Pancytopenia

Question 1

What is pancytopenia?

Answer 1

A deficiency of blood cell of ALL lineages (but generally excludes lymphocytes)
Commonly see reduced Hb, platelets and neutrophil count

Question 2

Is pancytopenia a diagnosis?

Answer 2

No

Question 3

Does pancytopenia always mean bone marrow failure?

Answer 3

No

Question 4

What is the life span of a red cell?

Answer 4

120 days

Question 5

What is the life span of a neutrophil?

Answer 5

7-8 hours

Question 6

What is the lifespan of a platelet?

Answer 6

7-10 days

Question 7

Generally, what can cause pancytopenia?

Answer 7

Reduced production

Increased destruction

Question 8

What are the causes of reduced production in pancytopenia?

Answer 8

Bone marrow failure; inherited or acquired (primary or secondary)

Question 9

What are the characteristics of inherited marrow failure syndromes?

Answer 9

Cancer predisposition
Impaired hematopoiesis
Congenital anomalies
Arises due to defects in DNA repair/ ribosomes

Question 10

What is an example of an inherited bone marrow failure syndrome?

Answer 10

Fanconi's Anaemia: 
Short stature
Skin pigment abnormalities 
Radial ray abnormalities
Hypogenitalia
Endocrinopathies
GI defects
CV
Renal 
Haem

Question 11

What are the haematological abnormalities seen in fanconi’s anaemia?

Answer 11

Macrocytosis followed by thrombocytopenia then neutropenia
Bone marrow failure (aplasia): 84% by 20 years
Leukaemia risk: 52% by 40 years

Question 12

What is the pathogenic basis of the haematological abnormalities seen in fanconi’s anaemia?

Answer 12

Unable to correct inter-strand cross-links (DNA damage)

Question 13

What are examples of acquired primary bone marrow failure (an intrinsic marrow problem)

Answer 13

Idiopathic aplastic anaemia (autoimmune attack against haemopoietic stem cells) 
Myelodysplastic syndromes (MDS) 
Acute leukaemia

Question 14

What cytokines are involved in aplastic anaemia?

Answer 14

IFN-gamma

TNF- alpha

Question 15

Describe myelodysplastic syndromes?

Answer 15

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

Question 16

What cancer is linked with myelodysplastic syndromes?

Answer 16

Can progress into AML

Question 17

How is aplastic anaemia diagnosed?

Answer 17

Bone marrow biopsy

Question 18

What are the causes for aplastic anaemia?

Answer 18

Fanconi's anaemia 
Autoimmune 
Drugs 
Virus; parvovirus B19, hepatitis 
Irradiation

Question 19

Why can acute leukaemia cause pancytopenia?

Answer 19

Proliferation of blasts from leukemic stem cell
Failure to differentiate or mature into normal cells
Prevents normal haemopoietic stems from developing by hijacking the haemopoietic niche and marrow microenvironment

Question 20

What can cause secondary bone marrow failure?

Answer 20

Drug induced (chemo, chloramphenicol, alcohol)
B12 / folate deficiency (nuclear maturation can affect all lineages)
Infiltrative; non-haemopoietic malignant infiltration, lymphoma
Misc; viral; HIB, parvovirus B19
Storage diseases

Question 21

How will the bone marrow look in B12/ folate deficiency?

Answer 21

Hypercellular

Question 22

What can result in pancytopenia via increased destruction?

Answer 22

Hypersplenism

Question 23

What does the red pulp of the spleen contain?

Answer 23

Sinusoids and cords

Question 24

What does the cord of red pulp contain?

Answer 24

Macrophages
Fibroblasts
Cells in transit (RBC, WBC, platelets, CD8 T cells)

Question 25

What is the function of the spleen?

Answer 25

Detects, retains and eliminates unwanted foreign or damaged material Facilitates immune responses to blood borne antigens

Question 26

Why does hypersplenism result in increased destruction of cells?

Answer 26

Increased splenic pool | Increased destruction that exceeds bone marrow capacity, usually assoc with significant splenomegaly

Question 27

Does splenic size correlate with hypersplenism?

Answer 27

No; any cause of splenomegaly could result in hypersplenism but splenic size alone is not predictive of the degree of hypersplenism

Question 28

What can cause hypersplenism?

Answer 28

Splenic congestion; portal hypertx, CCF Systemic; RA (felty's) Haemo: splenic lymphoma

Question 29

What can the clinical features of pancytopenia reflect?

Answer 29

Lack of circulating blood cells | Cause of pancytopenia

Question 30

What are the consequences of lack of circulating cells in pancytopenia?

Answer 30

Anaemia Neutropenia Thrombocytopenia

Question 31

What are the features of anaemia?

Answer 31

Fatigue SOB CV compromise; dizziness, palpitations

Question 32

What are the features of neutropenia?

Answer 32

Infections; determine severity and duration

Question 33

What are the features of thrombocytopenia?

Answer 33

Bleeding; purpura, petechiae, wet bleeding including visceral bleeds

Question 34

How is the cause of pancytopenia established?

Answer 34

Hx including FMHx Clinical findings FBC, blood film Additional tests; B12/folate, LFTs, virology, autoantibody tests Bone marrow aspirate Specialised tests; chromosome fragility testing for fanconi's syndrome

Question 35

What will cause hypocellular marrow cellularity in pancytopenia?

Answer 35

Aplasitc anaemia

Question 36

What will cause hypercellularity in marrow cellularity in pancytopenia?

Answer 36

``` Myelodysplastic syndromes (proliferation and apoptosis) B12/ folate deficiency (late maturation failure, early proliferation and apoptosis) Hypersplenism ```

Question 37

What is the treatment for pancytopenia?

Answer 37

Supportive | Specific; dependent on cause (pancytopenia due to B12/folate deficiency)

Question 38

What is the supportive treatment for pancytopenia?

Answer 38

Red cell transfusions Platelet transfusions Antibiotic prophylaxis; antibacterials, antifungals

Question 39

Should you wait for microbial results before antibiotic treatment in neutropenic fever?

Answer 39

NO; give broad spectrum antibiotics that specifically cover gram negs

Question 40

What is the specific treatment for pancytopenia caused by a primary bone marrow disorder?

Answer 40

Malignancy; chemo Congenital; bone marrow transplantation Idiopathic aplastic anaemia; immunosuppression

Question 41

What is the specific treatment for pancytopenia caused by a secondary bone marrow disorder?

Answer 41

Drug reaction; STOP Viral; treat HIV Replace B12/ folate

Question 42

What is the specific treatment for pancytopenia caused by hypersplenism?

Answer 42

Treat cause if poss | Consider splenectomy