathies
What is seen with a G6PD: glucose-6-phosphate dehydrogenase deficiency?
This is an X-linked recessive hereditary disease featuring abnormally low levels of the G6PD enzyme, which plays an important role in red blood cell function. Individuals with the disease may exhibit non-immune hemolytic anemia in response to a number of causes.
What is G6PD closely linked to?
It is closely linked to favism, a disorder characterized by a hemolytic reaction to consumption of fava (broad) beans.
What are the four forms of G6PD deficiency?
1.Hereditary non-spherocytic hemolytic anemia
2.Severe deficiency
3.Mild deficiency
4.Non-deficient variant
What are the clinical implicatins of decreased G6PD?
1. G6PD deficiency
2. Congenital non-spherocytic anemia
3. Non-immune hemolytic disease of the new born (Asian & Mediterranean)
-In the Mediterranean variant G6PD levels are grossly deficient in ALL RBCs:
Patients with this variant experience hemolysis induced by:
diabetic acidosis
infections
oxidant drugs
fatal hemolytic crisis after ingestion of fava beans
What are the clinical conditions presenting with an increased G6PD?
1. Untreated megaloblastic anemia (pernicious anemia)
2. Thrombocytopenia
3. Hyperthyroidism
4. Viral hepatitis
What are heinz bodies? In what test are they observed?
Heinz bodies (also referred to as "Heinz-Ehrlich bodies")
These are inclusions within red blood cells composed of denatured hemoglobin. Heinz bodies are observed on the peripheral smear.
What are the conditions presenting with Heinz body formation?
1. G6PD deficiency
2. Congenital Heinz Body hemolytic anemia
3. Unstable HGB variants
4. Homozygous Beta thalassemia
5. Found in the blood of “normal” people poisoned by drugs or are following certain treatment protocols
6. Present in some newborn and splenectomized patients
What are the test for Iron deficiency?
Serum Iron
TIBC
Serum Transferrin
Serum Ferritin
True or False:

A serum iron test without a TIBC and transferrin determination has very little diagnostic value?
True

A test referred to as total iron binding capacity (TIBC) correlates with serum transferrin levels.
What test is the most sensitive lab test for iron deficiency anemia?
Serum Ferritin
What are some clinical conditions observed with increased serum iron?
Increased serum iron:
Hemolytic anemia
Acute iron poisoning (children)
Hemochromacytosis
Transfusions
Inappropriate iron therapy
Acute hepatitis
Vit B6 deficiency
Lead poisoning
Acute leukemia
Nephritis
What is serum ferritin and what does it indicate? Increased v. Decreased?
The ferritin levels measured have a direct correlation with the total amount of iron stored in the body. If ferritin is high there is iron in excess, which would be excreted in the stool. If ferritin is low there is a risk for lack in iron which sooner or later could lead to anemia.
What are some conditions observed with decreased serum iron?
Decreased serum iron:
1. IDA
2. Chronic blood loss
3. Chronic diseases (i.e. Lupus, RA, chronic infections)
4. 3rd trimester pregnancy
5. Progesterone BCP
6. Inadequate absorption
7. Chronic hemolytic anemia
What is Serum Transferrin?
Transferrin is a blood plasma protein which binds iron very tightly but reversibly

Transferrin is found in the mucosa and binds iron, thus creating an environment low in free iron, where few bacteria are able to survive.
What is increased serum ferritin seen with?
IDA
Pregnancy
Estrogen therapy
What clinical cond. is decreased serum transferrin seen with?
Microcytic anemia of chronic disease
Protein deficiency or loss from burns or malnutrition
Chronic infection
Acute liver Disease
Renal disease
Genetic deficiency
Iron overload
What does Total Iron Binding Capacity (TIBC) measure? What else it it dependant on for clinical significance?
The test measures the extent to which iron-binding sites in the serum can be saturated. Because the iron-binding sites in the serum are almost entirely dependent on circulating transferrin, this is really an indirect measurement of the amount of transferrin in the blood.
What are the Clinical conditions which present with an increase TIBC? Total iron binding capacity
Clinical conditions presenting with an increased TIBC
IDA
Pregnancy (late)
Acute and chronic blood loss
Acute hepatitis
What are the clinical conditions which present with a decreased TIBC?
Clinical conditions presenting with a decrease in TIBC

Hypoproteinemia
Hemochromacytosis
Cirrhosis of the liver
Nephrosis & other renal disease states
Thalassemia
Hyperthyroidism
What factors interfere with the TIBC test?
Interfering factors:

Drugs that increase iron – ethanol, estrogens, and BCP
Drugs causing decreased iron – aspirin, testosterone, and some antibiotics
Hemolysis of the sample
Iron contamination by lab glassware
Menstruation (loss of iron) and Premenstrual (increased iron)
What is the most common cause of microcytic anemia?
IDA
Predict the results of a CBC with a dx of IDA? What further testing must be conducted for an appropriate Dx?
The diagnosis of IDA relies on routine testing, which includes a complete blood count (CBC).

Low HGB and HCT...diagnostic of anemia, however further studies will be necessary to determine its cause.

One of the first abnormal values to be noted on a CBC will be a:

Elevated red blood cell distribution width (RDW), reflecting a varied size distribution of red blood cells.

A low MCV, MCH or MCHC, and the appearance of the RBCs on visual examination of a peripheral blood smear will narrow the diagnosis to a microcytic anemia.

The diagnosis of iron deficiency anemia will be suggested by appropriate history (e.g., anemia in a menstruating woman), and by such diagnostic tests:

...as a low serum ferritin, a low serum iron level, an elevated serum transferrin and an elevated total iron binding capacity (TIBC).

Laboratory findings for IDA:

decreased HGB
decreased MCV
decreased serum ferritin
decreased serum iron

elevated transferrin
elevated TIBC
elevated RDW

*Serum ferritin is the most sensitive lab test for iron deficiency anemia.
Define Sideroblastic anemia?
Sideroblastic anemia is caused by the abnormal production of red blood cells as part of myelodysplastic syndrome, which can evolve into hematological malignancies (especially acute myelogenous leukemia). Thus, the body has iron available, but cannot incorporate it into hemoglobin.
What is the common features of sideroblastic anemia? What are some of the causes?
The common feature of sideroblastic anemias is a failure to completely form heme - whose biosynthesis takes place partly in the mitochondrion. This leads to deposits of iron in the mitochondria that form a ring around the nucleus of the developing red blood cell. Sometimes the disorder represents a stage in evolution of a generalized bone marrow disorder that may ultimately terminate in acute leukemia. Causes include:
Toxins: lead or zinc poisoning
Drug-induced: ethanol, isoniazid, chloramphenicol, cycloserine
Nutritional: pyridoxine or copper deficiency
Genetic: ALA synthase deficiency (X-linked)
Predict the laboratory findings for sideroblastic anemia?
Laboratory findings of sideroblastic anemia:
Increased ferritin levels
Decreased total iron-binding capacity
Hematocrit of about 20-30%
Serum Iron: High
High transferrin saturation
The mean corpuscular volume or MCV is usually normal or slightly increased; although it may occasionally be low, leading to confusion with iron deficiency.[1]
With lead poisoning, see coarse basophilic stippling of red blood cells on peripheral blood smear
Specific test: Prussian Blue stain of RBC in marrow. Shows ringed sideroblasts.