Given these CBC results: (WBC 2.5K, platelets 60K, Hb 9 g/dL), which of the following is most compatible? 1. Paroxysmal nocturnal hemoglobinuria 2. Anemia of renal disease 3. Anemia associated with pica 4. Anemia of chronic disease/inflammation 5. Anemia of the elderly

1. Paroxysmal nocturnal hemoglobinuria

Hypoproliferative Anemia Application Exercises - (Harrington) Flashcards by Timothy Carll

What is this? What is biochemical abnormality might be associated with this finding?

Hypersegmented neutrophil

Due to tetrahydrofolate or vitamin B12 deficiency

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Given these CBC results: (WBC 2.5K, platelets 60K, Hb 9 g/dL), which of the following is most compatible?

Paroxysmal nocturnal hemoglobinuria
Anemia of renal disease
Anemia associated with pica
Anemia of chronic disease/inflammation
Anemia of the elderly

Paroxysmal nocturnal hemoglobinuria

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Name (2) forms of hypoproliferative anemia characterized by impaired proliferation or differentiation of stem cells

aplastic anemia

pure red cell aplasia

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Name (5) forms of hypoproliferative anemia characterized by impaired proliferation/maturation of erythroid precursors (ineffective erythropoiesis)

megaloblastic anemia

anemia of renal failure

anemia of chronic disease

anemia of liver disorders

myelodysplastic syndromes

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Name (3) forms of hypoproliferative anemia characterized by defective hemoglobin synthesis

iron deficiency anemia

sideroblastic anemia

thalassemias

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Name (3) causes of hypoproliferative anemia characterized by marrow replacement or infiltration

hemoatopoietic tumors

metastatic tumors

granulomatous inflammation

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Give two invariant lab features of all hypoproliferative anemias

anemia

low reticulocyte count

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Approximately what proportion of platelets are normally stored in the spleen?

1/3

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Give (5) differential diagnoses for hypersplenism

Portal hypertension

Extramedullary hematopoiesis

Leukemias/lymphomas

Myeloproliferative neoplasms

Storage disorders

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Methionine sythetase requires what two cofactors?

methyl-THF and vitamin B12

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Name the enzyme responsible for the conversion of folate to tetrahydrofolate.

Is this a one-step process?

Which drug blocks the action of this enzyme?

dihydrofolate reductase

No. Two-steps (both performed by DHFR)

Methotrexate (MTX)

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Describe this cell

What caused this?

What disease is this associated with?

Bite cell

Mononuclear cell phagocytosis of denatured protein (Heinz bodies) in the RBC cytoplasm

G6PD deficiency

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Describe the morphologic changes seen in the peripheral blood and bone marrow in megaloblastic anemia

Peripheral blood

hypersegmented neutrophils (5 or more nuclear lobes)
macrocytic anemia with oval macrocytes
anisopoikilocytosis (size and shape variation)

Bone marrow

hypercellularity
giant bands
nuclear to cytoplasmic dyssynchrony

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Which type of cell found in the stomach secretes acid? What other important product does it secrete?

Which cell type secretes pepsin?

Parietal cells. Also secrete intrinsic factor (IF)

chief cells

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In which part of the GI tract is vitamin B12 normally absorbed. What else is required?

Vitamin B12 is absorbed chiefly in the ileum, bound to IF.

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Name the two deficiencies that cause megaloblastic anemia

Vitamin B12, Folate

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Where do we normally get vitamin B12?

What can cause vitamin B12 deficiency?

Animal products

Causes:

Impaired absorption (IF deficiency, ileal resection, pancreatic insufficiency)
Increased requirement (example: pregnancy)
Decreased intake (vegans)
Tapeworm (diphyllobothrium latum)

If dietary B12 is eliminated, how fast does B12 deficiency develop?

What about folate?

Very slowly. Stores within the body can last for years

Folate stores deplete faster (months)

Which is normally associated with neurological issues - folate deficiency or vitamin B12 deficiency?

vitamin B12 deficiency

Define pernicious anemia

What are some typical lab findings?

Deficiency of vitamin B12 secondary to IF abnormalities (due to Ab against IF)

Labs: low B12, low reticulocyte count, auto-Ab to IF or parietal cells, elevated methylmalonic acid

Where do we normally get dietary folate?

What can cause folate deficiency?

In the setting of pregnancy, what does folate deficiency lead to?

Green veggies

Causes:

Increased requirement (pregnancy, states of high cell turnover)
Decreased intake (alcoholism, malnutrition)
Defective absorption (jejunal resection)
Folic acid antagonists

Pregnancy: neural tube defects, including spina bifida occulta, anencephaly, etc

Describe these cells

Name the disease(s) typically associated with these.

Schistocytes

Red cell fragmentation disorders: DIC, TTP/HUS, traumatic hemolysis (mechanical heart valve)

What hemoglobin concentration is considered severely low?

<7 g/dL Hb

Name (5) physiologic compensatory mechanisms seen in the setting of anemia

Increased 2,3-DPG (increase unloading in tissues) Shunting Increased cardiac output Increased respiratory rate Increased red cell production

Give the differential diagnosis for microcytic, hypochromatic anemia (3 diseases)

Iron deficiency anemia (IDA) thalassemias Anemia of chronic disease (ACD)

Name some causes of iron deficiency

Dietary lack (i.e. milk-fed infants) Impaired absorption Increased requirement Chronic blood loss (GI, menstrual bleeding)

Describe the process by which heme iron is absorbed into the blood

* heme iron in the intestinal lumen is transported through the cell membrane by the heme transporter * heme iron is transferred to mucosal ferritin * The ferroportin-1 channel transfers ferritin-bound iron (Fe2+) through the basolateral surface of the cell, where it is converted to Fe3+ by hephaestin * Fe3+ is bound and transported by plasma transferrin

Describe the process by which non-heme iron is absorbed into the blood

* Non-heme iron (Fe3+) in the intestinal lumen is converted to Fe2+ by duodenal cytochrome C * Fe3+ enters the cell via the DMT1 transporter and is bound by mucosal ferritin * Fe2+ leaves the basolateral face of the endothelium via Ferroportin 1 * Fe2+ is converted to Fe3+ via hephaestin (basolateral surface of endothelial cell) * Fe3+ is bound by plasma transferrin

What enzyme is secreted by the liver in response to elevated iron? What specifically does it block?

Hepcidin Blocks ferroportin, the Fe2+ transporter located on the basolateral surface of the duodenal epithelial cells

What is the most sensitive assay for iron deficiency anemia? What is a relatively insensitive assay for IDA?

Serum ferritin - very high sensitivity and specificity Serum iron

What is total iron binding capacity (TIBC)?

Reflects the amount of protein available to bind iron in the blood - essentially equivalent to transferrin concentration

How is % iron saturation calculated?

% iron saturation = serum iron / TIBC

For IDA, describe each of the follow as increased, decreased, or no change: * Reticulocytosis * Marrow storage iron * Sideroblastic iron * Serum ferritin * Serum iron * TIBC * % iron saturation

* decreased * decreased * decreased * decreased * decreased * increased * decreased

For IDA, describe each of the follow as increased, decreased, or no change: * Reticulocytosis * Marrow storage iron * Sideroblastic iron * Serum ferritin * Serum iron * TIBC * % iron saturation

* decreased * increased * decreased * increased * decreased * no change / decreased * no change / increased

What is the most common anemia in hospitalized patients? How severe is the anemia (generally)? What are its major clinical associations? What is the general mechanism behind the anemia?

Anemia of chronic disease (ACD) usually mild to moderate Clinical associations: chronic infections, immune dysfunction disorders, neoplastic disorders Heptcidin-mediated (acute phase reactant) block in iron transport from macrophages into erythroid precursors.

Name (4) major physiologic responses to inflammatory stimulus that leads to ACD

All due to activated monocytes and T-cells (INF-gamma, TNF-alpha, IL-1, IL-6) * Increased hepatic synthesis of hepcidin * inhibited EPO release -\> decreased erythropoiesis * Direct inhibition of erythroid proliferation * Augmented hematophagocytosis

Is ACD microcytic, normocytic, or macrocytic?

normocytic (80%) or microcytic (20%)

What is the treatment for ACD?

treatment of underlying disorder EPO or iron therapy

What is **anemia or renal failure**?

Decreased EPO production due to kidney damage

Describe **pure red cell aplasia**

selective abscence of erythroid precursors often associated with thymic hyperplasia, thymomas, autoimmune disorders, drugs, LGLL

What is myelophthisic anemia?

Anemia secondary to bone marrow infiltration by metastatic carcinoma Leukoerythroblastic reaction with teardrop cells may be observed