Hypoproliferative Anemia Flashcards
What are some different ways someone could have iron deficiency anemia (IDA)?
Iron depletion in diet
Lost in chronic blood loss or malabsorption leading to decreased iron stores and incorporation into hemoglobin
How does IDA present on PB smear?
Microcytic, hypochromic anemia with pronounced anisopoikilocytosis
What is particularly important with a diagnosis of IDA in someone >50 yo?
GI carcinoma until proven otherwise
How does anemia of chronic disease occur?
Increased hepcidin levels from inflammatory markers
Blocks the transfer of iron from marrow macrophages to sideroblasts
How does anemia of chronic disease present on PB smear?
Normocytic, normochromic (80%)
Microcytic (20%)
Increased serum ferritin
Decreased TIBC
What is the most common anemia of hospitalized patients?
Anemia of chronic disease
Seen in inflammatory, infectious and neoplastic conditions
What is the treatment for anemia of chronic disease?
Treat the underlying disorder
EPO/iron therapy
What is anemia of renal failure? How does it appear on PB smear?
Decreased EPO secondary to kidney disease –> decrease erythropoiesis
Normocytic, normochromic
What two deficiencies can lead to megaloblastic anemia/
Folate or vitamin B12 deficiency
How do folate or vitamin B12 deficiency lead to anemia?
Impair DNA synthesis (specifically thymidine) which produces nuclear to cytoplasmic asynchrony in erythroid and granulocytic maturation
How does Megaloblastic anemia appear on PB smear?
Macrocytic
Macroovalocytes
Hypersegmented neutrophils
Nuclear to cytoplasmic asynchrony in marrow
How can you differentiate if megaloblastic anemia is caused by folate or vit B12?
Neurologic deficits in vitamin B12
What is aplastic anemia?
Suppression of BM pluripotent stem cells likely by autoreactive T cells
Normocytic, normochromic
Pancytopenia
What are some things that can cause aplastic anemia?
Exposure to toxins, drugs, infectious agents
What is myelophthisic anemia?
Cytopenias related to marrow infiltration by a carcinoma or storage disorder
What do you see on PB smear in myelophthisic anemia?
Tear drop cells Leukoerythroblastic reaction (immature cells in PB)
What causes anemia of liver disease?
unknown
Seen with chronic hepatitis and cirrhosis
Why does anemia of liver disease look like on PB smear?
Macrocytic
What causes pure red cell aplasia?
Unknown but thought to be autoimmune destruction of erythroid precursors in the marrow
What are some things associated with pure red cell aplasia?
Thymic hyperplasia, thymoma, large granular lymphocytic leukemia, autoimmune disease
What are some things that may cause a megaloblastic anemia?
Dihydrofolate reductase deficiency (methotrexate)
Thymidylate synthetase deficiency (5-FU)
Folate deficiency
Vitamin B12 deficiency
Explain how we take in vitamin B12.
Bound to protein in food
Released in stomach by HCl & pepsin
Binds mainly to R-protein
In duodenum, R protein degraded, releasing B12 which then binds IF
Complex of B12:IF binds receptor and absorbed in terminal ileum
What are some things that may cause impaired absorption of B12?
IF deficiency, Ileal resection, pancreatic insufficiency
Decreased intake
Increased requirement
Tapeworm (diphyllobothrium lathum)
What are some clinical manifestations of vit B12 deficiency?
Megaloblastic anemia/Pernicious anemia
Subacute combined degeneration–dorsal and lateral tract demyelination, parasthesias, spastic paraparesis, sensory ataxia
What is pernicious anemia?
Deficiency of B12 secondary to IF abnormalities
What would the lab findings look like in pernicious anemia?
Low vit B12 levels
Low retics
Auto-antibody to IF or parietal cells (if pernicious anemia)
Elevated methylmalonic acid (substrate that needs B12)
What are some causes of folate deficiency?
Decreased intake (alcoholism, poverty) Increased requirements (growth, pregnancy, states of high cell turnover, hemolytic anemias, leukemias) Defective absorption (jejunal resection/malabsorption) Folic acid antagonists
What are some clinical presentations of folate deficiency?
Megaloblastic anemia
Neural tube defects (spina bifida occulta)
What shouldn’t you treat vit B12 deficiency with folate?
Anemia will reverse, neurological manifestations will not
Differentials for microcytic, hypochromic anemia
IDA
Thalassemia
Anemia of chronic disease
What are some of the different uses of iron in the body?
Component of heme (80%)
Component of myoglobin, cytochromes, catalases (20%)
Storage
What are some causes of IDA?
Dietary lack (milk-fed infants)
Impaired absorption (duodenum)
Increased requiredment
Chronic blood loss (GI sources, menstrual)
What are some ways iron is absorbed and transported?
Heme iron –> heme iron transporter
Non-heme iron –> reduced by duodenal cytochrome c (vit D, DMT-1)
Mucosal ferritin
Ferroportin transporter –> regulated by Hepcidin
Hephaestin –> oxidized to 3+, binds transferring to cells
What is TIBC essentially equivalent to?
Transferrin