Changes

November to December 2025 — reviewed. A literature search was conducted in October 2025 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last version of this topic. The topic structure has been amended to aid navigation and reduce duplication. The management sections have been expanded and updated in line with current evidence in the literature.

Update

Goals

To support primary healthcare professionals to:

• Review when platelet counts are abnormal.
• Determine the underlying cause of abnormal platelet counts, where possible.
• Manage people with abnormal platelet counts appropriately.
• Arrange emergency admission or specialist referral for people with abnormal platelet counts with appropriate urgency, if needed. 

Outcome measures

No outcome measures were found during the review of this topic.

Audit criteria

No audit criteria were found during the review of this topic.

QOF indicators

No QOF indicators were found during the review of this topic.

QIPP — Options for local implementation

No QIPP indicators were found during the review of this topic.

NICE quality standards

Suspected cancer: recognition and referral

• GPs have direct access to diagnostic endoscopy, ultrasound, MRI, X-ray and CT for people with suspected cancer.
• People presenting in primary care with symptoms that suggest oesophageal or stomach cancer have an urgent direct access upper gastrointestinal endoscopy.
• Adults presenting in primary care with symptoms that suggest colorectal cancer, who do not meet the referral pathway criteria, have a test for blood in their faeces.
• People with suspected cancer who are referred to a cancer service are given written information encouraging them to attend. 

[NICE, 2017]

What is it?

• Platelets, or thrombocytes, are anucleate haematopoietic cells derived from bone marrow megakaryocytes [Aruch, 2020]. The number of circulating platelets is under tight homeostatic control, regulated by the cytokine thrombopoietin. Platelets have a lifespan of 7–10 days, and are responsible for [Morrell, 2014; Sonmez, 2017; Curry, 2020]:
  • Haemostasis and thrombosis — platelets express and secrete adhesion molecules that accumulate in response to endothelial injury, helping in clot formation.
  • Inflammation, infection, and immune host response — platelets secrete immune modulators which are chemotactic for neutrophils, monocytes, and lymphocytes. This interaction results in the formation of platelet-granulocyte or platelet-leukocyte aggregates that trigger a further inflammatory response. Platelets also engulf microbes and prevent the dissemination of bacteria by clot formation.
• The normal laboratory reference range for platelets is 150–450 × 10⁹/L [Curry, 2020]. Laboratory reference ranges may vary [Gauer, 2022].
  • Platelet count varies with age, sex, pregnancy, ethnicity, and genetics (for example, familial thrombocytosis) [Gauer, 2022]. 
• Thrombocytosis is defined as a platelet count greater than 450 × 10⁹/L [Harrison, 2010] [Aruch, 2020].
  • Primary thrombocytosis is caused by an underlying abnormality in bone marrow function, such as a myeloproliferative or myelodysplastic neoplasm [Mathur, 2019; Aruch, 2020].
  • Secondary (reactive) thrombocytosis (80% of cases) describes a proliferation of platelets caused by a response to growth factors released from an underlying inflammatory or malignant condition, and not a primary haematological disorder [Mathur, 2019; Aruch, 2020].
• Thrombocytopenia is defined as a platelet count below 150 × 10⁹/L, which may be subdivided into [Curry, 2020; Gauer, 2022]:
  
  • Mild — over 100 × 10⁹/L.
  • Moderate — 50–100 × 10⁹/L.
  • Severe — less than 50 × 10⁹/L.

How common is it?

Thrombocytosis

• A primary care-based prospective cohort study of 50,000 people aged 40 years or over found that thrombocytosis was present in 1.5–2.2% of the study population [Bailey, 2017].
  
  • 11.6% of men with thrombocytosis were diagnosed with cancer compared with 4.1% of men without thrombocytosis. 
  • 6.2% of women with thrombocytosis were diagnosed with cancer compared with 2.2% of women without thrombocytosis.
  • The risk of cancer increased to 18.1% for men and 10.1% for women if a second platelet count was found to be raised within 6 months.
  • Lung and colorectal cancer were the most commonly diagnosed malignancies.
  • One-third of patients with thrombocytosis and lung or colorectal cancer had no other symptoms indicative of malignancy.

Thrombocytopenia

• Thrombocytopenia is a frequent complication of cancer and its treatment. The incidence and degree of thrombocytopenia are dependent on the type of malignancy, stage, and treatment [Liebman, 2014]. 
• Expert opinion in a review article cites evidence in the literature that the incidence of immune thrombocytopenic purpura is about 1.6–3.9 per 100,000 person-years. It also notes that thrombocytopenia may be seen in up to 76% of people with chronic liver disease and is present in about 20% of people with megaloblastic anaemia due to vitamin B12 and folate deficiency [Sharma, 2014].
• A chapter in the Oxford Textbook of Medicine notes that primary immune thrombocytopenia affects men and women equally, except between the ages of 30–60 years, where it is more common in women. In children, 55–60% of cases occur following an acute viral illness [Curry, 2020].
• Expert opinion in a review article notes that thrombocytopenia develops in 5–10% of all pregnancies [Gauer, 2022]. A chapter in the Oxford Textbook of Medicine states that primary immune thrombocytopenia is estimated to occur in 1 in 1000 to 1 in 10,000 pregnancies [Curry, 2020].

What are the causes of thrombocytosis?

There is a wide range of causes of thrombocytosis, which can be classified as primary or secondary (reactive) [Harrison, 2010]. The degree of thrombocytosis is not helpful in differentiating a reactive from a primary process [Aruch, 2020]. The haematology laboratory report may help guide appropriate further investigations and management.

• Primary thrombocytosis
  • Primary thrombocytosis is caused by an underlying abnormality in bone marrow function, usually due to a myeloproliferative or myelodysplastic disorder. It typically arises from autonomous proliferation of a mutated haematopoietic stem cell or myeloid progenitor cells that give rise to megakaryocytes (platelet parent cells), due to abnormally activated cellular signalling pathways. It can be classified into the following conditions [Harrison, 2010; Mathur, 2019; Aruch, 2020]:
    • Polycythaemia vera — characterized by a raised haemoglobin, haematocrit, and red cell mass, and a marked thrombocytosis in up to 15% of cases.
    • Chronic myeloid leukaemia — may initially present with isolated thrombocytosis. Other features include an elevated white blood cell (WBC) count over 100 × 10⁹/L in 50% of people. Peripheral blood smear shows WBCs are mostly neutrophils, although basophil and eosinophil counts are also commonly raised. See the CKS topic on Haematological cancers - recognition and referral for more information.
    • Essential thrombocythaemia — diagnosis requires a persistent thrombocytosis and the exclusion of secondary causes. Blood film shows varying degrees of platelet anisocytosis and may be atypical hypogranular platelets. There is a risk of thrombotic and bleeding complications, and transformation to myelofibrosis, polycythaemia vera, or acute leukaemia over time.
    • Primary myelofibrosis — may present with a marked thrombocytosis, with or without anaemia, teardrop poikilocytosis, leucocytosis, and a leucoerythroblastic blood film.
    • Myelodysplastic syndromes — typically normochromic or oval macrocytic red blood cells (RBCs) and hypogranular and hypolobulated granulocytes. More commonly associated with thrombocytopenia.
    • Other — including unclassified myeloproliferative neoplasms and myelodysplastic syndromes.
• Secondary thrombocytosis
  • Secondary thrombocytosis proliferation of platelets is driven by thrombopoietic growth factors and cytokines released in response to an inflammatory stimulus caused by a variety of conditions, including [Harrison, 2010; Mathur, 2019; Aruch, 2020]:
    • Iron deficiency — the most common cause of secondary thrombocytosis. See the CKS topic on Anaemia - iron deficiency for more information.
    • Inflammation — including rheumatoid arthritis, systemic lupus erythematosus, axial spondyloarthritis (including ankylosing spondylitis), giant cell arteritis, inflammatory bowel disease, sarcoidosis, and granulomatosis with polyangiitis.
    • Infection — including bacterial infections and hepatitis B.
    • Malignancy, including lung, endometrial, gastro-oesophageal, colorectal, renal, or ovarian cancer. See the CKS topics on Gastrointestinal tract (lower) cancers - recognition and referral, Gastrointestinal tract (upper) cancers - recognition and referral,  Gynaecological cancers - recognition and referral, Lung and pleural cancers - recognition and referral, and Urological cancers - recognition and referral for more information.
    • Splenectomy or hyposplenism (including coeliac disease) — there may be nuclear fragments (Howell-Jolly bodies) on blood smear examination.
    • Acute or chronic bleeding after surgery, trauma, or another cause.
    • Following strenuous exercise.
    • Medication such as corticosteroids.

What are the causes of thrombocytopenia?

There are multiple possible causes of thrombocytopenia, which may result from different mechanisms of reduced platelet production, increased platelet destruction, and increased platelet sequestration [Curry, 2020]. The haematology laboratory report may help guide appropriate further investigations and management.

• Congenital [Provan, 2019] [Curry, 2020] [Gauer, 2022]
  • May decrease platelet production or affect platelet function. Examples include Wiskott-Aldrich syndrome (an X-linked disorder causing reduced platelet production and altered platelet function), Alport syndrome, specific forms of von Willebrand disease, and Fanconi anaemia.
• Reduced platelet production [Provan, 2019] [Curry, 2020] [Ashworth, 2022] [Scully, 2023] 
  • Bone marrow infiltration
    • Haematological malignancy — for example, acute leukaemia, which tends to cause pancytopenia and abnormal lymphoblasts or myeloblasts may be seen on the blood film. Other causes include lymphoma and myeloma. See the CKS topics on Haematological cancers - recognition and referral and Multiple myeloma for more information.
    • Myelofibrosis and myelodysplastic syndrome.
    • Storage disorders (Gaucher's disease) and granulomatous disorders (such as sarcoidosis).
    • Thrombotic microangiopathies associated with cancer — most commonly breast, gastric, prostate, or lung adenocarcinoma, which is often metastatic. See the CKS topics on Breast cancer - recognition and referral, Gastrointestinal tract (upper) cancers - recognition and referral, Lung and pleural cancers - recognition and referral, and Prostate cancer for more information.
  • Drugs and toxins — can cause bone marrow suppression including alcohol (may also cause hypersplenism, nutritional deficiency, and megaloblastic anaemia); drugs such as chemotherapy agents and nonsteroidal anti-inflammatory drugs (NSAIDs). 
  • Aplastic anaemia — bone marrow failure and low megakaryocyte numbers result in low platelet levels.
  • Vitamin B12 and folate deficiency — megaloblastic anaemia and hypersegmented neutrophils may be seen on peripheral blood smear. See the CKS topic on Anaemia - B12 and folate deficiency for more information.
• Increased platelet destruction [Provan, 2019] [Curry, 2020] [Ashworth, 2022] [Gauer, 2022] [Scully, 2023]
  • Primary immune thrombocytopenic purpura (ITP) — this is an acquired immune-mediated disorder and is a diagnosis of exclusion, characterized by an isolated thrombocytopenia with no underlying cause or precipitant. ITP is the commonest cause of thrombocytopenia in early pregnancy.
  • Thrombotic microangiopathies — these are defined by thrombocytopenia, microangiopathic haemolytic anaemia, and thrombosis.
    • Thrombotic thrombocytopenic purpura (TTP) is a rare life-threatening medical emergency. It is usually acquired, immune-mediated, and idiopathic, or associated with autoimmune disease such as lupus erythematosus or scleroderma, pregnancy, postpartum, drugs (such as ciclosporin, quinine, clopidogrel, simvastatin), or infection such as HIV. It is caused by a  cleaving protein deficiency of the von Willebrand factor. This can lead to neurological, cardiac, gastrointestinal, and/or renal end-organ damage and has a high mortality rate, if untreated.
    • Haemolytic uraemic syndrome (HUS) is characterized by microangiopathic haemolytic anaemia, thrombocytopenia, and acute kidney injury, caused by infection with verotoxin-producing Escherichia coli, salmonella, or shigella, usually with a prodrome of bloody diarrhoea.
    • Disseminated intravascular coagulation (DIC) is an acquired syndrome characterized by widespread intravascular activation of the coagulation cascade. It typically presents with bleeding, and may be triggered by sepsis, trauma, toxins, and some malignancies.
    • Pregnancy-related — including haemolysis with elevated liver enzymes and low platelets (HELLP) syndrome or pre-eclampsia/eclampsia. In the presence of new-onset hypertension, a platelet count of less than 100 × 10⁹/L is a haematological diagnostic criterion for pre-eclampsia. Additionally, TTP may present at any trimester in pregnancy, but is more common in the third trimester and post-partum. See the CKS topic on Hypertension in pregnancy for more information.
  • Immune thrombocytopenia associated with other autoimmune disorders — such as rheumatoid arthritis, lupus nephritis, systemic lupus erythematosus, antiphospholipid syndrome, acute scleroderma, sarcoidosis, vasculitis, thyroid disease.
  • Chronic kidney disease.
  • Drug-induced — including calcineurin inhibitors, digoxin, quinidine, quinine, aspirin, nonsteroidal anti-inflammatory drugs, clopidogrel, heparin, bendroflumethiazide, penicillins, sulfonamides, antiseizure medication such as valproic acid. Thrombocytopenia usually occurs after 2–3 days if the medication has been used previously, or after 1–3 weeks if it is a new medication.
  • Infection — typically viral (HIV, hepatitis B or C, cytomegalovirus, Epstein-Barr virus, adenovirus, herpes simplex virus, varicella), bacterial (such as leishmaniasis, meningococcus, pneumococcus), parasitic (such as malaria), or fungal infection can result in transient thrombocytopenia.
  • Post-transfusion purpura (rare) —  presents with severe thrombocytopenia typically developing 5–12 days after a blood transfusion in people who have been previously sensitized to foreign platelet antigens.
  • Paroxysmal nocturnal haemoglobinuria — a clonal stem cell defect leads to maturation defects in megakaryocytes.
• Increased platelet sequestration and disorders of platelet distribution [Provan, 2019] [Curry, 2020] [Ashworth, 2022] [Scully, 2023]
  • Splenomegaly and hypersplenism — approximately 30% of circulating platelets are normally pooled in the spleen. Splenomegaly results in an increase in the size of the pool of platelets sequestered.
  • Portal hypertension — may be caused by heart failure, hepatic vein thrombosis or vena cava thrombosis (Budd-Chiari syndrome), chronic liver disease, and rarely arteriovenous malformation of the splenic vessels.
  • Haemodilutional — may occur after major surgery or large volume blood transfusion. Gestational thrombocytopenia can occur at any time during pregnancy, but most commonly occurs in the mid-second to third trimester. A mean platelet count decrease of 10% is caused by a combination of increased blood volume, increased platelet activation and clearance, and platelet sequestration in the placenta. The platelet count should resolve spontaneously within 1–2 months after delivery.
• Pseudothrombocytopenia [Provan, 2019] [Curry, 2020]
  • This is a spurious laboratory result which occurs when platelets clump together after blood is collected into ethylenediaminetetraacetic acid (EDTA). It occurs in 0.1% of blood samples due to a clinically insignificant autoantibody which causes platelet agglutination. There is no history of bleeding and there are normal circulating platelet counts on the blood film.

How should I assess a person with thrombocytosis?

Review any previous blood test results for thrombocytosis or a rising trend in platelets. The degree of thrombocytosis is not helpful in differentiating a reactive from a primary process.

• Ask about:
  • Any potential cause of secondary thrombocytosis, such as chronic infection, inflammation, or autoimmune conditions, surgery or trauma, cancer, previous splenectomy, or iron deficiency anaemia.
  • Any symptoms suggesting malignancy, such as unexplained fatigue, change in bowel habit, dysphagia, dyspnoea, persistent dyspepsia, post-menopausal bleeding, rectal bleeding, unexplained cough, haemoptysis, and/or weight loss.
  • Any acute symptoms of a myeloproliferative disorder, such as headache, visual changes, atypical chest pain, paraesthesia, itch, vertigo, dizziness, syncope, and seizures.
  • Any venous thrombotic complications, including deep vein thrombosis; hepatic vein thrombosis; pulmonary embolism; or arterial thrombotic complications, including stroke, transient ischaemic attack, acute coronary syndrome, peripheral arterial disease, or erythromelalgia (a microvascular complication seen in essential thrombocythaemia causing redness and burning pain in the extremities).
  • Any bleeding episodes, including gastrointestinal, genitourinary, or easy bruising (for example, due to essential thrombocythaemia).
  • Any risk factors for cardiovascular disease or arterial or venous thrombosis. See the CKS topics on CVD risk assessment and management, Deep vein thrombosis, and Pulmonary embolism for more information.
  • Any history of previous pregnancy complications, such as recurrent miscarriage, bleeding in pregnancy, fetal loss, severe pre-eclampsia, placental abruption, or significant ante- or post-partum haemorrhage.
  • Any family history of familial thrombocytosis, thrombophilia, or cancer.
  • Medication such as corticosteroids or nonsteroidal anti-inflammatory drugs (NSAIDs) which may precipitate bleeding episodes in essential thrombocythaemia.
• Examine the person to assess for signs of a possible underlying cause:  
  • Assess for signs of acute or chronic bleeding, anaemia, infection, inflammatory or autoimmune conditions, and malignancy.
  • Assess for signs of arterial or venous thrombosis.
  • Assess for hepatosplenomegaly — suggests a primary thrombocytosis such as essential thrombocythaemia.
  • Check peripheral pulses if there is suspected erythromelalgia (causes red, tender extremities) — pulses are often normal.
• Arrange investigations to assess for a possible underlying cause, depending on clinical judgement.
  
  • Repeat the full blood count (FBC) and peripheral blood smear, which may show other features suggesting an underlying cause, including acute infection, inflammation, or iron deficiency.
    • A blood smear can confirm true thrombocytosis and exclude spurious causes (such as other red cell abnormalities including microspherocytes and fragments).
    • In reactive thrombocytosis, the platelets are mostly small with a low mean platelet volume, compared with essential thrombocythaemia or people with normal platelets.
    • In chronic infective or inflammatory processes, there may be signs of anaemia of chronic disease.
  • Check for iron deficiency. See the CKS topic on Anaemia - iron deficiency for more information.
  • C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) — these are usually raised in secondary thrombocytosis, but normal values do not exclude inflammation or malignancy.
  • Bloods for genetic mutations such as Janus kinase-2 (JAK-2), MPL, and/or CALR depending on local laboratory test availability — if positive, suggests a myeloproliferative neoplasm such as essential thrombocythaemia or polycythaemia vera.
  • Virology screen such as hepatitis B. See the CKS topic on Hepatitis B for more information.
  • Coeliac screen. See the CKS topic on Coeliac disease for more information.
  • Consider arranging initial investigations for occult malignancy, such as chest X-ray, renal tract and pelvic ultrasound scan, serum Ca-125, and faecal immunohistochemical test (FIT). See the CKS topics on Lung and pleural cancers - recognition and referral, Gynaecological cancers - recognition and referral, Gastrointestinal tract (lower) cancers - recognition and referral, and Urological cancers - recognition and referral for more information.

How should I assess a person with thrombocytopenia?

Review any previous blood test results for thrombocytopenia or a falling trend in platelets.

• Ask about:
  • Any history of excessive or prolonged bleeding, such as nosebleeds, gum bleeding, skin bruising, haematuria, menorrhagia, gastrointestinal or genitourinary bleeding, haemoptysis, retinal haemorrhage, or after surgery, dental procedures, or trauma.
  • Any non-specific symptoms such as fatigue, fever, night sweats, unexplained weight loss, or bone pain, which may suggest malignancy, HIV infection, or another underlying cause such as acute thrombotic thrombocytopenic purpura (TTP).
  • Any neurological symptoms (often transient) such as confusion, headache, paraesthesia, weakness, seizures, speech disturbance or visual disturbance or cardiac symptoms such as chest pain.
  • Any gastrointestinal symptoms such as abdominal pain or diarrhoea.
  • Any recent illnesses or infections, autoimmune or inflammatory conditions, malignancy, pregnancy status, surgery, or blood transfusion.
  • Any symptoms in pregnancy, such as headache, visual disturbance, or right upper quadrant pain (particularly beyond 20 weeks' gestation), which may suggest pre-eclampsia and/or haemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. See the CKS topic on Hypertension in pregnancy for more information.
  • Any history of previous pregnancy complications, including post-partum haemorrhage or fetal loss.
  • Alcohol intake, nutrition and diet, vaccination and travel history (for example, to malaria-endemic areas), and drug misuse.
  • Any family history of thrombocytopenia or bleeding disorders.
  • Any prescribed or over-the-counter drugs that can cause thrombocytopenia or increase bleeding risk, such as recent heparin exposure, nonsteroidal anti-inflammatory drugs (NSAIDs), antiplatelet or anticoagulant therapy.
  • Any previous history of thrombocytopenia, other haematological disorders, or venous thromboembolism.
• Examine the person to assess for signs of a possible underlying cause. 
  • Check pulse and blood pressure — acute TTP may present with hypotension; pre-eclampsia and HELLP syndrome may present with hypertension in pregnancy. See the CKS topic on Hypertension in pregnancy for more information.
  • Neurological signs such as confusion, paresis, aphasia, dysarthria, visual disturbance, and coma — may suggest acute TTP.
  • Fever, pallor, jaundice — may suggest acute TTP or infection.
  • Signs of joint, soft tissue, or mucocutaneous bleeding, retinal haemorrhage, petechiae, purpura, bruising, or skin necrosis — may suggest acute TTP or ITP.
  • Lymphadenopathy, hepatosplenomegaly — may indicate acute leukaemia, lymphoma, liver disease, hypersplenism, viral infection.
  • Other evidence of liver disease. See the CKS topics on Cirrhosis and Jaundice in adults for more information.
  • Digital ischaemia and/or swollen extremities, bony tenderness, joint deformity, and signs of connective tissue disease.
• Arrange investigations to assess for a possible underlying cause, depending on clinical judgement.
  • Repeat the full blood count and blood film with reticulocyte count (raised in TTP), and assess the trend.
    • There may be microcytic anaemia if blood loss, or fragmented red blood cells (schistocytes) seen on peripheral blood film, suggesting microangiopathic haemolytic anaemia in TTP, for example.
    • A raised reticulocyte count may suggest haemolysis if there is associated anaemia.
    • Leucoerythroblastic changes such as teardrop-shaped red blood cells and immature white blood cells suggest bone marrow infiltration.
    • Atypical lymphocytes may suggest a viral infection.
    • Excessive giant or small platelets may suggest inherited thrombocytopenia.
  • Coagulation screen, including prothrombin time/fibrinogen to identify clotting abnormalities — the coagulation screen may be normal in TTP.
  • Urea and electrolytes — may present with acute kidney injury in acute TTP or may suggest haemolytic uraemic syndrome (HUS). See the CKS topic on Acute kidney injury for more information.
  • Liver function tests — may be normal in acute TTP; may be raised bilirubin if haemolysis.
  • Thyroid function tests — to exclude Graves' disease.
  • HbA1c — to exclude diabetes mellitus. See the CKS topics on Diabetes - type 1 and Diabetes - type 2 for more information.
  • Vitamin B12 and folate levels, iron studies — to exclude deficiency. See the CKS topics on Anaemia - B12 and folate deficiency and Anaemia - iron deficiency for more information.
  • Autoimmune screen — antiphospholipid antibodies, antinuclear antibodies, lupus anticoagulant, rheumatoid factor, anti-CCP antibodies — to exclude associated autoimmune disease.
  • HIV, hepatitis B and C screen, and other virology screens such as Epstein-Barr virus, cytomegalovirus, or varicella virus — to exclude a viral precipitant of TTP. See the CKS topics on Hepatitis B, Hepatitis C, and HIV infection and AIDS for more information.
  • Urine dip and urine albumin:creatinine ratio (ACR) — to assess for non-visible haematuria and proteinuria. See the CKS topic on Acute kidney injury for more information.
  • Stool sample for culture and sensitivity — if HUS is suspected. See the CKS topic on Diarrhoea - adult's assessment for more information.
  • Pregnancy test — if clinically indicated.

Scenario: Management of abnormal platelet counts

From age 16 years onwards.

Search strategy

Scope of search

A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on the primary care assessment and initial management of people with abnormal platelet counts of unknown cause.

Search dates

January 2021 - October 2025

Key search terms

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline:

• "Thrombocytosis"/di [Diagnosis]
• *"Thrombocytosis"/bl [Blood]
• Thrombocytopenia/bl, di [Blood, Diagnosis]
• Blood Platelets/ep [Epidemiology]
• Blood Platelets/ab [Abnormalities]
• "Predictive Value of Tests"/
• "low platelet count".ti,ab.
• “elevated or high platelet count”.ti,ab.
• Thrombocytosis or thrombocytop?enia or thrombocyth?emia.ti,ab.

Sources of guidelines

• National Institute for Health and Care Excellence (NICE)
• Scottish Intercollegiate Guidelines Network (SIGN)
• Royal College of Physicians
• Royal College of General Practitioners
• Royal College of Nursing
• NICE Evidence
• Health Protection Agency
• World Health Organization
• National Guidelines Clearinghouse
• Guidelines International Network
• TRIP database
• GAIN
• NHS Scotland National Patient Pathways
• New Zealand Guidelines Group
• Agency for Healthcare Research and Quality
• National Health and Medical Research Council (Australia)
• Royal Australian College of General Practitioners
• British Columbia Medical Association
• Canadian Medical Association
• Alberta Medical Association
• University of Michigan Medical School
• Michigan Quality Improvement Consortium
• Singapore Ministry of Health
• National Resource for Infection Control
• Patient UK Guideline links
• UK Ambulance Service Clinical Practice Guidelines
• RefHELP NHS Lothian Referral Guidelines
• Medline (with guideline filter)
• Driver and Vehicle Licensing Agency
• NHS Health at Work (occupational health practice)

Sources of systematic reviews and meta-analyses

• The Cochrane Library:
  • Systematic reviews
  • Protocols
  • Database of Abstracts of Reviews of Effects
• Medline (with systematic review filter)
• EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

• NIHR Health Technology Assessment programme
• The Cochrane Library:
  • NHS Economic Evaluations
  • Health Technology Assessments
• Canadian Agency for Drugs and Technologies in Health
• International Network of Agencies for Health Technology Assessment

Sources of randomized controlled trials

• The Cochrane Library:
  • Central Register of Controlled Trials
• Medline (with randomized controlled trial filter)
• EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

• Drug & Therapeutics Bulletin
• TRIP database
• Central Services Agency COMPASS Therapeutic Notes

Sources of national policy

• Department of Health
• Health Management Information Consortium (HMIC)

Patient experiences

• Healthtalkonline
• BMJ - Patient Journeys
• Patient.co.uk - Patient Support Groups

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

• British National Formulary (BNF)
• electronic Medicines Compendium (eMC)
• European Medicines Agency (EMEA)
• LactMed
• Medicines and Healthcare products Regulatory Agency (MHRA)
• REPROTOX
• Scottish Medicines Consortium
• Stockley's Drug Interactions
• TERIS
• TOXBASE
• Micromedex
• UK Medicines Information

Stakeholder engagement

Our policy

The external review process is an essential part of CKS topic development. Consultation with a wide range of stakeholders provides quality assurance of the topic in terms of:

• Clinical accuracy.
• Consistency with other providers of clinical knowledge for primary care.
• Accuracy of implementation of national guidance (in particular NICE guidelines).
• Usability.

Principles of the consultation process

• The process is inclusive and any individual may participate.
• To participate, an individual must declare whether they have any competing interests or not. If they do not declare whether or not they have competing interests, their comments will not be considered.
• Comments received after the deadline will be considered, but they may not be acted upon before the clinical topic is issued onto the website.
• Comments are accepted in any format that is convenient to the reviewer, although an electronic format is encouraged.
• External reviewers are not paid for commenting on the draft topics.
• Discussion with an individual or an organization about the CKS response to their comments is only undertaken in exceptional circumstances (at the discretion of the Clinical Editor or Editorial Steering Group).
• All reviewers are thanked and offered a letter acknowledging their contribution for the purposes of appraisal/revalidation.
• All reviewers are invited to be acknowledged on the website. All reviewers are given the opportunity to feedback about the external review process, enabling improvements to be made where appropriate.

Stakeholders

• Key stakeholders identified by the CKS team are invited to comment on draft CKS topics. Individuals and organizations can also register an interest to feedback on a specific topic, or topics in a particular clinical area, through the Getting involved section of the Clarity Informatics website.
• Stakeholders identified from the following groups are invited to review draft topics:
  • Experts in the topic area.
  • Professional organizations and societies (for example, Royal Colleges).
  • Patient organizations, Clarity has established close links with groups such as Age UK and the Alzheimer’s Society specifically for their input into new topic development, review of current topic content and advice on relevant areas of expert knowledge.
  • Guideline development groups where the topic is an implementation of a guideline.
  • The British National Formulary team.
  • The editorial team that develop MeReC Publications.
• Reviewers are provided with clear instructions about what to review, what comments are particularly helpful, how to submit comments, and declaring interests.

Patient engagement

Clarity Informatics has enlisted the support and involvement of patients and lay persons at all stages in the process of creating the content which include:

• Topic selection
• Scoping of topic
• Selection of clinical scenarios
• First draft internal review
• Second draft internal review
• External review
• Final draft and pre-publication

Our lay and patient involvement includes membership on the editorial steering group, contacting expert patient groups, organizations and individuals.

Evidence exclusion criteria

Our policy

Scoping a literature search, and reviewing the evidence for CKS is a methodical and systematic process that is carried out by the lead clinical author for each topic. Relevant evidence is gathered in order that the clinical author can make fully informed decisions and recommendations. It is important to note that some evidence may be excluded for a variety of reasons. These reasons may be applied across all CKS topics or may be specific to a given topic.

Studies identified during literature searches are reviewed to identify the most appropriate information to author a CKS topic, ensuring any recommendations are based on the best evidence. We use the principles of the GRADE and PICOT approaches to assess the quality of published research. We use the principles of AGREE II to assess the quality of published guidelines.

Standard exclusions for scoping literature:

• Animal studies
• Original research is not written in English

Possible exclusions for reviewed literature:

• Sample size too small or study underpowered
• Bias evident or promotional literature
• Population not relevant
• Intervention/treatment not relevant
• Outcomes not relevant
• Outcomes have no clear evidence of clinical effectiveness
• Setting not relevant
• Not relevant to UK
• Incorrect study type
• Review article
• Duplicate reference

Organizational, behavioural and financial barriers

Our policy

The CKS literature searches take into consideration the following concepts, which are discussed at the initial scoping of the topic.

• Feasibility
  • Studies are selected depending on whether the intervention under investigation is available in the NHS and can be practically and safely undertaken in primary care.
• Organizational and Financial Impact Analysis
• Studies are selected and evaluated on whether the intervention under investigations may have an impact on local clinical service provision or national impact on cost for the NHS. The principles of clinical budget impact analysis are adhered to, evaluated and recorded by the author. The following factors are considered when making this assessment and analysis.
  • Eligible population
  • Current interventions
  • Likely uptake of new intervention or recommendation
  • Cost of the current or new intervention mix
  • Impact on other costs
  • Condition-related costs
  • In-direct costs and service impacts
  • Time dependencies
• Cost-effectiveness or cost-benefit analysis studies are identified where available. 

We also evaluate and include evidence from NICE accredited sources which provide economic evaluations of recommendations, such as NICE guidelines. When a recommended action may not be possible because of resource constraints, this is explicitly indicated to healthcare professionals by the wording of the CKS recommendation.

Declarations of interest

Our policy

Clarity Informatics requests that all those involved in the writing and reviewing of topics, and those involved in the external review process to declare any competing interests. Signed copies are securely held by Clarity Informatics and are available on request with the permission of the individual. A copy of the declaration of interest form which participants are asked to complete annually is also available on request. A brief outline of the declarations of interest policy is described here and full details of the policy is available on the Clarity Informatics website. Declarations of interests of the authors are not routinely published, however competing interests of all those involved in the topic update or development are listed below. Competing interests include:

• Personal financial interests
• Personal family interest
• Personal non-financial interest
• Non-personal financial gain or benefit

Although particular attention is given to interests that could result in financial gains or losses for the individual, competing interests may also arise from academic competition or for political, personal, religious, and reputational reasons. An individual is not obliged to seek out knowledge of work done for, or on behalf of, the healthcare industry within the departments for which they are responsible if they would not normally expect to be informed.

Who should declare competing interests?

Any individual (or organization) involved in developing, reviewing, or commenting on clinical content, particularly the recommendations should declare competing interests. This includes the authoring team members, expert advisers, external reviewers of draft topics, individuals providing feedback on published topics, and Editorial Steering Group members. Declarations of interest are completed annually for authoring team and editorial steering group members, and are completed at the start of the topic update and development process for external stakeholders.

Competing interests declared for this topic:

None.