Red Cell Disorders_Clinical Pathology Boards Review

  1. All of the following could cause a spurious decrease in MCV except:
    A) Giant platelets
    B) Excess EDTA
    C) In vitro hemolysis
    D) Elevated WBC
    • D - this causes an increase in MCV
    • *Excess EDTA artifactually dehydrates the cells
  2. Name two causes of a spurious increase in MCV.
    Elevated WBC and agglutination
  3. All of the following could cause a spurious increase in MCHC except:
    A) Clotting
    B) Erroneous increase in Hb
    C) Erroneous increase in Hct
    D) Hemolysis
    E) Auto-agglutination
    C - erroneous decreases in Hct will increase MCHC
  4. Name two causes of spurious decrease in MCHC.
    Eroneous decrease in Hb or erroneous increase in RBC or Hct
  5. How are the following values calculated:
    • MCV = Hct x 1000/RBC = size avg circulating RBC
    • MCHC = Hb/Hct (Hct x 100 for automated) = Hb concentration within circulating RBCs
    • MCH = Hb/RBC = Hb content of avg RBC
    • Hct = MCV x RBC
  6. What method is used to measure Hb? What absorbance (in nm) reflects the amount of Hb present? What form of Hb is NOT detected with this method?
    CyanoHb method (Hb converted to hemiglobin cyanide/HiCN by dissolving blood in K+Ferricyanide and K+Cyanide, which oxidizes Hb to hemiglobin (Hi;metHb), then converts it to HiCN); 540 nm; SHb (SulfHb)
  7. All of the following are directly measured by automated instruments except:
    A) RDW
    B) MCV
    C) RBC
    D) Hct
    E) Total Hb
    D - Hct is calculated from MCV and RBC, which are measured directly by automation or directly measured by manual technique (ratio of packed RBC column height:total height)
  8. In automated RBC count by impedance, how does the instrument detect a single cell? How is the cell size detected?
    Detects momentary increase in voltage via momentary increase in resistance by the cell within the aperture; amount of voltage change is proportional to cell size
  9. Name 4 causes of microcytic anemia.
    • Mnemonic TICS
    • 1) Thalassemia
    • 2) Iron deficiency
    • 3) Chronic inflammation (can get mac to bring Fe to RBC)
    • 4) Sideroblastic anemia - can't incorporate Fe into heme
  10. Bone marrow findings in patients with sideroblastic anemia?  Peripheral blood findings? What is the mode of inheritance and responsible gene for the inherited form?
    Ringed sideroblasts, increased Fe stores, erythroid hyperplasia +/- dyserythropoiesis; microcytic (inherited) or macrocytic (acquired) anemia, wide RDW with bimodal distribution, Pappenheimer bodies, basophilic stippling; X-linked recessive involving ALAS2 gene (aminolevulinic acid synthetase)
  11. Image Upload 1
    Patient found to have microcytic anemia with elevated serum iron, high ferritin, and a high transferrin percent saturation level. Dx?
    Sideroblastic anemia (pictured are Pappenheimer bodies - violet granules in RBC periphery)
  12. Syndrome with sideroblastic anemia + cytopenias + exocrine pancreas dysfunction? What is the cause?
    Pearson syndrome; deletion in mitochondrial DNA
  13. Cause of primary acquired sideroblastic anemia? Secondary? What are most acquired cases caused by?
    Refractory anemia with ringed sideroblasts (MDS) - most common cause overall; medications (esp TB meds, Chloramphenicol - get vacuolated erythroids), alcohol, radiation, copper deficiency, toxicities (Pb, Fe, Zn -watch out for that toothpaste!); MDS
  14. What is the treatment for sideroblastic anemia?
    Vitamin B6/pyridoxine
  15. All of the following can cause a non-megaloblastic macrocytic anemia (100-110) except:

  16. Is IgM or IgG more amenable to plasmapharesis? Why?
    IgM because it is widely distributed in the plasma and not in extravascular fluid
  17. Which of the following can lead to echinocytes (burr cells):
    A) Gastric cancer
    B) Thalassemia
    C) Lead poisoning
    D) HELLP
    E) Alcohol
    • A
    • *Lead poisoning = basophilic stippling, HELLP = schistocytes, and alcohol = stomatocytes
  18. Of the following, which is associated with stomatocytes:
    A) Asplenia
    B) Hemolytic Anemia
    C) Dilantin
    D) Myelophthisis
    E) Pyruvate kinase deficiency
    • C
    • *Asplenia = Howell-Jolly, Pappenheimer, target cells & acanthocytes, Hemolytic Anemia = basophilic stippling and spherocytes, myelophthisis = teardrop cells (e.g. myeloprolif d/o), Pyruvate kinase def = echinocytes
  19. What is the RBC morphology associated with the McLeod phenotype?
    Acanthocytes (spur cells)
  20. With the exception of hereditary spherocytosis, all of the following can cause spherocytes except:
    A) Old blood
    B) Uremia
    C) Oxidant damage
    D) Burns
    E) Venoms
    B - uremia causes echinocytes
  21. What RBC shapes can be seen with the following diseases/conditions:
    1) Liver disease
    2) Iron deficiency
    3) Renal disease
    4) G6PD deficiency
    5) Abetalipoproteinemia
    • 1) Target cells and acanthocytes
    • 2) Elliptocytes (pencil cells) and target cells
    • 3) Echinocytes (from uremia)
    • 4) Bite cells
    • 5) Acanthocytes (Low LDL, VLDL, IDL, chylomicrons so can't absorb fat and lack of phospholipids in RBC membranes → acanthocytes)
  22. Acanthocytes are caused by weird things. Name 7 conditions/diseases associated with acathocytes.
    • 1) Abetalipoproteinemia
    • 2) Anorexia nervosa
    • 3) Hypothyroidism
    • 4) Liver disease
    • 5) Splenectomy
    • 6) MDS
    • 7) McLeod phenotype
  23. All of the following cause basophilic stippling except:
    A) Lead or arsenic poisoning
    B) Sideroblastic anemia
    C) Thalassemia
    D) Hemolytic anemias
    E) Pyrimidine 5' nucleotidase
    F) Myeloproliferative disorders
    F - MDS not MPD causes basophilic stippling
  24. What two RBC inclusions can be seen with hyposplenism?
    Pappenheimer bodies and Howell-Jolly bodies (usually accompany each other)
  25. What is a Howell-Jolly body? Pappenheimer body?
    Nuclear remnants (usually eliminated by spleen); iron-containing mitochondria
  26. Image Upload 2
    What is this ring and what is the cause?
    Cabot ring made up of nuclear (microtubule) remnants, caused by splenectomy, megaloblastic anemia, etc.
  27. What lab values change with hereditary spherocytosis? What is the gold std test? What is the defect?
    MCHC increases due to relative cellular dehydration, also see LDH and bilirubin elevated from extravascular hemolysis; osmotic fragility test with hypotonic NaCl solution; cytoskeleton protein defects in ankyrin (most common), band 3, protein 4.2, and spectrin
  28. What is the most common cause of hereditary elliptocytosis? How many elliptocytes must be circulating to meet the dx? In what population is this condition most commonly found?
    α spectrin; >25% & must be 2x as long as they are wide; African Americans
  29. Image Upload 3
    A neonate presents with severe anemia, which eventually resolves on its own. This is the patient's peripheral smear. At what temperature is hemolysis expected to occur in these cells?
    • (Hereditary pyropoikilocytosis)
    • 45°C (vs 49°C for nml cells); neonates (transient)
  30. How does the spherocytic type of hereditary elliptocytosis occur? What causes the stomatocytic type and in population is this typically found?
    double heterozygosity for HS and HE; band 3 protein defect (protection against P vivax) in Southeast Asians, esp malaysia
  31. In severe hereditary spherocytosis, what is the treatment? What other condition are patients at risk for as they age?
    Splenectomy; pigmented gallstones
  32. What physical findings is present in all chronic hemolytic disorders except SS dz? Which disorder is most common in Northern Europeans?
    Splenomegaly from RBC destruction due to extravascular hemolysis; Hereditary Spherocytosis
  33. In hereditary stomatocytosis with hydrocytosis syndrome, what protein is decreased? What does MCV and MCHC show?
    Stomatin; MCV high and MCHC is low
  34. In hereditary stomatocytosis with xerocytosis syndrome (water loss), what is the MCHC level? What gene is involved? Is it more or less severe than the overhydrated hydrocytosis syndrome?
    MCHC is increased; 16q23-24; less severe
  35. In hereditary stomatocytosis what treatment should be avoided and why? What is the associated membrane abnormality?
    Therapeutic splenectomy is avoided b/c of tendency towards post-splenectomy thrombosis; Na/K permeability
  36. What RBC feature is associated with the Rh null RBC phenotype?
    • Image Upload 4
    • Stomatocytosis
  37. What is the most common cause of cigar/pencil cells?
    Iron deficiency
  38. What do RBCs generate to combat oxidative damage via the pentose phosphate pathway? What does ATP generation do for the cell?
    NADPH; maintain Na/K/Ca pumps and glycolysis
  39. What RBC function is affected by G6PD deficiency? How is the mutation inherited? Which G6PD type occurs in African Americans? Mediterraneans? Which is more severe?
    NADPH generation through pentose phosphate shunt, reducing glutathione regeneration for glutathione peroxidase; X-linked "recessive"; G6PD A-; G6PD Med (more severe)
  40. All of the following RBC morphologies can be seen in a normal peripheral smear of a patient with G6PD deficiency except:
    A) Poikilocytosis
    B) Spherocytosis
    C) Bite cells
    D) Heinz bodies
    E) Blister cells
    D - Heinz bodies can only be viewed with the use of supravital dyes like methyl violet, crystal violet, or brilliant cresyl blue
  41. What two RBC morphologies are caused by denatured Hb?
    Heinz bodies and bite cells
  42. Name three reasons to use supravital staining.
    • 1) Manual reticulocyte count (highlights reticular network of rRNA)
    • 2) Heinz bodies
    • 3) Hb H inclusions
  43. Name two tests for G6PD deficiency. When should testing NOT be performed?
    1) Ascorbate cyanide test to test for sensitivity to oxidative stress and 2) Fluorescent spot test incubating NADP and G6P to test for NADPH production (fluoresces); during a hemolytic crisis b/c young cells survive, which have abundant G6PD so perform 3 months post-crisis
  44. Image Upload 5
    This patient had a large number of these cells after his splenectomy for chronic hemolysis (autohemolysis test did not correct with glucose). What disease does this patient likely have and what pathway is affected? How is it inherited?
    (echinocytes are pictured) Pyruvate kinase deficiency, which catalyzes RLS in Embden-Meyerhoff (glycolysis) pathway, generating ATP; AR
  45. For the following hemoglobinopathies, give the qualitative dysfunction:
    1) HbS and HbC
    2) Hb Zurich
    3) Hb Chesapeake
    4) HbM Boston
    • 1) solubility
    • 2) unstable Hb
    • 3) altered O2 affinity
    • 4) Methemoglobins
  46. What RBC disorder causes an increase in HbA2? Decrease?
    β thalassemia; α thalassemia
  47. What type of mutation constitutes the vast majority of mutations at the HBB/β globin gene locus? α thal syndromes? What is the disease caused by a point mutation in the untranslated region of the α chain gene?
    Point mutations in HBB gene (chromosome 11p15.5); Large structural deletions on chromosome 16
  48. What is the disease caused by a point mutation in the untranslated region of the α chain gene? What is the genotype for α thal 2 (α+ thal) and in what population is this the most common thalassemia genotype? What α genotype is prevalent in the Asian population?
    Hb Constant spring; one deleted α gene (-α/); African americans; two deleted α genes (--/), which is called α thal 1 (αo thal)
  49. What MCV/RBC ratio favors thalassemia? Iron deficiency?
    <13 (high RBC usu >5 and low MCV); >15
  50. What types of mutations usually result in a βo allele (absent chain prod)? β+ allele (diminished prod)? Other mutations?
    Nonsense or frameshift muts; promoter sequence mutations (locus control region/LCR or 5' untranslated region); 1) silent alleles to promoter's CACCC box or 5' untranslated region, or 2) complex alleles from deletion of noncoding intervening segs of HBB gene cluster → δ-β- or γ-δ-β- chains
  51. Which type of thalassemia has more target cells on peripheral smears?
    β thal
  52. Does HbS increase or decrease with S-β thal? S-α thal?
    S-β has increase in HbS (>50%) because you're trying to make more abnormal β chains to compensate for the decreased % normal β chains; S-α has a decreased % abnormal β chains because you can make normal β chains, it's the α chains that are low
  53. Which of the following genotypes result in major or intermedia β thalassemia (give all that apply):
    A) homozygous β++
    B) homozygous βoo
    C) δβ fusion (Hb Lepore)
    D) -δ/-β thalassemia
    E) heterozygous βo
    F) heterozygous β+o
    A through D, and F all cause major or intermedia β thal
  54. All of the following can be seen in βo/β or β+/β minor β thalassemia except:
    A) Asymptomatic
    B) Mild microcytic anemia
    C) Occasional transfusion requirement
    D) HbA2 > 3.5% (range: 4-8%)
    E) normal HbF
    C - minor β thal does not require transfusions
  55. In what situation can β thal minor have normal % HbA2 (typically you expect an increase)?
    If the patient also iron deficient, they will show normal HbA and HbA2 bands instead of increased HbA2 → erroneously reported as c/w α thal trait
  56. In both δ-β thal and heterozygous Hb Lepore (δ & β fusion), there is a normal % HbA2 and elevated HbF. How can they be differentiated?
    • On Hb electrophoresis, Hb Lepore has a band in the S region (6-15%) on acetate and migrates with HbA on acid
    • When HbS<30% (this is almost never present in this quanity) suspect Lepore
  57. What is the most common cause of death among children with β thal major? What does Hb electrophoresis show with respect to HbF, HbA2, and HbA?
    Infection; high HbF, N/↑ HbA2, little/no HbA
  58. In α thal, where is the gene located? How many copies on each gene? What is the genotype for α thal 2 (α+ thal)? α thal 1 (αo thal)? Which genotype is only prevalent in Asians?
    Chromosome 16; 2 copies on each gene (4 total chain producing loci) One normal, one deleted α gene (-α/); two deleted α genes (--/); α thal 1, which can result in HbH or Hb Bart disease
  59. For the following α thal genotypes, what is the syndrome and what does the CBC and electrophoresis show?
    1) -α/αα
    2) -α/-α or --/αα
    3) --/--
    4) --/αcsα
    5) --/-α
    • 1) Silent carrier; normal for both
    • 2) α thal trait; thalassemic and normal HbA and HbA2 bands
    • 3) Hb Bart (hydrops); hypochromia, nRBCs; fast migrating Hb H
    • 4) HbH dz; thalassemic and Heinz bodies; fast migrating Hb Barts
    • 5) same as #4
  60. Which α thal syndrome has β4 tetramers? γ4 tetramers?
    HbH; Hb Bart
  61. Which β thalassemias can mimic HPFH? How can they be distinguished?
    β thal and Hb Lepore (δβ fusion) because major has up to 95% HbF and Lepore major has 100% Hb F (minor has 5-20% Hb F); Lepore has ↓HbA2 and ↓ MCV while HPFH has ↑ MCV with pancellular Hb F distribution
  62. Which thalassemia is present at birth? When does the other thalassemia present?
    α thal; β thal at 6-9 months
  63. In what population is β thal most common?
  64. What three diseases can cause an acquired Hb H?
    • 1) erythroleukemia (FAB M6)
    • 2) myeloprolif d/o
    • 3) MDS
  65. In the Hb Constant Spring heterozygote, what does the CBC show?
    Resembles α thal minor but with minimal microcytosis
  66. Image Upload 6
    Supravital stain with brilliant cresyl blue. Dx? What are these inclusions?
    Hb H with BCB inclusions; β tetramers
  67. Which is more severe: β+ mediterranean or β+ american? HB H vs. β thal major?
    β+ mediterranean; β thal major because α chains are much less soluble than β chains so there is immediate formation of insoluble α tetramers in β thal major
  68. All of the following lead to echinocytes except:
    A) High pH caused by contact with glass slides
    B) Prolonged/excess EDTA (e.g. underfilling tube)
    C) Renal failure
    D) Making peripheral blood smear right after a transfusion
    E) High K+ or ATP in RBCs
    • E - low K+ or low ATP causes echinocytes
    • *Transfused blood and prolonged EDTA both cause formation of lysolecithin and decreased ATP
  69. In McLeod syndrome, what is the mutation and how does it manifest clinically? Lab findings? What other disease can these patients have?
    XK recessive mutation of a membrane transport protein in the Kell blood group; peripheral neuropathy, cardiomyopathy and hemolytic anemia presenting in their 50's; acanthocytosis, mild hemolysis, ↑CK and ↑LDH; CGD (genes close on same chromosome)
  70. Asplenism shows the following RBC morphologies except:
    A) Target cells
    B) Howell-Jolly bodies
    C) Heinz bodies
    D) Pappenheimer bodies
    E) Acanthocytes
    C - only seen in oxidative injury
  71. All of the following can lead to Howell-Jolly bodies except:
    A) Nml infancy
    B) Myeloproliferative disorders
    C) Amyloidosis
    D) Megaloblastic anemia
    E) GVHD
    F) Sickle Cell Dz splenic autoinfarction
    • B - MDS can lead to Howell-Jolly bodies, not MPD
    • *Note: anything leading to asplenia or functional asplenia can have Howell-Jolly bodies
  72. Which of the following (may be more than one) can be seen on a peripheral smear of a patient with megaloblastic anemia:
    A) Cabot rings
    B) Howell-Jolly bodies
    C) Basophilic stippling
    D) Dacryocytes
    E) Pappenheimer bodies
    F) Ovalocytes
    A, B, D and F; C and E are due to sideroblastic anemia
  73. What causes rouleaux?
    Large asymmetrical proteins (Ig, fibrinogen) decreasing zeta potential/negative charge → loss normal RBC repulsion
  74. Don't confuse these entities. For the following, give the associated disease:
    1) IgG Anti-Broad Rh
    2) IgM anti-I
    3) IgG anti-P
    4) anti-Pr
    5) PIG-A mutation in RBC GPI synthesis
    6) IgM and/or IgG immune complexes precipitate at low temps
    • 1) WAIHA
    • 2) Cold agglutinin disease
    • 3) PCH
    • 4) Cold agglutinin disease
    • 5) PNH
    • 6) Cryoglobulinemia
  75. All of the following antibodies are associated with cold autoagglutinin disease (CAD) except:
    A) anti-I
    B) anti-Pr
    C) anti-P
    D) anti-IH
    E) anti-i
    • C - anti-P is associated with paroxysmal cold hemoglobinuria (PCH), not cold agglutinin disease
    • *anti-I is most common!
  76. Fill in the blanks: In cold autoagglutination, the agglutinins are Ig__ antibodies that react most strongly at _____°C but can react up to _____°C. At 4°C, benign cold agglutinins have a titer of ____ and pathologic titers are often ____.  On CBC, the MCV is _____, Hct ____ and RBC is ____. The only reliable CBC index with cold agglutinins is _____.
    IgM; 4°C; 32-37°C; <64; >1000; ↑, ↓, ↓; Hb
  77. All of the following are potential causes of cold agglutinin disease except:
    A) HCV
    B) EBV
    C) Mycoplasma
    D) Idiopathic
    A - causes cryoglobulinemia
  78. Which of the following is false regarding cold agglutinin disease antibody specificities:

    • E)
    • *anti-H is specific to type O cord and adult blood (A2 and sometimes A1)
  79. What are the main advantages to reticulocyte counting by flow cytometry? How can a reticulocyte's age be determined? Which receptor is only present on very immature reticulocytes?
    Much more precise and can subdivide into mature and immature forms; RNA content; transferrin (CD71)
  80. How can the following be calculated:
    1) Corrected Reticulocyte Count (CRC)
    2) Reticulocyte Production Index (RPI)
    3) Absolute Reticulocyte Count (ARC)
    • 1) CRC = % retics x (Hct/45); used to correct for spurious retic increases due to low Hct
    • 2) RPI - CRC X (1/Correction Factor); CF = 1 when Hct normal, 2 when Hct 30, 3 if Hct 15
    • 3) % retics x RBC count
  81. What does the reticulocyte production index correct for?
    maturation time and degree of anemia
  82. What intrinsic hemolytic anemia is not hereditary?
    PNH (acquired & intracorpuscular)
  83. Point mutation for sickle cell? In what state do RBCs sickle? What does Hb S protect against? What % of African-Americans carry this trait?
    Glutamate to Valine at the 6 position of beta chain; deoxygenated; P. falciparum; 10%
  84. The metabisulfite and dithionate/Sickledex (look for turbidity - diothionate reduces abnml Hb → precipitation) solubility tests will be positive for all of the following except:
    A) Hb S-α thal
    B) HbC
    C) HbS-C
    D) HbS-β thal
    E) HbC-harlem
    • B - tests cover all HbS combos plus C-harlem
    • *Metabisulfite also covers Hb Barts
  85. T/F: HbA2 can be increased in SS or SA trait
  86. T/F: Irreversibly sickled cells (ISC) percentage predicts SS episodic crises
    False - the ISC % is constant and does not predict crises but is inversely correlated with RBC survival
  87. What is the average lifespan of SC red cells? SS red cells? Normal red cells?
    27 days; 17 days; 120 days
  88. What virus accounts for almost 70% of all aplastic crises in SSD?
    Parvovirus B19
  89. What two sickle diseases are most susceptible to both ocular complications and splenic sequestration crises, esp after viral illness?
    Hb S-β+ thal & HbS-C
  90. Elevations of all of the following contribute to thromboses related to SSD except:

  91. What crisis is associated with SSD and concomitant G6PD deficiency? What two lab findings are associated with this crisis?
    Hyperhemolytic crisis - sudden exacerbation of anemia; profound reticulocytosis and hyperbilirubinemia
  92. HbF and HbA2 levels in HbS dz? HbF and HbA2 levels in S-β thalassemia?
    • SS: both increased: HbF 1-20% and HbA2 1-4% (mild increase)
    • S-β thal: HbF 1-15%, increased HbA2, >50% HbS
  93. HbF and HbA2 levels in:
    A) β-thalassemia major
    B) β-thalassemia minor
    C) β-thalassemia compound heterozygote (β+/β°)
    • A) HbF 95%-98%, HbA2 2-5%
    • B) HbF 0.5-4%, HbA2 >3.5%
    • C) HbF 70-90%, HbA2 2-5%
  94. Give the expected % Hb S for the following sickle diseases:
    1) Hb S-α (two chain del)
    2) Hb S-A
    3) Hb S-C
    4) Hb S-β+
    5) Hb S-βo
    6) Hb SS
    • 1) Hb S-α = 25-30%
    • 2) Hb S-A = 35-45%
    • 3) Hb S-C = ~50%
    • 4) Hb S-β+ = 55-65%
    • 5) Hb S-βo = >80%
    • 6) Hb SS = >80%
  95. What are SSD patients prone to due to numerous transfusions?
    1) Aalloantibodies causing immediate and DHTRs; and 2) paradoxical worsening of anemia after transfusions, likely from minor Ag incompatibility
  96. Name four common bacterial infections in SSD patients post-splenectomy.
    • 1) Salmonella
    • 2) Haemophilus (H. influenza type B/HITB)
    • 3) M. pneumoniae
    • 4) S. pneumoniae
  97. In SSD, 1 in 3 patients have the angiographic appearance of what disease?
    Moyamoya - segmental arterial stenoses with puff of smoke collaterals
  98. All of the following are clinical manifestations of SSD except:
    A) Osteonecrosis
    B) Priapism
    C) Pregnancies with hypertension and babies born large for gestational age (LGA)
    D) Gallstones
    E) Isosthenuria and papillary necrosis
    C - babies have IUGR and increased prematurity
  99. What is the A:S ratio in Hb SA?
    60:40 due to greater affinity of α chains to normal β over βs chains.
  100. In a patient with S-α thal, how many α chains are deleted if there is 30-35% HbS? 25-30% Hb S?
    One; two
  101. In HbSC, what two SS-associated complications are equally or more common in SC? What does the peripheral smear show and how does it compare to Hb C?
    • Image Upload 7
    • Avascular necrosis and proliferative retinopathy; mild sickling and target cells vs. target cells and crystals in Hb C (pictured above)
  102. What infectious organism incorporates GPI into its own cell membrane to defend against the host immune system?
    S. mansoni
  103. What are two tests used to demonstrate hypersensitivity to complement mediated lysis in PNH? How do they work? Which is more sensitive? More specific?
    • 1) Sucrose hemolysis test - Incubate pt RBC in isotonic sucrose (promote *C binding) and enhanced hemolysis = PNH
    • 2) Acidified serum (Ham) test - Incubate pt RBCs in hetero & homologous acidified serum (activate *C) and enhanced hemolysis with both hetero & homo = PNH
    • Sucrose test is more sensitive; Ham more specific
  104. What markers are diminished in flow cytometry for PNH? What cells express these markers?
    • CD55 - decay-accelerating factor, inactivates cell-bound *C
    • CD59 - membrane inhibitor of reactive lysis, prevents C9 MAC complex formation
    • RBCs, Leuks, and Plts
  105. What is the most specific PNH test and how does it work?
    FLAERA - fluorescein aerolysin bacteria toxin - binds RBCs via GPI and initiates hemolysis
  106. All of the following clinical findings are seen in PNH except:
    A) increased hemolysis with isotonic sucrose
    B) increased hemolysis with acid heterol and homolog serum
    C) decreased LAP score
    D) Decreased CD55 and CD59 expression
    E) decreased NADH to NAD conversion
    E - this is pyruvate kinase def
  107. All of the following clinical findings are seen in PNH except:
    A) chronic normocytic normochromic anemia
    B) thrombo- and leukocytopenia
    C) Hypercellular BM with possible evolution to aplastic anemia or AML
    D) Episodic hemolysis, esp at night
    E) Increased leukocyte alkaline phosphatase (LAP) score
    F) Thrombophilia with numerous venous thromobotic events
    • E - LAP score is decreased
    • *Thromboses are most common cause of mortality in PNH
  108. All of the following are diminished in PNH except:
    A) CD55 or CD59
    B) CD45 or CD48
    C) CD14
    D) CD16 or CD66
    E) AchE
    B - CD48 is decreased not CD45
  109. All of the following can be seen in the peripheral smear of a patient with megaloblastic anemia except:
    A) Macroovalocytes
    B) Hypersegmented neuts (at least one with 6 lobes or >5% with 5 lobes) & left-shifted WBC from maturation arrest
    C) Tear-drop poikilocytes
    D) Giant platelets
    E) Heinz bodies
    E - you can see Howell Jolly but not Heinz bodies
  110. Define RBC nuclear:cytoplasmic dyssynchrony or megaloblastic changes.
    • Image Upload 8
    • Cytoplasm mature but nucleus still immature
    • See above: Precursors of later orthochromatophilic erythroblast stage (four arrowheads) w/too much cytoplasm. Have nuclear cytoplasmic asynchrony whereby nuclear maturation is delayed or incomplete but the cells continue to accumulate cytoplasm → “megaloblastic” erythroids.
  111. To meet the criteria for aplastic anemia, what are the levels for ANC, Plt, reticulocytes, and BM cellularity?
    • ANC <500/μL
    • Plt <20x109/l
    • Retics <1%
    • BM <25% of expected cellularity for age
  112. What is the cause for most aplastic anemias? Name three associated clonal disorders.
    Immune mediated; PNH, AML and MDS
  113. What is the most common type of congenital dyserythropoietic anemia? How do the erythroid precursors appear and what test is positive? What RBC antigen is present in high density?
    type 2 (hereditary erythroblast multinuclearity with positive acidified serum/HEMPAS); multinucleate with positive acidified serum test; i antigen (just like Blackfan-Diamond!)
  114. All of the following can cause acquired red cell aplasia except:
    A) Hodgkin Lymphoma
    B) Thymoma
    C) Medications
    D) Collagen vascular disease
    E) Anti-erythropoietin Abs
    A - LGL leukemia has been linked to acquired pure red cell aplasia
  115. What disorder, which presents by 5yo, is characterized by overexpression of i antigen on RBCs, increased Hb F with 75% of patients being responsive to corticosteroid tx? What related disease does not have elevated Hb F?
    Congenital pure red cell aplasia/Blackfan-Diamond Syndrome; transient erythrocytopenia of childhood (TEC)
  116. What syndrome is associated with aplasia of the following cell lines:
    1) Neutrophils
    2) RBCs
    3) Platelets
    • 1) Kostman syndrome
    • 2) Balckfan-Diamond syndrome
    • 3) Thrombocytopenia-absent radii (TAR) syndrome
  117. All of the following are congenital anomalies associated with Fanconi anemia except:

  118. How is Fanconi anemia inherited? What clonal hematopoietic defects develop in addition to aplastic anemia? These patients are also hypersensitive to what types of drugs?
    AR chromosomal breakage syndrome; MDS and AML (monocytic diff M4 & M5); clastogenic/chrom breakage-inducing drugs (diepoxybutane and mitomycin C)
  119. Which of the following causes extravascular hemolysis?
    A) snake envenomation
    B) microangiopathic hemolytic anemia
    C) non-ABO hemolytic anemia
    D) Infections (malaria, babesia, Clostridium)
    E) Complement fixation of RBC surface: PNH or PCH
    C - non-ABO hemolysis typically leads to extravasular hemolysis
  120. Name 4 EPO-secreting neoplasms.
    • 1) RCC
    • 2) Cerebellar hemangioblastoma
    • 3) uterine leiomyomas
    • 4) HCC
  121. What is Gaisbock syndrome?
    Spurious erythrocytosis due to dehydration
  122. What is the defect in PNH? Clinical presentation?
    Single defect in RBC glycosyl phosphatidyl inositol (GPI) anchors via PIG-A gene, which attach to proteins to deflect destruction by complement; classic episodic hemolysis at night (though not usually), chronic normocytic normochromic anemia, frequent thromboembolic events or bleeding, may evolve to leukemia or aplastic anemia
  123. What cells do the following stains highlight:
    1) NSE
    2) Sudan black B
    3) CAE
    4) PAS
    • 1) monos
    • 2) grans, monos
    • 3) grans
    • 4) blasts (lymphoid and myeloid)
  124. What degrades MPO quickly?
    Wet specimens
  125. What Hb types cannot be distinguished by alkaline electrophoresis? How does acid help?
    Hb S, HbD, and HbG; resolves HbS from HbD, and HbS from HbG but doesn't resolve D from G
  126. What are the Hb bands from the negative cathode to the positive anode in ALKALINE gel?
    • A2 CEO, Save me Dear God From Anemia, Bart goes to the NIH =
    • A2, C, E, O; S, D, G; F; A; B; NIH
  127. What are the Hb bands from the positive anode to the negative cathode in ACID gel?
    • Crazy Sick AGED Father =
    • C; S; A, G, E, D; F
  128. What two Hbs are FDA approved for quantification by HPLC?
    Hb A2 (α2δ2) and HbF
  129. How is Kostman defect characterized?
  130. What Hb is elevated in SS patients? How is it protective?
    Hb F (α2γ2); 1) has no beta chain, 2) inhibits HbSS polymerization, and 3) binds O2 with more affinity
  131. What is the most common trigger of acute pain crisis in SS patients from vasoocclusive events within the bone?
    exposure to cold, dehydration, infxn, or ETOH
  132. What is Hb M? When does cyanosis appear? Where does it run on routine gels? What toxicity is it used to tx? How is elevated metHb itself treated?
    Group of Hbs that prefer ferric/Fe3+ (metHb) state and binds O2 poorly; at 6mos old or when metHb reaches 10% of total Hb or 1.5g/dL; with HbA; MetHb chelates CN-; methylene blue reduces metHb to Hb
  133. What causes increased SHb? How does it differ from metHb? Can it be treated?
    Sulfur or C. perfringes causes Hb oxidation in presence of sulfar, SHb ppts to form Heinz bodies; no can't be reduced like metHb
  134. T/F: HbG is associated with a variant form of HbA2.
  135. Percent HbA and HbD in HbA/D? What about HbA/G?
    • A/D: 50% A/D and 50% A
    • A/G: 25% HbA/G and75% A
  136. How do Hb D and G present clinically? How are they distinguished on electrophoresis?
    Clinically nml; cellulose acetate runs with HbS ("Save me Dear God") and with HbA on citrate (AGED), D is a β chain defect and HbG is an α chain defect so may produce two HbA2 bands (one abnml, one nml)
  137. What is the defect in Hb E? What does CBC show? Percentages of E/A and A in HbE/A?
    β26glu →lys, common in SE Asia; thalassemic indices (low MCV) w/ numerous target cells; E/A 30% and A 70% (made at reduced rate than other β defects (usu ~50%) b/c of splicing defect)
  138. On cellulose acetate, how many and what bands are seen in Hb Constant Spring heterozygote adult and newborn?
    • Adult has four bands: αβ (HbA), αcsβ (HbCS), αδ (HbA2), and αcsδ
    • Newborn two bands: HBF (αγ) and αcsγ
  139. What are the high affinity O2 Hbs? Dx finding?
    Left-shift in O2 dissociation (Hb Chesapeake and Hb Denver), can't be resolved on gel or HPLC but they have erythrocytosis on CBC; P50 HbO2
  140. What is the usual trigger for PCH? What Ig is involved? What unusual finding is in the peripheral blood? What does DAT show?
    Children post-viral illness and syphilis; biphasic anti-P IgG hemolysin (aka Donath-Landsteiner Ab) binds Ag at cold temp, then lyses when incubated at warm temp → paroxysmal episodes of hemoglobinuria & jaundice; intraneutrophilic hemophagocytosis; DAT+ for anti-C3 and negative for anti-IgG
  141. What is the mechanism causing petechiae vs. palpable purpura?
    • Petechiae - plt defect, microvascular defects/bleeding
    • Purpura - leukocytoclastic vasculitis, ex. cryoglobulinemia
  142. How does high Pb levels affect Fe?
    Prevents Fe absorption in gut so there's an inverse relationship
  143. Where does intrinsic factor bind Vit B12? Where is folate absorbed?
    Ileum (pancreatic enzymes release Fe from R factor), bound to IF and transcobalamin I and II; jejunum
  144. What is the quantity of HbA2 and HbF in -δ/-β thalassemia? Clinical picture of heterozygotes? Homozygotes?
    Normal or decreased HbA2, increased HbF (5-20%); thalassemia minor picture; thalassemia intermedia picture (100% HbF)
  145. Sickle cell trait is usually asx with no abnormal lab findings and no sickling on peripheral smear. What clinical manifestations can they have if they do become symptomatic?
    • Splenic infarcts at high altitude
    • Renal medullary CA
    • Mild isosthenuria (unconcen urine)
  146. All of the following is true regarding Fe deficiency anemia except:
    A) ↑anisocytosis (↑RDW)
    B) Poikilocytosis
    C) BM w/mild erythroid hyperplasia
    D) ↑Zn protophorphyrin
    E) Thrombocytopenia
    E - there is thrombocytosis in Fe deficiency anemia
  147. Which of the following disorders show AR inheritance?
    A) Hereditary spherocytosis
    B) Hereditary elliptocytosis
    C) G6PD deficiency
    D) Pyruvate kinase deficiency
    E) Hereditary stomatocytosis
    D (G6PD is X-linked, the rest are AD)
  148. Difference between MCH and MCHC?
    • MCH is Hb content of the average RBC
    • MCHC is the amount of Hb relative to size of RBC
  149. All of the following cause free erythrocyte protoporphyrins (FEP) to increase except:
    A) Iron deficiency anemia
    B) Thalassemia
    C) Lead Poisoning
    D) Anemia of Chronic Disease
    B - FEP is a marker of failed incorporation of iron into heme
  150. Amino acid abnormality in HbC and HbS?
    • HbC: β6Glu→Lys
    • HbS: β6Glu→Val
  151. Defect in HbD vs. HbG?
    • HbG is α-chain defect (get two Hb A2 bands, one abnml and one normal)
    • HbD is a β-chain defect
  152. Hbε is embryonic Hb made in the yolk sac in the 1st trimester. Give the three types.
    Portland (ζ2β2), Gower 1 (ζ2ε2), and Gower 2 (α2ε2)
  153. Among the Hb chains (αβγδ), give the chromosomes involved and the number of pairs of genes.
    • α - two pairs, chromosome 16
    • All others are chromosome 11
    • β - one pair
    • γ - two pairs
    • δ - one pair
  154. What does the PB smear look like in HbS trait? Potential clinical complications?
    Totally normal; splenic infarcts at high altitude and renal medullary CA
  155. Defect type in O-Arab? Clinical features in O/β thal? What does CBC show?
    β chain defect; more severe with anemia, hypersplenism (S/O-Arab also severe dz); CBC normal
  156. Name five unstable hemoglobins.  Which one is least and most severe?
    Zurich, Koln, Hasharon, Hammersmith (most severe), Bushwick (least severe)
  157. Clinical findings in unstable Hbs? Peripheral smear findings?  How can we test for it? Relationship with methemoglobin?
    Hemolysis triggered by oxidative stress (includes heterozygotes); Heinz bodies and bite cells; incubate with 17% isopropanol - lyses cells; prone to metHb conversion
  158. What are clinical findings in high affininty Hbs (Chesapeake, Denver, Olympia and Koln)?
  159. Where does C-Harlem run on acid gel? O-Arab?
    • C-Harlem - with HbS (runs with C on acetate gel)
    • O-Arab - just past HbS
  160. How is HbA2 altered in β-thalassemia with iron deficiency or megaloblastic anemia? Coinherited α-thalassemia?
    Lowers HbA2; improved CBC indices
  161. How does iron deficiency affect HbA2 levels? What should you suspect if HbA2 >10%?
    Decreases levels; co-migrating Hb variant
  162. All of the following cause increased HbF levels except:
    A) aplastic anemia or PNH
    B) pregnancy
    C) hereditary spherocytosis or elliptocytosis
    D) alpha thalassemia
    E) porphyrias
    D - only beta thal elevates HbF
  163. What type of MDS most commonly leads to acquired Hb H dz? Males or females? Cause?
    RARS; males; marked downregulation of all four alpha genes from ATRX gene mutation on Y chromosome
Card Set
Red Cell Disorders_Clinical Pathology Boards Review
Red Cell Disorders Clinical Pathology Boards Review