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Thrombocytopenia is a condition characterised by an abnormally low platelet count (<150 x 109/L). Platelets (also known as thrombocytes) are disc-shaped cell fragments whose function is to react to blood vessel injury by clumping to initiate the formation of a blood clot. Thrombocytopenia increases the risk of bleeding, however, most cases of thrombocytopenia are detected on a routine full blood count (FBC) in otherwise asymptomatic patients. The average platelet life span is around 5 days, meaning ongoing platelet production is required to maintain adequate levels.1,2

Aetiology and Risk Factors

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. These can be further classified as either congenital or acquired.1

Disorders affecting platelet production


  • Megakaryocytic hypoplasia
  • Bernard-Soulier syndrome (BSS)
  • Wiskott-Aldrich syndrome (WAS)
  • Congenital leukaemia
  • Fanconi’s anaemia

Decreased production

  • Viral infections (e.g. herpes simplex, cytomegalovirus, varicella-zoster, Epstein-Barr, Rubella, enterovirus, mumps, hepatitis, HIV)
  • Aplastic anaemia
  • Marrow infiltration by a malignancy (e.g. leukaemia, lymphoma, myeloma, metastatic malignant disease)
  • Drugs (e.g. chemotherapy)
  • Alcohol
  • Paroxysmal nocturnal haemoglobinuria
  • Megaloblastic anaemia

Decreased platelet survival


  • Idiopathic thrombocytopenic purpura (ITP)
    • This is typically an illness of young women.
    • ITP in other patient groups should prompt suspicion of an alternative diagnosis (i.e. non-Hodgkin’s lymphoma, certain drugs or myelodysplastic syndrome).2
  • Systemic lupus erythematosus
  • Rheumatoid arthritis
  • Sarcoidosis
  • Antiphospholipid syndrome



  • Post-transfusion thrombocytopenic purpura (PTTP)
  • Neonatal alloimmune thrombocytopenia (NAIT)
  • Drug-induced (e.g. heparin, carbamazepine, ibuprofen, rifampin, trimethoprim, vancomycin)
  • Thrombotic thrombocytopenic purpura (TTP)
  • Haemolytic uraemic syndrome (HUS)
  • Disseminated intravascular coagulation (DIC)
  • Pregnancy – (HELLP syndrome)
  • Splenomegaly and hypersplenism
  • Dilutional thrombocytopenia – caused by transfusion of large volumes of blood which may be depleted of functioning platelets, this often results from prolonged storage


Platelet function disorders


  • Wiskott-Aldrich syndrome, Glanzmann’s thrombasthenia, Bernard-Soulier syndrome
  • Disorders of receptors and signal transduction (e.g. thromboxane A2 receptor defect)
  • Disorders of the platelet granules



  • Medications and chemicals (e.g. aspirin, other NSAIDs, clopidogrel, dipyridamole, beta-lactam antibiotics, dextran, alcohol)
  • Herbal supplements and foods (e.g. ginkgo biloba, garlic, bilberry, ginger, ginseng)
  • Chronic kidney disease
  • Heart valve disease
  • Acquired vWD may occur in patients with aortic stenosis
  • Myeloproliferative disorders (e.g. essential thrombocytopenia)
  • Myelodysplastic syndromes


This occurs when platelets undergo a phenomenon called ‘clumping’. Platelets stick together causing a false low reading when passed through an auto-analyser. It is not indicative of a bleeding diathesis or platelet dysfunction.

Clinical Features

When taking a history try to identify when the patient’s symptoms began, to establish whether this is an acute or chronic presentation.1


  • Epistaxis; may be excessive, frequent or prolonged
  • Bleeding gums or bleeding from tooth extractions
  • Gastrointestinal or genitourinary bleeding; haemoptysis, haematemesis, haematuria, haematochezia and melaena
  • Menorrhagia (especially in vWD, often made worse when NSAID is given to treat dysmenorrhoea)
  • Postpartum haemorrhage
  • Excessive bleeding during or after surgery (even minor)
  • Bleeding after aspirin
  • Spontaneous bruising


Be aware of non-specific associated symptoms that may indicate malignancy: 2

  • Bone pain
  • Night sweats
  • Nausea
  • Anorexia
  • Fatigue/malaise
  • Weight loss
  • Weakness
  • Shortness of breath
  • Left upper quadrant discomfort (e.g. splenomegaly)
  • Excessive thirst, urination and constipation (myeloma)

Thrombocytopenia may also be secondary to infection and inflammatory/autoimmune disorders, so try to identify symptoms suggestive of these pathologies.

Clinical examination

  • Petechiae (<2 mm)
  • Purpura (0.2-0.1 cm)
  • Ecchymoses
  • Examine for any underlying cause
  • Check for lymphadenopathy and/or hepatosplenomegaly.


Differential Diagnoses

As described above, there are many causes of thrombocytopenia, so when considering your differential diagnosis it may be useful to consider what clinical features are present in order to refine the list.

Consider if this presentation is likely to be due to an inherited or congenital cause, or if it is more likely to be acquired. Helpful points to enquire about include a family history of bleeding disorders, current or new medications, viral infections and past medical history (including malignancy).

Try to then consider possible differential diagnoses using the following three groups:

  • Disorders of platelet production
  • Disorders of platelet survival
  • Disorders of platelet function

If the patient has presented with bleeding only, consider immune destruction of platelets or drug/toxin related thrombocytopenia. 2


When a low platelet count is picked up incidentally, the full blood count must be repeated and a blood smear performed.1

First, it is important to exclude pseudothrombocytopenia. Repeat the platelet count using a tube coated with heparin or citrate.

Specific investigations for thrombocytopenia include:

  • Full blood count (FBC) and blood film
  • Prothrombin time (PT) and activated partial thromboplastin time (aPTT)
  • Renal function
  • Thyroid function tests
  • Bone marrow examination to exclude dysplasia (in those with systemic symptoms suggestive of haematological cancer or over 60 years old)


There are also specific assays of inherited platelet dysfunction:

  • Light transmission aggregometry
  • Flow cytometry (e.g. for GT)
  • Molecular genetic diagnosis of heritable platelet disorders

Further investigations and management will depend on the suspected or confirmed underlying cause.

Prompt referral to a haematologist/oncologist is required if the peripheral blood smear is abnormal.2

Thrombocytopenia blood film
Blood film showing thrombocytopenia 6



Referral to hospital is not usually required if the patient has modest isolated thrombocytopenia (platelet count 100-150 x 109/L), without atypical features such as lymphadenopathy or fever.1

FBC should, however, be rechecked in primary care to ensure that blood counts do not deteriorate. Safety-net patients by explaining that they should come in immediately if they notice new symptoms such as bruising or bleeding.

Urgent referral should be undertaken when there is:

  • Severe thrombocytopenia (20 x 109/L)
  • Severe bleeding
  • Red cell fragments or blasts on the blood film
  • If the patient has constitutional symptoms, bruising, minor bleeding, or abnormalities on examination or blood film.

Consider a discussion with a haematologist if the platelet count is less than 100 x 109/L.


Management of inherited platelet disorders

  • Those patients with severe platelet dysfunction require frequent platelet transfusions.
  • Topical measures can be used for surface bleeds, such as compression with gauze soaked in tranexamic acid, fibrin sealants and packing for nosebleeds.
  • Antifibrinolytic agents are useful for minor surgery.
  • Desmopressin will increase vWF and factor VIII in the plasma, resulting in increased platelet adhesiveness and aggregation.
  • Stem cell/bone marrow transplantation may be successful in some diseases.
  • Female hormones can control excessive bleeding during menarche for patients with certain bleeding disorders.
  • Prevention techniques: vaccination against hepatitis B, avoidance of NSAIDs, good dental hygiene and correction of iron deficiency


Management of acquired platelet disorders

  • This will be specific to the underlying cause, can often include desmopressin and platelet transfusion.
  • Antifibrinolytic therapy may be of use in mucosal bleeding, however, should be avoided in patients with haematuria or DIC.
  • Recombinant activated clotting factor VII [rFVIIa] can be used for both inherited and acquired platelet disorders, however, care must be taken as it is associated with an increased risk of thrombosis.


  • The major complications of thrombocytopenia include excessive and uncontrolled bleeding (e.g. gastrointestinal haemorrhage, intracranial haemorrhage).3

Key Points

  • Thrombocytopenia is defined as a platelet count of <150 x 109/L.
  • The main clinical signs associated with thrombocytopenia include petechiae, bruising, haemoptysis, haematemesis, haematuria, haematochezia and melaena.
  • Important investigations to diagnose thrombocytopenia include FBC with blood smear and clotting studies. Other investigations are used to determine the underlying cause.


  1., Thrombocytopenia and Platelet Function Disorders, Published 14.01.2015. Available from: [LINK]
  2. BMJ Best Practice, Assessment of Thrombocytopenia, Published 2018. Available from: [LINK]
  3. National Heart, Lung and Blood Institute, Thrombocytopenia. Available from: [LINK]
  4. James Heilman, MD. Licence: CC BY-SA. Available from: [LINK]
  5. AfroBrazilian. Licence: CC BY-SA. Available from: [LINK]
  6. Prof. Erhabor Osaro. Licence: CC BY-SA. Available from: [LINK]



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