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5 Red Blood Cell Disorders > 5.6,7 Intravascular Hemolysis and Underproduction > Flashcards

5.6,7 Intravascular Hemolysis and Underproduction Flashcards

1
Q

Glutathione

A

(GSH)

  • antioxidant required to neutralize H2O2. GSH becomes oxidized to GS-SG in the process, and requires NADPH to reduce it back to GSH.
  • NADPH production requires G6PD
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1
Q

G6PD deficiency

-causes of oxidative stress include (3)

A
  1. infections
  2. drugs (include antimalarials, sulfa drugs)
  3. fava beans
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2
Q

G6PD deficiency

-what do you see on blood smear? why?

A
  • Heinz bodies and Bite cells.
  • Oxidative stress precipitates Hb in RBCs (Heinz bodies)
  • Splenic macrophages bite off Heinz bodies. (intravascular hemolysis)
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2
Q

Mycoplasma pneumoniae

-what anemia can this cause?

A

Cold immune hemolytic anemia

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3
Q

Aplastic anemia that is autoimmune:

-what is one possible mech?

A

Abnormal T cell activation releases cytokines that damage the bone marrow.

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4
Q

Paroxysmal Nocturnal Hemoglobinuria (PNH)

-common complications (3)

A
  1. Thrombosis (lysed platelets release contents, which induce thrombosis)
  2. iron deficiency anemia (chronic loss of Hb in urine)
  3. AML (myeloid stem cell may have acquire more mutations)–10% of pts.
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4
Q

Microangiopathic hemolytic anemia

-what other anemia can it cause?

A

-iron deficiency anemia, b/c of chronic hemolysis

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5
Q

G6PD deficiency

-disease variants

A
  1. African
    - mildly reduced G6PD half-life, so mild intravascular hemolysis (RBCs live 90 days)
  2. Meditarranean
    - severely reduced G6PD half-life, so severe intravascular hemolysis (RBCs live 30 days)
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5
Q

Pt with dark brown urine and back pain.

-suspect what?

A

G6PD deficiency

-hemoglobinuria and back pain hours after exposure to oxidative stress

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6
Q

Warm Immune hemolytic anemia

  • causes (3)
  • which is most common
A
  1. SLE
  2. CLL
  3. drugs (classically penicillin and cephalosporins)
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7
Q

Paroxysmal Nocturnal Hemoglobinuria (PNH)

-mech of genetic defect

A
  • acquired defect in myeloid stem cells, resulting in absent GPI (glycosylphophatidylinositol), the anchoring protein required for DAF (decay accelerating factor).
  • DAF is required for protection against complement damage by inhibiting C3 convertase.
  • lack of DAF means all myeloid cells (RBCs, platelets, granulocytes) are lysed.
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7
Q

Direct Coombs test

A

aka DAT–direct agglutinin test

  • check for immune hemolytic anemia
  • checks for Ab/complement coated RBCs. Add anti-IgG/complement to pt’s blood–RBCs already coated will agglutinate.
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8
Q

Microangiopathic hemolytic anemia

-mech

A
  • RBCs are sheared and destroyed as they pass through microthrombi
  • presence of schistocytes.
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9
Q

G6PD deficiency

-how does pt typically present?

A

Pt presents with hemoglobinuria and back pain hours after exposure to oxidative stress (eg fava beans)

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10
Q

Infectious mononucleosis

-what anemia can this cause?

A

Cold immune hemolytic anemia

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11
Q

Warm Immune hemolytic anemia:

-mech

A

IgG binds RBCs in warmer temp of central body. RBC membrane (b/c of IgG opsonization) is consumed by splenic macrophages, resulting in spherocytes.

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12
Q

Immune hemolytic anemia

-what lab tests to dx?

A
  1. direct Coombs test (DAT)
    - check for presence of Ab/complement-coated RBCs.
  2. indirect Coombs test
    - check for presence of anti-RBC Ab in pt’s blood
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13
Q

DAF

-what does it do

A

decay accelerating factor

  • inhibits C3 convertase
  • This is the protein on blood cell surfaces that protects them from complement mediated damage.
  • It’s secured to blood cells by anchoring protein GPI, which is defective in PNH
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14
Q

Indirect Coombs test

A
  • checks for immune hemolytic anemia
  • Looks for presence of anti-RBC Ab in pt’s blood. Take pt’s blood, add test RBCs and anti-IgG–if pt has anti-RBC Ab, agglutination will occur
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15
Q

Pt with heart valve replacement:

-what anemia to be concerned about?

A

Microangiopathic hemolytic anemia

-RBCs sheared by valve flaps

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16
Q

Parvovirus B19

  • what does it cause
  • tx
A
  • infects erythroid precursors and halts erythropoeisis. Aplastic crisis can occur if the pt is already very anemic
  • Tx is supportive (self limiting infection)
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17
Q

Warm immune hemolytic anemia

-what do you see on blood smear

A

-spherocytes, b/c IgG opsonized RBCs have their membrane consumed by splenic macrophages

18
Q

Immune hemolytic anemia:

extravascular or intravascular hemolysis?

A

Warm: predominantly extravascular

Cold: predominantly extravascular, but can be intravascular if complement activation is strong enough to induce MAC-mediated RBC destruction in vessels

20
Q

Bite cells on blood smear:

-what is going on, and what does the pt have?

A
  • Bite cells are caused by splenic macrophages biting off Heinz bodies from RBCs.
  • Heinz bodies are precipitations of Hb, formed by oxidative stress
  • Pt probably has G6PD deficiency and oxidative stress.
22
Q

What leukemia is PNH assoc with and why?

A

PNH can transform into AML 10% of the time.

-this is b/c PNH is a myeloid stem cell mutation, and additional mutations would result in AML

22
Q

Myelophthisic process

  • what is this
  • what do you see on blood smear
A
  • Pathologic process (eg metastatic cancer) that replaces bone marrow, causing a normocytic anemia by underproduction.
  • tear drop cells on blood smear, from myelofibrosis
23
Q

Paroxysmal Nocturnal Hemoglobinuria (PNH)

-what other anemia is this assoc with and why?

A

Iron deficiency anemia

-b/c chronic Hb loss in urine means losing iron

23
Q

Malaria

  • species names and their frequency of fevers
  • what is the name of the mosquito species
A
  1. Plasmodium falciparum–daily fever
  2. P vivax–every other day
  3. P ovale–every other day
    - Anopheles mosquito
25
Q

Pt taking cephalosporins.

-what anemia to be concerned about?

A
  • Warm immune hemolytic anemia
  • cephalosporins are the most common cause of drug-induced warm immune hemolytic anemia (drug binds to RBCs, making body think RBC is foreign and creating Ab against them)
26
Q

Aplastic anemia

-tx

A
  1. marrow stimulating factors (eg EPO, GM-CSF, G-CSF)
  2. immunosuppresants (idiopathic cases may be autoimmune, from abnormal T cell activation with release of cytokines)
  3. bone marrow transplant, last resort
27
Q

Paroxysmal Nocturnal Hemoglobinuria (PNH)

-what tests for dx

A
  1. screening: Sucrose test
    - sucrose activates complement, so you’ll see lysed cells in PNH
  2. confirmation: Acidified serum test, or flow cytometry
    - acid activates complement
    - flow cytometry detects lack of DAF
28
Q

Paroxysmal Nocturnal Hemoglobinuria (PNH)

-clinical presentation (2)

A
  1. Pancytopenia from intravascular hemolysis (RBCs, WBCs, platelets lysed) through complement
  2. Dark brown urine–hemolysis causes hemoglobinemia, causing hemoglobinuria. (a few days later, hemosiderinura appears in urine–also dark brown urine)
29
Q

G6PD deficiency

  • mech of disease
  • what biochem processes involved?
A
  • Genetic defect leads to reduced half-life of G6PD (necessary for RBC protection from oxidative stress) and therefore reduced lifespan of RBCs.
  • G6PD is required to produce NAPDH, which is required to regenerate reduced glutathione (GSH). GSH then neutralizes H2O2 and becomes oxidized to GS-SG in the process.

H2O2 + GSH –> GS-SG

GS-SG –> GSH (reduction to GSH requires NADPH, which is byproduct G6PD )

29
Q

Pt being treated for malaria:

-what anemia (not malaria-induced anemia) to be concerned about?

A

Intravascular hemolytic anemia caused by antimalarial drugs (eg primaquine) in a pt who is G6PD deficient.

-Dangerous. Be sure to check pt hx before using antimalarials.

30
Q

Anemia due to underproduction of RBCs

-causes (3 categories)

A
  1. causes of microcytic and macrocytic anemias
  2. Renal failure (low EPO)
  3. damage to bone marrow precursor cells (parvovirus B19, aplastic anemia, myelophthisic process)
31
Q

Pt with renal failure:

what anemia to be concerned about?

A

-loss of EPO causes bone marrow underproduction of blood cells. (normocytic)

33
Q

Paroxysmal Nocturnal Hemoglobinuria (PNH)

-main cause of death

A

thrombosis (from platelet destruction–leaked contents cause thrombosis)

-thrombosis of hepatic, portal, or cerebral veins.

35
Q

Pt complains of dark brown urine after waking up in the morning.

Suspect what?

A

Paroxysmal Nocturnal Hemoglobinuria (PNH)

36
Q

Paroxysmal Nocturnal Hemoglobinuria (PNH)

-what do you see on blood smear and CBC?

A

Pancytopenia, so low WBCs, RBCs, platelets.

-nothing abnormal in blood smear

37
Q

Paroxysmal Nocturnal Hemoglobinuria (PNH)

-when do symptoms normally present and why?

A

-Dark brown urine appears typically in the morning after waking up. This is b/c intravascular hemolysis tends to happen during sleep. During sleep, there is mild resp acidosis from shallow breathing, and the acidosis activates complement.

39
Q

Warm Immune hemolytic anemia

-what are the 2 ways in which certain drugs can cause this?

A
  1. Drug may attach to RBC membrane, forming a complex that an autoimmune Ab binds to. (eg penicillin)
  2. Drug may induce creation of Ab that bind to self antigens on RBC (eg methyldopa)
41
Q

Cold Immune hemolytic anemia

-mech

A
  1. IgM binds RBCs and fixes complement in extremities (colder)
  2. RBCs typically inactivate complement MAC attack. Residual C3b remains and opsonizes RBCs–splenic macrophages eat RBC membrane, creating spherocytes. (extravascular hemolysis)

(However, severe complement activation can cause MAC-mediated intravascular hemolysis)

42
Q

Cold immune hemolytic anemia

-assoc with what 2 causes?

A

Infection from:

  1. Mycoplasma pneumoniae
  2. infectious mono
43
Q

Malaria

  • what kind of anemia does it cause?
  • clinical presentation (2)
A
  • predominantly intravascular hemolytic anemia, normocytic
    1. cyclical fever–timing is based on hemolysis from the life cycle of the species of Plasmodium
    2. splenomegaly–from mild extravascular hemolysis (splenic macrophages consumed infected RBCs)
44
Q

Immune hemolytic anemia

-tx (3)

A

(remove offending drug if any)

  1. . steroids
  2. . IVIG (splenic macrophages eat these instead of RBCs. This buys time for RBCs)
  3. . splenectomy (last resort–removes source of Ab and location of RBC destruction)
45
Q

Aplastic anemia

  • what is it
  • reticulocyte count?
  • causes
  • what do you see on bone marrow biopsy
A
  1. damage to hematopoeitic stem cells
  2. low reticulocyte count (
  3. drugs, chemicals, radiation, viral infections, autoimmune
  4. hypocellular, fatty marrow
46
Q

Normocytic anemia:

-how to differentiate between one caused by hemolysis or caused by underproduction?

A
  • Use corrected reticulocyte count.
  • If >3%, good bone marrow response. suggests hemolysis
  • If
47
Q

Microangiopathic hemolytic anemia

-what do you see on blood smear

A

-schistocytes, from shearing of RBCS

48
Q

Pt with G6PD deficiency

-how to counsel about kids and others in the family who may have it

A
  • X-linked recessive. (sex linked)
  • Pt is almost always male, and his brothers may have G6PD deficiency too.
  • None of his kids will have the disease (girls will be carriers, boys get mom’s X chromosome instead)
49
Q

GPI

A

glycosylphosphatidylinositol

  • The anchoring protein in blood cells that DAF attaches to.
  • defect in GPI leads to PNH
51
Q

G6PD deficiency

-lab tests to dx

A
  1. screening: Heinz preparation
    - Look for Heinz bodies with special stain
  2. confirmation: enzyme studies
    - measure G6PD
    - note: Heinz test not used anymore
52
Q

Microangiopathic hemolytic anemia

-causes include (6)

A
  1. TTP–thrombotic thrombocytopenic purpura
  2. HUS–hemolytic uremic syndrome
  3. DIC–disseminated intravascular coagulation
  4. HELLP syndrome–hemolysis, elevated liver enzymes, low platelets
  5. prosthetic heart valves
  6. aortic stenosis
53
Q

Anemia due to underproduction of RBCs, caused by damage to bone marrow precursor cells:

-causes (3)

A
  1. parvovirus B19 infection of erythroid precursors
  2. aplastic anemia
  3. myelophthisic process
54
Q

Immune hemolytic anemia (IHA)

  • mech of anemia
  • divided into what categories?
A

-autoimmune Ab mediated destruction of RBCs (IgG or IgM)

(extravascular hemolysis, normocytic anemia)

  1. Warm agglutinin (IgG)
  2. Cold agglutinin (IgM)

5 Red Blood Cell Disorders (8 decks)

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