Anemias

Question 1

What anemias are microcytic?

Answer 1

iron deficiency, anemia of chronic disease, thalassemia, sideroblastic anemia, hemoglobinopathies (sickle cell)

Question 2

What is the major cause of iron deficiency in affluent countries?

Answer 2

blood loss (Upper GI examples: Peptic ulcer disease, esophageal varices, gastritis) or Lower GI examples: Hemorrhoids, diverticula, colorectal cancer, Inflammatory Bowel Disease)

Question 3

What is the most specific test for iron deficiency?

Answer 3

serum ferritin, normal is around 15-200 ng/mL. There is no clinical situation other than iron deficiency in which extremely low values of serum ferritin are seen.

Question 4

What are symptoms of anemia highly dependent on?

Answer 4

the rate of blood loss… the more acute, the more symptoms appear. With chronic loss, usually takes substantial loss before patient becomes symptomatic

Question 5

What is pagophagia?

Answer 5

pica for ice; this is considered quite specific for the iron deficiency state

Question 6

What disease processes does microcytic anemia in the context of low or normal RDW indiciate?

Answer 6

Anemia of chronic disease or thalassemia

Question 7

When does anemia of chronic disease occur?

Answer 7

Occurs in the setting of chronic inflammatory diseases and malignancy. Believed to involve trapping of iron by activated macrophages, which renders the iron unavailable for erythropoiesis.

Question 8

How could you differentiate between anemia of chronic disease and iron deficiency anemia?

Answer 8

total iron binding capacity (TIBC) is high in IDA and low in ACD. ACD ferritin is high and IDA ferritin is low

Question 9

What diseases are commonly associated with anemia of chronic disease?

Answer 9

Rheumatoid arthritis, SLE, HIV, TB, Carcinomas, Lymphomas, Leukemias

Question 10

What is seen on a megaloblastic anemia blood smear?

Answer 10

presence of oval macrocytes and hypersegmented neutrophils

Question 11

What is seen on a nonmegaloblastic anemia blood smear?

Answer 11

absence of neutrophil hypersegmentation along with the presence of round macrocytes

Question 12

What disease processes are associated with megaloblastic macrocytic anemias?

Answer 12

Abnormalities of DNA metabolism (B12 deficiency, Folate deficiency, Drug side effects)

Question 13

Why are the features of RBCs identical in folate and B12 deficiencies?

Answer 13

The two vitamins are intertwined biochemically so the final common pathway that impairs DNA synthesis in hematopoietic cells is the same when either vitamin is deficient

Question 14

How can you differentiate between folate and B12 deficiencies?

Answer 14

Neurological symptoms occur only with B12 (Cobalamin) deficiency

Question 15

What five factors does absorption of B12 depend on?

Answer 15

Adequate dietary intake. Acid-pepsin in the stomach. Pancreatic proteases. Gastric secretion of a functional intrinsic factor. An ileum with functioning Cobalamin-Intrinsic Factor receptors

Question 16

What can interfere with absorption of B12?

Answer 16

vegan diet, gastrectomy/bariatric surgery, gastritis, pernicious anemia, crohn’s disease, ileal resection, pancreatic insufficiency

Question 17

What is pernicious anemia?

Answer 17

Autoimmune disease. Parietal cells fail to secrete enough intrinsic factor to absorb vitamin B12

Question 18

What are symptoms of pernicious anemia?

Answer 18

Weakness, glossitis (enlarged, usually smooth tongue), paresthesias of extremities, GI symptoms such as diarrhea, nausea, vomiting, and pain; severe anemia can reveal signs of cardiac failure

Question 19

How should you evaluate pernicious anemia?

Answer 19

Review patient’s drug list. Measurement of serum B12 and folate. Peripheral blood smears to look for megaloblasts (macroovalocytes) and hypersegmented neutrophils

Question 20

How do you differentiate between B12 deficiency and folate deficiency with lab tests?

Answer 20

Serum concentrations of homocysteine (HC) as well as serum and urinary concentrations of methylmalonic acid (MMA) are elevated in B12 deficiency. In comparison, only homocysteine (HC) is elevated in folate deficiency.

Question 21

What is the treatment for B12 deficiency?

Answer 21

Parenteral B12 administration, Sublingual B12.
Initially, give 1000microgram injections daily for several days, followed by weekly administration, then monthly administration. Vegans can take oral therapy 25-100micrograms daily

Question 22

What is an important caveat to remember when before treating a suspected folate deficiency?

Answer 22

A person treated with folate who has a B12 deficiency may have their symptoms masked, which is bad because neurological damage from the B12 deficiency can be irreversible

Question 23

What is the most common cause of folate deficiency?

Answer 23

nutritional due to poor diet and/or alcoholism

Question 24

What drugs can interfere with folate metabolism?

Answer 24

Trimethoprim, Methotrexate, Phenytoin

Question 25

What are causes of nonmegaloblastic macrocytic anemias?

Answer 25

Alcoholism, Liver Disease, Aplastic Anemia, Drug-Induced, Myelodysplastic Syndrome, Pregnancy, Myeloma, Hypothyroidism

Question 26

What show ups on a peripheral smear with anemia due to liver disease.

Answer 26

multiple target cells which have an area of central density surrounded by a halo of pallor

Question 27

What’s in the differential diagnosis for normocytic anemia?

Answer 27

normal pregnancy, overhydration, renal disease, marrow problems, *mixed anemia (iron and vitamin B12 deficiency), acute blood loss, liver disease (can be macrocytic), systemic inflammation, zero production (Aplastic anemias [can be macrocytic]), endocrine disorder (hypothyroidism), HEMolytic anemias

Question 28

Why is it important to order a peripheral smear?

Answer 28

a mixed anemia would usually show up with a normal MCV because you have microcytic cells from an iron deficiency and macrocytic cells from a B12 deficiency the mean corpuscular volume may be normocytic

Question 29

What does a reticulocyte count tell you?

Answer 29

Reflects the ability of the bone marrow to produce mature red blood cells. an increase in the reticulocyte count provides evidence that the bone marrow is adequately responding to the anemia

Question 30

When is the reticulocyte count most useful?

Answer 30

in the context of a normocytic anemia: Acute Blood Loss, Hemolytic Anemia, Response to Iron, Folate, or B12 Replacement

Question 31

What are lab tests indicative of hemolysis?

Answer 31

decreased haptoglobin, elevated indirect bilirubin, elevated lactate dehyrdogenase

Question 32

What is the purpose of the direct Coombs’ Test?

Answer 32

helps to differentiate between immune and nonimmune hemolytic anemias

Question 33

What determine’s a positive Coombs’ test?

Answer 33

When the red blood cells of a patient are coated with immunoglobulin or complement, addition of antihuman antibodies will cause agglutination (indicates possibility of immune hemolysis)

Question 34

What does G6PD do?

Answer 34

helps red blood cells resist oxidant stress

Question 35

Describe G6PD deficiency?

Answer 35

X-Linked Disorder-Fully expressed in affected males
Women who are heterozygous will contain both normal and G6PD RBCs. Affected patients are usually asymptomatic, but may have episodic anemia while a few have chronic hemolysis

Question 36

What is microangiopathic hemolytic anemia?

Answer 36

Occurs when capillaries are partially occluded by fibrin, which leads to fragmentation of red cells
Peripheral smear characteristically shows schistocytes and helmet cells

Question 37

What is warm autoimmune hemolytic anemia?

Answer 37

Most cases involve IgG autoantibodies. Can vary from mild to a particularly severe anemia. Peripheral blood smear shows polychromasia and spherocytes. Often is idiopathic but may be caused by underlying diseases such as RA and SLE

Question 38

What are spherocytes?

Answer 38

small, dark, dense hyperchromic red cells without central pallor. These findings are compatible with hereditary spherocytosis or autoimmune hemolytic anemia

Question 39

What is hereditary hemochromatosis?

Answer 39

an increase in intestinal iron absorption results in deposits of excessive amounts of iron in with eventual tissue damage and impaired function of organs (liver, pancreas, heart, joints, and pituitary)

Question 40

What is the HFE defect?

Answer 40

substitution of tyrosine for cysteine. MHC-I-like protein that interacts with the transferrin receptor. Mutants have altered interaction with the transferrin receptor

Question 41

What is the liver pathology in HFE defect?

Answer 41

Usually the first organ affected. Hepatomegaly present in 95% of symptomatic pts

Question 42

What is the cardiac patholgy in HFE defect?

Answer 42

Presenting problem in 15% of pts. Mostly CHF and arrhythmias

Question 43

What is the pancreatic pathology in HFE defect?

Answer 43

Causes diabetes in 65% of pts. Affected pts tend to have a family history of diabetes

Question 44

What is the skin pathology in HFE defect?

Answer 44

Excessive skin pigmentation is present in 90% of symptomatic pts. Metallic or slate grey hue is characteristic and due to increased iron and melanin in the dermis.

Question 45

What is pituitary pathology in HFE defect?

Answer 45

Hypogonadism can develop in men and women.

Decreased libido, impotence, amenorrhea, testicular atrophy, and gynecomastia.

Question 46

What is the joint pathology in HFE defect?

Answer 46

Arthritic changes in 25-50% of symptomatic pts.

Often starts in the hands (MCP joints of index and middle finger). Pseudogout can occur.

Question 47

What lab results diagnose HFE?

Answer 47

Transferrin saturation >50%, Ferritin elevated (>1000 usually associated with cirrhosis).

Question 48

What is treatment of HFE defect?

Answer 48

500 mL of blood lowers the iron content by 200-250mg. May take one to two years of 1/wk to 2/wk blood draws to achieve normal ferritin and transferrin saturation.