Thrombocytopenia describes a low platelet count. The normal platelet count is between 150 to 450 x 109/L. There are a long list of causes of a low platelet count. They can be split into problems with production or destruction.
Problems with Production
- B12 or folic acid deficiency
- Liver failure causing reduced thrombopoietin production in the liver
- Myelodysplastic syndrome
Problems with Destruction
- Medications (sodium valproate, methotrexate, isotretinoin, antihistamines, proton pump inhibitors)
- Immune thrombocytopenic purpura
- Thrombotic thrombocytopenic purpura
- Heparin-induced thrombocytopenia
- Haemolytic-uraemic syndrome
A mild thrombocytopenia may be asymptomatic and found incidentally on a full blood count.
Platelet counts below 50 x 109/L will result in easy or spontaneous bruising and prolonged bleeding times. They may present with nosebleeds, bleeding gums, heavy periods, easy bruising or blood in the urine or stools.
Platelet counts below 10 x 109/L are high risk for spontaneous bleeding. Spontaneous intracranial haemorrhage or GI bleeds are particularly concerning.
Differential Diagnosis of Abnormal or Prolonged Bleeding
The blood contains a clotting system that allow it to make blood clots to stop bleeding. This system can break down in a number of ways. A few key differentials to remember for your exams are:
- Thrombocytopenia (low platelets)
- Haemophilia A and haemophilia B
- Von Willebrand Disease
- Disseminated intravascular coagulation (usually secondary to sepsis)
Immune Thrombocytopenic Purpura (ITP)
Confusing this is also called autoimmune thrombocytopenic purpura, idiopathic thrombocytopenic purpura and primary thrombocytopenic purpura. They all refer to the same condition.
ITP is a 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.
Management options include:
- Prednisolone (steroids)
- IV immunoglobulins
- Rituximab (a monoclonal antibody against B cells)
The platelet count needs to be monitored and the patient needs education about concerning signs of bleeding such as persistent headaches and melaena and when to seek help. Additional measures such as carefully controlling blood pressure and suppressing menstrual periods are also important.
Thrombotic Thrombocytopenic Purpura
This is a 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.
The blood clots develop due to a problem with a specific protein called ADAMTS13. This protein normally inactivates von Willebrand factor and reduces platelet adhesion to vessel walls and clot formation. A shortage in this protein 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.
Deficiency in the ADAMTS13 protein can be due to an inherited genetic mutation or due to autoimmune disease where antibodies are created against the protein.
Treatment is guided by a haematologist and may involve plasma exchange, steroids and rituximab (a monoclonal antibody against B cells).
Heparin Induced Thrombocytopenia
Heparin induced thrombocytopenia (HIT) involves the development of antibodies against platelets in response to exposure to heparin. These heparin induced antibodies specifically target a protein on the platelets called platelet factor 4 (PF4). These are anti-PF4/heparin antibodies.
The HIT antibodies bind to platelets and activate clotting mechanisms. This causes a hypercoagulable state and leads to thrombosis. They also break down platelets and cause thrombocytopenia. Therefore there is an unintuitive situation where a patient on heparin with low platelets forms unexpected blood clots.
Diagnosis is by testing for the HIT antibodies in the patients blood. Management is by stopping heparin and using an alternative anticoagulant guided by a specialist.
Last updated April 2019