Yellow and Red PTS

Question 1

What is the definition of polycythaemia vera?

Answer 1

myeloproliferative disorder characterised by neoplasia of mature myeloid cells, in particular those involved in the red cell lineage, within the bone marrow.

Question 2

Epidemiology of PCV

Answer 2

• The peak incidence of PCV is 50-70 years old
• It is slightly more common in men

Question 3

Criteria for JAK2 positive PCV

Answer 3

-A1 Raised haematocrit (>0.52 in men or > 0.48 women) or Raised red cell mass (>25% above predicted)

A2 Mutation in JAK2

Question 4

Criteria for JAK2 negative PCV

Answer 4

Requires one A1-A4 plus another A or 2 B criteria
Look at Nazias notes

Question 5

Risk factors for PCV

Answer 5

• Age > 40 years
• Family history

Question 6

What is PCV?

Answer 6

increased blood cell levels (particularly RBCs) due to overproduction by the bone marrow.
Mutation in single haeamatopoietic stem cell - JAK2 gene

Question 7

What do Kidneys produce? (pathophysiology of PCV)

Answer 7

EPO - binds to receptors on the hematopoietic stem cells and activates JAK2 gene. This causes the cell to divide and thus produce more blood cells.

Question 8

What happens in mutation of JAK 2 Gene

Answer 8

JAK2 gene activated, and these cells are able to divide even in the absence of erythropoietin.

The mutated cells proliferate, and rapidly become the predominant hematopoietic cells in the bone marrow.

Question 9

What does PCV ( a primary polycythaemia) result in?

Answer 9

Increased red blood cells (polycythaemia) as well as increased neutrophils (neutrophilia) and platelets (thrombocytosis).

This causes hyperviscosity, increasing the risk of thrombosis.

Question 10

What is myelofibrosis

Answer 10

• cells start to die out and scar tissue forms.
• At that point, the bone marrow can no longer produce blood cells
• leading to anaemia, thrombocytopenia, and leukopenia.
• This is known as the spent phase (myelofibrosis).

Question 11

Why does scarring happen in PCV?

Answer 11

Usually in response to cytokines that are released from the proliferating cells. One particular cytokine is fibroblast growth factor.

Question 12

Signs of PCV

Answer 12

• Splenomegaly: because the excess red blood cells buildup in the spleen, which usually helps with removing excess cells.
• Conjunctival plethora (excessive redness to the conjunctiva in the eyes)
• Plethoric appearance
• Palmar erythema
• Hypertension

Question 13

Symptoms of PCV

Answer 13

• Fatigue
• Dizziness
• Headache
• Blurred vision
• Increased sweating
• Facial flushing
  Erythromelagia

Question 14

Primary investigations for PCV?

Answer 14

FBC
U&Es
LFTs
ABG
Ferritin
EPO
JAK2 V617F mutation
BM Biopsy

Question 15

What other investigations are there to consider for PCV?

Answer 15

If JAK2 negative, perform additional investigations:

• Red cell mass:increased > 25%
• Abdominal ultrasound:splenomegaly may not be palpable if mild, therefore ultrasound is performed to elucidate this.
• If EPO is normal or low:JAK2 exon 12 analysisandbone marrow biopsy
• If EPO is high: further imaging (e.g. CT head and neck) to exclude a rare tumour

Question 16

Treatment/ management of PCV

Answer 16

Venesection - first line
Hydroxyurea - reduce thrombosis risk
Aspirin 75mg
Ruxolitinib - JAK2 inhibitor

Question 17

Complications of PCV

Answer 17

Thrombosis
Stroke
MI
DVT
Haemorrhage
Gout
Leukaemia
Myelofibrosis

Question 18

What is thrombocytopenia

Answer 18

Thrombocytopenia describes a low platelet count. The normal platelet count is between 150 to 450 x 109/L.

Question 19

Causes of thrombocytopenia can be split into

Answer 19

Problems with production
Splenic sequestration
Problems with destruction
Medication

Question 20

Problems with production

Answer 20

• Sepsis
• B12 or folic acid deficiency
• Liver failure causing reducedthrombopoietinproduction in the liver
• Bone marrow suppression
• Leukaemia
• Myelodysplastic syndrome

Question 21

Splenic sequestration

Answer 21

• In liver cirrhosis, portal hypertension causes blood to back up into the spleen, causing congestive splenomegaly.
• The spleen physically enlarges and also starts to hyperfunction - hypersplenism.
• Here, the spleen generously allows up to 90 percent of the total plateletsin, which means that nearly none are left in the blood.

Question 22

Problems with destruction

Answer 22

• Immune thrombocytopenic purpura
• Heparin-induced thrombocytopenia
• Thrombotic thrombocytopenic purpura

Question 23

Presentation of thrombocytopenia

Answer 23

Asymptomatic
Bruising
Heavy periods
Nose bleeds
Haematuria

Question 24

Differential diagnosis of thrombocytopenia

Answer 24

• Platelet concentration can fall as a result of large volume transfusions of platelet-free products
• Pseudothrombocytopenia: clotting of platelet factors can falsely make platelet count appear low
• Haemophilia Aandhaemophilia B
• Von Willebrand Disease

Question 25

What is Immune thrombocytopenic purpura (ITP)

Answer 25

condition where antibodies are created against platelets. This causes an immune response against platelets, resulting in the destruction of platelets and a low platelet count.

Question 26

What is primary ITP

Answer 26

when ITP occurs by itself

Question 27

What is secondary ITP?

Answer 27

triggered by another condition e.g. hepatitis C, HIV, or lupus

Question 28

Pathophysiology of ITP

Answer 28

ITP is caused by autoantibodies that bind to the platelet receptor Gp2B3A, and target platelets for destruction in the spleen. ITP is like the platelet equivalent of autoimmune haemolytic anemia. Some patients develop both conditions together - Evan’s syndrome.

Question 29

S + S of ITP

Answer 29

Mostly asymptomatic - **Petechiae** - **Purpura** (red or purple spots on the skin caused by bleeding underneath skin) - **Easy bruising** - **Epistaxis** (nose bleed) - **Menorrhagia** (heavy menstruation) - **Gum bleeding**

Question 30

Investigations for ITP

Answer 30

FBC Blood film Platelet autoantibodies Abdominal ultrasound

Question 31

Management of ITP

Answer 31

- Secondary ITP: **treat underlying cause** - **Prednisolone (steroids)** - **IV immunoglobulins** - **Rituximab** (a monoclonal antibody against B cells) - **Splenectomy** - **Vaccinations** should be arranged for patients undergoing a splenectomy - Additional measures such as carefully **controlling blood pressure and suppressing menstrual periods** are also important.

Question 32

WHAT IS thrombotic thrombocytopenic pupura (TTP)

Answer 32

condition where tiny blood clots develop throughout the small vessels of the body using up platelets and causing thrombocytopenia, bleeding under the skin and other systemic issues. It affect the small vessels so it is described as a microangiopathy.

Question 33

Why do blood clots develop in TTP

Answer 33

blood clots develop due to a problem with a specific protein called  ADAMTS13

Question 34

What does protein ADAMTS13 do?

Answer 34

- protein normally: - inactivates von Willebrand factor   - reduces  platelet adhesion  to vessel walls - stops  clot formation

Question 35

Pathophysiology of TTP

Answer 35

shortage in ADAMTS13 leads to von Willebrand factor overactivity and the formation of blood clots in small vessels. This causes platelets to be used up leading to thrombocytopenia. The blood clots in the small vessels break up red blood cells, leading to haemolytic anaemia.

Question 36

5 classic symptoms of TTP

Answer 36

- **Thrombocytopenia** - **Microangiopathic hemolytic anaemia** - **Fatigue** - **Fever** - **Renal insufficiency**

Question 37

Investigations for TTP

Answer 37

FBC: normocytic anaemia Blood film Uconjugated bili: raised LDH : raised haptoglobin Creatinine levels Coombs test

Question 38

Management for TTP

Answer 38

- **Plasma exchange:** gets rid of the patient’s plasma along with all of the large von willebrand factor multimers, and replaces it with new plasma - **Steroids** - **Rituximab** (a monoclonal antibody against B cells).