Bhl Week 1: Hemolytic Anemias Ii

Front 1

Cold-reacting immune hemolysis usually involves which antibody?

Is complement involved?

Back 1

IgM
(fixes to RBC at cooler temperatures, fixes complement, and then may dissociate from the surface of the RBC).

*Complement is involved

Front 2

What type of hemolysis occurs in cold-reacting immune hemolysis-- intravascular or extravascular?

Back 2

Either intravascular or extravascular hemolysis can occur.
It depends on the amount of complement bound-->
large amount of complement = intravascular hemolysis
moderate amount of complement = extravascular hemolysis

Front 3

Warm-reacting immune hemolysis usually involves which antibody?

Is complement involved?

Back 3

IgG

*Complement may or may not be involved

Front 4

Are most cases of immune hemolytic anemias cold-reacting or warm-reacting?

Back 4

Warm-reacting (>70%)

Front 5

List 2 diseases that are cold-reacting immune hemolytic anemias.

Back 5

1. Cold agglutin disease
2. Paroxysmal cold hemoglobinuria (PCH)

Front 6

Cold-reacting immune hemolysis is often related to what type of infections?

Back 6

1. Mycoplasma pneumoniae pneumonia
2. Acute EBV infection

Front 7

Describe how hemolysis can be intravascular or extravascular in cold-reacting immune hemolysis.

Back 7

Intravascular --> complement-mediated through membrane attack complex

Extravascular --> recognition of complement on RBCs by macrophages

Front 8

What is acrocyanosis?

Back 8

Fingers, tips of ears, toes turn blue in cold temperatures.
(RBCs tend to agglutinate in cool temperatures and the aggregates tend to plug up capillaries)

Front 9

What is the primary problem associated with Cold agglutinin disease?

Back 9

Aggregates of RBCs tend to plug up small blood vessels in the periphery (fingers, toes, etc) where it is cooler, causing the fingers and toes to turn blue = ACROCYANOSIS

Front 10

How might idiopathic cold agglutinin syndrome be treated?

Back 10

May or may not need treatment:
1. Keep extremities warm
2. If further treatment is necessary, immunosuppressive agents like cyclophosphamide are sometimes used

Front 11

What is the Donath-Lansteiner antibody and which disease is it associated with?

Back 11

IgG antibody associated with Paroxysmal Cold Hemoglobinuria (PCH)

Front 12

Paroxysmal Cold Hemoglobinuria most commonly occurs in what type of individuals?

Back 12

Children
(after infection or vaccination)

Front 13

Is hemolysis usually intravascular or extravascular in warm-reactive immune hemolytic anemia?

Back 13

Extravascular

Front 14

Is hemolysis intravascular or extravascular in Paroxysmal Cold Hemoglobinuria?

Back 14

Intravascular

Front 15

List the 3 general variants of warm-reactive immune hemolytic anemia.

Back 15

1. Primary (idiopathic)
2. Secondary
3. Drug-related

Front 16

What type of abnormal cell is a characteristic finding on the blood smear in extravascular hemolysis?

Back 16

Spherocytes

Front 17

List 3 characteristic findings in a blood smear of warm-reacting immune hemolysis.

Back 17

1. Spherocytes
2. Polychromasia
3. Nucleated RBCs (in severe cases)

Front 18

What are the antibodies usually directed against in warm autoimmune hemolytic anemias?

Back 18

Usually directed against the Rh system
(All RBCs which have any Rh system antigens--just about everyone--will be reactive)

Front 19

If a person with warm autoimmune hemolytic anemia needs a blood transfusion, will the "most compatible" or "least compatible" blood be given?

Back 19

Least compatible
(Transfused RBCs are usually not destroyed any faster than the patient's own RBCs, so it doesn't make the hemolysis any worse)

Front 20

List 3 possible causes of secondary warm-reactive autoimmune hemolytic anemia.

Back 20

1. Infections
2. Autimmune disorders: SLE, RA
3. Lymphoproliferative disorders

Front 21

Idiopathic warm autoimmune HA usually occurs in which individuals?

Does it tend to be acute or chronic?

Back 21

Women

*Tends to be chronic

Front 22

What are the 3 mechanism involved in drug-related immune hemolytic anemia?

Back 22

1. Drug adsorption (penicillin) type
2. Neoantigen (formerly immune complex) type
3. Autoimmune (Aldomet) type

Front 23

Is drug adsorption (Penicillin) type hemolytic anemia usually intravascular or extravascular?

Back 23

Extravascular

Front 24

Is hemolysis usually intravascular or extravascular in neoantigen type hemolytic anemia?

Back 24

Intravascular-- often sudden and severe

Front 25

Which group of drugs are most often associated with drug-related immune hemolytic anemia?

Back 25

Cephalosporins (3rd generation)

Front 26

Which of the drug-related immune hemolytic anemias actually involves a true autoimmune reaction? (antibody directed against RBC antigen, not drug)

Which drugs are involved?

Back 26

Autoantibody (Aldomet) Type

1. Aldomet (a-methyldopa)
2. Levodopa
3. Procainamide

Front 27

Which drug-related immune hemolytic anemia involves antibodies directed against drugs bound to the surface of RBCs?

Back 27

Drug Adsorption (Penicillin) type

Front 28

Which drug-related immune hemolytic anemia involves antibodies to drugs on RBC surfaces that then fix complement (proceeding to MAC)?

Back 28

Neoantigen type

Front 29

Which microorganisms directly infect erythrocytes, leading to hemolysis?

Back 29

1. Malaria species
2. Babesia microti (tick bites)

Front 30

What enzyme does Clostridium perfringes produce to destroy RBC membranes?

Back 30

Lysolecithinase

Front 31

Besides direct infection of RBCs, what other types of infection can lead to hemolysis?

Back 31

1. Mechanical intravascular fragmentation due to DIC
2. Increased macrophage activity due to circulating immune complexes

Front 32

Mechanical intravascular fragmentation of RBCs results in production of _________ on the blood smear.

Back 32

Schistocytes

Front 33

List 3 possible causes of mechanical intravascular hemolysis.

Back 33

1. Malfunctioning mechanical heart valve
2. "March hemoglobinuria"
3. Microangiopathic hemolysis

Front 34

Which condition is associated with abnormal von Willebrand factor multimers in the blood that can spontaneously cause platelets to aggregate?

Back 34

Thrombotic thrombocytopenic purpura (TTP)

*Associated with thrombocytopenia

Front 35

Which type of microangiopathic hemolysis is associated with Shiga toxin?

Back 35

Hemolytic uremic syndrome
E. coli strain O157:H7

Front 36

What does HELLP syndrome stand for?

Back 36

Hemolysis, Elevated Liver enzymes, Low Platelets

*Associated with pregnancy

Front 37

What's the difference between preeclampsia and eclampsia?

Back 37

Preeclampsia --> edema, proteinura, and hypertension

Eclampsia --> further complicated by neurologic abnormalities (seizures)

Front 38

Give 2 examples of very potent oxidant drugs that cause cause oxidant hemolysis.

Back 38

1. Dapsone
2. Sulfasalazine

Front 39

Which disease is an acquired defect that is intrinsic to the RBC?
(exception to the rule)

Back 39

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Front 40

What is the key feature related to hemolysis in PNH?

Back 40

Loss of normal defense mechanisms against complement-mediated hemolysis.

Front 41

What is the MAIN problem in Paroxysmal Nocturnal Hemoglobinuria?

Back 41

Thrombosis

Front 42

What types of cells are affected in Paroxysmal Nocturnal Hemoglobinuira?

Back 42

All types of blood cells, not just red cells
(hematopoietic stem cells or very early precursors)

Front 43

What is a big difference between PNH and PCH?

Back 43

PCH is antibody-mediated
PNH is caused by loss of RBC complement-protective mechanisms

Front 44

What gene is mutated in PNH?

Back 44

PIG-A gene
(acquired, somatic mutation on X- chromosome)

Front 45

List 3 manifestations of PNH.

Back 45

1. Chronic intravascular hemolysis
2. Thrombophilia
3. Bone marrow failure

Front 46

What disease is a relatively common cause of Budd-Chiari syndrome (hepatic vein thrombosis)?

Back 46

PNH

Front 47

What protein is deficient in PNH?

Back 47

Glycosylphosphatidylinositol (GPI) anchor proteins
(Anchors multiple proteins to cell surface)

Front 48

Which protective complement compounds are lost in PNH?

Back 48

CD55 and CD59

Front 49

What is the cause of symptoms such as difficulty swallowing or priapism in males sometimes seen in PNH?

Back 49

Free Hemoglobin liberated from the lysed RBCs scavenges nitric oxide, which acts to dilate smooth muscles

Front 50

What is a common cause of death in patients with PNH?

Back 50

Thromboembolic disease

Front 51

List 5 symptoms sometimes seen in PNH.

Back 51

1. Fatigue
2. Difficulty swallowing or pain on swallowing
3. Priapism in males
4. Thromboembolic disease
5. Gross hematuria in first morning urine (rare)

Front 52

How is the diagnosis of PNH made?

Back 52

Flow cytometry on peripheral blood, looking for presence or absence of CD55, CD59, and other GPI-anchored proteins on cell surfaces

*Look at both RBCs and WBCs

Front 53

List 4 complications of PNH.

Back 53

1. Thromboembolic disease
2. Infections
3. Transformation to aplastic anemia
4. Transformation to acute myeloid leukemia (rare)

Front 54

List 4 medications that can be used for patients with PNH.

Back 54

1. Glucocorticoids (decrease hemolysis)
2. Danazole (androgenic steroid)
3. Anticoagulation
4. Eculizumab (Soliris)-- antibody against C5 complement component

Front 55

Eculizumab may increase risk of what type of infections?

Back 55

Neisseria infections
(pts should be vaccinated prior to use)

Front 56

Which medication can be used for PNH and is an antibody against the C5 component of the complement system?

Back 56

Eculizumab (Soliris)