Splenic rupture in infectious mononucleosis is a rare but life-threatening complication — occurring in approximately 0.1–0.5% of EBV cases, most commonly in the second to third week of illness when splenic enlargement peaks. The spleen in EBV is infiltrated with EBV-infected lymphocytes and becomes fragile and susceptible to rupture from relatively minor trauma (including vigorous palpation, contact sports, or even coughing). The clinical implication: all patients with confirmed or suspected EBV infectious mononucleosis should be advised to avoid contact or collision sports, strenuous exertion, heavy lifting and activities with a risk of abdominal trauma during the acute illness and while the spleen remains enlarged. The duration should be individualised according to symptoms, clinical recovery, sport and specialist/local advice — avoid contact sport for at least 4 weeks from symptom onset (NICE CKS); beyond that there is no validated clearance rule. GPs should not routinely palpate the spleen vigorously in a patient with suspected EBV — a gentle examination or ultrasound is safer. Any patient with EBV who develops sudden left upper quadrant pain requires emergency assessment for rupture or infarction — 999 if severe, after trauma, or with syncope, tachycardia, hypotension or peritonism. The return to contact sports after EBV should be guided by resolution of symptoms, clinical recovery, the sport and normal abdominal examination. Routine ultrasound to clear return to sport is not required for every patient, and ultrasound normalisation does not establish zero risk.

The mnemonic for causes of massive splenomegaly (extending to or beyond the umbilicus) is clinically useful: CML (Chronic Myeloid Leukaemia), Myelofibrosis, Malaria (chronic), Leishmaniasis, and Gaucher disease — these five conditions characteristically cause the largest spleens. A very large spleen should prompt urgent investigation and specialist assessment; urgency depends on symptoms, rate of growth, cytopenias, complications and suspected cause. The spleen in CML can weigh up to 5 kg — early satiety from gastric compression, left-sided pleuritic pain from splenic infarction, and referred left shoulder pain (Kehr's sign) are characteristic symptoms. Felty syndrome deserves specific mention as a commonly tested condition — it is the triad of: rheumatoid arthritis (typically seropositive, long-standing) + splenomegaly + neutropenia (ANC <2 × 10⁹/L). The mechanism is complex: splenic sequestration of neutrophils + anti-neutrophil antibodies + granulopoiesis suppression. The clinical significance: patients with Felty syndrome have a high risk of recurrent bacterial infections (from neutropenia), leg ulcers, and lymphoma (7× increased risk compared to RA without Felty). Treatment: methotrexate or biological DMARDs for RA control; G-CSF for severe neutropenia; splenectomy in rare refractory cases.

The blood film is as crucial for splenomegaly as it is for anaemia — the peripheral blood film provides direct morphological evidence of the underlying diagnosis in many cases of splenomegaly. Key findings: atypical lymphocytes + monospot positive = EBV (but monospot may be negative in the first 7 days, negative in young children, and falsely negative in elderly); blast cells = acute leukaemia; smear cells (Gumprecht shadows) + lymphocytosis = CLL; teardrop poikilocytes (dacrocytes) + leucoerythroblastic picture = myelofibrosis; spherocytes + reticulocytosis = hereditary spherocytosis or autoimmune haemolytic anaemia; left-shifted granulocytes (band forms, metamyelocytes, myelocytes, promyelocytes) = CML or leukaemoid reaction; ring sideroblasts = MDS. The haematologist's review of the blood film should be requested urgently for any patient with unexplained splenomegaly — the result will direct the next investigation step more efficiently than any algorithm.

Haemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening condition associated with splenomegaly that GPs must recognise — it is characterised by: fever (prolonged), splenomegaly, cytopenias (at least 2 cell lines), hyperferritinaemia (often very high — a very high ferritin with fever and cytopenias should trigger same-day haematology contact), hypertriglyceridaemia, elevated soluble CD25 (sIL-2R), haemophagocytosis on bone marrow biopsy, and low/absent NK cell activity. HLH can be primary (familial, genetic — young children) or secondary (triggered by infection — most commonly EBV, or malignancy — particularly T-cell lymphoma, or autoimmune disease — SLE, adult-onset Still's disease). The key primary care recognition point: a patient with unexplained prolonged fever + splenomegaly + falling blood counts + very high ferritin should prompt same-day haematology contact. HLH is life-threatening if untreated; treatment is specialist-led.

The OGD (oesophagogastroduodenoscopy) surveillance for varices in portal hypertension follows NICE NG50 (updated 2023) — after a diagnosis of cirrhosis, offer upper GI endoscopy (unless starting carvedilol or propranolol to prevent decompensation); in practice any patient with confirmed portal hypertension should have an OGD to assess for oesophageal and gastric varices. If large varices are found: primary prophylaxis with non-selective beta-blocker (carvedilol or propranolol per the hepatology/current portal-hypertension pathway — do not initiate or titrate propranolol solely from spleen size) or endoscopic variceal ligation (EVL). GPs managing patients with cirrhosis and splenomegaly must ensure: (1) the patient is under hepatology follow-up; (2) the OGD surveillance is up to date (every 3 years if no varices on the first endoscopy — NICE NG50; more often if small varices, per the hepatology team); (3) the patient has been warned about variceal haemorrhage warning signs (haematemesis, melaena, sudden dizziness) and instructed to call 999 immediately. Acute variceal bleeding carries significant mortality — prevention with primary prophylaxis under the hepatology pathway is preferable.

Gaucher disease (type 1 — non-neuropathic) is one of the most rewarding rare disease diagnoses to make in primary care because specialist treatment can substantially improve splenomegaly, cytopenias and bone disease — treatment choice and regimen are determined by the specialist Gaucher service. The challenge is that Gaucher disease is underdiagnosed (estimated prevalence 1 in 40,000–60,000, but Ashkenazi Jewish prevalence 1 in 450) and the diagnosis is often delayed by years because the symptoms mimic more common conditions (anaemia, splenomegaly from 'portal hypertension'). The diagnostic clue: massive splenomegaly + pancytopenia + bone pain (Erlenmeyer flask deformity on X-ray — widening of the distal femur) in a patient with no evidence of haematological malignancy or portal hypertension. Serum chitotriosidase (a macrophage enzyme elevated in Gaucher disease) is an excellent screening test — dramatically elevated (>1000 nmol/h/ml vs normal <100). Glucocerebrosidase enzyme assay on a dried blood spot is diagnostic.

The OPSI (Overwhelming Post-Splenectomy Infection) risk is the most important long-term complication of splenectomy and requires lifelong vigilance — the spleen is the body's primary filter for encapsulated bacteria (which evade phagocytosis without opsonisation by complement and antibody). Without the spleen, these bacteria can cause rapidly fatal septicaemia. The lifetime risk of OPSI is approximately 3–5% (higher in children and in the first 2 years post-splenectomy). Every asplenic patient (surgical splenectomy OR functional asplenia — sickle cell disease, coeliac disease, SLE) should have in their medical record: (1) documentation of vaccinations (pneumococcal PCV20 per the current Green Book chapter 25, revaccinated every 5 years; meningococcal ACWY + B; annual flu; routine Hib-containing immunisation complete); (2) a risk-based prophylactic antibiotic prescription (phenoxymethylpenicillin, or a macrolide if allergic) + a standby course with a standing instruction to take it immediately at first sign of infection; (3) a patient-held emergency card explaining that they are asplenic and require immediate antibiotics; and (4) an alert on the electronic record that displays at every consultation. GPs reviewing asplenic patients at annual review must check: vaccinations up to date? Prophylactic antibiotic prescription current and patient taking it? Standby course in date? Patient knows any fever, rigors or systemic illness needs immediate same-day medical assessment (999 for collapse, confusion, severe breathlessness, meningism or rapid deterioration)?

The spleen as a filter for malaria-infected red blood cells explains why asplenic patients are at dramatically increased risk from Plasmodium falciparum malaria — the spleen normally identifies and removes parasitised erythrocytes from the circulation through its unique filtration system (the red pulp cords force red cells through narrow slits that parasitised cells cannot traverse). Without the spleen, parasitised cells circulate unchecked, causing hyperparasitaemia and severe falciparum malaria with a much higher case fatality rate. Asplenic patients travelling to malaria-endemic regions should be counselled particularly strongly about: chemoprophylaxis (not optional — regimen according to destination and current TravelHealthPro advice; DEET and nets do not substitute for it), personal protective measures (DEET 50%+ repellent, long sleeves/trousers at dawn/dusk, permethrin-treated bed nets), and seeking medical attention immediately with any fever within 3 months of return (the travel declaration 'I am asplenic' should be communicated to the treating physician).

The splenomegaly safety-net for splenic rupture must be given verbally AND documented in writing at every consultation where significant splenomegaly is identified — 'If you develop sudden severe left-sided or central abdominal pain, particularly if it spreads to your left shoulder tip (Kehr's sign — referred pain from subphrenic blood), call 999 immediately. Do not drive yourself to hospital. This could mean your spleen has ruptured, which is a surgical emergency.' Kehr's sign (left shoulder tip pain from diaphragmatic irritation by subphrenic blood) is the key referred pain pattern of splenic rupture that can be mentioned to the patient — it is often the presenting symptom before the classical abdominal pain develops. This simple piece of patient education, properly documented, can be life-saving.