- Platelet counts below 30x109/l can result in clinically significant bleeding.

- Thrombocytopenia can be caused by aplastic anaemia.

- Infectious diseases, especially viruses, can cause thrombocytopenia.

- Idiopathic thrombocytopenic purpura is an immune thrombocytopenia.

- A benign low platelet count is seen in 5 per cent of pregnancies.


Thrombocytopenia is the term applied when the peripheral blood platelet count falls below 150x109/l. The problem is common in practice, but generally it presents no major clinical problems.

However, if the platelet count falls below 30x109/l, significant bleeding might occur. The most serious consequence of bleeding in this situation is an intracranial haemorrhage.

This review will cover the essential points related to thrombocytopenia, and provide a starting point for primary care doctors to institute appropriate investigations and treatment.

Ultimately many of these patients end up being referred for specialist assessment, but some investigations can be usefully carried out before the referral is made (see table right). These might provide major clues that can indicate the aetiology of the thrombocytopenia.

The reason thrombocytopenia is taken so seriously is because platelets play a key role in primary haemostasis. Following cuts or other injury, the platelets are responsible for securing initial haemostasis. The clotting factors come in later and help maintain the clot around the platelet plug.

This explains why individuals taking aspirin bleed longer following cuts.

Aspirin interferes with normal platelet function, and so interferes with this initial part of the haemostatic process. It also explains why haemophiliacs have a normal bleeding time.

Quantitative or qualitative?

Their platelets work perfectly well, but it is their coagulation factor deficiency that is the cause of their problem. Disorders of platelets may either be quantitative, that is to say they are present in reduced numbers, or qualitative - they exhibit abnormal function.

Pseudothrombocytopenia The commonest cause of pseudothrombocytopenia is when platelet clumping occurs due to the ethylene-dinitro-tetra-acetic acid (EDTA) anticoagulant in the FBC collection bottle. EDTA is ideal for haematology because it does not distort the blood cells. The incidence of pseudothrombocytopenia in this context is about 0.1 per cent. The haematology laboratory can exclude this occurrence by examining the blood film.

This will show the presence of numerous large platelet clumps. To confirm that the in vivo platelet count is normal, the FBC should be taken in citrate rather than EDTA.


- Repeat FBC and request blood film to confirm thrombocytopenia is real, and exclude other diseases such as chronic lymphocytic leukaemia and myelodysplastic syndromes.

- U&E to detect renal impairment or haemolytic uraemic syndrome and LFTs (liver disease).

- Viral serology (Epstein Barr virus, hepatitis screening; HIV if appropriate).

- Immunoglobulins to exclude common variable immunodeficiency; autoimmune screen (anti-nuclear antibodies, to exclude autoimmune diseases such as SLE).

- B12 and folate can cause pancytopenia or single cytopenia such as thrombocytopenia.


Thrombocytopenia can occur due to reduced platelet production, or increased platelet destruction. In the latter, the cause might be non-immunological, or the platelets might be destroyed through an immunological mechanism that is antibody or immune complex-mediated.

Bone marrow failure Bone marrow failure syndromes are where there is a failure of bone marrow precursor (stem) cells. This is in contrast to myelodysplastic syndromes, where normal or increased numbers of abnormal cells are produced.

The bone marrow failure syndromes are a diverse group of disorders with a common endpoint, where there is a loss of haematopoietic stem cells.

This type of marrow failure can be acquired or inherited. Aplastic anaemia is the classic example of a bone marrow failure syndrome. Often no cause is found (idiopathic aplastic anaemia), but there are a number of known causes. Commonly used drugs that can cause aplastic anaemia include chloramphenicol, gold compounds and prochlorperazine.

Viruses might be responsible, including hepatitis C, Epstein Barr and cytomegaloviruses.

Chemicals can also trigger the disorder, although the mechanism is unknown.

Pesticides, dyes and aromatic hydrocarbons such as toluene and benzene have all been implicated.

Increased platelet destruction Disseminated intravascular coagulation (DIC) is an uncommon but serious cause of non-immunological thrombocytopenia. In DIC, there is excessive activation of the coagulation cascade caused by some major underlying disorder. Conditions that can precipitate this include sepsis, trauma and pre-eclampsia.

The main consequence of DIC is bleeding, which might be so severe that there is generalised oozing from venepuncture sites, central lines and other indwelling cannulae, as well as from the gastrointestinal and genito-urinary tracts.

DIC should be suspected in any very sick patient bleeding from multiple sites. Their management requires urgent admission to hospital.

Thrombotic thrombocytopenic purpura Thrombotic thrombocytopenic purpura (TTP) and haemolytic uraemic syndrome (HUS) are syndromes that overlap and are characterised by disseminated microangiopathy. TTP is more common in adults, while HUS is seen more often in children.

The disorders are very uncommon, so GPs are unlikely to see them. But there have been outbreaks of HUS that have been caused by E coli 0157.

This is the verotoxin-producing strain.

Both TTP and HUS require urgent admission for specialist care. They should be considered in patients with thrombocytopenia who have renal impairment and a fever.

One distinguishing factor is that neurological disturbances are a feature of TTP, but not of HUS.


- Thrombocytopenia can occur due to lack of platelet production, or increased destruction.

- Disseminated intravascular coagulation is uncommon but a serious cause of non-immunological thrombocytopenia.

- Thrombotic thrombocytopenic purpura (TTP) and haemolytic uraemic syndrome (HUS) are characterised by disseminated microangiopathy.

- There have been outbreaks of HUS caused by E coli 0157.


Blood transfusion

Thrombocytopenia can occur if a patient has a large blood transfusion. Any transfusion in which the patient's total blood volume is replaced over a short time period - usually considered to be 24 hours or less - might lead to thrombocytopenia. This effect is largely due to dilution.

Liver disease

Liver disease can lead to many complications, both haematological and non-haematological. In alcoholics with associated liver disease, thrombocytopenia can occur due to a variety of mechanisms including hepatic cirrhosis, splenomegaly and folic acid deficiency.

However, thrombocytopenia might be found in the absence of these pathologies.

This is probably due to the toxic effects of alcohol directly on the bone marrow, since ethanol is a poison and can suppress the production of platelets.

Infectious diseases

Many infectious diseases can cause thrombocytopenia, and this effect is shown by a number of different infecting agents that might be bacterial, fungal, viral or protozoal.

Viruses that are frequently implicated include mumps, varicella, Epstein Barr virus and rubella, but in reality any virus might induce thrombocytopenia.

Viral infection is the commonest cause of mild or transient thrombocytopenia.

This is defined as a platelet count between 100x109/l to 150x109/l.

HIV infection

HIV infection induces thrombocytopenia through a variety of mechanisms, including immune thrombocytopenia with reduced platelet lifespan, and through direct infection of the megakaryocytes.

About 40 per cent of HIV-positive patients develop thrombocytopenia at some point of their illness.

In approximately 10 per cent of HIV-positive people, thrombocytopenia is the presenting feature. Thrombocytopenia might be a feature of both vitamin B12 and folate deficiency.

Mild thrombocytopenia is found in 20 per cent of patients with megaloblastic anaemia caused by vitamin B12 deficiency. The underlying mechanism of thrombocytopenia in this situation is the ineffective production of platelets.


- A massive transfusion might lead to thrombocytopenia.

- In alcoholics, thrombocytopenia can occur due to number of reasons.

- HIV infection can induce thrombocytopenia.

- Thrombocytopenia might be a feature of both vitamin B12 and folate deficiency.


Although there are other forms of immune thrombocytopenia, idiopathic thrombocytopenic purpura (ITP) is the most important.

What causes ITP?

In ITP, the platelets are coated with anti-platelet autoantibodies and removed prematurely by the spleen, liver and lymph nodes, causing a reduced platelet count. The cause of ITP is unknown, and the clinical course is variable and unpredictable.

The acute form normally occurs in childhood and lasts for less than six months. It is seasonal, and typically follows a trivial viral infection or a vaccination.

Clinical features of acute ITP

The disorder is most common in children between two and five years and, unlike adult chronic ITP, there is no sex predominance. Affected children are generally well. Physical signs of thrombocytopenia usually take the form of bruising or petechial haemorrhages. Splenomegaly, hepatomegaly and lymphadenopathy are not features of acute ITP. If they are present, then ITP is not likely to be the problem. An FBC should show an isolated thrombocytopenia with otherwise normal indices. The platelet count is often less than 10x109/l. Anaemia might be present in cases where there has been significant bleeding.

Management If the child is well, and the picture fits the diagnosis of ITP, then little else need be done except for reassurance. Patients should be referred to a paediatric haematologist, who will monitor recovery and arrange any other investigations. Most children with acute ITP will get better without any specific therapy. Treatment with steroids or intravenous immunoglobulin is only used when bleeding is a problem.

Chronic ITP

Chronic ITP is the most common form of ITP in adults, and affects women more than men, an occurrence typical of autoimmune disease. It runs a prolonged course (more than six months), and often continues for years or even for life.

Spontaneous recovery is unusual. Patients might be asymptomatic or have purpura, bruising, gum bleeding, retinal haemorrhage, epistaxis, melaena or menorrhagia. The degree of bleeding is dependent on the platelet count.

Patients with platelet counts below 10x109/l are at the greatest risk, but most patients have few serious bleeding problems. Splenomegaly is not a feature of chronic ITP.


The diagnosis is made on clinical grounds. There is no test for ITP, and all other disorders that can produce a low platelet count need to be excluded. If all these investigations are found to be negative, then the patient is treated as having ITP. Secondary causes to consider include systemic lupus erythematosus (SLE), lymphoproliferative disease and HIV infection.

An FBC will confirm an isolated thrombocytopenia, and a blood film will exclude red cell fragments (as seen in TTP), and other diseases such as leukaemia or parasitic infections. An autoimmune screen will help exclude SLE.

Treatment is generally initiated in secondary care. Corticosteroids, given as prednisolone at a dose of 1mg/kg/day, or intravenous immunoglobulin, are the main treatments.


- In ITP, the platelets are removed prematurely by the spleen, liver and lymph nodes.

- Acute ITP is most common in children between the ages of two and five, and no treatment is usually required.

- This is a clinical diagnosis because there is no test for ITP.


Low platelet counts are seen in 5 per cent of pregnancies, but most are a benign dilutional thrombocytopenia that has no clinical consequences for mother, fetus or the newborn because it is not antibody-mediated.

A few patients will have true ITP and this can cause bleeding in the mother and the baby because the mother's IgG can cross the placenta and coat the fetal or neonatal platelets. The severity of the mother's thrombocytopenia does not predict that of the fetus or newborn. Usually gestational thrombocytopenia occurs in the third trimester, and is mild and self-limiting.

ITP in pregnancy often occurs earlier, is more severe and can have serious consequences for mother and baby due to bleeding. Thrombocytopenia in pregnancy requires specialist assessment by a haematologist.

Drug-induced immune thrombocytopenia

Despite many reports of drugs capable of inducing immune-mediated platelet destruction, there is good evidence for only a handful of these, namely heparin, quinine/quinidine, gold and co-trimoxazole. Heparin-induced thrombocytopenia is a serious drug-induced platelet disorder, but it is not often seen in general practice.

Affected patients are usually hospital inpatients on unfractionated rather than low molecular weight heparin.

The reaction is antibody-mediated and causes marked thrombocytopenia, but it is the accompanying thrombosis that causes the most serious problems, often affecting the limbs.

Many drugs will induce thrombocytopenia in a predictable fashion that can be anticipated, such as chemotherapy for malignancy.

When to refer

One factor when considering the degree of urgency for referral for a haematological opinion is the platelet count.

Levels of 100-150x109/l in a well patient can be non-urgent.

If the level is 50-100x109/l, the need is fairly urgent, and if it is below 50x109/l, refer urgently. If the patient is ill, then any degree of thrombocytopenia deserves referral.


- Dilutional thrombocytopenia of pregnancy usually has no clinical consequences.

- ITP in pregnancy can be severe and have serious consequences for mother and baby.

- Heparin, quinine/quinidine, gold and co-trimoxazole can cause immune-mediated thrombocytopenia.

Further reading

Oxford Handbook of Clinical Haematology, second edition by D Provan, C R J Singer, T Baglin and J Lilleyman, published by Oxford University Press (2004).

George J N. Platelets. Lancet 2000; 355: 1,531-9.

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