S5 L2 - When haemopoiesis goes wrong... in other ways

Question 1

• *Overproduction of cells:**
• *-** Due to…
• Which mutation do many patient’s have?
• Which drug can be used to help stop the effect of this mutation? How does this drug work?
• Myeloproliferative disorders - clinical features…

Answer 1

Overproduction of cells:
- Due to…
Physiological reaction to a stimulus
Myeloproliferative disorders (neoplasms)
- Which mutation do many patient’s have?
JAK2 (Janus Kinase 2 gene)
- Which drug can be used to help stop the effect of this mutation? How does this drug work?
Imatinib (drug) - binds competitively to kinase domain
- Myeloproliferative disorders - clinical features…
Overproduction of 1+ of blood element, marrow fibrosis, thromobotic/haemorrhagic, extramedullary haemopoiesis, potential to transform to leukaemia, overlapping clinical features

Question 2

• *Myeloproliferative disorders**
• Names of 4 (need to know about 4)
• Acronym

Answer 2

PEMC

• Polycythaemia vera
• Essential thrombocytopenia
• Myelofibrosis
• Chronic myeloid leukaemia

Question 3

1. Essential thrombocythaemia
   - What is this?
   - Why does this occur?
   - What does this lead to?
   - What is important to make sure when diagnosing?
   - Management
   - What can it transform into?

Answer 3

What is this? Why does this occur?
“too many platelets” due to: Overproduction by megakaryocytes in the bone marrow
Risk of:
Many thrombotic event (blood clot in vein or artery)
What is important to make sure when diagnosing?
Make sure the high platelet count is consistent and not temporary, e.g. temporary includes due to infection, inflammation, RA arthiritis, haemorrhage
Management:
- Aspirin
- CVS risk factors managed
- screen for JAK2 mutation
- Hydroxycarbomide (inhibits DNA synthesis) - same drug as used in sickle cell disease

—-> Can transfom into acute leukaemia

Question 4

• *2. Polycythaemia vera**
• What is this
• Which mutation
• Risk of…
• Common age
• Management
• Causes of polycythaemia (other causes - where does polycythaemia vera linked in?)
• Important to make sure it is not other causes
• Can transform into…

Answer 4

2. Polycythaemia vera
- What is this:
High red blood cell (high hematocrit)
- Which mutation
JAK2 mutation
- Risk of…
— arterial thrombosis, venous thrombosis, haemorrhage into skin or GI tract, pruiritis (itchy), splenomegaly
- Common age:
Median age is 60
- Management:
Venesection, aspirin, manage CVS risk
- Causes of polycythaemia:
pic
Relative: normal red mass, with decreased plasma
Absolute; increased red cell mass
- Important to make sure it is not other cause

–> Can transfrom into acute leukamia, myelofibrosis

Question 5

• *3. Myelofibrosis**
• What happens, what is this condition
• Blood count
• One important sign
• Other signs and symptoms
• Management

—> Can transform to…

Answer 5

*asked lots in exams*
- What happens, what is this condition:
Heavily fibrotic bone marrow, little space for haemopoiesis, leads to extramedullary haemopoeisis in the spleen
- Blood count:
proliferative phase - all blood counts are high
then progressive drop - leads to pancytopenia (all low blood counts)
- One important sign:
MASSIVE spleenomegaly
- Other signs and symptoms:
Fatigue, sweating, splenomegaly, early satiety, splenic infarction
- Management:
Blood transfuions

—> Can transform to…
Essential thrombocytopenia, polycytheamia vera, leukaemia

Question 6

• *4. Chronic Myeloid Leukaemia**
• Genetic mutation
• What is the blood count like
• Some symptoms

Answer 6

- Genetic mutation
Philadelphia chromosome
- What is the blood count like
Very high WCC
- Symptoms
Splenomegaly, hyperviscosity, bone pain

Question 7

Under production

• *Pancytopenia**
• What is this?
• Causes

Answer 7

- What is this?
Abnormally low white blood cells, red blood cells and platelets
- Causes
B₁₂/folate deficiency
Bone marrow infiltrated by malignancy
Radiation
Chemotherapy
Marrow fibrosis
Viruses e.g. EBV, HIV, viral hepatitis
Idoplasitc aplastic anaemia
Congenital bone marrow failure

Question 8

• *Aplastic anaemia**
• What is this
• Treatment
• Death often due to…

Answer 8

- What is this
Pancytopenia with hypocellular bone marrow in the absence of abnormal infiltrate with no increase in reticulin
- Treatment
Needs a bone marrow transplant
- Death often due to…
Neutropenic infection (low neutrophils, lots of bleeding)

Question 9

• *Thrombocytopenia**
• What is this
• Causes
• Consequences of thromocytopenia
• What blood count do patients start to show symptoms

Answer 9

- What is this:
Low platelet count
- Causes:
pic
- Consequences of thromocytopenia:
purpura, petechiae, mucosal bleeding, nosebleeds, bleeding from puncture sites, severe bleeding, easily bruised, bleeding on retina
- What blood count do patients start to show symptoms
Normal is 150-400, start symptoms at around 30

Question 10

• *Autoimmune thrombocytopenia purpura**
• What is this/what happens
• Causes
• Treatment
• One treatment that doesn’t work

Answer 10

- What is this/what happens:
Autoantibodies against glycoproteins on the platelets. These attach to the platelet. the spleen gets rid of them
- Causes:
May occur spontaneously
- Treatment:
Immunosuppressants e.g. corticosteroids
- One treatment that doesn’t work
Blood transfusions (as new RBC also get damaged)