Thrombocytopenia

Question 1

Describe what is meant by thrombcytopenia [1]

Answer 1

Thrombocytopenia describes a low platelet count; below 150-450 x 109/L.

Question 2

What are the overarching categories for why thromocytopenia occurs [2]

Answer 2

Increased platelet destruction or reduced platelet production

Question 3

Give 7 reasons for reduced platelet count thrombocytopenia and 6 reasons for increased platelet destruction

Answer 3

Reduced platelet count:
* Certain viral infections (e.g., Epstein-Barr virus, cytomegalovirus and HIV)
* B12 deficiency
* Folic acid deficiency
* Liver failure, causing reduced thrombopoietin production by the liver
* Leukaemia
* Myelodysplastic syndrome
* Chemotherapy

Increased platelet destruction:
* Medications (e.g., sodium valproate and methotrexate)
* Alcohol
* Immune thrombocytopenic purpura (ITP)
* Thrombotic thrombocytopenic purpura (TTP)
* Heparin-induced thrombocytopenia (HIT)
* Haemolytic uraemic syndrome (HUS)

Question 4

What complications of thrombocytopenia are most concerning? [2]

Answer 4

Intracranial haemorrhage

Gastrointestinal bleeding

Question 5

What are the top 4 differential diagnosis of abnormal bleeding? [4]

Answer 5

• Thrombocytopenia
• Von Willebrand disease
• Haemophilia A and haemophilia B
• Disseminated intravascular coagulation (usually secondary to sepsis)

Question 6

Which drugs can cause thrombocytopenia? [7]

Answer 6

• Heparin
• Gold
• Alemtuzumab
• Pembrolizumab
• Nivolumab
• Sodium valproate
• Methotrexate

Question 7

Which rheumatological diseases can present with thrombocytopenia? [2]

Answer 7

SLE and rheumatoid arthritis

Question 8

Describe what is meant by Immune Thrombocytopenic Purpura [3]

Answer 8

(AKA autoimmune thrombocytopenic purpura, idiopathic thrombocytopenic purpura and primary thrombocytopenic purpura)

• antibodies are created against platelets, leading to their destruction
• antibodies are produced of IgG and target the platelet membrane glycoproteins GPIIb/IIIa
• the bone marrow compensates by making more megakaryocytes

Question 9

How does ITP typically present? [5]

Answer 9

• petechiae: small red dots on the skin.
• purpura: formed by petechiae joined together, can also occur
• Mild epistaxis is common; can lead to continous epistaxis
• prolonged and heavy menstrual cycles.
• large gastrointestinal bleeds

Question 10

What are paradoxical thrombotic events in ITP? [1]

Answer 10

patients with ITP may present with strokes and TIA

Question 11

Describe the initial you investigations would conduct for a patient with suspected ITP [2]

Answer 11

full blood count & blood film:
- isolated decrease in platelets
- normal counts of other cell lineages
- no evidence of fragments on film

Virology screen:
- For HIV, HBV and Hep screen

Question 12

Desribe the treatment plan for ITP

Answer 12

First line treatment:
- Oral prednisone at 1mg/kg daily with proton pump inhibitors
- Over 2 - 4 weeks and weaned off a few weeks after
AND
- Pooled normal human immunoglobulin (IVIG)

Second line:
- Mycophenolate mofetil- mmunosuppressive agent
AND
- thrombopoietin receptor agonist (e.g romiplostim)
AND
- Rituximab
AND
- Fostamatinib spleen tyrosine kinase (Syk) inhibitor
AND
- Splenectomy

Question 13

What is meant by Evans syndrome? [1]

Answer 13

Evan’s syndrome
ITP in association with autoimmune haemolytic anaemia (AIHA)

Question 14

Describe the MoA of Rituximab [1]

Answer 14

TOM TIP: B cells produce antibodies. Rituximab is worth remembering as a monoclonal antibody that targets the CD20 proteins on the surface of B cells. By attacking B cells and reducing their numbers, it reduces the production of the antibodies that are responsible for autoimmune disease. It treats many autoimmune conditions, from rheumatoid arthritis to ITP.

Question 15

Describe what is meant by the condition Thrombotic Thrombocytopenic Purpura [1]

What results from ^? [3]

Answer 15

Tiny thrombi develop throughout the small vessels, using up platelets. As the problem is in the small vessels, it is described as a microangiopathy. This causes:

• Thrombocytopenia
• Purpura
• Tissue ischaemia and end-organ damage

Get FAT RN:

• Fever
• Anaemia
• Thrombocytopenia
• Renal failure
• Neuro problems

Question 16

In TTP, thrombi develop due to a problem with a specific protein called [].

Answer 16

Thrombi develop due to a problem with a specific protein called ADAMTS13

Question 17

In TTP, thrombi develop due to a problem with a specific protein called ADAMTS13. What is the role of this protein? [3]

Answer 17

• Inactivates von Willebrand factor
• Reduces platelet adhesion to vessel walls
• Reduces clot formation

Question 18

Deficiency in the ADAMTS13 protein can be due to? [2]

Answer 18

An inherited genetic mutation (hereditary)

Autoimmune disease, where antibodies are created against the protein (acquired)

Question 19

What are the clinical features of TTP? [5]

Answer 19

• Rare, typically adult females
• Fever
• Fluctuating neuro signs (microemboli)
• Microangiopathic haemolytic anaemia
• Thrombocytopenia
• Renal failure

FAT RN

Question 20

What worsens the TTP? [1]

Answer 20

Abx

Question 21

What is the basic treatment for TTP? [3]

Answer 21

plasma exchange, steroids, rituximab, Vincristine

Question 22

Describe the phenomona of Heparin-Induced Thrombocytopenia [2]

Answer 22

Development of antibodies against platelets in response to heparin (usually unfractionated heparin, but it can occur with low-molecular-weight heparin).

Heparin-induced antibodies target a protein on platelets called platelet factor 4 (PF4).

The HIT antibodies activate the clotting system, causing a hypercoagulable state and thrombosis (e.g., deep vein thrombosis)

They also break down platelets and cause thrombocytopenia

Question 23

How do you diagnose HIT? [1]

Answer 23

HIT antibodies on a blood sample.

Question 24

How long after adminstering heparin does HIT usually occur? [1]

Answer 24

5-10 days

Question 25

Describe the management of HIT [2]

Answer 25

Management involves stopping heparin and using an alternative anticoagulant guided by a specialist (e.g., fondaparinux or argatroban).