Pancytopenia

Question 1

definition of pancytopenia?

-what is seen in bloods clinically?

Answer 1

deficiency of blood cells of ALL lineages (but generally exclude lymphocytes)

Anaemia + Neutropenia +thrombocytopenia

Question 2

What happens in a steady state in terms of haematopoiesis

Answer 2

cell loss balanced by cell production

Question 3

name the two main reasons pancytopenia occurs?

Answer 3

Reduced production

Increased destruction

Question 4

Give the cause of reduced production of haematocytes & the 2 subtypes

Answer 4

Bone marrow failure
inherited syndromes
Acquired (primary/secondary)

Question 5

give the triad found in inherited Marrow failure Syndromes?

Answer 5

Impaired haemopoiesis
Cancer pre-disposition
Congenital anomalies

Question 6

Give the hallmarks of Fanconi’s anaemia (9)

• underlying defect?
• clinical presentation? (bloods, age)

Answer 6

short stature
skin pigment abnormalities
Radial ray abnormalities
Hypogenitilia
Endocrinopathies
GI defects
Cardiovascular
Renal
Haematological

-unable to correct inter-strand cross-links

-Macrocytosis then thrombocytopenia then neutropenia
age 7 presentation
BM failure 84% risk by 20 yrs

Question 7

give the 3 main causes of Primary Acquired BM failure?

Answer 7

Aplastic anaemia

Myelodysplastic syndromes (MDS)

Acute leukaemia

Question 8

Aplastic anaemia

• what is it?
• describe the pathogenesis?
• what is seen in the Bone marrow?

Answer 8

• Autoimmune attack against haemopoietic stem cell
• Auto-reactive T cells, attack Cells at the LT-HSC, MPP and CMP levels, this causes the release of IFN-y and TNF-a. This means that there are reduced levels of erythrocytes, platelets and granulocytes
• complete aplasia with all the haemopoitic cells replaced by fat

Question 9

Myelodysplastic syndrome

• definition?
• Give the 3 features of MDS?
• what is there a risk of this developing into?

Answer 9

-Are a group of cancers in which immature blood cells in the bone marrow do not mature and become healthy blood cells.

-Dysplasia
Hypercellular marrow
Increased apoptosis of progenitor and mature cells (ineffective haemopoiesis)

-AML- acute myeloid leukaemia

Question 10

Why can acute myeloid leukaemia cause pancytopenia?

Answer 10

get proliferation of abnormal cells from leukaemic stem cells

There is a failure to differentiate or mature into normal cells

Prevent normal haemopoietic stem/progenitor development by hijacking i.e. altering the haemopoietic niche and marrow microenvironment

Question 11

Give the 4 causes of secondary BM failure

Answer 11

Drug induced e.g. chemo, chloramphenicol, alcohol

B12/folate deficiency (nuclear maturation can affect all lineages)

Infiltrative- non-haemopoieotic malignant infiltration, lymphoma

viral/storage disease Remember HIV

Question 12

give the 3 main causes for the increased destruction of Blood cells

Answer 12

Hypersplenism
sepsis
Immune

Question 13

What is hypersplenism?

-give the 3 main causes and examples?

Answer 13

increased destruction of blood cells that exceeds bona marrow capacity, usually assoc with splenomegaly
increased splenic pool i.e. more cells stay in the spleen

-Splenic congestion
Portal hypertension
congestive cardiac failure

systems disease
RA

Haematological disease
Splenic lymphoma

Question 14

Give the clinical features associated with Pancytopenia (5)

Answer 14

Anaemia causes:
Fatigue
SOB
CV compromise

Neutropenia:
Infections (more likely gram neg/ fungal)

Thrombocytopenia:
bleeding (purport and petechiae)

Question 15

investigations in Pancytopenia?

Answer 15

Hx inc fam hx
FBC, blood film
B12/ folate, LFTs, virology autoantibodies
BM examination
specialised tests will be guided by above (cytogenetics)

Question 16

describe the marrow cellularity in:

• aplastic anaemia
• MDS, B12/folate def, hypersplenism

Answer 16

• hypocellular

- hypercellular

Question 17

Treatment of pancytopenia

• supportive?
• specific (Primary BM disorder, secondary BM disorder, hypersplenism)

Answer 17

-Supportive
Red cell transfusions
Platelet transfusions
Antibiotic treatment and prophylactic use

-Primary bone marrow disorder
Malignancy- consider chemo
Congenital- consider BM transplant
idiopathic aplastic anaemia- immunosuppression

-Secondary BM disorder
drug reaction- STOP
Viral- treat e.g. HiV
Replace B12/folate

-Hypersplenism
Treat cause if possible
consider splenectomy

Question 18

Treatment of neutropenic fever?

Answer 18

If patient has a temperature >37.5 or clinical evidence of significant sepsis and neutrophil count <0.5 x 10^9/L then initiate antibiotic therapy within 1 hour.
1. Standard risk patient
- Neutropenia
- Sepsis
- SEWS <6
Commence piperacillin/tazobactam (penicillin allergy: teicoplanin + aztreonam)
No routine gentamicin

2. High risk patient
   - Neutropenia
   - Severe sepsis/septic shock
   - SEWS >=6 or acute leukemia or allogenic transplant
   Commence piperacillin/tazobactam + gentamicin (penicillin allergy: teicoplanin + aztreonam + gentamicin)
   Monitor all patients hourly. Reassess antibiotic therapy after 48-72 hours.