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Compendium Hematopathology > Diseases of red blood cells > Flashcards

Diseases of red blood cells Flashcards

1
Q

Hereditary spherocytosis

  • Clinical presentation
  • Incidence
  • Inheritance
  • Gene affected
  • Laboratory findings
A
  • Clinical presentation
    • neonatal jaundice
    • adult with gallstones and splenomegaly
    • anemia or compensating reticulocytosis
  • Incidence in US is 1 in 5,000
    • common in Northern Europe with incidence of 1 in 1,000
    • most common red cell disorder in person of northern European descent
  • Autosomal dominant usually
  • ANK1 (ankyrin)
  • Labs
    • increased MCHC
    • MCV and MCH are normal
    • elevated retic
    • extravascular hemolysis findings
      • increased LDH
      • increased bilirubin
    • osmotic fragility and autohemolysis tests abnormal
    • unlike autoimmune hemolytic anemia, which also shows spherocytes, the DAT is negative
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2
Q

Hereditary elliptocytosis/hereditary ovalocytosis

  • Inheritance
  • Mutation
  • Laboratory findings
  • Incidence
  • Types and clinical presentation
A
  • Usually autosomal dominant
  • Mutations in spectrin alpha chain
  • Labs
    • elliptocytes are twice as long as they are wide, comprise >25% of red cells
    • mild extravascular hemolysis
  • 1 in 2,500 in the US to 1 in 100 in parts of Africa
  • Types
    1. common type
      • African Americans
      • hereditary pyropoikilocytosis
        • sensitivity of red cells to heat
        • this is a transient neonatal expression of common HE
    2. spherocytic type
      • double heterozygosity for HS and HE
    3. stomatocytic type, aka Southeast Asian Ovalocytosis
      • Malaysia
      • caused by band 3 protein defect
      • confers protection against P vivax
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3
Q

G6PD deficiency

  • G6PD is needed for
  • pathophysiology
  • Labs
  • Geographic distribution
  • Inheritance pattern
  • Testing should be done when?
A
  • G6PD is needed for production of NADPH and reduced glutathione for protection from oxidants
  • G6PD deficient red cells are hypersensitive to oxidant stress, including
    • medications
      • methylene blue
      • sulfa drugs
      • nitrofurantoin
      • primaquine
    • fava beans
    • infection
  • Hemolysis is episodic, precipitated by oxidant stress
  • Labs
    • poikilocytosis
    • bite cells
    • blister cells
    • heinz bodies (with supravital stains)
    • findings of extravascular hemolysis (jaundice, increased LDH)
  • Prevalent in Africa, southern Europe, Middle East, Southeast Asia, and Oceania
  • X linked recessive inheritance
  • testing for this shoud be done when patient is not hemolyzing to avoid false negative from reticulocytes with adequate G6PD
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4
Q

Pyruvate kinase deficiency

  • PK does what?
  • Labs
  • Inheritance pattern
  • Geographic distribution
A
  • PK catalyzes rate limiting step in the Embden-Meyerhof (glycolysis) pathway; main source of red cell ATP
  • Labs
    • chronic hemolysis (extravascular) - jaundice, elevated LDH
    • echinocytes (dessicocytes)
  • Autosomal recessive
  • Worldwide
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5
Q

Hemoglobin S

  • amino acid change
A
  • valine encoded instead of glutamate at position 6 of the beta chain (glu to val)
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6
Q

Sickle cell trait

  • % of hemoglobin types
  • CBC and smear
  • Screening test
  • Clinical manifestations
A
  • Genotype SA
  • Hemoglobin types
    • 35-45% HbS
    • 50-65% HbA
    • <3% HbA2
  • Normal CBC and smear
  • Screening tests are positive
    • metabisulfite test
    • dithionate test
  • Clinical presentation
    • usually asymptomatic
    • increased incidence of
      • hematuria
      • isothenuria
      • papillary necrosis
      • medullary carcinoma of the kidney
    • exercise induced rhabdomyolysis
    • splenic infarcts in hypoxic conditions, such as exposure to high altitude
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7
Q

Sickle Cell Disease

  • Genotype
  • Length of time of RBC survival
  • Hemoglobin types
A
  • SS
  • RBC survival is 17 days instead of 120 days
  • Types of hemoglobin
    • >80% HbS
    • 1-2% HbF
      • inhibits HbS polymerization
      • at birth HbF prevents development of clinical symptoms
      • by 6 months HbS > 50%, when symptoms start
      • combined sickle cell disease hereditary persistence of fetal hemoglobin (SS-HPFH) is clinically mild
      • treatment with hydroxyurea is meant to increase HbF
    • 1-4% HbA2
    • 0% HbA
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8
Q

Hb SC disease

A
  • 50% HbS and 50% HbC
  • clinical manifestations are intermediate in severity between SS and SA
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9
Q

Hemoglobin SA/alpha thalassemia

percentages of hemoglobin types

A
  • decreased percentage of HbS as compared to SA
  • in single gene alpha deletion, there is 30%-35% HbS
  • in 2 alpha gene deletions there is 25%-30% HbS
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10
Q

SA/beta thalassemia

A
  • increased proportion of HbS (>50%)
  • 1-15% HbF
  • disease manifestations can be severe
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11
Q

Hemoglobin C

  • amino acids
  • trait (hemoglobin percentages, symptoms, smear)
  • disease (hemoglobin percentages, symptoms, smear)
A
  • glutamate becomes lysine at position 6 on beta chain
  • Hemoglobin C trait (AC)
    • 40-50% hemoglobin C
    • generally asymptomatic
    • peripheral smear has target cells
  • Hemoglobin C disease (CC)
    • Types
      • 90% HbC
      • 7% HbF
      • 3% HbA2
      • 0% HbA
    • Mild hemolytic anemia
    • Splenomegaly
    • Numerous target cells
    • Hexagonal or rod shaped crystals
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12
Q

Hemoglobin E

  • amino acids
  • geographic distribution
  • prevalence
  • CBC
  • smear
  • symptoms
A
  • Beta 26 glutamate to lysine
  • Southeast Asia
  • 2nd most common abnormal hemoglobin worldwide (after S)
  • CBC shows thalassemic indices and the peripheral smear numerous target cells
  • typically mild, but coinheritance with beta thalassemia may be severe
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13
Q

Hemoglobin D and G

A
  • Clinically normal
  • HbD is beta chain defect
  • HbG is an alpha chain defect
  • Both run with HbS on alkaline gel
  • absence of HbS can be determined by sickle screen study or by citrate gel
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14
Q

Hemoglobin Lepore

  • CBC
  • geographic distribution
  • electrophroesis
  • genes
A
  • Thalassemic red cell indices
  • Mediterranean, especially Italy
  • Runs with HbS on alkaline gel, but usually only ~15% of total Hb
    • Actual HbS is rarely present in this quantity, so Lepore should be suspected
  • Sickle screening tests are negative
  • Hb Lepore is result of fusion between delta and beta genes
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15
Q

Hemoglobin Constant Spring

A
  • thalassemic red cell indices
  • Southeast Asia
  • mutation in alpha gene stop codon, producing abnormally long transcript
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16
Q

Unstable hemoglobins

  • smear (also seen in what conditions?)
  • types of Hb
A
  • result in Heinz bodies and bite cells
  • Hb Hammersmith, Ann Arbor, Koln
  • Note: Hb Bart and HbH (severe alpha thal) are also associated with Heinz body anemia
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17
Q

Methemoglobin

  • what is it
  • % of total Hb
  • low level maintained by
  • hereditary versus acquired
  • appearance of blood
  • ways to measure it
  • treatment
A
  • Hemoglobin with iron in the oxidized ferric (Fe+++) state
  • Cannot combine with O2
  • Normally, up to 1.5% of total Hb is Hi (methemoglobin)
    • low level maintained by the action of the NADH dependent methemoglobin reductase system
  • hereditary methemoglobinemia
    • deficient methemoglobin reductase or abnormal HbM upon which this enzyme cannot act
    • cyanosis appears at 6 months of age
  • acquired methemoglobinemia
    • exposure to drugs or chemical that increase formation of Hi
    • nitrites, quinones, phenacetin, and sulfonamides
  • blood is grossly chocolate brown
  • cooximeter can measure methemeglobin directly (pulse ox and ABG cannot detect Hi)
  • treatment = methylene blue, which reduces Hi to Hb
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18
Q

Sulfhemoglobin

  • what is it
  • smear
  • % total hemoglobin normally and when cyanosis occurs
  • precipitated by
A
  • hemoglobin oxidized in presence of sulfur
  • when further oxidized, SHb preciptates to form Heinz bodies
  • SHb cannot transport oxygen
  • normally, SHb <1% of total Hb
  • cyanosis manifests at 3-4% or 0.5 G/dl
  • SHb may increase after exposure to sulfonamides and in presence of C perfingens bacteremia (enterogenous cyanosis)
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19
Q

Carboxyhemoglobin

A
  • CO binds tightly to hemoglobin forming carboxyhemoglobin (HbCO)
  • CO has even greater avidity for fetal hemoglobin
  • CO directly toxic to intracellular oxidative mechanisms
  • toxic effects vary with proportion of HbCO
  • Normally HbCO is <=1%
  • ABG and pulse ox cannot detect HbCO
  • Smokers have up to 6%
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20
Q

Thalassemic indices

A
  • Microcytosis
  • Low hematocrit
  • Normal to elevated RBC count
  • RDW normal to slightly increased (in contrast, markedly increased in IDA)
  • MCV/RBC count ratio < 13 favors thalasemmia
  • MCV/RBC count ratio > 15 favors IDA
  • Smear shows microcytsosis, target cells, basophilic stippling
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21
Q

Beta thalassemia

  • genetics (chromosome, alleles, mutations)
  • symptoms start when
  • heterozygotes vs homozygotes (HbA2, HbF, HbA)
  • intermedia vs major
  • delta-beta thalassemia
  • Hb Lepore - relative amounts of Hb
  • tetramers in Beta thal
A
  • one copy of the beta gene on each chromosome 11, which make two genes
  • most beta thal results from point mutation
  • pathogenic alleles Bo or B+
  • Symptoms not be apparent until 6 months of age
  • Heterozygotes (Beta thal trait) have
    • high HbA2 (>3.5%)
    • normal to increased HbF
    • may show normal A2 if patient is iron deficient
  • Homozygotes have
    • increased HbF (50-95%)
    • normal to elevated HbA2
    • little to no HbA
  • Beta thal intermedia and major are distinguished by dependence of the latter on transfusion
  • in delta-beta thalassemia (deletion of delta and beta) there is a
    • normal HbA2
    • elevated HbF (5-20%)
  • In Hb Lepore (fusion of delta and beta) there is
    • normal quantity of HbA2
    • slightly elevated HbF
    • band in S region comprising 6-15% (Hb Lepore)
  • Form alpha tetramers
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22
Q

Alpha thalassemia

  • describe genes
  • genetic alteration
  • haplotypes
  • symptoms and labs in single gene, 2 gene, 3 gene, and 4 gene deletions
A
  • 2 copies of the alpha gene on each chromosome 16
  • most thalassemia result from large structural deletion
  • haplotypes characterized as
    • alpha thal 2 (alpha+ thalassemia)
      • chr. 16 has one normal and one deleted alpha gene
      • most common genotype in African Americans
    • alpha thal 1 (alpha0 thal)
      • chr 16 has 2 deleted alpha genes
      • Asians
  • single gene deletions
    • asymptomatic
    • normal CBC
    • normal electrophoresis
  • 2 gene deletions
    • alpha thal trait
    • thalassemic indices
    • normal percentage of A2 (normal electrophoresis)
    • in absence of iron deficiency, this can be interpreteted as c/w alpha thal trait
  • 3 gene deletions
    • HbH disease (beta tetramers)
    • hemolytic anemia
    • Heinz bodies
    • fast moving HbH on electrophoresis
  • 4 gene deletions
    • Hb Bart disease
    • fetal (gamma) hemoglobin tetramers
    • severe hemolysis - hydrops fetalis
    • hypochromic nRBCs
    • Hb Bart on electrophoresis
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23
Q

S alpha thalassemia

A

30-35% HbS with one alpha gene and 25-30% with 2 alpha thal gene deletions

24
Q

Normal expression of HbF

A
  • 30-40% of total hemoglobin at term
  • < 10 % at 6 months
  • <5% at 1 year
  • <1% at 2 years
25
Q

Hereditary persistence of fetal hemoglobin

A
  • Delayed switch from gamma to beta or delta
  • HbF in pancellular distribution
  • 1 in 100 of HbSS have HPFH
    • 25% HbF
    • do not have anemia or vasoocclusive episodes
  • Electrophoresis showing HbS, F, and A2 has two causes
    • Combined sickle cell HPFH (clinically mild)
    • Combined sickle cell Beta thal (clinically severe)
26
Q

Non hereditary causes of elevated HbF

A
  • Megaloblastic anemia
  • Aplastic anemia
  • PNH
  • Fanconi anemia
  • Juvenile myelomonocytic leukemia
  • Acute eyrthroid leukemia
  • HbF heterocellular
27
Q

Warm autoimmune hemolytic anemia

  • describe antibody
  • lab tests
  • smear
  • secondary causes
  • how do cells react in a panel
A
  • IgG against broad Rh antigens
  • DAT is positive usually
  • Hemolysis is extravascular
  • spherocytes
  • 5-10% have positive DAT without hemolysis
  • WAIHA may be primary or secondary
  • Secondary causes of WAIHA
    • CLL/SLL
    • Inherited immunodeficiency
    • IgA deficiency
    • Bruton agammaglobulinemia
    • Collagen vascular disease
    • Thymoma
  • All cells in panel react at AHG phase
28
Q

Cold autoagglutinin disease (CAD)/cold autoimmune hemolytic anemia (CAIHA)

  • list IgM antibodies
  • reactions occur at what phase in panels?
  • nonpathologic cold agglutinins
  • pathologic cold agglutinins
  • primary versus secondary CAIHA
A
  • IgM antibodies, often against I
    • others include i, H, Pr, and IH
      • Pr is rare and destroyed by enzymes; present in cord and adult blood
      • H and IH are neutralized by saliva and are almost always benign
    • can activate complement, thus reactions seen at the antiglobulin phase using polyspecific sera (IS and AHG phases)
    • agglutinated by C3d but not IgG
  • Cold agglutinins may be pathological or nonpathologic
    • nonpathologic cold agglutinins
      • react at 4 degrees, up to 22 degrees
      • titer < 64 at 4 degrees
    • pathologic cold agglutinins
      • reactive over a broad thermal range and cause spontaneous autoagglutination at room temperature
      • titer > 1000 at 4 degrees
  • CAIHA may be primary or secondary
    • Idiopathic cold autoimmune hemolytic anemia or cold agglutinin syndrome is chronic condition in older people
      • monoclonal IgM
    • Secondary CAIHA is a transient condition often associated with infection
      • M pneumonia associated with anti I
      • EBV associated with anti i
29
Q

Paroxysmal cold hemoglobinuria

A
  • PCH is most often seen in children
    • Secondary to virus (e.g., measles, mumps, chicken pox, mono)
    • Originally described in syphilis
  • Presents with paroxysmal episodes of hemoglobinuria associated with cold exposure
  • Occasionally peripheral blood smear shows intraneutrophilic hemophagocytosis
  • Treatment: keep patient warm and transfusing prewarmed blood as needed
  • Caused by IgG biphasic hemolysin (Deonath-Landsteiner antibody)
    • Anti P
    • Biphasic because it produces hemolysis only when incubated at 4 degrees then 37 degrees
30
Q

Cryoglobulinemia

  • detection method
  • types
  • clinical findings
  • renal biopsy
  • EM findings
  • blood smears
A
  • Cryoglobulins precipitate reversibly at low temperatures
  • Detection
    • Blood is drawn and kept at 37 degrees
    • Centrifuge at 37 degrees and the remaining serum is stored at 4 degrees for at least 3 days
    • Then centrifuged at 4 degrees; precipitate that forms is a cryoprecipitate
    • Precipitate can be subjected to electrophoresis
  • 3 types
    • Type I: monoclonal Ig found in multiple myeloma or Waldenstrom
    • Type II: mixture of monoclonal IgM and polyclonal IgG
      • IgM has RF (anti IgG) activity
      • This is the most common type of cryo
      • Types II and III affect people with lymphoproliferative disorders, chronic infection, chronic liver disease, and autoimmune diseases (especially SLE)
      • HCV is most common cause
    • Type III
      • polyclonal IgG and polyclonal IgM
  • Clinical presentation
    • systemic immune complex disease
    • palpable purpura (leukocytoclastic vasculitis)
    • arthralgia
    • hepatosplenomegaly
    • lymphadenopathy
    • anemia
    • sensorineural deficits
    • glomerulonephritis
      • renal biopsies: MPGN, thrombotic microangiopathy
    • in all tissues there is vasculitis
    • EM shows subendothelial immune complex deposits with fibrillary or tubular structure in a fingerprintlike pattern
    • in blood smears, pale purple cloudy aggregates of protein
31
Q

Paroxysmal nocturnal hemoglobinuria

Caused by

A
  • PNH is an acquired clonal red cell disorder
  • membrane defects result from decreased glycosyl phosphatidyl inositol (GPI) anchors
    • Many GPI anchored proteins function to deflect complement mediated destruction
    • Affected cells have decreased
      • decay accelerating factor (CD55)
      • membrane inhibitor reactive lysis (CD59)
      • acetylcholinesterase (AchE)
      • CD16
      • CD48
  • GPI is encoded by the phosphatidyl inositol glycan class A (PIG-A) gene on X chromosome
    • PNH is a result of various PIG-A mutations
32
Q

PNH Clinical Presentation

A
  • Can be episodic hemolysis, especially at night
  • More commonly, chronic hemolytic anemia
  • Thrombocytopenia and leukopenia
  • May evolve into aplastic anemia and/or AML
  • PNH may evolve from aplastic anemia
  • may present with thrombosis
33
Q

PNH lab findings

A
  • Hams test and sucrose hemolysis test have low sensitivity
  • Flow cytometry of peripheral blood is test of choice
    • decreased GPI anchored proteins on neutrophils, monocytes, and red cells
    • Red cell analysis: CD55 and CD59
      • Type I - normal
      • Type II - partial deficiency
      • Type III - complete deficiency
    • Granulocytes/monocyte analysis: CD14, CD15, CD16, and CD33
    • Patients with >20% type III RBCs or >50% abnormal granulocytes are at high risk for thrombosis and hemolysis
    • fluorescent aerolysin (FLAER) obtained from Aeromonas hydrophila binds to GPI specifically and can be used instead of antibodies to detect GPI anchored antigens
    • Leukocyte alkaline phosphatase (LAP) score id decreased in PNH

Compendium Hematopathology (8 decks)

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