Cytopenias & BM failure syndromes

Question 1

a) Classification of pancytopenia based on PB findings
b) What is expected in a BM trephine biopsy

Answer 1

a) Decrease in all cell lines: Erythroid <120(F)-130(M)g/L, myeloid <1.8x10^9/L, megakaryocytic <15x10^9/L
b) trilineage hypoplasia

Question 2

convert g/dL to g/L for Hb

Answer 2

x10

Question 3

Cytopenias classification in PB findings

Answer 3

• Erythroid <120(F)-130(M)g/L
• myeloid <1.8x10^9/L
• megakaryocytic <15x10^9/L

Question 4

Characteristic of Schwachman-Diamond syndrome (SDS) in PB & BM

Answer 4

PB: neutropenia*> anaemia > Trhombocytopenia
BM: Myelodysplasia; L shift granulopoeisis

Question 5

Characteristic of Fanconi anaemia in PB & BM

Answer 5

PB: Cytopenia; RBC aniso & poikilocytosis
BM: Trilineage hypoplasia; Dysreythopoisis; Recative mastocytosis

Question 6

Characteristic of Diamond-Blackfan anaemia (DBA) in PB & BM

Answer 6

PB: Anaemia* & sometimes macrocytic RBC; normal-neutropenia; Thrombocytopenia-cytosis
BM: Erythroid hypoplasia => trilineage hypoplasia (#); Trilineage dysplasia (looks); megakaryocytic hyperplasia; Fibrosis

Question 7

Characteristic of Severe congenital neutropenia (SCN) in PB & BM

Answer 7

PB: Severe neutropenia <0.5 x10^9/L
BM: Dec myeloid precursors, dec M:E, Myeloid maturation arrest

Question 8

Characteristic of Congenital amegakaryocytic thrombocytopenia (CAMPT) in PB & BM

Answer 8

PB: severe Thrombocytopenia
BM: normal cellularity but reduced/absent megakaryocytes

Question 9

Diamond-Blackfan anaemia (DBA):
a) manifestation (shown/display) &
b) translation cause of mutation in RPS19

Answer 9

a) during infancy
b) mutation => prevent assembly of ribosomal proteins => ribosomopathy

Question 10

Schwachman-Diamond syndrome (SDS):
a) manifestation (shown/display)

Answer 10

a) Shortly after birth
- recurrent infections
- pancreatic exocrine insufficiency
- skeletal abnormalities

Question 11

Severe congenital neutropenia (SCN)
a) manifestation (shown/display) &

Answer 11

a) neonatal period in infancy –>Severe congenital neutropenia

Question 12

Congenital amegakaryocytic thrombocytopenia (CAMPT)
a) mutation in what gene & effects
b) cond. is confirmed w/

Answer 12

a) mutation in MPL => abnormal expression/function of thrombopoetin (TPO) receptor (always on) => plasma TPO levels Hi
b) molecular genetics

Question 13

What is neoplasia w/ Inherited BM function syndrome (IBMFS) & give e.g

Answer 13

• IBMFS => development of neoplasia
• Haematological neoplasm & other neoplasia
  e.g. Fanconi Anaemia and Head & neck squam. cell carcinoma (HNSCC)

Question 14

What is aplastic anaemia

Answer 14

pancytopenia (*dx) w/ hypocellular BM w/out abnormal infiltrate or BM fibrosis
• majority of cases are iodiopathic/acquired: due to immune-mediated destruction of hematopoietic stem &/or progenitor cells

Question 15

what is Clonal Haematopoesis of intermediate potential (CHIP)

Answer 15

• prescence of neoplasm-assoc. somatic mutation in blood/BM in person with no known haem. neoplasm (i.e. CHIP predisposes neoplasia)
• mutation => loss-of-function of TET2 (>enz methylate DNA)

Question 16

thrombocytopenia w/ absent radii syndrome (TAR)
a) pathophysiology
b) cond. is confirmed w/ (dx)

Answer 16

a) MK have abnormal resp. to TPO
b) @ birth: severe thrombocytopenia & abnormality in arms
BM: small MK

Question 17

Radioulnar synostosis (fusion of bones) with amegakaryocytic thrombocytopenia
a) pathophysiology

Answer 17

a) similar to Congenital amegakaryocytic thrombocytopenia (CAMPT)
• BM: rare MK
• mutated HOXA11

Question 18

X-linked thrombocytopenia with dyserythropoiesis
a) mutation in what gene & effects
b) cond. is confirmed w/

Answer 18

a) mutations in GATA1 => thrombocytopenia & anaemia
• BM: hypercellular w/ dysplasia in eryth. & myeloid
b) molecular testing: GATA1 mutation