RBC Disorders

Question 1

What is the significance of the corrected reticulocyte count?

Answer 1

Indicates effective erythropoiesis (good marrow response to anemia) if ≥3%

Question 2

Extramedullary hematopoiesis

Answer 2

• Erythropoiesis outside of bone marrow, often in liver or spleen
• Due to intrinsic bone marrow disease or accelerated erythropoiesis (ex. with severe hemolysis)
• Hepatosplenomegaly, “hair-on-end” sign on skull XR

Question 3

Anemia

Answer 3

• Decreased Hb, Hct, or RBC
• Normal SaO2 and PaO2
• Pulmonary valve murmur, pallor, high-output cardiac failure (from decreased viscosity)

Question 4

What does increased RDW (RBC distribution width) indicate?

Answer 4

Iron-deficiency anemia

Question 5

What do iron studies look like in anemia of chronic disease?

Answer 5

• Increased serum ferritin

* Decreased serum iron, TIBC (transferrin), iron saturation

Question 6

What are the 4 chains in each HbA, HbF, HbH, and Hb Bart?

Answer 6

• HbA: 2 alpha, 2 beta
• HbF: 2 alpha, 2 gamma
• HbH: 4 beta
• Hb Bart: 4 gamma

Question 7

Causes of iron deficiency anemia

Answer 7

Inadequate iron intake, menorrhagia, GI blood loss, pregnancy/lactation, premature infants, celiac sprue, hemolysis

Question 8

Clinical findings in iron deficiency anemia

Answer 8

• Microcytic
• Causative: esophageal web, achlorhydria (low stomach acid)
• Associated: glossitis, angular cheilosis, koilonychia (spoon nails)
• Conjunctival pallor, palmar creases, craving (pica) for rice

Question 9

Lab findings in iron deficiency anemia

Answer 9

• Decreased MCV, serum iron, serum ferritin, iron saturation
• Increased TIBC, RDW, FEP
• Thrombocytosis

Question 10

Anemia of chronic disease

Answer 10

• Chronic inflammation, alcoholism, malignancy
• Normal or decreased MCV
• Increased serum ferritin, FEP
• Decreased serum iron, TIBC, iron saturation
• Treat with EPO or hepcidin antagonist

Question 11

Alpha thalassemia

Answer 11

• Black population have 1 deletion on each chromosome
• Southeast Asian population has 2 deletions on one chromosome
• 3 deletions = HbH, causing severe hemolytic anemia
• 4 deletions = Hb Bart, incompatible with life
• Decreased MCV, Hb, Hct
• Increased RBC
• Normal RDW, serum ferritin, FDP
• May show target or teardrop cells

Question 12

Beta thalassemia minor

Answer 12

• Mild microcytic anemia
• Decreased MCV, Hb, Hct
• Increased RBC
• Normal RDW, serum ferritin, FDP
• Target and teardrop cells present
• Hb electrophoresis: increased HbA2 (2 alpha/2 delta) and HbF

Question 13

Beta thalassemia major (Cooley anemia)

Answer 13

• Severe hemolytic anemia; RBCs with alpha-chain inclusions removed by splenic macrophages
• Jaundice, increased UCB
• Extramedullary hematopoiesis: hepatosplenomegaly, “hair-on-end” skull XR
• Increased RDW
• Reticulocytes, teardrop cells, Howell-Jolly bodies (nuclear remnants), nucleated RBCs
• Hb electrophoresis: no HbA, only HbA2 and HbF
• Blood transfusion (danger of iron overload, requires chelation) or bone marrow transplant

Question 14

Sideroblastic anemia

Answer 14

• Alcoholism, B6 deficiency, lead poisoning, XLR inherited
• Deficiency in heme synthesis of developing RBCs; iron accumulates and RBCs die
• Children: abdominal colic, constipation, encephalopathy, growth retardation (lead in epiphyses)
• Peripheral neuropathy, kidney damage, lead lines in guns
• Increased serum iron, iron sat, ferritin; decreased MCV, TIBC

Question 15

Megaloblastic anemia

Answer 15

• Macrocytic
• Folic acid or B12 deficiency (increased homocysteine levels)
• Impaired DNA synthesis leads to enlarged, nucleated RBCs that are eventually destroyed
• Oval macrocytes
• Pernicious anemia may cause B12 deficiency; Abs vs parietal cells, type 2 hypersensitivity, achlorhydria; yellow skin, associated w/ other autoimmune diseases (test: Abs vs intrinsic factor binding)

Question 16

Nonmegaloblastic macrocytosis

Answer 16

• Macrocytes round, not oval
• Normal WBCs, platelets
• Liver disease from alcohol: no anemia
• Alcohol alone: mild anemia, reversible

Question 17

Aplastic anemia

Answer 17

• 15-25 yrs old or >60 yrs old
• Immune destruction of myeloid stem cells; sometimes TERT mutation
• Fever, bleeding, fatigue
• Pancytopenia, reticulocytopenia, hypocellular marrow
• Pure RBC aplasia possible from leukemia drugs, parvovirus

Question 18

Chronic renal failure

Answer 18

• ACD and decreased EPO
• Burr cells (RBC with undulating membrane)
• Prolonged bleeding time

Question 19

Extrinsic hemolytic anemia

Answer 19

• RBCs destroyed by macrophages in spleen

* Increased UCB, LDH

Question 20

Intrinsic hemolytic anemia

Answer 20

• RBCs destroyed in vessel

* Increased plasma and urine Hb, hemosiderinuria

Question 21

Hereditary spherocytosis

Answer 21

• Autosomal dominant
• Spectrin (membrane protein) defect yields spherocyte RBCs, which are destroyed in spleen
• Jaundice, gallstones, splenomegaly
• Normocytic anemia, increased RDW
• Treat with splenectomy

Question 22

Hereditary elliptocytosis

Answer 22

• Autosomal dominant
• Membrane protein defect
• May cause mild hemolytic anemia, splenomegaly
• Splenectomy for symptomatic pts

Question 23

Paroxysmal nocturnal hemoglobinuria

Answer 23

• Acquired stem cell mutation
• Complement-mediated lysis of RBCs, neutrophils, and platelets at night (aided by resp acidosis)
• Possible iron deficiency leading to microcytic anemia, risk of vessel thrombosis, risk for developing AML
• Normocytic anemia with pancytopenia, negative LAP stain, decreased haptoglobin, increased Hb
• Diagnose with flow cytometry
• Treat with corticosteroids, Eculizumab to inhibit terminal complement activation

Question 24

Paroxysmal cold hemoglobinuria

Answer 24

• Transient hemolytic anemia in kids with measles, mumps, flu, chicken pox; also associated with syphilis
• IgG cold Ab (when moving from cold to warm environment, activates complement)
• Fever, rigor, hemoglobinuria, back/leg/abd pain
• May cause renal failure
• Associated with Raynaud’s
• Treat with plasma exchange to remove Ab

Question 25

G6PD deficiency

Answer 25

* XLR * Deficient H2O2 neutralization; it oxidizes Hb, which precipitates in Heinz bodies, which lyse the RBC * Oxidant stresses include infection, drugs (ex. quinolones), fava beans * Sudden onset back pain, hemoglobinuria, jaundice * Normocytic anemia, bite cells

Question 26

Pyruvate kinase deficiency

Answer 26

* Autosomal recessive * PEP isn't converted to pyruvate in glycolysis * Low ATP damages RBC membrane; cell dehydrates, creating echinocytes * Jaundice, splenomegaly * Normocytic anemia

Question 27

Immune hemolytic anemias

Answer 27

* Autoimmune, drug induced, or alloimmune * IgG hemolysis: spherocytes * Complement hemolysis * IgM hemolysis: RBC agglutination * Jaundice, hepatosplenomegaly, Raynaud's (in cold AIHA) * Positive Coombs test * Normocytic anemia * Treat with corticosteroids, immune suppression, IV IgG (last resort; blocks from host IgG)

Question 28

Micro- and macroangiopathic hemolytic anemias

Answer 28

* Often caused by aortic valve stenosis * Micro: thrombi cause RBC fragmentation, schistocytes * Macro: valve defect damages RBC * Normocytic anemia (possibly microcytic if longstanding)