Pancytopenia Flashcards
(88 cards)
1
Q
What does ‘pan’ mean?
A
Generalised
2
Q
What does ‘cyto’ mean?
A
Prefix denoting a cell
3
Q
What does ‘penia’ mean?
A
Lack/deficiency (in blood)
4
Q
What is pancytopenia?
A
A deficiency of blood cells of ALL lineages (but generally excludes lymphocytes).
5
Q
** What is pancytopenia? **
A
A deficiency of blood cells of ALL lineages (but generally excludes lymphocytes).
6
Q
What does pancytopenia NOT always mean?
A
Bone marrow failure
7
Q
For steady state, cell production = cell destruction
A
T
8
Q
In erythropoiesis, what cells are seen in the blood and not the bone marrow?
A
- Reticulocyte
* Erythrocyte
9
Q
Neutrophils are properly segmented
A
T
10
Q
What is the immediate precursor to platelets?
A
Megakaryocyte
11
Q
Megakarocytes are p________
A
Polypoid
12
Q
In what cells does ‘the nucleus divides very quickly without the cytoplasm having divided’
A
Megakarocyte
13
Q
What is the life span of red cells?
A
120 days
14
Q
What is the lifespan of platelets?
A
7-10 days
15
Q
What is the lifespan of neutrophils?
A
7-8 hours
16
Q
If bone marrow fails, in order of first to drop and last to drop, list the cells.
A
- Neutrophils
- Platelets
- Red cells
17
Q
What are the 2 main groups of causes of pancytopenia?
A
- REDUCED production
2. INCREASED destruction
18
Q
What is the basic cause of reduced production of cells, leading to pancytopenia?
A
Bone marrow failure
19
Q
Name the 2 main things that lead to bone marrow failure.
A
- Inherited syndromes
2. Acquired conditions (where ‘production machinery’ comes to a halt)
20
Q
Name the 2 main things that lead to bone marrow failure.
A
- Inherited syndromes
2. Acquired conditions (where ‘production machinery’ comes to a halt) - primary or secondary
21
Q
Describe primary vs secondary acquired bone marrow failure.
A
Primary
(something has gone wrong in the bone marrow)
Secondary
(something else is going on, and even though bone marrow cells are healthy, they’re not able to produce healthy blood cells)
22
Q
What are the 3 main groups of characteristics of inherited marrow failure syndromes?
A
- Cancer predisposition
- Impaired haempoiesis
- Congenital anomalies
23
Q
What do these inherited marrow syndromes arise due to?
A
Defects in DNA repair/ribosomes
24
Q
Inherited bone marrow failure conditions are very common
A
F - they are very rare
25
What is the most common inherited bone marrow failure syndrome?
Faconi's anaemia
26
What does faconis anaemia lead to clinically?
* Short stature – skeletal abnormalities.
* Skin pigment abnormalities – café au lait spots.
* Radial ray abnormalities
* Hypogenitilia
* Endocrinopathies
* GI defects
* Cardiovascular
* Renal
* Haematological
27
What is the mean age of presentation of inherited bone marrow failure syndromes?
7 years old
28
What do these haematological abnormalities of an inherited bone marrow failure syndrome occur due to?
An inability to correct inter-strand cross-links (DNA damage)
So, there patients are unable to correct their own DNA damage
29
In terms of cell deficiencies, what happens in inherited bone marrow failure syndromes?
Macrocytosis, followed by thrombocytopenia, then neutropenia
30
In patients with haematological abnormalities of inherited bone marrow failure syndromes, what are they unable to do?
Correct their own DNA damage
31
What is there a 52% risk of by 40 years in those with inherited bone marrow failure syndromes?
Leukaemia
32
In primary acquired bone marrow failure, there is no obvious cause
T
33
What type of defect is usually seen in people with a primary acquired bone marrow defect?
A stem cell defect
34
In acquired PRIMARY bone marrow failure, there is what type of problem?
An INTRINSIC marrow problem
35
Name 3 conditions associated with primary acquired bone marrow failure.
* Idiopathic aplastic anaemia
* Myelodysplastic syndromes (MDS)
* Acute Leukaemias
36
What does idiopathic aplastic anaemia occur due to?
An autoimmune attack against haemopoietic stem cell(s).
37
Who do myelodysplastic syndromes occur more commonly in?
> 60 yo
38
What is white cell count like in acute leukaemia?
It can be variable.
May start off with pancytopenia as white cells haven’t yet spilled into blood
May also start off high due to lots of primitive cells
39
What cells fail to be produced in aplastic anaemia?
* Erythrocytes
* Platelets
* Granulocytes
Due to auto-immune attack on haematopoietic stem cells
40
What cell is attacked in aplastic anaemia?
Haematopoietic stem cells
41
Haematopoietically active marrow = red marrow
T
42
What is seen on histology of someone with aplastic anaemia?
In aplastic anaemia, all the haematopoietic islands are replaced by fat and fibrosis etc
43
'clone of autoreactive T cells which are detected' is seen in what condition?
Aplastic anaemia
44
What cells (that damage stem cells) are increased in aplastic anaemia?
IFN and TNF
45
Describe what happens in bone marrow in myelodysplastic syndrome.
* Dysplasia.
* HYPERCELLULAR marrow.
* Increased APOPTOSIS of progenitor and mature cells (ineffective haemopoiesis).
46
What is a myelodysplastic syndrome?
Myelodysplastic syndromes (MDS) are a group of cancers in which immature blood cells in the bone marrow do not mature and therefore do not become healthy blood cells.
47
Why is the bone marrow in myelodysplastic syndromes HYPERCELLULAR?
Because the abnormal production of cells occurs at a fast rate. (greater than rate of apoptosis).
48
The bone marrow in myelodysplastic syndromes is _____ cellular
HYPERCELLULAR
49
What does hyper cellular bone marrow have a propensity to evolve into?
AML
50
Why can leukaemia cause pancytopenia?
Basically HSC need a nice bone marrow to live in (their niche), if LSC (leukaemic stem cells ) come along they ruin the nice niche environment for the HSP so they no longer can make the nice normal blood cells (failure of differentiation of normal cells)
This prevents abnormal HSC development
A random mutation of a normal HSC makes an abnormal LSC
51
** Outline the 2 main causes of secondary bone marrow failure. **
* Drug induced e.g chemotherapy, chloramphenicol, alcohol– these all cause aplasia thus are hypocellular
* B12/folate deficiency (nuclear maturation can affect all lineages) -remember hypercellular
52
B12/folate deficiency results in a HYPO/HYPERcellular bone marrow
HYPERCELLULAR
53
Drug induced secondary bone marrow failure e.g chemo, alcohol all cause HYPO/HYPERcellular bone marrow failure.
HYPOCELLULAR
54
Why does B12/folate deficiency result in secondary bone marrow failure?
Results in nuclear maturation defects which can affect all lineages
55
Why is bone marrow hyper cellular in b12/folate deficiency?
* Hypoxia leads to an increase in epo
* Increased proliferation of primitive compartments.
But throughput to more premature compartments decreases as don’t have the resources to make mature cells properly
56
What drugs can cause secondary bone marrow failure? Via what mode of action?
* Chemo
* Chloramphenicol
* Alcohol
They all cause bone marrow aplasia
57
Give 2 examples of infiltrative causes of secondary bone marrow failure.
* Non-haemopoietic malignant infiltration.
| * Lymphoma.
58
What is increased destruction of bone marrow associated with?
Hypersplenism - the spleen is causing the cells to be phagocytosed, the bone marrow tries to compensate (hypercellularity) but can't = pancytopenia
59
Describe the structure of the spleen (mention red pulp and sinusoids).
Red pulp has sinusoids.
| Sinusoids are much bigger than capillaries and have a fenestrated basement membrane.
60
Describe the BM of sinusoids.
Fenestrated
61
The spleen is a very vascular organ. Describe the blood supply to the spleen.
* Supplied by splenic artery (branch of coeliac axis)
| * Drained by splenic vein (with SMV forms portal vein)
62
What is hypersplenism?
* Increased splenic pool.
| * Increased destruction that exceeds bone marrow capacity, usually associated with a significantly enlarged spleen
63
A pancytopaenia, associated with an increased size of the spleen.
T
64
How does hypersplenism cause pancytopenia?
If spleen is trapping all of these cells that are being produced, the bone marrow will try to compensate. Will become hypercellular. If can’t compensate – will become pancytopenic
65
Any cause of what can POTENTIALLY result in hypersplenism?
Splenomegaly
66
A pancytopenia is associated with an increased size of the spleen, why?
* All blood cells pass through the spleen
* If transit slows down, there are macrocytes there that immediately starts to be phagocytosed the cells
* It is important that circulation of cells through the spleen is at a certain speed
* If the spleen is trapping all the cells passing through it, the bone marrow will try compensate by becoming hypercellular
* If the bone marrow cannot compensate, it becomes pancytopenic
67
Name the 3 different categories of causes of hypersplenism.
* Splenic congestion
* Systemic disease
* Haematological disease
68
Name 2 causes of splenic congestion (which result in hypersplenism).
* Portal hypertension
| * Congestive heart failure
69
Name a systemic disease (which results in hypersplenism).
* Rheumatoid arthritis – Felty’s syndrome
70
Name a haematological disease (which results in hypersplenism).
* Splenic lymphoma
71
What are the 5 manifestations of Felty's syndrome.
* Splenomegaly
* Anaemia
* Neutropenia
* Thrombocytopenia
* Arthritis (rheumatoid)
72
The clinical features of pancytopenia can reflect either ...
* Lack of circulating blood cells
| * The cause of pancytopenia
73
Pancytopenia =
Anaemia + thrombocytopenia + neutropenia
74
** Pancytopenia =
Anaemia + thrombocytopenia + neutropenia
75
Describe neutropenia and state what type of infection people with this are most likely to get.
* Infections – of great severity and duration
Neutrophils often form the barriers of the mucosal membranes (endothelial cells) where there is contact with germs
People with neutropenia are predisposed to gram -ve infections (more than gram +ve infections) from the bowel
76
List 4 signs of thrombocytopenia.
* Bleeding
* Purpura
* Petechiae
* ‘Wet’ bleeds including visceral bleeds
77
How is Faconi's anaemia detected?
Chromosome fragility testing used to check for inability to correct DNA damage
78
** How is Faconi's anaemia detected? **
Chromosome fragility testing used to check for inability to correct DNA damage
79
** Outline the tests you would do to find the cause of a pancytopenia. **
* History
* Family history
* Clinical findings
* FBC, blood film
* Bone marrow aspirate
* Core biopsy via Jamshidi needle
* Specialist test
80
** Teat neutropenic fever promptly based on local unit antibiotic policy without waiting for (microbiology) results **
T - always ask about fever in the OSCE
81
Name a hypocellular cause of pancytopenia.
Aplastic anaemia
82
Name 3 causes of hypercellular pancytopenia.
1. Myelodysplastic syndromes – proliferation and apoptosis.
2. B12/folate deficiency – late maturation ‘failure’ + early proliferation + apoptosis.
3. Hypersplenism.
83
Outline the treatment for pancytopenia.
1. Supportive
| 2. Specific - depending on the cause
84
Outline the supportive treatment of pancytopenia.
* Red cell transfusion
* Platelet transfusion
* Antibiotics (tx or prophylaxis)
85
Outline the treatments for primary bone marrow disorders.
* Malignancy – chemotherapy
* Congenital – bone marrow transplant
* Idiopathic aplastic anaemia – immunosuppression (since this is an autoimmune attack on the cells)
86
Treatment for hypersplenism?
* Treat cause if can.
| * Consider splenectomy (although not always appropriate).
87
If someone is having a drug reaction that is causing a secondary bone marrow failure, what should you do?
STOP drug
88
If someone is B12/folate deficient which is causing secondary bone marrow failure, what should you do?
REPLACE B12/folate
