CS I Unit 1.1a: Hematology Pt. 1

Which stem cell line do our RBCs come from?

Myeloid

What is the only immature RBC type that may be present in systemic circulation under normal conditions?

Reticulocytes

Review: a person is said to be anemic if ____, ____, and/or ____ are low

Their RBC count, Hb, and/or Hct are low

A decrease of RBC count of greater than ____ for a person's gender/age will classify them as anemic

10%

What does a hemoglobin test measure?

Hb content in the blood

What does a hematocrit test measure? What factor can heavily influence this value and why?

The percentage of whole blood volume that is RBCs; since this value is a percentage, it is heavily influenced by plasma volume (aka volume-overloaded or volume-depleted states)

What are the 4 RBC indices, and what are they used for?

(1) Mean Corpuscular Volume (MCV)

(2) Mean Corpuscular Hemoglobin (MCH)

(3) Mean Corpuscular Hemoglobin Concentration (MCHC)

(4) Red Blood Cell Distribution Width (RDW)

Used to categorize anemias (based on RBC size, weight, Hb concentration)

How do the RBC indices differ from a H/H test?

The indices are measuring characteristics of individual RBCs, while the hemoglobin/hematocrit test is measuring the entire blood sample as a whole

What does the MCV measure? What are its 3 classifications?

Average size or volume of each RBC; microcytic, normocytic, macrocytic

What is the MCV range for normocytic (normal) RBCs?

80-100 fL

If a person had a mixture of both microcytic and macrocytic RBCs, what type of anemia would they have based on the MCV?

Would still be considered a normocytic anemia since the MCV goes by the AVERAGE RBC size

What 3 anemias do decreased MCV values indicate? What kind of cells do these diseases display?

Iron-deficiency, thalassemias, lead poisoning; MICROcytic

What are some diseases indicated by an increased MCV value? What kind of cells do they display?

B12 deficiency, folic acid deficiency, alcoholism, chronic liver disease, hypothyroidism, chemotherapy, hemochromatosis, reticulocytosis (Increased MCV because immature cells aka reticulocytes are bigger than mature RBCs); MACROcytic

What does the MCH measure?

Amount or weight of Hb in the average RBC

What does the MCHC measure?

Average concentration (%) of Hb within each RBC

Together, what are the 3 classifications defined by the MCH and MCHC?

Hypochromic, normochromic, hyperchromic

What is the MCH/MCHC range for normochromic (normal) RBCs?

32-36% (or g/dL)

Why does the hyperchromic state "not really exist" in RBCs? What are 2 conditions that may cause this appearance, however?

Hyperchromic is defined as an MCH/MCHC >37%, but a 37% Hb concentration is right around the physical limit that RBCs can ever reach due to size constraints; (1) volume-contracted states or (2) spherocytosis (cells that have lost their biconcave state)

What does the RDW measure? Why is it useful?

The degree of variability in the size of RBCs; basically tells you if the MCV value is accurate, or if has been skewed by big outliers

What is the clinical significance of a decreased RDW? How about an increased value?

Decreased = not clinically significant because there's not much variability in cell size

Increased = indication of anisocytosis

What is anisocytosis?

Variation (abnormality) in RBC size

What is poikilocytosis?

Variation (abnormality) in RBC shape

What is a CBC, and what tests fall under it? How is a peripheral blood smear different?

CBC = absolute count of erythrocytes, can use indices tests to specify morphology (H/H, MCV, MCH, MCHC, MDW)

Peripheral blood smear = prepared slide physically analyzed by a hematopathologist to further evaluate morphology, calculate WBC differentials, count platelets, or identify parasites

How are megaloblastic cells different from macrocytic cells?

Megaloblastic cells are large and IMMATURE (and can also affect WBCs and platelets) while macrocytic are just large mature RBCs; thus a subcategory of macrocytic anemia

What is often responsible for megaloblastic cells?

B12 and folate deficiencies, or some other factor that is impairing the cells' DNA synthesis and causing nuclear maturation to lag behind cytoplasmic maturation

What do are some observable characteristics of megaloblastic cells?

Large nucleated RBCs, hypersegmented neutrophils, large platelets

What is polychromasia?

Grayish-blue coloration of RBCs that still contain nuclear material (reticulocytes, nucleated RBCs)

What are nucleated RBCs (nRBCs), and what might they indicate?

Immature cells released into circulation before enucleation; bone marrow issues

What is basophilic stippling, and what may it indicate?

Ribosomal/RNA remnants (looks like pepper); lead poisoning, thalassemia

What are Howell-Jolly Bodies, and what may they indicate?

Clusters of DNA remnants (look like chocolate chips); asplenia (because the spleen hasn't chopped the nuclear remnants out)

What are Heinz bodies, and what may they indicate?

Denatured Hb that has precipitated onto the surface of the RBC (also look like chocolate chips, but on surface of cell and red like Heinz ketchup); any hemoglobinopathy, G6PD deficiency

What do spherocytes look like, and what may they indicate?

Spherical (rather than biconcave) RBCS; hereditary spherocytosis (a type of hemolytic anemia)

What do target cells look like, and what may they indicate?

Look like targets; anything that affects Hb synthesis (hemoglobinopathies like sickle-cell and thalassemia)

What do schistocytes looks like, and what may they indicate?

Broken RBCs within circulation; implies some sort of intravascular hemolysis is occurring

What do tear drop cells look like, and what may they indicate?

Tear drops; some bone marrow pathology (like myelofibrosis)

What does Rouleaux formation look like, and what may it indicate?

RBCs stack up on each other; excessive protein in the blood

What is the reticulocyte count, and why is it so important?

Measures the percentage of reticulocytes out of all the RBCs and reflects the daily replacement of circulating RBCs; you CANNOT properly diagnose anemia without this test because it is a key indication of BM function & erythropoiesis

How does the reticulocyte count reflect bone marrow activity & clue us in to the type of anemia?

Reticulocytosis is an expected response to anemia (because the body should want to ramp up the production of RBCs to fix the anemic state), so if the person sees less than a 2-3x increase in the reticulocyte count within 10 days of being anemic, this indicates that defective bone marrow may be to blame for the anemia

What is the reticulocyte index (RI), and why is it better than the reticulocyte count?

Adjusts the reticulocyte count for the degree of anemia

(sometimes the reticulocyte count may increase due to fewer mature RBCs in circulation rather than properly-functioning bone marrow, giving the illusion of normalcy. The RI fixes this issue by evaluating whether the body's response is appropriate for the level of anemia)

What are some diseases indicated by a decreased RI value?

Nutritional deficiencies (iron, B12, folate), lead poisoning, many types of marrow dysfunction (such as aplastic anemia)

What are some diseases indicated by an increased RI value?

Hemolysis, hemorrhage (post-bleed), early treatment for nutritional deficiencies, general reticulocytosis

Is a bone marrow smear performed regularly? When might it be useful?

No; hypoproliferative anemias (low RI) with a normal iron status, suspected aplastic anemia

What does a serum iron test measure? Is this the best test to use?

The quantity of iron bound to transferrin; good initial screening test for iron deficiency, but NOT the best test

What may decreased serum iron indicate?

Iron deficiency, active hematopoiesis

What may increased serum iron indicate?

Hemochromatosis, lead toxicity

What does a total iron binding capacity (TIBC) test measure?

Measures ALL proteins available to bind iron (includes transferrin) (so basically like all the "open seats" for iron)

What is the difference between concentration and saturation measurements in the TIBC?

Concentration measures the amount (in mg/dL) of iron-binding proteins (like transferrin), while saturation measures the percentage of iron-binding proteins that are saturated (aka have iron bound to them)

What do increased and decreased concentrations of transferrin indicate? What about increased and decreased saturation?

Concentration Increase: iron deficiency (body producing more to try and compensate)

Concentration Decrease: iron overload

Saturation Increase: iron overload

Saturation Decrease: iron deficiency

What does a serum ferritin test measure? Is this the best test to use?

Measures iron stores in the body (amount of ferritin in the blood); most sensitive test for iron deficiency - this value will drop FIRST before anything else

What signs would indicate a lead level test is necessary?

Microcystis with normal iron or basophilic stippling

What can elevated levels of both methylmalonic acid (MMA) and homocysteine (HCY) indicate?

Confirm true B12 deficiency

What is pernicious anemia? What are two definitive tests to diagnose it?

B12-deficiency anemia caused by the autoimmune destruction of parietal cells in the stomach,; measure intrinsic factor antibody (IFA) and anti-parietal cell antibody (APCA/APA) levels

What is intrinsic factor important for?

The uptake/absorption of B12 in the intestines

What lab results regarding bilirubin would indicate hemolysis, and why?

Increased levels of unconjugated/indirect bilirubin (before it reaches the liver) in circulation that was released upon cell hemolysis

What is haptoglobin? What lab results of haptoglobin would indicate hemolysis, and why?

Liver protein that binds to "free" circulating Hb and brings it back to the liver for processing and recycling; decreased levels (as much of it has been used up scavenging Hb)

What is lactate dehydrogenase (LDH)? What lab results of LDH would indicate hemolysis, and why?

Enzyme involved in the glycolysis pathway; highly concentrated in RBCs, so hemolysis can cause increased levels

What does glucose-6-phosphate dehydrogenase (G6PD) do? What can a deficiency of this enzyme lead to?

Protects RBCs from oxidative stress; deficiency can lead to hemolytic anemia as cells die from oxidative damage

What is Hb electrophoresis, and what is it used for?

Gold standard test used to identify and D/Dx hemoglobinopathies (like sickle-cell and thalassemia)

In general, sickle-cell is due to abnormalities in ____ while thalassemia occurs due to ____?

Sickle-cell = abnormal Hb structure

Thalassemia = reduced synthesis of normally-structured globin chains

Normal adult hemoglobin (HbA) consists of which chains? What percentage should this be in a normal, healthy adult?

2 alpha and 2 beta chains; 95%

What Hb electrophoresis results do we expect if a patient has alpha-chain formation abnormalities (aka alpha-thalassemia trait)? Why?

"Normal" results because ALL types of Hb (HbA, HbA2, HbF) rely on alpha chains, so if there is an abnormality in their production their levels will all decrease proportionally

What are 2 tests we can do before Hb electrophoresis to see if a person has sickle cell disease? How does each generally work?

Sickledex (abnormal Hb precipitates out), sickle cell prep (induces "sickling: of RBCs with abnormal Hb)

What is COOMBS testing used for? What is the difference between direct and indirect tests?

Diagnose autoimmune hemolytic anemia (AIHA); direct = detects antibodies and/or complement proteins that are BOUND to RBC surface in serum; indirect = detects ones that are UNBOUND (aka present in serum) that may attack RBC

What is the significance of a JAK2 (V617F) mutation? What disease is this commonly seen in?

Causes cells from myeloid cell lime to be hypersensitive to cytokine stimulation, thus prone to overproliferation; positive result is present in 80% of polycythemia vera (PV) cases