Thrombocytopenia Flashcards
Describe what is meant by thrombcytopenia [1]
Thrombocytopenia describes a low platelet count; below 150-450 x 109/L.
What are the overarching categories for why thromocytopenia occurs [2]
Increased platelet destruction or reduced platelet production
Give 7 reasons for reduced platelet count thrombocytopenia and 6 reasons for increased platelet destruction
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)
What complications of thrombocytopenia are most concerning? [2]
Intracranial haemorrhage
Gastrointestinal bleeding
What are the top 4 differential diagnosis of abnormal bleeding? [4]
- Thrombocytopenia
- Von Willebrand disease
- Haemophilia A and haemophilia B
- Disseminated intravascular coagulation (usually secondary to sepsis)
Which drugs can cause thrombocytopenia? [7]
- Heparin
- Gold
- Alemtuzumab
- Pembrolizumab
- Nivolumab
- Sodium valproate
- Methotrexate
Which rheumatological diseases can present with thrombocytopenia? [2]
SLE and rheumatoid arthritis
Describe what is meant by Immune Thrombocytopenic Purpura [3]
(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
How does ITP typically present? [5]
- 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
What are paradoxical thrombotic events in ITP? [1]
patients with ITP may present with strokes and TIA
Describe the initial you investigations would conduct for a patient with suspected ITP [2]
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
Desribe the treatment plan for ITP
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
What is meant by Evans syndrome? [1]
Evan’s syndrome
ITP in association with autoimmune haemolytic anaemia (AIHA)
Describe the MoA of Rituximab [1]
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.
Describe what is meant by the condition Thrombotic Thrombocytopenic Purpura [1]
What results from ^? [3]
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
In TTP, thrombi develop due to a problem with a specific protein called [].
Thrombi develop due to a problem with a specific protein called ADAMTS13
In TTP, thrombi develop due to a problem with a specific protein called ADAMTS13. What is the role of this protein? [3]
- Inactivates von Willebrand factor
- Reduces platelet adhesion to vessel walls
- Reduces clot formation
Deficiency in the ADAMTS13 protein can be due to? [2]
An inherited genetic mutation (hereditary)
Autoimmune disease, where antibodies are created against the protein (acquired)
What are the clinical features of TTP? [5]
- Rare, typically adult females
- Fever
- Fluctuating neuro signs (microemboli)
- Microangiopathic haemolytic anaemia
- Thrombocytopenia
- Renal failure
FAT RN
What worsens the TTP? [1]
Abx
What is the basic treatment for TTP? [3]
plasma exchange, steroids, rituximab, Vincristine
Describe the phenomona of Heparin-Induced Thrombocytopenia [2]
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
How do you diagnose HIT? [1]
HIT antibodies on a blood sample.
How long after adminstering heparin does HIT usually occur? [1]
5-10 days
Describe the management of HIT [2]
Management involves stopping heparin and using an alternative anticoagulant guided by a specialist (e.g., fondaparinux or argatroban).
