Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

WILLIAM'S HEMATOLOGY > 41 Paroxysmal Nocturnal Hemoglobinuria > Flashcards

41 Paroxysmal Nocturnal Hemoglobinuria Flashcards

1
Q

PNH arises from clonal expansion of one or several hematopoietic HS/PCs that have acquired a somatic mutation of the _______________ gene

A

X-chromosome gene PIGA (phosphatidylinositol gly class A)

Located on Xp22.1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

TRUE OR FALSE

Paroxysmal nocturnal hemoglobinuria (PNH) is a disorder of hematopoietic stem/progenitor cells (HS/PCs)

A

TRUE

Paroxysmal nocturnal hemoglobinuria (PNH) is a disorder of hematopoietic stem/progenitor cells (HS/PCs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

The clinical manifestations of PNH are

A

Hemolytic anemia, thrombophilia, and marrow failure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Only manifestation that is unequivocally a consequence of somatic mutation of PIGA

A

Hemolytic anemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

TRUE OR FALSE

PNH is a clonal disease and is a malignant neoplasm

A

FALSE

PNH is a clonal disease, but not a malignant neoplasm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

The major cause of morbidity and mortality in PNH

A

Thrombosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

The peak incidence of PNH

A

Third and fourth decades of life

like with AA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

The hallmark clinical manifestation of PNH

A

Chronic intravascular hemolysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

The chronic intravascular hemolysis that is the hallmark clinical manifestation of PNH is mediated by the

A

Alternative pathway of complement (APC)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Normal human erythrocytes are protected against APC-mediated cytolysis, primarily by

A

Decay-accelerating factor (CD55) : regulates the formation and stability of the C3 and C5 convertases

Membrane inhibitor of reactive lysis (CD59): blocks the formation of the MAC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

The pathophysiologic basis of the direct antiglobulin test–negative, intravascular hemolysis in PNH

A

Deficiency of CD55 and CD59 on the erythrocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Another remarkable feature of PNH is phenotypic mosaicism (based on PIGA genotype) that determines the degree of GPI-AP deficiency.

PNH III :
PNH II:
PNH I:

A

PNH III: completely deficient in GPI-APs
PNH II: partially (~90%) deficient
PNH I: GPI-APs at normal density

PNH II cells are relatively resistant to spontaneous hemolysis, and patients with a high percentage of type II cells have a relatively benign clinical course with respect to hemolysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

The most common phenotype of PNH

A
  • Type I and type III cells (most common; high grade hemolysis)
  • Type I, type II, and type III (the second most common phenotype; minimal hemolysis)
  • Type I and type II cells (the least common phenotype; minimal hemolysis)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Nocturnal hemoglobinuria being a presenting symptom in PNH occurs in approximately_____of patients

A

25%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

TRUE OR FALSE

Venous thrombosis is as common as arterial thrombosis

A

FALSE

Venous thrombosis, often occurring at unusual sites (Budd-Chiari syndrome, mesenteric, portal vein, dermal or cerebral veins), may complicate PNH.

Arterial thrombosis is less common.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Recommendation for Screening Patients for Paroxysmal Nocturnal Hemoglobinuria

A
  • History of episodic hemoglobinuria
  • Evidence of nonspherocytic, Coombs’-negative (direct antiglobulin test) intravascular hemolysis (must have high serum LDH)
  • Patients with aplastic anemia (screen at diagnosis and once yearly even in the absence of intravascular hemolysis)
  • Patients with refractory anemia (RA) or refractory cytopenias with multilineage dysplasia (RCMD) variants of myelodysplastic syndrome (MDS)
  • Patients with venous thrombosis involving unusual sites (usually have evidence of intravascular hemolysis):
    Budd-Chiari syndrome
    Other intraabdominal sites
    Cerebral veins
    Dermal veins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

The clinical manifestations of PNH depend largely on

A

Size of the PIGA mutant clone

The extent of the associated marrow failure also contributes to disease manifestations.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

The most commonly associated marrow failure syndromes with PNH

A

Aplastic anemia and refractory anemia/MDS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

TRUE OR FALSE

Analysis of PMNs is more informative than analysis of RBCs because of selective destruction of GPI-AP–deficient red blood cells.

A

TRUE

Analysis of PMNs is more informative than analysis of RBCs because of selective destruction of GPI-AP–deficient red blood cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

GPI-AP–deficient cells is smaller than 1% of the total

A

Subclinical PNH

Patients with PNH-sc have neither clinical nor biochemical evidence of hemolysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Classification of PNH that may benefit from Eculizumab

A
  • Classic PNH
  • PNH in the setting of another marrow failure syndrome (Dependent on the size of the PNH clone)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Serves as an important surrogate marker for estimating and following the rate of intravascular hemolysis

Concentration is always abnormally high in patients with clinically significant hemolysis

A

Serum lactate dehydrogenase (LDH)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

By using high-sensitivity flow cytometry, approximately____% of patients with aplastic anemia and ____% of patients with low-risk MDS have been found to have a detectable population of GPI-AP–deficient erythrocytes and granulocytes.

A

50% AA

15% MDS

24
Q

The pore-forming bacterial protein, ________, secreted from Aeromonas hydrophila, binds to the GPI moiety of GPI-APs and, upon oligomerization, forms transmembrane channels that induce osmotic cytolysis.

A

Aerolysin

25
Q

A genetically modified form of aerolysin has been developed that does not induce cytolysis

Can be used in flow cytometric assays to detect GPI-AP–deficient cells.

A

FLAER

26
Q

Tests that have largely been abandoned as diagnostic assays because they are both less sensitive and less quantitative than flow cytometry.

A

Acidified serum lysis test (Ham test) and the sucrose lysis test (sugar water test)

27
Q

TRUE OR FALSE

Patients with classic PNH are often iron deficient from chronic iron loss in the form of hemoglobinuria and hemosiderinuria

A

TRUE

Patients with classic PNH are often iron deficient from chronic iron loss in the form of hemoglobinuria and hemosiderinuria

28
Q

TRUE OR FALSE

Nonrandom cytogenetic abnormalities are common in PNH.

A

FALSE

Nonrandom cytogenetic abnormalities are rare in PNH.

29
Q

Used to distinguish classic PNH from PNH in the setting of another marrow abnormality.

A

Marrow aspirate and biopsy

30
Q

PNH clone size is determined by the percentage of

A

GPI-AP–deficient neutrophils

NOT RBCs

31
Q

The threshold that separates subclinical PNH from clinical PNH is reached when the neutrophil clone size is in the range of ____ with a corresponding GPI-AP–deficient erythrocyte population of ________

A

25% neutrophil

3% to 5% RBC

32
Q

Among patients who present with clinical PNH in the setting of marrow failure, treatment for complications of PNH (eculizumab for hemolysis or anticoagulation for thrombosis) is required in approximately _____ % of cases.

A

50%

There is no evidence that treatment with immunosuppressive therapy influences clonal expansion either positively or negatively.

33
Q

Patients with RA with a population of PNH cells (RA-PNH+) had a distinct clinical profile characterized by the following features:

A
  • (1) less pronounced morphologic abnormalities of blood cells,
  • (2) more severe thrombocytopenia,
  • (3) lower rates of karyotypic abnormalities,
  • (4) higher incidence of human leukocyte antigen (HLA)-DR15,
  • (5) lower rate of progression to acute leukemia, and
  • (6) higher probability of response to cyclosporine therapy
34
Q

TRUE OR FALSE

A relatively good response to immunosuppressive therapy for patients with PNH with MDS and aplastic anemia

A

TRUE

A relatively good response to immunosuppressive therapy for patients with PNH with MDS and aplastic anemia

35
Q

A humanized monoclonal antibody that binds to complement C5, preventing its activation to C5b and thereby inhibiting MAC formation

A

Eculizumab

36
Q

Mild to moderate anemia and reticulocytosis usually persist after treatment with Eculizumab because of:

A

Ongoing extravascular hemolysis mediated by opsonization of PNH erythrocytes by activated complement C3, because eculizumab does not block the activity of the APC C3 convertase

37
Q

Dose of Eculizumab

A

Intravenous infusion on a biweekly schedule after an initial loading period of five weekly treatments

38
Q

Giving Eculizumab makes patient at risk for which infections

A

Neisseria species (patients with congenital deficiency of complement C5)

Meningococcal species

All patients must be inoculated with a meningococcal vaccine two weeks before starting therapy, but the vaccine is not 100% effective.

39
Q

Breakthrough hemolysis with Eculizumab use can be diagnosed by monitoring the

Patients treated with eculizumab may become symptomatic (fatigue, lethargy, worsening anemia, hemoglobinuria) near the end of the 14-day treatment cycles.

A

CH50 or the concentration of free eculizumab

Detectable levels of CH50 (≥10% of normal) and concentrations of eculizumab lower than 50 mcg/mL suggest suboptimal dosing of eculizumab.

This issue can be addressed by increasing the dose of eculizumab from 900 mg every 2 weeks to 1200 mg every 2 weeks or by shorting the dosing interval from 14 days to 12 days.

40
Q

A humanized, monoclonal antibody that binds to complement C5

Engineered to take advantage of immunoglobulin recycling by the neonatal Fc receptor hence an extended the half-life allowing for dosing every 8 weeks

A

Ravulizumab

Noninferior to eculizumab

Cheaper

41
Q

The main value of glucocorticoids in treatment of PNH

A

Attenuating acute hemolytic exacerbations

Other than eculizumab/ravulizumab, there is no specific treatment for PNH, and for patients who are not being treated with eculizumab/ ravulizumab, treatment is largely supportive.

42
Q

Used successfully to treat the anemia of PNH

A

Androgen therapy

Danazol 400 mg twice a day

SE: liver toxicity, prostatic hypertrophy, and virilizing effects

43
Q

TRUE OR FALSE

Hemofiltration is recommended to prevent transfusion reaction arising from the interaction between donor leukocytes and recipient antibodies

A

TRUE

Hemofiltration is recommended to prevent transfusion reaction arising from the interaction between donor leukocytes and recipient antibodies

44
Q

TRUE OR FALSE (IRON REPLACEMENT)

Replacement is often associated with exacerbation of hemolysis, regardless of the route of administration.

A

TRUE

Replacement is often associated with exacerbation of hemolysis, regardless of the route of administration.

Compared with parenteral replacement, oral administration of iron may be accompanied by less severe hemolytic exacerbations

45
Q

Recommended dose of folate to compensate for increased utilization associated with heightened erythropoiesis that is a consequence of ongoing hemolysis

A

Folate (1 mg/day)

46
Q

The only curative therapy for PNH

A

HSCT

47
Q

Indications for Transplantation

A
  • Marrow failure
  • Major complications of PNH
  • Refractory, transfusion-dependent hemolytic anemia
  • Recurrent, life-threatening thromboembolic complications
48
Q

Overall survival for unselected PNH patients who undergo transplantation using a HLA-matched sibling donor is in the range of _______.

A

50% to 60%

49
Q

Patients with more than ________% GPI-AP–deficient neutrophils be offered prophylactic anticoagulation.

A

More than 50% to 60%

50
Q

Anticoagulant recommended for patients with PNH who require chronic anticoagulation either for treatment of a thromboembolic event or for prophylaxis.

A

Warfarin

There are no evidence-based data to guide the use of low-molecular-weight heparin or direct oral anticoagulants

51
Q

Arterial or venous

Thromboembolic events in patients with PNH usually involve the ________ system

A

Venous system

52
Q

Acute thrombotic events require anticoagulation with

A

Heparin

53
Q

Patients with PNH who experience a thromboembolic event should be anticoagulated__________ (duration)

A

Indefinitely

54
Q

TRUE OR FALSE

For patients being treated with eculizumab/ravulizumab who have no prior history of thromboembolic complications, prophylactic anticoagulation is necessary.

A

FALSE

For patients being treated with eculizumab/ravulizumab who have no prior history of thromboembolic complications, prophylactic anticoagulation may not be necessary.

Eculizumab reduces the risk of thromboembolic complications.

55
Q

TRUE OR FALSE

Prophylaxis in pregnancy is recommended among patients with PNH

A

TRUE

Prophylaxis in pregnancy is recommended among patients with PNH

Anticoagulation with heparin should begin immediately once pregnancy is confirmed

56
Q

Commonly involved sites of thrombosis during pregnancy and the postpartum period:

A

Cerebral and hepatic veins

Similar to nonpregnant patients with PNH

57
Q

TRUE OR FALSE

Gross hemoglobinuria as a presenting symptom may be more common in young patients with PNH.

A

FALSE

Gross hemoglobinuria as a presenting symptom may be less common in young patients with PNH.

WILLIAM'S HEMATOLOGY (109 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions