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clinical medicine 2 > Anemia Due to Peripheral Erythrocyte Destruction > Flashcards

Anemia Due to Peripheral Erythrocyte Destruction Flashcards

1
Q

Hemolysis of RBCs (anemia due to peripheral erythrocyte destruction) may result from what?

(4 things)

A
  • congenital hemoglobin abnormalities
  • erythrocyte membrane abnormalities
  • enzyme abnormalities for RBC metabolism
  • acquired via immune processes or infection
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2
Q
  • What condition(s) are examples of RBC hemolysis due to congenital hemoglobin abnormalities?
  • What condition(s) are examples of RBC hemolysis due to erythrocyte membrane abnormalities?
  • What condition(s) are examples of RBC hemolysis due to enzyme abnormalities for RBC metabolism?
A
  • hemoglobinopathies or thalassemias
  • hereditary spherocytosis
  • G6PD deficiency
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3
Q
  • Which RBC hemolysis causes are instrinsic survival defects?
  • Which ones are extrinsic (includes factors outside of the cell)?
A
  • congenital hemoglobin abnormalities, erythrocyte membrane abnormalities, enzyme abnormaties for RBC metabolism
  • acquired via immune process or infection
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4
Q
  • Thalassemias are (…) disorders
  • Describe what thalassemia is
  • What does thalassemia lead to which is the hallmark of all thalassemia syndromes?
A
  • autosomal recessive disorders
  • slowed or defective synthesis of globin chains of the hemoglobin molecule (alpha or beta)
  • imbalanced globin chain synthesis
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5
Q
  • Major thalassemia disorders are through (…) inheritance
  • Minor thalassemia disorders are through (…) inheritance
A
  • homozygous inheritance
  • heterozygous inheritance
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6
Q

What is the most common single-gene disorder in the world, with an estimated carrier numbers of more than 270 million, and more than 300,000 children are born each year with one of the syndromes or one of the structural hemoglobin variants?

A

thalassemia

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7
Q

Thalassemia syndromes are more common in (…) ancestry

A

mediterranean

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8
Q
  • What are the characteristics of RBCs in thalassemia disorders?
  • Many subtypes range from (…) to (…) severity
  • Very severe cases may require monthly (…)
A
  • thin, delicate, and deficient in hemoglobin (hypochromic)
  • mild to extremely severe
  • blood transfusions
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9
Q
  • What is the oxygen carrying protein of the erythrocyte?
  • A single erythrocyte contains as many as (…) hemoglobin molecules
  • Hemoglobin has how many pairs of polypeptide chains?
  • It also has four colorful (…) complexes
A
  • hemoglobin
  • 300 hemoglobin molecules
  • two pairs (globulins)
  • iron-protoporphyrin complexes
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10
Q
  • What is the most common type of adult hemoglobin?
  • What chains does this hemoglobin have?
  • What is a large, flat, iron-protoporphyrin disk that is synthesized in the mitochondria and can carry one molecule of oxygen?
A
  • hemoglobin A
  • two alpha chains and two beta chains
  • heme
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11
Q

What are the different types of hemoglobin and what are their characteristics?

A
  • hemoglobin A1: 90% of total hemoglobin
  • hemoglobin A2: 1.5%-3.5% of total hemoglobin
  • hemoglobin F: 50-90% in neonates; has higher affinity for oxygen than adults
  • hemoglobin S: presence abnoral, indicates sickle cell anemia
  • plasma: acts as a buffer system if too much acid is in the body; last line of defense
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12
Q
  • Low levels of hemoglobin A1 indicate (…)
  • High levels of hemoglobin A2 indicate (…)
  • Hemoglobin F is normally high in (…) but long term elevations may indicate (…)
  • Hemoglobin S is indicative of (…)
  • High levels of plasma may indicate (…)
A
  • anemia/blood loss
  • thalassemia
  • neonates; thalassemia
  • sickle cell disease
  • hemolitic anemia
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13
Q

In alpha thalassemia, what is not formed correctly and what do you have an excess of?

A
  • alpha chains not formed correctly
  • excess beta chains
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14
Q

In beta thalassemia, what is not formed correctly and what do you have an excess of?

A
  • beta chains not formed correctly
  • excess alpha chains
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15
Q
  • In beta thalassemia, not only is there an excess of alpha chains, but there is also (…) being formed which is a good thing
  • However, the excess alpha chains can lead to (…) and (…)
  • Hemolysis of RBCs can cause (…) leading to pooling and plasma volume expansion and can cause (…)
A
  • hemoglobin F (high ozygen affinity)
  • hemolysis and destruction of RBC precursors
  • splenomegaly; anemia
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16
Q
  • Anemia due to beta thalassemia can be treated with (…)
  • This along with increased iron aborpstion can cause (…)
  • This can lead to what negative outcomes?
A
  • transfusions
  • iron loading
  • endocrine deficiencies, cirrhosis, cardiac failure, death
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17
Q

In alpha thalassemia, the (…) chains are affected; (…) chains are affected in beta thalassemia

A
  • alpha chains
  • beta chains
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18
Q

What are the different classifications of beta thalassemia?

A
  • beta thalassemia minor
  • beta thalassemia intermedia
  • beta thalassemia major: Cooley anemia; can be fatal
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19
Q

What are the different alpha thalassemia classifications?

A
  • alpha trait: single gene
  • alpha-thalassemia minor: 2 genes
  • alpha thalassemia major: 4 genes; fatal
  • hemoglobin H disease: 3 genes (moderate form)
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20
Q

Normally (…) genes control beta-chain synthesis and (…) genes control alpha-chain synthesis

A
  • 2
  • 4
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21
Q

What do the three main types of beta-thalassemia cause (or how severe/mild they are)?

A
  1. beta-thalassemia minor: mild anemia
  2. beta-thalassemia intermedia: mild anemia
  3. beta-thalassemia major: AKA cooley’s disease, severe
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22
Q

Which beta-thalassemia is transfusion dependent?

A

beta-thalassemia major

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23
Q

What do the four main types of alpha thalassemia cause (or how severe/mild they are)?

A
  1. alpha trait: mildest form, usually symptom-free
  2. alpha-thalassemia minor: similar to beta-minor, mild anemia
  3. alpha-thalassemia major: severe, usually fatal in utero
  4. hemoglobin H disease: moderate, may show symptoms
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24
Q

Which alpha-thalassemia is usually fatal in utero?

A

alpha-thalassemia major

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25
Q

Which thalassemia is this describing:
- mild-to-moderate hypochromic-microcytic anemia
- mild splenomegaly
- bronze coloring of the skin
- hyperplasia of the bone marrow
- usually asymptomatic

hemochromatosis features

A

beta-thalassemia minor

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26
Q

Which thalassemia is this describing:
- severe anemia
- resulting in large cardiovascular burden
- may be quite ill

A

beta-thalassemia major

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27
Q
  • What are the hemoglobin levels in beta-thalassemia major?
  • What are the hemoglobin levels in beta-thalassemia intermedia?
  • What can be seen in both beta-thalassemia intermedia and major?
A
  • <7
  • 7-10
  • liver/spleen enlargement
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28
Q

Which alpha thalassemia is this describing:
- symptom free, having mild microcytosis at most

A

alpha trait

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29
Q

Which alpha thalassemia is this describing:
- clinical manifestations: virtually identical to those of beta-thalassemia minor

A

alpha thalassemia minor

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30
Q

Which alpha thalassemia is this describing:
- moderate form; seen in areas high in malaria transmission

A

hemoglobin H disease

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31
Q

Which alpha thalassemia is this describing:
- hydrops fetalis, a condition in which large amounts of fluid build up in a baby’s tissues and organs, causing extensive swelling
- fulminant intrauterine congestive heart failure (fetus has a grossly enlarged heart and liver)
- diagnosis usually made postmortem

A

alpha thalassemia major

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32
Q
  • What is important in the diagnosis of thalassemias?
  • Thalassemia syndromes are sometimes found in (…) which is done in 42 out of 50 states
  • The primary evaluation of thalassemias is based on (…)
  • Labs show (…) anemia, leading to further investigation
  • Individuals with a MCV below (…) and an MCH below (…) with normal iron parameters need to be further investigated. RBC numbers are usually (…) than normal
A
  • family history
  • newborn screenings
  • hematologic changes
  • microcytic anemia
  • 80 fL; 27 pg; higher
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33
Q

In the presence of anemia with thalassemic red cell changes, the next step is the evaluation of hemoglobin fractions (HbA, HbA2, HbF, or hemoglobin variants) by (…) or, even better, by high-performance (…)

A
  • electrophoresis on cellulose acetate at alkaline pH
  • liquid chromatography
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34
Q

What is the diagnostic test of choice for thalassemia syndromes?

A

Hg electrophoresis

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34
Q

What are the band sizes of HbA2, HbF, and HbA1 on Hg electrophoresis for these different thalassemias:
- normal
- beta-thalassemia trait
- beta-thalassemia major

A
  • HbA2: thin; HbF: thin; HgA1; thick
  • HbA2: thicker; HbF: thin; HbA1: thick
  • HbA2: thicker; HbF: thick; HbA1: thin
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35
Q

In sickle cell trait and sickle cell anemia, what shows up as a thick band on the Hg electrophoresis?

A

HbS

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36
Q

What should you be looking for in patient history in an individual with suspected thalassemia?

A
  • race
  • family history
  • age of onset
  • development
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37
Q

What should you be looking for in a clinical examination on an individual with suspected thalassemia?

A
  • pallor
  • jaundice
  • splenomegaly
  • skeletal deformity
  • pigmentation
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38
Q

What should you be looking for on blood count and films in an individual with suspected thalassemia?

A
  • Hb MCV, MCH, retics
  • RBC inclusions in blood or bone marrow
  • HbH precipitation
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39
Q

What are these lab values in IDA?
- Mentzer’s index (MCV/RBC)
- RDW
- Iron, ferritin, transferrin saturation
- TIBC
- other diagnostic tools

A
  • > 13
  • high
  • low
  • high
  • work up the cause of iron deficiency
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40
Q

What are these lab values in thalassemia?
- Mentzer’s index (MCV/RBC)
- RDW
- Iron, ferritin, transferrin saturation
- TIBC
- other diagnostic tools

A
  • <13
  • normal
  • normal
  • normal
  • alpha thal: molecular test; beta thal: electrophoresis
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41
Q

What type of cell shapes may you see in thalassemia major and minor?

A

target cells

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42
Q

What are these lab values in Iron deficiency:
- MCV
- Reticulocyte count
- Ferritin
- Mentzer index for children (MCV/RBC)
- Hb electrophoresis

A
  • low
  • low
  • low
  • > 13
  • normal; may have reduced HbA2
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43
Q

What are these lab values in beta thalassemia:
- MCV
- Reticulocyte count
- Ferritin
- Mentzer index for children (MCV/RBC)
- Hb electrophoresis

A
  • low
  • minor: low or increased; major: increased
  • normal
  • <13
  • increased HbA2, reduced HbA, probably increased HbF
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44
Q

What are these lab values in alpha thalassemia:
- MCV
- Reticulocyte count
- Ferritin
- Mentzer index for children (MCV/RBC)
- Hb electrophoresis

A
  • low
  • minor: normal; H: increased
  • normal
  • <13
  • adults: normal; newborns: may have HbH or HbBart’s
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45
Q

What drives the diagnosis of thalassemia?

A

electrophoresis

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46
Q

What is the treatment for thalassemia minor?

A
  • no specific treatment
  • genetic counseling
  • pregnant females may become more anemic in 2nd/3rd trimester = support with folic acid/iron as needed
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47
Q

Patients with thalassemia minor should receive iron supplements only if needed as they are at risk for (…) if ferritin is normal

A

iron overload

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48
Q

What is the treatment for thalassemia major?

A
  • genetic counseling
  • blood transfusions (dependent)
  • iron chelation therapy
  • splenectomy
  • bone marrow, cord blood, stem cell transplantation
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49
Q

What is currently the only cure for thalassemia major?

A

bone marrow, cord blood, stem cell transplantation

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50
Q

Why would someone with thalassemia major get a splenectomy?

A

spleen is enlarged, can be killing RBCs too early, and gets to a point where it can rupture which is dangerous

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51
Q
  • Treatments for thalassemia major have prolonged life expectancy into the (…)
  • Death is usually from (…)
  • What is the conventional treatment for thalassemia major?
A
  • 30s and 40s
  • cardiac failure
  • regular blood transfusion theray and iron chelation
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52
Q
  • What is the primary goal of conventional treatment for thalassemia major (regular blood transfusion and iron chelation)?
  • When is this treatment usually administered?
  • What is the desired hemoglobin levels?
  • What do providers use to minimize transfusion reactions and pathogen transmission?
  • What adverse effect of transfusion is rare, but severe?
A
  • to control the ineffective erythropoiesis, its consequences, and the burden of iron on the body
  • every 2-5 weeks
  • at least 12 g/dL
  • use leuko-reduced packed RBCs
  • transfusion-related acute lung injury
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53
Q
  • Patients with thalassemia major may require (…) due to hypersplenism
  • The mortality post-splenectomy is (…) due to severe and overwhelming infection
  • (…) is inevitable but a serious complication due to both transfusions and hyperabsorption of dietary iron
  • This can cause (…)
A
  • splenectomy
  • 50%
  • iron overload
  • iron-induced cardiac disease
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54
Q

What is a major recycler of RBCs?

A

the spleen

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55
Q

What is the treatment for thalassemia intermedia?

A
  • more complicated treatment due to various phenotypes
  • transfusion therapy, splenectomy, modulation of HbF production, and HSCT (hematopoietic stem cell transplant)
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56
Q

Studies are showing it may be beneficial to start (…) for thalassemia intermedia earlier than classically waiting until complications arise

A

HSCT

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57
Q

What are the other names of hereditary spherocytosis?

A
  • congenital hemolytic anemia
  • congenital acholuric jaundice
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58
Q
  • What is the most common of the hemolytic disorders in which no hemoglobin abnormality exists?
  • How is this disorder inherited?
A
  • hereditary spherocytosis
  • autosomal dominant
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59
Q

What does this describe:
- congenital abnormality of proteins or spectrins of the erythrocyte membrane, leading to an increased concentration of intracellular sodium (and thus water)

A

hereditary spherocytosis

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60
Q
  • (…) leads to thickened, almost spheric, erythrocytes that are fragile and susceptible to spontaneous hemolysis which decreased survival in circulation
  • What does this disorder result in?
A
  • hereditary spherocytosis
  • chronic anemia with reticulocytosis and episodes of mild jaundice due to hemolysis
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61
Q

What are the 3 symptoms of an acute crisis of hereditary spherocytosis?

A
  • gallstones
  • fever
  • abdominal pain
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62
Q
  • What is the primary mechanism of hemolysis?
  • The lifespan of RBC can shorten to (…) days
  • Usually, someone can compensate through childhood with increased (…)
A
  • splenic destruction of deformed RBCs (abnormal RBCs trapped in microcirculation and ingested by phagocytes)
  • 20-30 days
  • erythropoiesis
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63
Q

What is the differential diagnosis of spherocytes on a peripheral smear?

A
  • hereditary spherocytosis
  • autoimmune hemolytic anemia
  • thermal injurys
  • microangoipathic/macroangiopathic hemolytic anemias
  • hepatic disease
  • clostridium septicemia
  • transfusion reactions with hemolysis
  • poisoning w/ certain snake, spider, and Hymenoptera venoms
  • severe hypophosphatemia
  • heinz body anemias
  • ABO incompatibility (neonates)
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64
Q
  • What is the classic triad of clinical manifestations of hereditary spherocytosis (chronic not acute crisis)?
  • Hereditary spherocytosis can rarely present as (…) in utero or shortly after birth
  • It is most commonly diagnosed later in (…) and even into (…)
  • What do complications of hereditary spherocytosis include?
A
  • anemia, jaundice, splenomegaly
  • severe hemolytic anemia
  • childhood; adulthood
  • increased gallstones (bilirubin), aplastic/hemolytic and megaloblastic crises
65
Q

What is the testing process for hereditary spherocytosis?

A
  • family history
  • CBC with peripheral smear (suggestive not diagnostic), reticulocyte count, bilirubin
  • osmotic fragility test or flow cytometry analysis of RBC EMA binding diagnostic
66
Q
  • What is the diagnostic test of choice for hereditary spherocytosis?
  • What does this test tell you?
A
  • osmotic fragility test
  • will tell you if cells break open when water is added
67
Q

What is the treatment for hereditary spherocytosis?

A
  • daily folic acid supplementation to increase production of health RBCs
  • may need partial splenectomy
68
Q
  • Before a splenectromy, patients should be immunized with vaccines against which three viruses?
  • What does postsplenectomy care include?
A
  • pneumococcus, Haemophilus influenzae type B, and meningococcus
  • counseling of pts/parents to seek prompt medical care in case of febrile illness
69
Q
  • What is characterized by the presence of elliptical or oval cigar-shaped erythrocytes on peripheral blood smears of affected individuals?
  • What is the principal defect of this disorder?
  • Where do most defects of this disorder occur?
A
  • hereditary elliptocytosis
  • mechanical weakness or fragility of the erythrocyte membrane skeleton
  • spectrin
70
Q

What is the principal structural protein of the erythrocyte membrane skeleton?

A

spectrin

71
Q
  • What are the clinical manifestations of hereditary elliptocytosis?
  • Most patients with hereditary elliptocytosis are (…) and are diagnosed incidentally during testing for unrelated conditions
  • The erythrocyte lifespan, normal in most patients, is decreased in only about (…)% of patients
  • These patients with decreased erythrocyte lifespan experience what symptoms?
  • Many of these patients have parents with typical HE and thus are (…) or (…) for defects inherited from each of the parents
A
  • heterogeneous presentation, ranging from asymptomatic carriers to patients with severe, life-threatening anemia
  • asymptomatic
  • 10%
  • hemolysis, anemia, splenomegaly, intermittent jaundice
  • homozygotes or compound heterozygotes
72
Q
  • What is the hallmark RBC found on a peripheral smear for hereditary elliptocytosis?
  • What also may be seen on the peripheral smear?
  • The osmotic fragility test for this condition is usually (…) but can be (…) in severe cases
A
  • cigar-shaped RBCs
  • ovalocytes, spherocytes, stomatocytes, and fragmented cells
  • normal; abnormal
73
Q
  • Therapy for hereditary elliptocytosis is (…)
  • In rare cases, occasional (…) may be required
  • In cases of severe hereditary elliptocytosis, (…) has been palliative because the spleen is the site of erythrocyte sequestration and destruction
  • Many practitioners think the same indications for splenectomy in (…) should be applied to patients with symptomatic hereditary elliptocytosis
  • Postsplenectomy patients with HE or HPP (hypophosphatasia) experience what?
A
  • rarely needed
  • RBC transfusions
  • splenectomy
  • hereditary spherocytosis
  • increased hematocrits, decreased reticulocyte counts, and improved clinical symptoms
74
Q
  • How is G6PD deficiency inherited?
  • What does the G6PD enzyme do?
  • A deficiency in G6PD does what?
  • People with G6PD deficiency are usually (…) unless stressors are present
  • Without G6PD, oxidative stressors do what?
A
  • x-linked, recessive
  • helps erythrocytes maintain metabolic processes, despite injurious conditions
  • shortens RBC lifespan
  • asymptomatic
  • damage hemoglobin and the plasma membranes of erythrocytes (Heinz bodies)
75
Q

What are found on a peripheral smear with individuals who have G6PD deficiency?

A

heinz bodies

76
Q
  • What is an X linked recessive disorder of erythrocyte metabolism in which the enzyme glucose-6-phosphate dehydrogenase is deficient?
  • This interferes with the conversion of (…) to (…)
  • This is important in prevention of (…) damage to RBCs
A
  • G6PD deficiency
  • NADP to NADPH
  • oxidative
77
Q
  • In a patient with G6PD deficiency, when they are exposed to oxidative stress, what can happen?
  • This occurs commonly after what occurances?
  • This occurs less commonly after what?
A
  • hemolytic anemia (hemolysis)
  • fever, acute viral/bacterial infections, diabetic acidosis
  • exposure to durgs or other substances that produce peroxide (oxidation of HgB and RBC membranes)
78
Q
  • What enzyme converts NADP to NADPH?
  • What does this generate?
  • What is an antioxidant that prevents RBC damage from reactive oxygen species such as free radicals, toxins, and infections?
A
  • G6PD
  • GSH (glucothione)
  • glucothione
79
Q

G6PD deficiency leads to lower (…) levels, which leaves RBCs vulnerable to (…) due to reduced energy available to maintain the RBC membrane

A
  • GSH (glucothione)
  • hemolysis
80
Q
  • What is the most common inherited disordre of erythrocyte metabolism with many variants and over 100 mutations and affects 400 million people world wide?
  • Which individuals is this disorder more common in?
  • Which individuals are rarely affected?
A
  • G6PD deficiency
  • males, especially african americans (10-15%) and some meditteranean populations
  • female carriers
81
Q
  • In G6PD deficient individuals, risk factors are related to (…)
  • What are the big two risk factors that trigger a G6PD deficiency episode?
  • What are other risk factors?
A
  • exposure to oxidative stress
  • infections (most common cause of hemolysis) and certain drugs
  • exposure to naphthalene (moth balls) and ingestion of fava beans
82
Q

What drugs are risk factors for G6PD deficient individuals?

A
  • antimalarial: primaquine, pamaquine
  • sulfa drugs: sulfanllamide, sulfoxone, sulfapyridine
  • nitrofurans
  • analgesics: aspirin
  • others: Vit K analogues, methylene blue, probenecid
83
Q
  • Classification of G6PD deficiency hemolytic anemia is based on what?
  • What are the different classes?
  • Which ones will be seen the most and represent more than 90% of G6PD variants?
A
  • based on severity and degree of enzyme deficiency
  • class I, II, III, IV, and V
  • class II and III
84
Q

Describe the different classes associated with G6PD deficiency hemolytic anemia

A
  • class I: chronic non-spherical hemolytic anemia (CNSHA) without precipitating cause + severe G6PD deficiency
  • class II: intermittent hemolysis + severe G6PD deficiency
  • class III: hemolysis after oxidant stress + mild G6PD deficiency
  • class IV and V are mild and clinically asymptomatic
85
Q
  • Most patients with G6PD deficiency are (…)
  • Those with (…) are usually healthy and have no splenomegaly
  • Presentation is dependent on the associated (…)
  • What are the most clinically signficant syndromes of G6PD deficiency?
A
  • asymptomatic
  • mild, episodic hemolysis
  • syndrome
  • acute hemolytic anemia (AHA), neonatal jaundice (NNJ), and chronic non-spherocytic hemolytic anemia (CNSHA) - rare
86
Q

A jaundice infant may have what type of deficiency?

A

G6PD

87
Q

What are the clinical manifestations of G6PD deficiency?

A
  • icterus neonatorum
  • acute hemolytic anemia (pallor, icterus, dark urine, back pain)
88
Q

Between hemolytic episodes in an individual with G6PD deficiency, what may happen?

A
  • no anemia
  • erythrocyte survival is normal
89
Q

What is a big trigger of hemolysis in an individual with G6PD deficiency?

A

malaria

90
Q

If a patient presents to ED that traveled to a country with malaria and is now presenting with an acute hemolytic anemic episode, what may they be deficient in?

A

G6PD

91
Q

What is the treatment for patients with G6PD deficiency?

A
  • prevention: high-risk groups tested
  • prevention: avoid triggers (malaria, oxidative stressors)
  • for hemolysis: blood transfusions and oral iron therapy
  • spontaneous recovery: generally follows treatment
92
Q

What is the accelerated destruction of RBCs?

A

hemolytic anemia

93
Q

What are the various ways to classify hemolytic anemia?

A
  1. congenital vs acquired
  2. intravascular vs extravascular hemolysis (extravascular mainly in liver and spleen); includes fragmentation/non-immune (heart valve)
  3. paroxysmal nocturnal hemoglobinuria (membrane defect)
  4. autoimmune hemolytic anemias
94
Q
  • Extravascular hemolysis occurs mainly where?
  • What describes when there are autoantibodies against antigens normally on the surface of the erythrocyte causing anemia?
A
  • liver and spleen
  • autoimmune hemolytic anemia
95
Q
  • What results from a deficiency in CD55 and CD59 and cause complement-mediated intravascular lysis and release of hemoglobin?
  • What are some symptoms of this?
A
  • paroxysmal noctural hemoglobinuria (membrane defect)
  • anemia, hemoglobinuria, severe fatigue, abdominal pain, thrombosis
96
Q

What is this describing:
any anemia resulting from an increased rate of erythrocyte destruction in the peripheral circulation; can take place in the vasculature or mainly in the liver and the spleen

A

hemolytic anemia

97
Q

What factors are involved in the hemolytic anemias?

A
  • environmental factors
  • membrane defects (an acquired somatic mutation)
98
Q

What are environmental factors that are involved in hemolytic anemias?

A
  • antibody: immunohemolytic anemias
  • mechanical trauma: TTP, HUS, heart valve
  • toxins, infectious agents: malaria, etc
99
Q

What are examples of membrane defects involved in hemolytic anemia?

A
  • paroxysmal nocturnal hemoglobinuria (acquired)
  • hereditary spherocytosis
  • spur cell anemia
100
Q
  • What is an abnormality of the RBC membrane which makes the RBC unusually sensitive to lysis by complement?
  • This is rare with insidious onset and chronic course (usually 30-40 y/o) characterized by episodes of what?
  • RBCs are usually (…) and various sizes, but there is no evidence of what 3 things?
A
  • paroxysmal nocturnal hemoglobinuria
  • hemolytic anemia, nocturnal hemoglobinuria, pallor, icterus/bronzing of skin, moderate splenomegaly, and sometimes hepatomegaly
  • macrocytic; spherocytosis, erythrophagocytosis, or abnormal leukocytosis
101
Q

What is this describing:
- RBCs appear spiculated and are destroyed prematurely, predominantly in the spleen; may be seen in patients with severe liver disease as a result of an abnormality in the cholesteral content of the RBC membrane

A

spur cell anemia

102
Q

What is spur cell also known as?

A

acanthocyte

103
Q

What are extrinsic hemolytic anemias?

A
  • autoimmune hemolytic anemias
  • drug-induced hemolytic anemia
104
Q
  • What are the different types of autoimmune hemolytic anemias?
  • What are they based on?
A
  • warm reactive antibody type, cold agglutinin type, cold hemolysin type (paroxysmal cold hemoglobinuria)
  • based on optimal temperature at which the antibody binds to the erythrocytes
105
Q

What is a form of immune hemolytic anemia that is usually the result of an allergic reaction against foreign antigens, called the hapten model?

A

drug-induced hemolytic anemia

106
Q

Describe what the hapten model is?

A

hypothesis that a small particle jumps on penicillin and triggers a hemolytic anemia episode

107
Q

What drugs can cause drug-induced hemolytic anemia?

A
  • penicillin
  • cephalosporins (more than 90%)
  • hydrocortisone
108
Q
  • What is an anemia secondary to premature destruction of RBCs caused by the binding of autoantibodies and/or complement to RBCs?
  • This is most common in which individuals?
  • Half of the patients are due to (…)
A
  • autoimmune hemolytic anemia (AIHA)
  • women < 50 years
  • idiopathic disease
109
Q
  • AIHA can be caused by a number of different autoantibodies, with (…) and (…) antibodies being the main causes (depending on which is involved, pathology will differ)
  • Classification of the antibodies is based on their activity at (…) and their (…)
A
  • IgG(acute) and IgM(chronic)
  • different temperatures and etiology
110
Q
  • In warm antibody mediated hemolytic anemia, autoantibodies are mainly of (…) and have high activity at physiological temperature of (…)
  • Warm antibody mediated hemolytic anemia makes up (…) of all hemolytic anemias
A
  • IgG; 37 degrees C
  • 70-80% (most common)
111
Q
  • AIHA involving IgG is generally characterized by (…), as IgG is poor at activating (…), but effectively binds (…) cells
  • IgG AIHA generally takes place in the (…)
  • Often idiopathic diseases are associated with AI diseases. What else (conditions associated with warm antibody mediated hemolytic anemia) ?
A
  • phagocytosis; complement; phagocytic cells
  • spleen
  • leukemia, lymphome, thymoma, myeloma, viral infections, and collagen-vascular disease
112
Q
  • In cold antibody mediated hemolytic anemia, (…) and (…) are the most common antibodies involved
  • Cold autoantibodies act best at temperatures of (…), so there is higher disease activity when the body falls into a hypothermic state
  • Usually, the antibody becomes active when it reaches the (…), at which point, it (…) RBCs, that is it makes bacteria or other cells more susceptible to the action of phagocytes
  • When RBCs return to (…) regions, they are damaged by complement
A
  • IgM and complement
  • 0 degrees C
  • limbs; opsonizes
  • central
113
Q
  • IgM is a potent activator of the (…) pathway, thus, AIHI involving IgM is characterized by (…) mediated lysis of RBCs
  • IgM also leads to (…) of RBCs, because phagocytic cells have receptors for the bound complement
A
  • complement; complement
  • phagocytosis
114
Q
  • IgM AIHA (cold mediated) takes place in (…)
  • It is often idiopathis; often follows (…) and (…) infections
  • It is also associated with what else?
A
  • Kupffer cells (phagocytic cells of the liver)
  • viral infections (mononucleosis) and mycoplasma pneumoniae infections
  • lymphoma or cold agglutinin disease
115
Q
  • Patients may present with one or both types of autoantibodies; if both are present, the disease is termed what?
  • What can induce both warm and cold AIHA?
  • Phagocytic AIHA is termed (…) while complement mediated lysis of RBCs is termed (…) AIHA
  • In order for intravascular AIHA to be recognizable, it requires overwhelming (…) activation, therefore most AIHA is (…) be it (…) or (…) mediated
  • AIHA cannot be attributed to any single autoantibody. To determine the autoantibody or autoantibodies present in a patient, the (…) is performed
A
  • “mixed-type” AIHA
  • HIV
  • extravascular; intravascular
  • complement; extravascular; IgG or IgM
  • Coombs test
116
Q
  • What is also known as the anti-globulin test or AGT?
  • What are the two different tests?
A
  • Coombs test
  • direct coombs test (DCT) and indirect coombs test
117
Q

What test is this describing:
- also known as direct anti-globulin test or DAT
- more common and checks for antibodies that are attached to the surface of RBCs

A

direct coombs test

118
Q

What is this describing:
- also known as indirect anti-globulin test or IAT
- checks for unattached antibodies that are circulating in the bloodstream
- also administered to determine if there was a potential bad reaction to a blood transfusion

A

indirect coombs test

119
Q

What does clumping (agglutination) of the direct coombs test indicate?

A

a condition that causes the destruction of RBCs by the immune system

120
Q

What can a positive direct coombs test be caused by?

A
  • autoimmune hemolytic anemia (AIHA)
  • drug toxicity
  • transfusion reaction
  • erythroblastosis fetalis (Rh incompatibility in pregnancy)
  • chronic lymphocytic leukemia (CLL); other leukemias
  • SLE
  • mononucleosis
  • mycoplasma (resistant to many antibiotics)
  • syphilis
121
Q

What drugs causing drug toxicity may induce a positive direct coombs test?

A
  • cephalosporins
  • dapsone
  • nitrofurantoin
  • NSAIDs
  • levodopa
  • quinidine
122
Q

What test does this describe:
antibodies circulating in your bloodstream that could cause your immune system to react to any red blood cells that are considered forrign to the body

A

indirect coombs test

123
Q

When may trigger a positive indirect coombs test?

A
  • particularly during a blood transfusion
  • erythroblastosis fetalis
  • incompatible blood match for a blood transfusion
  • hemolytic anemia due to an autoimmune reaction
  • drug toxicity
124
Q

What is a pregnant woman often given to check for antibodies during prenatal care, before labor?

A

indirect coombs test

125
Q

What is the clinical presentation of autoimmune hemolytic anemia?

A
  • dyspnea, fatigue
  • pallor, jaundice
  • tachycardia with flow murmur, if anemia pronounced
  • dark urine, back pain
  • splenomegaly
126
Q
  • What are the most common presentations of autoimmune hemolytic anemia?
  • Patients with intravascular hemolysis may present with (…) and (…)
  • Presence of (…) and/or (…) suggests an underlying lymphoproliferative disorder or malignancy
  • (…) may indicate hypersplenism as a cause
A
  • dyspnea and fatigue
  • dark urine and back pain
  • hepatomegaly, lemphadenopathy
  • splenomegaly
127
Q

If a young female presents with dark urine, back pain, has high bilirubin and is jaundice, what is the probable cause?

A

autoimmune hemolytic anemia

128
Q

Where does jaundice occur first in the body? Where else can it occur?

A
  • mucous membranes in the mouth first; other places include the skin, eyes, and nails
129
Q

What does the workout for autoimmune hemolytic anemia consist of?

A

primarily laboratory evaluation to confirm hemolysis and exclude other causes of anemia; most cases are idiopathic

130
Q

What are the basic features of autoimmune hemolytic anemia (retic, haptoglobin, indirect bilirubin, LDH)?

A
  • reticulocytosis
  • low haptoglobin levels
  • elevated indirect bilirubin
  • elevated LDH
131
Q

What are the initial tests for evaluating if someone has autoimmune hemolytic anemia?

A
  • CBC
  • reticulocyte count
  • LFTs
  • peripheral smear
132
Q
  • What test can you order to detect IgG or complement C3d bound to RBCs?
  • If this test is positive, what does it indicate and what is confirmed?
  • If this test is positive with IgG alone or IgG+C3d, it is most lifely due to (…)
  • If the test is positive with C3d alone, it is most likely due to (…)
  • A positive (…) implies presence of anti-RBC antibodies free circulating
A
  • direct antiglobulin tests (DAT, Coombs)
  • indicates presence of antibodies or complement on RBC surfaces; AIHA is confirmed
  • warm antibody autoimmune hemolytic anemia
  • cold antibody autoimmune hemolytic anemia
  • indirect coombs test
133
Q

What is the workup for warm autoimmune hemolytic anemia?

A
  • positive anticardiolipin and lupus anticoagulant, SPEP and IPEP
  • hepatitis serology, antinuclear antibody
  • urinary tests for hemosiderinuria or hemoglobinuria
  • imaging (to make sure not missing malignancy)
  • chest x-ray
  • CT scan of chest, abdomen and pelvis to rule out lymphoma
  • bone marrow biopsy (rare)
134
Q

Those with warm autoimmune hemolytic anemia have a high risk for developing (…)

A

blood clots

135
Q

What is the treatment overview for autoimmune hemolytic anemia (acquired, first line, second line)?

A
  • acquired: removal of the cause or treatment of the underlying disorder
  • first-line: corticosteroids (high dose)
  • second-line: splenectomy and rituximab (monocloal antibody)
136
Q

In AIHA, (…) is a humanized monoclonal antibody against C5 that is essential for the formation of MAC, can reduce the signs of intravascular hemolysis, the requirement for transfusions, and the tendency to thrombosis

A

eculizumab

137
Q

In the treatment of AIHA, (…) can also be used in patients with a history of a thrombosis. (…) can correct the iron deficiency; treatment with (…) does not exacerbate the hemolysis. (…) are helpful in supportive care

A
  • warfarin
  • oral iron
  • iron
  • transfusions
138
Q
  • Who should you refer patients with AIHA to?
  • What type of referral should you give patients as a second line treatment for WAIHA and in refractory cases
A
  • hematology
  • surgical referral for splenectomy
139
Q

What are some non-pharmacologic treatment methods for patients with AIHA?

A
  • discontinuation of any potentially offensive drugs
  • plasmapheresis exchange transfusion for severe life-threatening cases only
  • avoid cold exposure in patients with cold antibody AIHA
140
Q

What is the treatment of choice for TTP?

A

plasmapheresis exchange transfusion

141
Q

What is the treatment for warm AIHA?

A
  • corticosteriods (usually prednisone 1-2 mg/kg/day in divides doses initially)
  • rituximad (monoclonal antibody)
  • danazol (in conjunction with steroids)
  • splenectomy when inadequate response to steroids (indication of RBC sequestration)
  • immunosuppressive drugs/immunoglobulins, only after above fail to produce remission (azathioprine, cyclophosphamide)
142
Q

When a patient with warm AIHA is having an indequate response to steroids when there is indication of RBC sequestration, what should be done?

A

splenectomy

143
Q

If all other treatments have failed with a pt who has warm AIHA, what should be given?

A

immunosuppressive drugs or immunoglobulins

144
Q

What is the disposition of a patient with warm AIHA when given the proper treatment?

A

prognosis generally good unless anemia is associated with an underlying disorder with poor prognosis (leukemia, myeloma)

145
Q
  • A patient presents with warm AIHA, when is the first line of treatment provided?
  • If they respond to this, what should you do?
  • If this initial treatment results in a failure, what should be given?
  • If this second treatment fails, what is next?
  • If this third treatment fails, what is given to the patient?
A
  • prednisone (corticosteroid)
  • reduce prednisone from week 3-4
  • rituximab
  • splenectomy
  • immunosuppressive drug
146
Q

What drugs/therapies should you reserve for non steroid responders of warm AIHA?

A

rituximab and splenectomy

147
Q

What are the two different types of cold AIHA?

A
  1. transient cold agglutination
  2. chronic cold agglutination
148
Q

What is the treatment for transient cold agglutination AIHA?

A
  1. transfusion of packed RBCs
  2. antibiotics in case of definite bacterial infection (mycoplasma pneumoniae)
  3. consider short course of corticosteroids in case of severe HA
149
Q

What is the treatment for chronic cold agglutination AIHA?

A
  1. avoidance of cold and prompt treatment of febrile infections, vaccinations
  2. transfusion of prewarmed packed RBCs in if needed
  3. rituximab if relapsing or symptomatic of HA
150
Q

What is this describing:
- an abnormality of the RBC membrane, which makes the RBC unusually sensitive to lysis by complement

A

paroxysmal nocturnal hemoglobinuria

151
Q
  • Paroxysmal nocturnal hemoglobinuria is a deficiency in (…) and (…)
  • What can this cause?
A
  • CD55 and CD59
  • complement-mediated intravascular lysis and release of hemoglobin
152
Q

What symptoms are associated with paroxysmal nocturnal hemoglobinuria?

A
  • anemia
  • hemoglobinuria (dark urine at night)
  • severe fatigue
  • abdominal pain
  • thrombosis
153
Q
  • Classically, some pts with paroxysmal nocturnal hemoglobinuria (PNH) arise in the morning and pass (…)
  • The typical paroxysms of hemoglobinuria occur on a background of chronic, low-grade (…) that causes constance hemosiderinuria in PNH
  • About one third of cases evolve into (…)
A
  • dark urine
  • intravascular hemolysis
  • aplastic anemia
154
Q
  • What are 3 additional clinical features of PNH?
  • The basis of these symptoms is probably scavenging by free plasma hemoglobin of endogenous (…), a regulator of vasomotor and smooth muscle tone
  • In about one third of cases, (…) occurs in unusual sites and can cause intra-abdominal splanchnic vein thrombosis involving the hepatic veins or portal veins, or less frequently cerebral vein thrombosis
A
  • abdominal pain, dysphagia, erectile dysfunction
  • nitric oxide
  • venous thrombosis
155
Q

In PNH, (…) is the result of chronic intravascular hemolysis; subtle or overt signs of (…) are frequent

A
  • hemosiderinuria
  • bone marrow damage (leukopenia or thrombocytopenia)
156
Q
  • The treatment of classical PNH has been only supportive and based on (…) and (…)
  • What is now the treatment of choice for paroxysmal nocturnal hemoglobinuria
  • Before being treated with this drug, every patient should be vaccinated against (…) and in many countries, a long-term prophylaxis with (…) is also strongly recommended
A
  • regular transfusions and anticoagulation therapy in case of thrombosis
  • eculizumab (soliris)
  • meningococcus A, B, and C; oral penicillin
157
Q

Drug induced HA is uncommon but occurs through what 3 major mechanisms?

A
  1. antibody directed against Rh complex
  2. antibody directed against RBC-drug induced complex
  3. antibody directed against complex formed by drug and plasma proteins (causes destruction of RBCs)
158
Q
  • HA detected on laboratory testing, what should be done next?
  • What are the possible results to this test?
  • What should you consider if its negative?
  • If its positive C3, what should you do?
  • If this test is positive, what should you consider?
  • If its positive IgG and/or C3, what should you do next?
  • If this is positive, what should you consider?
  • If this is negative, what shoulld you consider?
A
  • Direct antiglobulin test (DAT) = Coombs test
  • positive IgG and/or C3, positive C3, negative
  • non-immune mediated etiology
  • obtain cold agglutinin titer
  • thermal amplitude testing and cold agglutination disease
  • elution to determine is autoantibody is present
  • warm AIHA
  • drug induced HA
159
Q

What is the treatment/management for drug induced HA?

A
  1. stop offending agen
  2. usually self-limited after stopping
  3. consider corticosteroids if anemia and symptoms and signs persist

clinical medicine 2 (9 decks)

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