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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
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.
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)
Excessive bleeding during or after surgery (even minor)
Bleeding after aspirin
Be aware of non-specific associated symptoms that may indicate malignancy: 2
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.
Petechiae (<2 mm)
Purpura (0.2-0.1 cm)
Examine for any underlying cause
Check for lymphadenopathy and/or hepatosplenomegaly.
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 fullbloodcount must be repeated and a bloodsmear 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)
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
Referral to hospital is not usually required if the patient has modestisolatedthrombocytopenia (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.
Urgentreferral should be undertaken when there is:
Severe thrombocytopenia (20 x 109/L)
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
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.
Patient.info, Thrombocytopenia and Platelet Function Disorders, Published 14.01.2015. Available from: [LINK]
BMJ Best Practice, Assessment of Thrombocytopenia, Published 2018. Available from: [LINK]
National Heart, Lung and Blood Institute, Thrombocytopenia. Available from: [LINK]
James Heilman, MD. Licence: CC BY-SA. Available from: [LINK]