Thrombocytopenia

• There are many causes of thrombocytopenia, which can be broken down into three broad categories; reduction in platelet production, a reduction in platelet survival and dilution of platelet numbers
• The average platelet life span is around 5 days
• Causes of reduction in platelet production:

  • Viral infections
  • Chemotherapy
  • Aplastic anaemia
  • Haematological malignancy - due to crowing of the bone marrow by malignant cells
  • Non-haematological metastatic malignancy
  • B12 and folate deficiency
  • Excess alcohol intake - indirect bone marrow toxicity and liver cirrhosis
• Immune-mediated decreased platelet survival:

  • Idiopathic thrombocytopenic purpura (ITP) - antibodies directed at the surface of platelets
  • SLE
  • RA
  • Sarcoidosis
  • Antiphospholipid syndrome
• Non-immune decreased platelet survival:

  • Medications - heparin, carbamazepine
  • Splenomegaly - sequesters more platelets than normal
  • Haemolytic uraemic syndrome
  • Thrombotic thrombocytopenic purpura
• Typical symptoms associated with thrombocytopenia include:

  • Spontaneous bruising or excessive bruising as a result of a minor injury
  • Bleeding gums
  • Epistaxis which may be excessive, frequent and prolonged
  • Gastrointestinal bleeding: haematemesis, haematochezia and melaena
  • Genitourinary bleeding: haematuria, post-coital bleeding
  • Menorrhagia
• Symptoms of occult malignancy should also be screened for including: 

  • Bone pain
  • Night sweats
  • Weight loss
  • Left upper quadrant discomfort (e.g. splenomegaly)
  • Excessive thirst, urination and constipation (myeloma)
• Typical clinical findings in patients with severe thrombocytopenia include:

  • Petechiae (<2 mm)
  • Purpura (0.2-0.1 cm)

  These can be found on the skin and the oral mucosa.

  Also look for lymphadenopathy and/or hepatosplenomegaly
• Blood tests relevant to thrombocytopenia include:

  • Full blood count (FBC)
  • Blood film
  • U&Es
  • Prothrombin time (PT) and activated partial thromboplastin time (aPTT)
  • B12 and folate
• Bone marrow biopsy may be indicated if there are concerns about underlying malignant invasion of the bone marrow (e.g. leukaemia) or aplastic anaemia.
• Indications for urgent referral to haematology include:

  • severe thrombocytopenia (20 x 109/L)
  • severe bleeding
  • red cell fragments or blasts on the blood film
  • a history of constitutional symptoms (e.g. fever, weight loss, night sweats), spontaneous bruising/bleeding or abnormalities on examination of the blood film.
• Patients with severe thrombocytopenia are advised:

  • to avoid contact sports and activities which increase their risk of significant trauma
  • to avoid NSAIDs (which impair platelet function)
  • to maintain good dental hygiene (to minimise the risk of gingival bleeding and the need for dental procedures)
  • to avoid deep intramuscular injections if possible
• Platelet transfusion:

  • Often required for patients with severe thrombocytopenia <10
  • Or for those who need a temporary boost before a procedure
  • Also used in the emergency setting if patient is actively bleeding
• Oral or intravenous preparations of tranexamic acid may also be used in the peri/post-operative period to increase clot stability and reduce the risk of bleeding.
• Steroids (e.g. prednisolone) are commonly used in the management of immune-mediated thrombocytopenia (e.g. ITP) to suppress immune-mediated destruction of platelets allowing for count recovery.
• Thrombopoietin receptor (TPO) agonists:

  • Eltrombopag
  • Directly stimulate the production of platelets by the bone marrow
  • Typically used as a second line treatment in ITP
  • Management of aplastic anaemia
• Allogenic bone marrow transplantation is only used in cases of severe thrombocytopenia unresponsive to other therapies (e.g. aplastic anaemia)