Thrombocytopenia Flashcards
ITP, TTP, HIT
What is thrombocytopenia
Describes a low platelet count
What is a normal platelet count
150-450 x 10^9/L
Give 5 causes of reduced platelet production?
- viral infections (e.g., EBV, CMV, HIV)
- B12 deficiency/ Folic acid deficiency
- Liver failure
- Leukaemia
- Myelodysplastic syndrome
- Chemotherapy
Give 5 causes of 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)
How may a person present when their platelet count falls below 50 x 10^9/L?
- Easy bruising
- Prolonged bleeding times
- Nosebleeds
- Bleeding gums
- Heavy periods
- Haematuria (blood in the urine)
- Rectal bleeding
What are the risks associated with platelet counts below 10 x 10^9/L?
can lead to spontaneous bleeding, including:
* Intracranial haemorrhage
* GI bleeding
What are the main differential diagnoses for abnormal bleeding?
- Thrombocytopenia
- Von Willebrand disease
- Haemophilia A and B
- Disseminated intravascular coagulation ( often secondary to sepsis)
What is Immune Thrombocytopenic Purpura?
an immune-mediated condition in which antibodies target the platelet glycoprotein IIb/IIIa or Ib-V-IX complex, resulting in a reduced platelet count.
How does Immune Thrombocytopenic Purpura differ between children and adults?
In children, ITP typically presents as an acute condition often following infections or vaccinations, whereas in adults, it tends to be more chronic.
Who is more commonly affected by Immune Thrombocytopenic Purpura in adults?
more common in older females
What are the common clinical presentations of Immune Thrombocytopenic Purpura in adults?
- Petechiae
- Purpura
- Bleeding (e.g., epistaxis)
- may be detected incidentally on routine blood tests
What investigations are used to diagnose Immune Thrombocytopenic Purpura?
- FBC - isolated thrombocytopenia
- Blood film
How is Immune Thrombocytopenic Purpura managed?
- 1st line: oral prednisolone
- IVIG - used in cases of active bleeding or when urgent procedures are needed
- rituximab (a monoclonal antibody that targets B cells)
- Thrombopoietin receptor agonists (e.g., romiplostim)
- splenectomy
What is thrombotic thrombocytopenic purpura (TTP)?
a condition where tiny thrombi form throughout small vessels, using up platelets and causing microangiopathy (disease of small vessels)
Explain the pathogenesis of thrombotic thrombocytopenic purpura
- there is a deficiency of ADAMTS13 which breakdowns large multimers of von Willebrand’s factor
- abnormally large and sticky multimers of von Willebrand’s factor cause platelets to clump within vessels
What is the normal function of the ADAMTS13 protein
- Inactivates von Willebrand factor
- Reduces platelet adhesion to vessel walls
- Reduces clot formation
Causes of thrombotic thrombocytopenic purpura?
- post-infection e.g. urinary, gastrointestinal
- pregnancy
- drugs: ciclosporin, oral contraceptive pill, penicillin, clopidogrel, aciclovir
- tumours
- SLE
- HIV
What are the key features of thrombotic thrombocytopenic purpura?
- Thrombocytopenia
- Purpura
- fever
- fluctuating neuro signs (microemboli)
- microangiopathic haemolytic anaemia
- Tissue ischaemia and end-organ damage
How is thrombotic thrombocytopenic purpura treated?
- Plasma exchange
- Steroids
- Rituximab
What is heparin-induced thrombocytopenia (HIT)?
a condition where antibodies develop against platelets in response to heparin (usually unfractionated, but also LMWH).
What protein do heparin-induced antibodies target in heparin-induced thrombocytopenia?
platelet factor 4 (PF4), a protein found on platelets
When does heparin-induced thrombocytopenia typically present?
5-10 days after starting heparin treatment
What happens when heparin-induced antibodies bind to platelets?
- they activate the clotting system, leading to a hypercoagulable state and thrombosis (e.g., DVT)
- They also cause platelet breakdown, resulting in thrombocytopenia.
What is the management for heparin-induced thrombocytopenia?
- Stopping heparin
- Using an alternative anticoagulant, such as fondaparinux or argatroban, under the guidance of a specialist.
