Splenomegaly in adults and children (found on examination or ultrasound)

Urgent laboratory tests (the same day)

• Thin and thick blood film (search for malaria)
• FBC with platelets
• The result must be returned no later than 4 hours after sampling: if the community laboratory cannot guarantee this, or in the presence of any sign of severity, refer to the emergency department.

• Confirm by abdominal ultrasound (spleen generally more than 10 cm in long axis).

Laboratory tests

• FBC with platelets (film read by the laboratory scientist if abnormal)
• AST
• ALT
• GGT
• Alkaline phosphatase
• Bilirubin
• Serum creatinine with eGFR (depending on the clinical context)if needednon-French guidelineThe American review on which this tab is based states that the initial work-up may include a full metabolic panel, creatinine included ^[1]. The British Lothian and York pathways and the Manitoba algorithm detail their work-up without naming it ^[5,6,7].
• Monospot test (adolescent or young adult with fever, sore throat, fatigue)if needednon-French guidelineIn a young adult with splenomegaly, general symptoms and sore throat, testing for heterophile antibodies often confirms mononucleosis and may be enough ^[1].
• PT (if liver disease or alcohol)if needednon-French guidelineHistory of liver disease or alcohol consumption: cirrhosis is a frequent cause (up to one third of splenomegaly) ^[1].
• HIV, hepatitis B and C, syphilis serology (if risk factor: risky sexual intercourse, injecting drug use)if needednon-French guidelineAt-risk sexual intercourse or intravenous drug use; weight loss, sweats, lymphadenopathy (HIV) ^[1].
• Reticulocyte countif needednon-French guidelineAnaemia or symptoms of anaemia: look for autoimmune haemolytic anaemia ^[1].
• LDHif needednon-French guidelineAnaemia or symptoms of anaemia: look for autoimmune haemolytic anaemia ^[1].
• Haptoglobinif needednon-French guidelineAnaemia or symptoms of anaemia: look for autoimmune haemolytic anaemia ^[1].
• Direct Coombs testif needednon-French guidelineAnaemia or symptoms of anaemia: look for autoimmune haemolytic anaemia ^[1].
• CRPif needednon-French guidelineThe Scottish NHS Lothian guide (2026) includes them in the primary care work-up, and a raised LDH is a reason for urgent referral in Manchester ^[5,8]. The American review on which this tab is based reserves CRP for suspected rheumatoid arthritis and LDH for anaemia ^[1].
• LDHif needednon-French guidelineThe Scottish NHS Lothian guide (2026) includes them in the primary care work-up, and a raised LDH is a reason for urgent referral in Manchester ^[5,8]. The American review on which this tab is based reserves CRP for suspected rheumatoid arthritis and LDH for anaemia ^[1].
• Serum protein electrophoresis, serum immunoglobulins (IgG, IgA, IgM) (to look for a lymphoid malignancy)if needednon-French guidelineLothian and York (UK) request them before haematologist advice, Manitoba (Canada) requests electrophoresis in anaemia, and a monoclonal peak is a reason for urgent referral in Manchester ^[5,6,7,8]. The American review on which this tab is based does not cite them ^[1].
• Antinuclear antibodies (ANA)if needednon-French guidelineLupus and rheumatoid arthritis are causes of splenomegaly: the Scottish NHS Lothian guide requests these antibodies when there are suggestive signs, Manchester an autoimmune work-up before referral ^[5,8], and the American review anti-citrullinated peptide antibodies in the presence of arthralgia ^[1].
• Anti-CCP antibodiesif needednon-French guidelineLupus and rheumatoid arthritis are causes of splenomegaly: the Scottish NHS Lothian guide requests these antibodies when there are suggestive signs, Manchester an autoimmune work-up before referral ^[5,8], and the American review anti-citrullinated peptide antibodies in the presence of arthralgia ^[1].
• EBV serologyif needednon-French guidelineThe British pathways request EBV serology (Lothian, Manchester) and CMV serology (York) before advice ^[5,6,8]. The American review on which this tab is based requests anti-CMV antibodies between 15 and 24 years of age in fever, malaise and sore throat ^[1].
• CMV serologyif needednon-French guidelineThe British pathways request EBV serology (Lothian, Manchester) and CMV serology (York) before advice ^[5,6,8]. The American review on which this tab is based requests anti-CMV antibodies between 15 and 24 years of age in fever, malaise and sore throat ^[1].

• Unexplained splenomegaly or hepatosplenomegaly with petechiae: immediate specialist opinion (suspected leukaemia), without waiting for community laboratory results.
• Confirm and measure by abdominal ultrasound (norms according to age).

Laboratory tests

• FBC with platelets
• Blood film examination
• Reticulocyte count
• CRP
• ASTif needednon-French guidelineHepatomegaly, jaundice or history of liver disease: liver disease and portal hypertension (cirrhosis, fibrosis, portal vein thrombosis, cavernoma) are causes of congestive splenomegaly; liver enzymes are part of their diagnosis ^[9].
• ALTif needednon-French guidelineHepatomegaly, jaundice or history of liver disease: liver disease and portal hypertension (cirrhosis, fibrosis, portal vein thrombosis, cavernoma) are causes of congestive splenomegaly; liver enzymes are part of their diagnosis ^[9].
• GGTif needednon-French guidelineHepatomegaly, jaundice or history of liver disease: liver disease and portal hypertension (cirrhosis, fibrosis, portal vein thrombosis, cavernoma) are causes of congestive splenomegaly; liver enzymes are part of their diagnosis ^[9].
• Alkaline phosphataseif needednon-French guidelineHepatomegaly, jaundice or history of liver disease: liver disease and portal hypertension (cirrhosis, fibrosis, portal vein thrombosis, cavernoma) are causes of congestive splenomegaly; liver enzymes are part of their diagnosis ^[9].
• Bilirubinif needednon-French guidelineHepatomegaly, jaundice or history of liver disease: liver disease and portal hypertension (cirrhosis, fibrosis, portal vein thrombosis, cavernoma) are causes of congestive splenomegaly; liver enzymes are part of their diagnosis ^[9].
• LDH (if anaemia or jaundice)if needednon-French guidelineAnaemia or jaundice: look for haemolytic anaemia (FBC, blood film, LDH, reticulocytes, bilirubin) ^[9].
• Haemoglobin electrophoresis (if thalassaemia or sickle cell disease suspected)if needednon-French guidelineMicrocytosis, haemolysis or origin from a high-prevalence region: electrophoresis follows the FBC and blood film when thalassaemia or sickle cell disease is suspected ^[9].
• Monospot test (adolescent with fever, sore throat and lymphadenopathy)if needednon-French guidelineIn adolescents, primary EBV infection is a very frequent cause of splenomegaly, usually with sore throat, fever and lymphadenopathy ^[9].