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(J2) RBCs and Bleeding Disorders > Hemolytic Anemias > Flashcards

Hemolytic Anemias Flashcards

1
Q

What are thalessemias?

A

anemia due to insufficient globin production

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2
Q

What populations are thalassemias most common in?

A
  • Mediterranean
  • African
  • Asian
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3
Q

What are the types and subtypes of thalessemia?

A

α-thalassemia

  • silent
  • α-thalassemia trait
  • HgH disease
  • hydrops fetalis

β-thalassemia

  • β-thalassemia major
  • β-thalassemia intermedia
  • β-thalassemia minor
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4
Q

What is the mechanism of α-thalassemias?

A

There are four total α genes located in pairs on chromosome 16

  • deletion of one or more of the α genes
  • the more copies deleted, the more severe the symptoms
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5
Q

What is silent carrier α-thalassemia?

(symptoms and course)

A
  • deletion of one α gene
  • asymptomatic
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6
Q

What would expected lab changes be in silent carrier α-thalaseemia?

A
  • miniscule reduciton in α-chain (electrophoresis)
  • normal hemoglobin structure (electrophoresis)
  • mild microcytosis
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7
Q

What is α-thalassemia trait?

(symptoms and course)

A
  • deletion of two α genes
  • asymptomatic
  • mild anemia
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8
Q

What would expected lab changes be in α-thalaseemia trait?

A
  • mild reduciton in α-chain (electrophoresis)
  • normal hemoglobin structures, HbA/HbA2 (electrophoresis)
  • mild hypochromic, microcytic anemia
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9
Q

What is HgH disease?

(symptoms and course)

A

-deletion of three α genes

-moderately severe anemia

  • formation of β-globin tetramers (HgH)
  • high O2 affinity -> hypoxia
  • precipitates and forms inclusions (hemolysis in the spleen)

**most common in Asian populations

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10
Q

What would expected lab changes be in HgH disease?

A
  • major reduciton in α-chain (electrophoresis)
  • abnormal hemoglobin structures, HgH (electrophoresis)
  • moderately severe hypochromic, microcytic anemia
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11
Q

What subtypes of α-thalassemia trait are there?

(what is the significance?)

A

both clinically identical in the individuals, difference is in children of the individual

Cis (Asians):

  • deletions are on same chormosome
  • increased risk of HgH in children

Trans (Africans):

  • deletions are on different chromosomes
  • less risk of HgH in children
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12
Q

What is thalassemic hydrops fetalis?

(symptoms and course)

​

A
  • deletion of all four α genes
  • lethal in utero
  • formation of γ-globin tetramers (hemoglobin Barts)
  • high O2 affinity -> hypoxia
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13
Q

What would expected lab changes be in thalassemic hydrops fetalis?

A
  • absenece of α-chain (electrophoresis)
  • abnormal hemoglobin structures, Hg Barts (electrophoresis)
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14
Q

What is the mechanism of β-thalassemias?

A

There are two total β genes located on chromosome 11

-mutations resulting no production (β0) or decreased production (β+)

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15
Q

What is β-thalassemia minor?

(symptoms and course)

A

one normal gene, one defective gene (β/β+) or (β/β0)

-asymptomatic

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16
Q

What would expected lab changes be in β-thalassemia minor?

A
  • mildly decreased HbA (electrophoresis)
  • mildly increased HbA2 (electrophoresis) (useful in differentiating from iron deficiecny anemia)
  • mild hypochromic, microcytic anemia
  • target cells
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17
Q

What is β-thalassemia intermedia?

(symptoms and course)

A

variable but with at least one partially effective gene (β/β+, β/β0, β+/β+, β+/β0)

  • onset shortly after birth (protection by HgF)
  • moderately severe anemia, not requiring blood transfusion
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18
Q

What would expected lab changes be in β-thalassemia intermedia?

A
  • decreased HbA (electrophoresis)
  • increased HbA<strong>2</strong> (electrophoresis)
  • moderately severe hypochromic, microcytic anemia
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19
Q

What is β-thalassemia major?

(symptoms and course)

A
  • no effective gene (β0/β0)
  • onset shortly after birth (protection by HgF)
  • severe anemia, requiring blood transfusions
  • secondary hemochromatosis
  • hematopoiesis in the skull
  • “crew cut” x-ray
  • “chipmunk facies”
  • extramedullary hematopoiesis
  • hepatosplenomegaly
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20
Q

What would expected lab changes be in β-thalassemia major?

A
  • increased HbF (electrophoresis)
  • no/minimal HbA (electrophoresis)
  • normal to low HbA2 (electrophoresis)
  • severe hypochromic, microcytic anemia
  • target cells
  • nucleated RBCs
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21
Q

What is pernicious anemia?

A

autoimmune gastritis resulting in B12 deficiency

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22
Q

What is the common presenation of pernicious anemia?

A
  • older adults (median age 60); uncommon under 30
  • more common in Scandanavian caucasians; present in all races
  • insidious, severe megaloblastic anemia
  • glossitis
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23
Q

What would expected lab changes be in pernicious anemia?

A
  • decreased B12
  • increased homocystiene (THF and B12 used in metabolism)
  • increased methylmalonic acid (B12 used in metabolism)
  • macrocytic anemia
  • hypersegmented PMNs
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24
Q

What is the mechanism of pernicious anemia?

A

-autoimmune T-cell destruction of gastric parietal cells (produce intrinsic factor)

  • intrinsic factor is required for absorption of B12 in the ileum
  • B12 is used in DNA precursor synthesis
  • decreased DNA synthesis is direct cause of megaloblastic anemia
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25
Q

What are possible complications with pernicious anemia?

A
  • damage to spinal cord (B12 needed in mylein production)
  • decreased sensation
  • spastic paresis
  • risk of gastric carcinoma
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26
Q

What are additional causes of B12 deficiency that lead to megaloblastic anemia?

A
  • pancreatic insufficiency (can’t remove salivary haptocorrin)
  • fish tapeworm
  • gastrectomy (loss of intrensic factor/acid/pepsin)
  • achlorhydria (loss of acid, pepsin can’t release B12 from food)
  • pregnancy (increased use)
  • disseminated cancer (increased use)
  • vegans
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27
Q

What is folate deficiency anemia?

A

macrocytic/megaloblastic anemia due to folate deficiency

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28
Q

What is the common presenation of folate deficiency anemia?

A

eldery or alcoholics

-relatively rapid (months), severe megaloblastic anemia

-glossitis

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29
Q

What are common causes of folate deficiency?

A
  • inadequate diet
    • alcoholism
    • elderly
  • ​increased requirement
    • pregnancy
    • cancer/hyperactive hematopoiesis
  • methotrexate (folate antagonist)
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30
Q

What would expected lab changes be in folate deficiency anemia?

A
  • decreased folate
  • increased homocystiene (THF and B12 used in metabolism)
  • normal methylmalonic acid (B12 used in metabolism)
  • macrocytic anemia
  • hypersegmented PMNs
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31
Q

What is the mechanism of folate deficiency anemia?

A
  • folate is used in DNA precursor synthesis
  • decreased DNA synthesis is direct cause of megaloblastic anemia
32
Q

How are folate and B12 related anemias best differentiated?

(labs, onset, symptoms)

A

Both are megaloblastic/macrocytic anemias, display glossitis, and have elevated homocystiene

  • folate deficiency will have normal methylmalonic acid while B12 will have elevated methylmalonic acid (B12 is used in metabolism)
  • methylmalonic acid derivatives are used in making myelin so B12 deficiencies may develop demylination symptoms, folate will not

B12 will onset slowly (high stores in liver), folate will onset more rapidly

B12 has neurologic symptoms, folate has minimal (as above)

33
Q

Why is it important to properly differentiate folate deficiency from B12 deficiency?

A

Treating B12 deficiency with folate will corrects the anemia but worsen neurologic symptoms.

34
Q

What is hereditary spherocytosis?

A
  • defect in cytoskeletal tethering proteins (ankyrin, spectrin, band 3)
  • loss of membrane blebs resulitng; disc shape -> spherical shape (spherocytes)
  • spherocytes traverse cicrulation fine except spleen where they are destroyed -> anemia

RBC life span 120 days -> 10-20 days

35
Q

What would expected lab changes be in hereditary spherocytosis?

A
  • increased RDW (get smaller over time as more blebs lost)
  • increased MCHC (same amount of hemoglobin in smaller volume)
  • increased unconjugated bilirubin (extravascular hemolysis)
  • spherocytes
36
Q

What is the common presentation of hereditary spherocytosis?

A
  • northern European descent
  • anemia
37
Q

What is used to diagnose hereditary spherocytosis?

A

Osmotic fragility test

  • normal RBCs will not lyse when exposed to a hypotonic solution
  • spherocytes will lyse in hypotonic solution due to increased fragility
38
Q

What are possible complications with hereditary spherocytosis?

A
  • gallstones (bilirubin in extravascular hemolysis)
  • aplastic anemia with parvovirus B19
39
Q

What is the treatment for hereditary spherocytosis?

What occurs as a result?

A

Splenectomy (only place where spherocytes are lysed)

  • > anemia resolves
  • > increased risk of encapsulated bacterial infections
  • >Howell-Jolly bodies appear in blood (RBCs with nuclear material that are normally cleared by the spleen)
40
Q

What is sickle cell anemia?

A

-homozygous recessive mutation of β-globin ( hydrophilic glutamic acid -> hydrophobic valine) producing HgS instead of HgA

41
Q

What would expected lab changes be in sickle cell anemia?

A
  • >90% HbS
  • increased HbF
  • no HbA

-moderately severe anemia

-sickle cells

-target cells and Howell-Jolly bodies (hyposplenism)

  • increased bilirubin
  • decreased haptoglobin
42
Q

What is the mechanism of sickle cell anemia?

A
  • deoxygenated HgS reversibly polymerizes into needle-like structures, cells take abnormal sickle shape when this occurs
  • repeated sickling decreased membrane integrity -> hemolytic anemia
    • hemolysis in the spleen (extravascular - primary)
    • hemolysis in vasculature (intravascular)
  • sickled cells may occlude microvasculature

protected by HbF early in life

43
Q

What is the common presentation of sickle cell anemia?

A
  • infants a few months old (HgF protects initially)
  • black
  • moderately severe anemia
  • dactylitis (in children)
  • “crew cut” head X-ray and “chipmunk facies” (expansion of hematopoiesis)
  • pain crisis
  • hepatomegaly (extramedullary hematopoiesis)
44
Q

What are potential complications of sickle cell anemia?

A

Microvascular occlusions

  • Dactylitis (swollen hands and feet) (most common presenting symptom in infants)
  • autosplenectomy (small, fibrotic spleen) due to repeated occlusions
    • increased risk of infection with encapsulated bacteria (H. infulenza most common cause of **death in children**)
    • Howell-Jolly bodies
  • acute chest syndrome: pulmonary occlusions (precipitated by pneumonia)
    • chest pain, SOB, infiltrates
    • most common cause of **death in adults**
  • ​renal necrosis -> hematuria and protenuria
  • ​pain crisis: severe pain caused by occlusions anywhere (including above)
  • stroke
  • blindness

Aplastic crisis (parvovirus B19)

Gallstones (increased bilirubin)

45
Q

What conditions precipitate sickling in sickle cell anemia?

A

Deoxygenation of HbS

  • hypoxia
  • dehydration
  • acidosis
46
Q

What is the treatment for sickle cell anemia?

A

hydroxyurea -> increased HbF

47
Q

What is sickle cell trait?

A
  • only one mutated β-globin gene ( hydrophilic glutamic acid -> hydrophobic valine)
  • <50% HbS
48
Q

What would expected lab changes be in sickle cell trait?

A
  • >50% HbA
  • <50% HbS
  • no HbF
  • no anemia
  • no sickle cells
  • possible hematuria
49
Q

What is the common presentation of sickle cell trait?

A

-black

  • asymptomatic
  • no anemia
  • hematuria
50
Q

What is the mechanism of sickle cell trait?

A
  • RBCs with <50% HbS do not sickle except in the renal medulla (very hypoxic)
  • occulusions lead to hematuria
51
Q

How can sickle cells be identified in a lab when they aren’t currenlty sickled?

A
  • metabisulfite will cause all cells with HbS to sickle, regardless of %
  • identifies both sickle cell disease and traits
52
Q

What is hemoglobin C disease?

A

-homozygous recessive mutation of β-globin (glutamic acid -> lysine) producing HgC instead of HgA

(ly”C’ine)

53
Q

What is the common presentation of hemoglobin C disease?

A
  • black
  • asymptomatic
  • mild anemia
  • splenomegaly
  • jaundice
54
Q

What would expected lab changes be in hemoglobin C disease?

A
  • HbC crystals in blood
  • mild anemia
  • increased bilirubin
55
Q

What is paroxysmal nocturnal hemoglobinuria (PNH)?

A

aquired mutation in myeloid stem cells resulting in loss of GPI resulting in susceptibility of myeloid derived cells (RBCs, WBCs, and platelets) to intravascular lysis via complement

-mild to moderate anemia

56
Q

What would expected lab changes be in paroxysmal nocturnal hemoglobinuria?

A

flow cytometry shows no CD55 or CD59

  • hemoglobinemia (after episode)
  • hemoglobinuria (after episode)
  • hemosiderinuria (delayed)
57
Q

What is the common presentation of paroxysmal nocturnal hemoglobinuria?

A

occasional hematuria in the after sleeping

58
Q

What is the mechanism of paroxysmal nocturnal hemoglobinuria?

A
  • GPI is used as an anchor for membrane proteins such as DAG (CD55)
  • DAG serves to prevent cells in the blood from being lysed by complement
  • loss of GPI -> loss of DAG -> susceptibility to complement mediated lysis
  • complement is activated while sleeping due to mild hypoxemia from shallow breating -> RBCs lyse over night -> hemoglobin in urine the next morning
59
Q

What is G6PD deficiency anemia?

A

X-linked recessive disorder reducing half-life of G6PD

-mild to marked intravascular anemia

60
Q

What would expected lab changes be in G6PD deficiency anemia?

A

after episodes:

  • anemia
  • hemoglobinemia
  • hemoglobinuria
61
Q

What is the common presentation of G6PD deficiency anemia?

A

-African or Mediterranean descent (worse in Mediterranean)

  • intermitent anemia (following exposure to oxidative stress)
  • back pain
62
Q

What is the mechanism of G6PD deficiency anemia?

A
  • G6PD is used to regenerate NADPH
  • NADPH reduces other substances, including ROS such as H2O2
  • RBCs are unable to make new proteins (lack of nucleous)
  • normal G6PD outlasts a RBCs life span (120 days)
  • G6PD deficiency varients have shorther half-lifes leaving older RBCs susceptible to damage from ROS
  • periods of increased oxidative stress cause intravascular hemolysisof older RBCs with insufficient G6PD

-Hgb preciptates as Heinz bodies

63
Q

What are the different variants of G6PD deficiency?

What is their significance?

A

African variant:

  • less reduced half-life
  • mild anemia

Mediterranean variant:

-more reduced half-life

-marked anemia

64
Q

What screening test is used to confirm G6PD deficiency anemia?

A

Heinz preparation

  • special stain that shows precipitated Hgb from G6PD deficiency, Heinz bodies, that are otherwise unseen
  • **must be performed weeks after an episode as during an episode cells old enough to have Heinz bodies have already been lysed
65
Q

What is immune hemolytic anemia?

A

IgG or IgM mediated destruction of RBCs

66
Q

What are the types of immune hemolytic anemia?

A
  • warm agglutinin (IgG)
  • cold agglutinin (IgM)
  • cold hemolysin (IgG)
67
Q

What is warm agglutinin anemia?

What conditions is it assocaited with?

A

-IgG mediated extravascular hemolysis of RBCs

-occurs at warm (body) temperature

associated with:

  • SLE
  • CLL
  • drugs (penecillin, cephalosporins, methyldopa)
68
Q

What is the mechanism of warm agglutinin anemia?

A

Extravascular hemolysis

  • IgG binds RBCs in warm core blood
  • portions of IgG bound membrane is phagocytosed in spleen -> spherocytes
  • spleen removes spherocytes

IgG is either autoreactive to RBCs or binds membrane bound drug

69
Q

What is cold agglutinin anemia?

What conditions is it assocaited with?

A
  • IgM mediated intravascular hemolysis of RBCs
  • occurs at colder temperatures (seen in extremities)

associated with:

  • Mycoplasma pneumoniae
  • mononucleosis
70
Q

What is the mechanism of cold agglutinin anemia?

A

Intravascular hemolysis

  • IgM binds RBCs in cold blood of extremities
  • IgM activates compliment causing some hemolysis

when RBC leaves extremity and warms up, IgM falls off and compliment is no longer activated -> very mild anemia

71
Q

What is cold hemolysin anemia?

What conditions is it assocaited with?

A
  • IgG mediated intravascular hemolysis of RBCs
  • occurs at colder temperatures (seen in extremities)

children following viral illness

72
Q

What are the main differences between warm and cold agglutinin anemia?

A

Warn:

  • more common
  • IgG -> spleen -> extravascular hemolysis
  • active in warm, central blood
  • idopathic or drug induced
  • more severe (can be active more)

Cold:

  • less common
  • IgM -> complement -> intravascular hemolysis
  • associated with certain infections
  • active in cold extremities
  • very mild anemia
73
Q

What test is used to identify immune hemolytic anemia?

A

Coombs test

Direct:

  • detects pressence of RBCs coated with Ig or complement
  • tested RBCs w/ added Ab that will bind Fc regions or complement if they are bound to RBC

Indirect:

  • detects pressence of Ab capable of binding RBCs and identifying target and at what temp
  • tested serum added special RBCs with known surface markers
74
Q

What is microangioplastic hemolytic anemia?

What conditions is it associated with?

A

RBCs are destroyed by abnormal vasculature (normally thrombi)

  • TTP (thrombotic thrombocytopenic purpura)
  • HUS (hemolytic uremic syndrome)
  • DIC (disseminated intravascular coagulation)
  • HEELP (hemolysis, elevated liver enzymes, and low platelets)
  • stenosis
  • mechanical heart valves
75
Q

What histological feature would you expect to see in microangiopathic hemolytic anemia?

A

Schistocytes: fragmented RBCs from sheer stress

76
Q

How does malaria relate to anemia?

A

Malaria is caused by the Plasmodium family of protozoa.

Part of their lifecycle occurs in RBCs and results in intravascular hemolysis when they emerge.

77
Q

What blood disorders are thought to be protective for malaria, hence they have an increased prevalence in regions with malaria?

A
  • sickle cell anemia (African)
  • thalassemias (Mediterranean, African, Middle Eastern, and Asian)
  • G6PD deficiency (African and Mediterranean)

(J2) RBCs and Bleeding Disorders (10 decks)

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