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 sports, abdominal trauma, and strenuous physical activity for a minimum of 4 weeks (or until a follow-up USS confirms splenic size has returned to normal). 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 should be treated as splenic rupture until proved otherwise — 999 immediately. The return to contact sports after EBV should be guided by: resolution of symptoms + normal abdominal examination + normal splenic size on USS.

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. Any spleen crossing the midline or extending to the iliac fossa should prompt urgent haematology referral regardless of the apparent benignity of the patient's presentation. 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 (typically >10,000 mcg/L — ferritin levels above 10,000 are strongly associated with HLH and should trigger immediate 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 + ferritin above 3,000–5,000 mcg/L should prompt same-day haematology contact. HLH is fatal in approximately 50% of untreated cases but treatable with HLH-2004 protocol (dexamethasone + etoposide + ciclosporin).

The OGD (oesophagogastroduodenoscopy) surveillance for varices in portal hypertension is a NICE recommendation — any patient newly diagnosed with cirrhosis or 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 (propranolol or carvedilol — reduces portal pressure by approximately 20%) 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 2 years if no varices, every 1 year if small varices without beta-blocker); (3) the patient has been warned about variceal haemorrhage warning signs (haematemesis, melaena, sudden dizziness) and instructed to call 999 immediately. The mortality from an acute variceal bleed is approximately 15–20% per episode — prevention with primary prophylaxis is far preferable.

Gaucher disease (type 1 — non-neuropathic) is one of the most rewarding rare disease diagnoses to make in primary care because enzyme replacement therapy (ERT) is dramatically effective — patients who have suffered for years with massive splenomegaly, anaemia, thrombocytopenia, and bone pain can achieve near-normal organ function with regular biweekly IV infusions of imiglucerase (recombinant glucocerebrosidase). 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, meningococcal ACWY + B, Hib, annual flu); (2) a penicillin V prescription + standing instruction to take 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? Penicillin V prescription current and patient taking it? Patient knows to present to ED or call 999 immediately with any febrile illness?

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 — choose the most effective regimen for the destination: atovaquone-proguanil for most regions), 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.