Platelets are essential for haemostasis and are key mediators of thrombo-inflammatory disease. Circulating activated or hyperresponsive platelets are linked to adverse cardiovascular outcomes.Our experimental data in mouse models indicates that the spleen regulates systemic platelet activation by selectively filtering activated platelets in thrombotic or inflammatory states, thereby limiting immunopathology and thrombus growth. We also observed increased splenic platelet accumulation in patients with myocardial infarction and sepsis. Loss of splenic function through splenectomy may abolish this counter-regulation, increasing thromboinflammatory risk, yet large-scale human evidence is lacking.
This project will use UK Biobank data to quantify the association between splenectomy and major thrombo-inflammatory outcomes (arterial thrombosis, deep vein thrombosis, pulmonary embolism, and sepsis). The exposed group will be participants with splenectomy (ICD-10/OPCS codes); where feasible we will focus on traumatic splenectomy to reduce confounding by indication. Controls will be participants without splenectomy, matched on age and sex. Covariates will include age, sex, BMI, major comorbidities (diabetes, hypertension, cardiovascular disease), and relevant medications (anticoagulants, antiplatelets, immunosuppressives).
We will conduct time-to-event analyses using Cox proportional hazards models with splenectomy status as the main exposure, adjusted for covariates. Follow-up will run from baseline or splenectomy date to first event, death or study end. Hazard ratios with 95 % confidence intervals will be estimated for each outcome separately. Sensitivity analyses will exclude participants with prior events and test proportional-hazards assumptions. We will also produce Kaplan-Meier curves and subgroup analyses stratified by age, sex, and comorbidities.