Anemias Flashcards
(34 cards)
Iron deficiency
Microcytic anemia (MCV incr final step in heme synthesis.
- Decr iron, incr TIBC, decr ferritin. Fatigue, conjunctival pallor.
- Microcytosis and hypochromia. May manifest as Plummer-Vinson syndrome (triad of iron deficiency anemia, esophageal webs, and atrophic glossitis).
α-thalassemia
Microcytic anemia (MCV decr α-globin synthesis.
- cis deletion prevalent in Asian populations; trans deletion prevalent in African populations.
- 4 allele deletion: No α-globin. Excess γ-globin forms γ4 (Hb Barts). Incompatible with life (causes hydrops fetalis).
- 3 allele deletion: HbH disease. Very little α-globin. Excess β-globin forms β4 (HbH).
- 1–2 allele deletion: no clinically significant anemia.
β-thalassemia
Microcytic anemia (MCV decr β-globin synthesis. Prevalent in Mediterranean populations.
HbS/β-thalassemia heterozygote: mild to moderate sickle cell disease depending on amount of β-globin production.
β-thalassemia minor
Microcytic anemia (MCV 3.5%) on electrophoresis.
β-thalassemia major
Microcytic anemia (MCV severe anemia requiring blood transfusion (2° hemochromatosis).
- Marrow expansion (“crew cut” on skull x-ray) –> skeletal deformities. “Chipmunk” facies.
- Extramedullary hematopoiesis (leads to hepatosplenomegaly). Incr risk of parvovirus B19- induced aplastic crisis.
- Major –> incr HbF (α2γ2). HbF is protective in the infant and disease only becomes symptomatic after 6 months.
Lead poisoning
Microcytic anemia (MCV decr heme synthesis and incr RBC protoporphyrin.
- Also inhibits rRNA degradation, causing RBCs to retain aggregates of rRNA (basophilic stippling).
- High risk in old houses with chipped paint
LEAD:
- Lead Lines on gingivae (Burton lines) and on metaphyses of long bones D on x-ray.
- Encephalopathy and Erythrocyte basophilic stippling.
- Abdominal colic and sideroblastic Anemia.
- Drops—wrist and foot drop. Dimercaprol and EDTA are 1st line of treatment.
- Succimer used for chelation for kids (It “sucks” to be a kid who eats lead).
Sideroblastic anemia
Microcytic anemia (MCV
Megaloblastic anemia
Macrocytic anemia (MCV > 100 fL). Impaired DNA synthesis--> maturation of nucleus of precursor cells in bone marrow delayed relative to maturation of cytoplasm. Abnormal cell division--> pancytopenia.
Folate deficiency
Macrocytic anemia (MCV > 100 fL). Causes: malnutrition (e.g., alcoholics), malabsorption, antifolates (e.g., methotrexate, trimethoprim, phenytoin), incr requirement (e.g., hemolytic anemia, pregnancy). Hypersegmented neutrophils, glossitis, decr folate, incr homocysteine but normal methylmalonic acid. No neurologic symptoms (distinguishes from B12 deficiency).
B12 deficiency (cobalamin)
Macrocytic anemia (MCV > 100 fL)
Causes: insufficient intake (e.g., strict vegans), malabsorption (e.g., Crohn disease), pernicious anemia, Diphyllobothrium latum (fish tapeworm), proton pump inhibitors.
Hypersegmented neutrophils, glossitis, decr B12, incr homocysteine, incr methylmalonic acid.
Neurologic symptoms: subacute combined degeneration (due to involvement of B12 in fatty acid pathways and myelin synthesis):
-Peripheral neuropathy with sensorimotor dysfunction
-Dorsal columns (vibration/proprioception)
-Lateral corticospinal (spasticity)
-Dementia
Orotic aciduria
Macrocytic anemia (MCV > 100 fL). Inability to convert orotic acid to UMP (de novo pyrimidine synthesis pathway) because of defect in UMP synthase. Autosomal recessive. Presents in children as megaloblastic anemia that cannot be cured by folate or B12 with failure to thrive. No hyperammonemia (vs. ornithine transcarbamylase deficiency— incr orotic acid with hyperammonemia).
Hypersegmented neutrophils, glossitis, orotic acid in urine.
Treatment: uridine monophosphate to bypass mutated enzyme.
sadf
Macrocytic anemia (MCV > 100 fL).
Nonmegaloblastic macrocytic anemias
Macrocytic anemia (MCV > 100 fL). Macrocytic anemia in which DNA synthesis is unimpaired. Causes: liver disease; alcoholism; reticulocytosis --> incr MCV; drugs (5-FU, zidovudine, hydroxyurea). Macrocytosis and bone marrow suppression can occur in the absence of folate/B12 deficiency.
Normocytic, normochromic anemia
Normocytic, normochromic anemias are classified as nonhemolytic or hemolytic. The hemolytic anemias are further classified according to the cause of the hemolysis (intrinsic vs. extrinsic to the RBC) and by the location of the hemolysis (intravascular vs. extravascular).
Intravascular hemolysis
Normocytic, normochromic anemia
Findings: decr haptoglobin, incr LDH, schistocytes and incr reticulocytes on peripheral blood smear; and urobilinogen in urine (e.g., paroxysmal nocturnal hemoglobinuria, mechanical destruction [aortic stenosis, prosthetic valve], microangiopathic hemolytic anemias).
Extravascular hemolysis
Normocytic, normochromic anemia
Findings: macrophage in spleen clears RBC. Spherocytes in peripheral smear, incr LDH plus incr unconjugated bilirubin, which causes jaundice (e.g., hereditary spherocytosis).
Anemia of chronic disease
Nonhemolytic, normocytic anemia Inflammation --> incr hepcidin (released by liver, binds ferroportin on intestinal mucosal cells and macrophages, thus inhibiting iron transport) --> decr release of iron from macrophages. -decr iron, decr TIBC, incr ferritin. -Can become microcytic, hypochromic
Aplastic anemia
Nonhemolytic, normocytic anemia
Caused by failure or destruction of myeloid stem cells due to:
-Radiation and drugs (benzene, chloramphenicol, alkylating agents, antimetabolites)
-Viral agents (parvovirus B19, EBV, HIV, HCV)
-Fanconi anemia (DNA repair defect)
-Idiopathic (immune mediated, 1° stem cell defect); may follow acute hepatitis
-Pancytopenia characterized by severe anemia, leukopenia, and thrombocytopenia. Normal cell morphology, but hypo cellular bone marrow with fatty infiltration (dry bone marrow tap).
-Symptoms: fatigue, malaise, pallor, purpura, mucosal bleeding, petechiae, infection.
-Treatment: withdrawal of offending agent, immunosuppressive regimens (antithymocyte globulin, cyclosporine), allogeneic bone marrow transplantation, RBC and platelet transfusion, G-CSF, or GM-CSF.
Chronic kidney disease
Nonhemolytic, normocytic anemia
decr EPO–> decr hematopoiesis.
Hereditary spherocytosis (extravascular)
- Intrinsic hemolytic normocytic anemia
- Defect in proteins interacting with RBC membrane skeleton and plasma membrane (e.g., ankyrin, band 3, protein 4.2, spectrin).
- Less membrane causes small and round RBCs with no central pallor (incr MCHC, incr red cell distribution width) –> premature removal of RBCs by spleen.
- Splenomegaly, aplastic crisis (parvovirus B19 infection).
- Labs: osmotic fragility test+. Eosin-5- maleimide binding test useful for screening. Normal to decr MCV with abundance of cells; masks microcytia.
- Treatment: splenectomy.
G6PD deficiency (extravascular/intravascular)
- Intrinsic hemolytic normocytic anemia
- Most common enzymatic disorder of RBCs.
- X-linked recessive.
- Defect in G6PD–> decr glutathione–> incr RBC susceptibility to oxidant stress. Hemolytic anemia following oxidant stress (classic causes: sulfa drugs, antimalarials, infections, fava beans).
- Back pain, hemoglobinuria a few days after oxidant stress.
- Labs: blood smear shows RBCs with Heinz bodies and bite cells.
- “Stress makes me eat bites of fava beans with Heinz ketchup.”
Pyruvate kinase deficiency (extravascular)
- Intrinsic hemolytic normocytic anemia
- Autosomal recessive.
- Defect in pyruvate kinase–> decr ATP–> rigid RBCs.
- Hemolytic anemia in a newborn.
HbC defect (extravascular)
- Intrinsic hemolytic normocytic anemia
- Glutamic acid-to-lysine mutation at residue 6 in β-globin.
- Patients with HbSC (1 of each mutant gene) have milder disease than have HbSS patients.
Paroxysmal nocturnal hemoglobinuria (Intravascular)
-Intrinsic hemolytic normocytic anemia
-Incr complement-mediated RBC lysis (impaired synthesis of GPI anchor for decay-accelerating factor that protects RBC membrane from complement). Acquired mutation in a
hematopoietic stem cell. Increased incidence of acute leukemias.
-Triad: Coombs “ hemolytic anemia, pancytopenia, and venous thrombosis.
-Labs: CD55/59 “ RBCs on flow cytometry.
-Treatment: eculizumab.
