Anemia

Anemia

Normocytic 80-100 fL

Microcytic: MCV <80 fL

Macrocytic > 100 fL

Hypochromic MCHC <32g/dL

Normochromic MCHC: 32-36g/dL

Classically seen in iron deficiency

Eliptocytes are a common finding in iron deficiency, and are sometimes referred to as penicillate cells

Widely spaced red cells = anemia

Hypochromic red cells are common in iron deficiency

Early Iron deficiency anemia

Thalassemia

Hemoglobinopathy

hemolysis

Variant hemoglobin production: SA, SS, SC,CC, CE, AC etc.

Loss of globin gene function through deletion or mutation

unexplained, new microcytic anemia should evaluate iron studies

Small fragmented red cells lead to lower MCV

Anemia of chronic disease

Lead poisoning

Check and trend CRP and ESR

Rare in the US, but children who live in households at or below the federal poverty level and those who live in housing built before 1978 are at the greatest risk of lead exposure. (The U.S. government banned lead-based house paint in 1978.) Also, communities of color are at higher risk of lead exposure because they may not have access to safe, affordable housing or face discrimination when trying to find a safe, healthy place to live.

Renal insufficiency

Acute blood loss

Anemia of chronic disease

Primary bone marrow disorder

Hemolytic anemia with reticulocytosis

Drugs (hydroxyurea, methotrexate, azathioprine), Alcohol use, Liver disease all lead to impaired DNA synthesis

Nutritional (Vitamin B12/Folate)

Clonal hematologic disorder

Hypothyroidism: Thyroid hormone stimulates erythropoietin and affects red cell production

Serum iron studies may not be picture perfect for iron deficiency, but at least one of the measures should be characteristic.

The peripheral blood morphology may be normal or may show subtle changes seen in iron deficiency

Iron Studies

Serum iron: A snapshot of what the iron level is right now, the serum iron level is dependent on daily activities and therefore can be variable day to day. A normal serum iron level does not exclude a diagnosis of iron deficiency, however a low iron level is more specific for iron deficiency

Total Iron Binding Capacity (TIBC): The amount of protein available to bind iron. Elevated in times of low iron in order to maximize iron transportation; however, TIBC is typically decreased in anemia of chronic disease.

% iron saturation: What percentage of the proteins which have the ability to transport iron currently have iron bound (low iron states will have low %saturation)

Ferritin: A protein made by almost all cells in response to increased iron. The ferritin level reflects the total body iron. It will be low when there is iron deficiency and high when there is an excess of iron in the body. It is also an acute phase reactant.

Transferrin receptor: Directly measures the level of transferrin in the blood, the principle protein that transports iron. The level depends upon liver function and a person’s nutritional status. Transferrin is a protein that may decrease during any inflammatory process.

These variant hemoglobin molecules are often unstable and : precipitate in the red cells, deforming them and leading to early destruction

In some cases there is sickling of the red cells. Sickle cells can be seen in HbSC, HbSS, HbSD, HbSE, and HgBS with thalassemia

In beta thalassemia there is loss of function of one of the two beta globin genes leading to relative excess of alpha globin production which leads to increased proportion of the minor hemoglobins (Hgb A2 and Hgb F).

In alpha thalassemia there is loss of fuction of one or more of the four alpha genes

Beta thalassemia trait: One of the genes is affected genotype of ß/ß0 or ß/ß+

Beta thalassemia major: both beta globin genes are involved, leading to a severe anemia (transfusion dependent)

αα / αα (normal)

αα/α- (silent carrier) no abnormal lab values except at birth when there would be Hgb Barts (γ tetrad) due to relatively fewer alpha per gamma. Predominant hemoglobin in newborns: HgbF (α2γ2)

αα/-- OR α-/α- (α-thalassemia trait) mildly abnormal lab values and usually asymptomatic

α-/-- (HbH disease/α-thalassemia intermedia) moderate microcytic anemia

--/-- (hydrops fetalis)

Iron is required for many microorganisms to grow. When infection is present, the body "hides away" its iron, making it less accessible to microorganisms. A similar response occurs in the setting of chronic inflammatory disease (such as osteoarthritis, chronic kidney disease, inflammatory bowel disease, cancer, and autoimmune disease), resulting in decreased iron availability not only to potential microbes but also to the body's own cells. Compare and contrast iron deficiency anemia to anemia of chronic disease in the iron studies table.

Target shaped red cells are often present in thalassemias and are due to increased surface to volume ratio (the red cells aren't filled as well with hemoglobin since the production is diminished)

Target cells can also be seen in liver disease (increased cholesterol in red cell membranes) and post splenecotomy

Folate

B12

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Folate is stored in the liver and taken up by proliferating cells. Folate is important in DNA synthesis and amino acid synthesis. Folate deficiency is easily corrected by dietary inta
Serum folate fluctuates rapidly with intake. Red cell folate is a measure of folate storage and is a better test for evaluating folate deficiency

Symptoms include tongue swelling, mouth sores, hair and nail issues, migraines, fatigue, stunted growth/development

Symptoms include cognitive decline (dementia), depression, low energy, numbness and tingling REMEMBER B12 shows neurologic deficits

B12 (Cobalimin) is required for DNA synthesis and hemoglobin synthesis

Rarely due to dietary deficiency. Seen in malabsorption, alcohol abuse, pernicious anemia, gastric bypass, and pancreatic insufficiency. Test for cobalamin level

B12 and Folate deficiency show similar morphologies in blood and bone marrow

Hypersegmented neutrophils

In bone marrow you will see "megaloblastic change" where the cells are much larger than expected. This is due to dyssynchrony between nuclear maturation (DNA synthesis issue) and cytoplasmic maturation

When there is acute red cell loss the normal response for the body is to make more. When the body is stressed to make more red cells more immature forms are allowed in the blood. These immature forms are called reticulocytes and are bigger than usual red cells. if there are enough reticulocytes circulating, there may be an increased MCV.

Increased reticulocytes by morphology shows increased polychromasia (bigger purpler red cells)

Make sure to look in the background of the blood smear for why there might be increased reticulocytes (i.e. red cell fragments)

When you have a clonal hematologic disorder there may be mutations in stem cells that impair usual DNA synthesis or lead to unusual DNA synthesis. This can occur in a disorder called "myelodysplastic syndrome" or MDS

Hemolysis Labs

Reticulocytosis (elevated in hemolysis) in otherwise healthy individuals

Increased lactate dehydrogenase (LDH) (found within cells – if they burst then serum LDH goes up)

Decreased haptoglobin (decreased in hemolysis: binds free hemoglobin – red cells burst releasing hemoglobin, haptoglobin decreases as it is used up)

Increased indirect (unconjugated) bilirubin (increased in hemolysis: free heme --> biliveridin --> bilirubin)

Plasma hemoglobin Increased in intravascular hemolysis (look at the plasma, is it red?)

Urine hemoglobin and hemosiderin

Acute loss of blood leads to less blood with normal red cell indices if the body hasn't had enough time to replace the blood lost (hemolysis and hemorrhage)

Anemia of chronic disease can cause microcytic or normocytic anemia. Most classically it is a normocytic anemia

In renal disease, there is often a decrease in the level of erythropoietin (red cell production stimulator) produced by the kidney. So you would produce normal red cells but the amount would be decreased.

In bone marrow disorders you can have clonal abnormalities as seen in MDS or you can develop aplastic anemia due to congenital abnormalities (Fanconi anemia) or viral illness (parvo B19 virus) leading to decreased or absent production of otherwise normal hematopoietic cells

Spherocytes