Neutrophil disorders

Question 1

Leukocyte adhesion deficiency 1 pathophys

Answer 1

• defective integrin receptor common beta chain of integrin
• results in inability to ingest and kill microbes opsonized by C3bi (so can’t phagocytose microbes)

Question 2

LAD clinical features

Answer 2

• high WBC
• recurrent infections (mainly cutaneous abscesses, gingivitis)
• many die before age 2

Question 3

LAD treatment

Answer 3

• transplant

Question 4

Gene most commonly incomplicated for cyclic neutropenia

Answer 4

ELANE (also for severe congenital neutropenia)

Question 5

Severe congenital neutropenia inheritence

Answer 5

autosomal dominant

Question 6

Kostmann syndrome + mutation

Answer 6

• Autosomal recessive form of SCN
• HAX1

Question 7

Cyclic neutropenia inheritance

Answer 7

autosomal dominant

Question 8

Cyclic neutroepnia clinical features

Answer 8

• usually benign
• pts with severe infections may require G-CSF

Question 9

Cyclic neutropenia sequelae

Answer 9

NOT associated with increased risk of AML

Question 10

Felty syndrome clinical features

Answer 10

• longstanding RA w/ end organ RA manifestations
• splenomegaly
• considerable morbidity from bacterial infection

Question 11

LGL clinical and lab features

Answer 11

Median age 60 + cytopenias (neutropenia +/- anemia (50%) or thrombocytopenia (20%) + splenomegaly (20-50%) + hepatomegaly (20%) + often underlying RA + lymphocyte count normal (25%) but more often mild chronic lymphocytosis + ***gradual decline in counts over time + b symptoms (25%)

Question 12

Shared finding between Felty’s syndrome and LGL-associated neutropenia

Answer 12

HLADR4

Question 13

Drugs associated with agranulocytosis

Answer 13

1) Anti-thyroid medications (carbamizole, methimiazole, thiouracil)
2) Antibiotics (cephalosporins, penicillins, sulfonamides, chloramphenicol)
3) anticonvulsants (carbamazapine, valproic acid)

Question 14

Non-immune chronic neutropenia clinical features

Answer 14

normal marrow + no autoimmune disease + benign clinical course

Question 15

CGD mechanism

Answer 15

Defect in NADPH oxidase leading to failure of respiratory burst

Question 16

CGD inheritance

Answer 16

x-linked

Question 17

CGD clinical features

Answer 17

• recurrent infections
• chronic inflammation leading to restrictive lung disease + gastric outlet obstructive + granulomatous colitis

Question 18

CGD treatment

Answer 18

• transplant
• interferon gamma

Question 19

Chediak-higashi clinical manifestations

Answer 19

• albinism
• recurrent bacterial infections
• neuropathies
• terminal event is HLH

Question 20

Gene mutation in autosomal recessive form of SCN (Kostmann syndrome)

Answer 20

• HAX1

Question 21

CHIC2 FISH significance

Answer 21

detects FIPL1/PDGFRA gene fusion
*fusion driven lymphoid/myeloid that can be treated with imatinib

Question 22

HLH on smear

Answer 22

*see photo

Question 23

Risk of graft failure is highly predicated on what?

Answer 23

of stem cells in graft
(so bone marrow grafts are lower risk of failure)

Question 24

Age as GVHD risk failure

Answer 24

Older age higher risk

Question 25

Preferred stem cell source for aplastic anemia

Answer 25

• bone marrow