Thrombocytopenia

geekymedics.com/thrombocytopenia

Zoe Pringle March 23, 2020

Introduction
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.

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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.1

The average platelet life span is around 5 days, meaning even brief disruption to platelet
production or survival can result in thrombocytopenia.

Reduction in platelet production

Reduced platelet production will quickly translate to reduced numbers of platelets in the
circulation due to their relatively short life span (5 days).

Some causes of reduced platelet production include:

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 Viral infections such as herpes simplex virus, cytomegalovirus, varicella-zoster virus,
Epstein-Barr virus, rubella, enterovirus, mumps, hepatitis, and HIV.
Chemotherapy agents: result in direct bone marrow toxicity, inhibiting the production of
platelets.
Aplastic anaemia: a form of bone marrow failure typically of idiopathic aetiology.
Haematological malignancy such as leukaemia: due to crowding of the bone marrow by
malignant cells.
Non-haematological metastatic malignancy: again due to invasion and crowding of the
bone marrow by malignant cells.
B12 and folate deficiency: typically causes macrocytic anaemia and in some cases
thrombocytopenia.
Excess alcohol intake: results in direct bone marrow toxicity and liver cirrhosis.
Congenital conditions including Fanconi’s anaemia, Wiskott-Aldrich syndrome (WAS)
and many others.

Decreased platelet survival

If platelets survive for a shorter duration and the bone marrow is unable to adequately
increase its production of platelets to match those being lost, thrombocytopenia will develop.

Platelet survival can be reduced by immune and non-immune causes.

Immune-mediated decreased platelet survival

Immune-mediated destruction of platelets typically occurs as a result of antibodies being

directed at various platelet components.

Some immune causes of decreased platelet survival include:

Idiopathic thrombocytopenic purpura (ITP): antibodies directed at the surface of

platelets result in their destruction.
Systemic lupus erythematosus
Rheumatoid arthritis
Sarcoidosis
Antiphospholipid syndrome

Non-immune decreased platelet survival

Some non-immune causes of decreased platelet survival include:

Medications (e.g. heparin, carbamazepine, ibuprofen, rifampin, trimethoprim,

vancomycin)
Splenomegaly: the spleen sequesters more platelets than normal, decreasing the total
circulating number of platelets.

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 Haemolytic uraemic syndrome (HUS): toxins from E.coli cause increased
thrombogenicity of the vascular endothelium which results in the consumption of
platelets due to thrombotic microangiopathy.
HELLP syndrome: platelets are consumed due to increased exposure to von
Willebrand’s factor resulting in widespread thrombotic microangiopathy.
Thrombotic thrombocytopenic purpura (TTP): reduction in the function of the enzyme
ADAMTS13 normally responsible for the breakdown of von Willebrand’s factor results
in platelets being excessively consumed due to a similar mechanism as that described
in HELLP syndrome.

Pseudothrombocytopenia
Pseudothrombocytopenia occurs when platelets undergo a phenomenon called
‘clumping’, in which they stick together causing a false low reading when passed through
an auto-analyser.

Clinical features

History

Patients with thrombocytopenia are often asymptomatic until platelets fall to very low
levels (often below 10) and as a result, most cases are detected incidentally on full blood
counts performed for unrelated reasons.

However, if a patient injures themselves or undergoes a procedure whilst significantly

thrombocytopenic (e.g. dental work, surgery) they are at risk of developing major
haemorrhage.

If you suspect a patient may have thrombocytopenia, it is important to take a thorough

bleeding history.

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

Other important areas to cover:

Recent infections

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 Surgical history: ask about previous surgery and if there were any issues with bleeding
or bruising.
Dental history: ask about previous dental procedures and if there was significant
bleeding.
Obstetric history: ask about delivery and associated complications (e.g. post-partum
haemorrhage)
Medication history: ask about current medications (including blood thinning medication)
and any recently prescribed medication or dose changes.
Family history: ask about any history of bleeding problems in the family.

Symptoms of occult malignancy should also be screened for including: 2

Bone pain
Night sweats
Weight loss
Left upper quadrant discomfort (e.g. splenomegaly)
Excessive thirst, urination and constipation (myeloma)

Clinical examination
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.

A lymphoreticular examination should be performed to look for evidence of underlying

haematological malignancy (e.g. lymphadenopathy and/or hepatosplenomegaly).

Petechiae on the lower leg from thrombocytopenia 4

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 Right upper limb with purpura caused by
thrombocytopenia in person with septic shock. 5

Investigations

Blood tests

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

Bone marrow biopsy may be indicated if there are concerns about underlying malignant
invasion of the bone marrow (e.g. leukaemia) or aplastic anaemia.

Genetic screening

Patients may undergo genetic screening if a congenital cause of thrombocytopenia is

suspected.

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 Blood film showing thrombocytopenia 6

Management
There is a wide range of management options for thrombocytopenia which differ depending
on the underlying aetiology. Below is a brief overview of a range of different management
options which may be considered for patients with thrombocytopenia.

Secondary care referral

Hospital referral 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 monitored closely in primary care to
ensure that platelets and other blood counts are not continuing to deteriorate (e.g. aplastic
anaemia). Patients should be advised to seek review if they experience any bleeding or
spontaneous bruising.

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.

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

Patient education

Patients with severe thrombocytopenia are advised:

to avoid contact sports and activities which increase their risk of significant trauma

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 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

If patients with thrombocytopenia require surgical or dental procedures, they may be

provided with treatments to temporarily increase their platelet count (e.g. platelet transfusion,
steroids) or increase clot stability (e.g. tranexamic acid).

Platelet transfusion
Platelet transfusions are often required for patients with severe thrombocytopenia (e.g.
<10 x 109/L) or for those who need a temporary boost to their levels for a procedure (e.g.
major surgery). Transfusions should be used sparingly as there is a risk of alloimmunisation
against HLA antigens and/or platelet glycoproteins.

Platelet transfusions are also used in the emergency setting if patients with
thrombocytopenia are actively bleeding.

Tranexamic acid
Tranexamic acid reduces the conversion of plasminogen to plasmin, preventing fibrin
degradation and increasing clot stability.

Gauze soaked in tranexamic acid may be used to manage superficial 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

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

TPO agonists such as Eltrombopag (daily tablet) and Romiplostim (weekly subcutaneous
injection) directly stimulate the production of platelets by the bone marrow. They are
typically used as a second-line treatment in ITP (if steroids fail) and also in the management
of aplastic anaemia.

Bone marrow transplantation

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Allogenic bone marrow transplantation is only used in cases of severe thrombocytopenia
unresponsive to other therapies (e.g. aplastic anaemia). Treatment involves induction
chemotherapy to wipe out the host’s stem cells and then infusion of donor stem cells in the
hope of curing the underlying pathology. There is a wide range of serious acute and chronic
complications of allogeneic bone marrow transplantation which are beyond the scope of this
article.

Complications
The major potential complication of thrombocytopenia is 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 average platelet life span is around 5 days, meaning even brief disruption to
platelet production or survival can result in thrombocytopenia.
Thrombocytopenia increases the risk of bleeding, however, most cases of
thrombocytopenia are incidentally detected on a routine full blood count (FBC) in
otherwise asymptomatic patients.
Typical clinical signs associated with severe thrombocytopenia include petechiae and
purpura on the skin and mucous membranes.
Key investigations for thrombocytopenia include a full blood count and blood film.
There is a wide range of management options for thrombocytopenia including patient
education, platelet transfusion, tranexamic acid, steroids and TPO receptor
antagonists.
The main potential complication of thrombocytopenia is major haemorrhage.

References
1. Patient.info, 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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