Leukocyte Count as an In‐Hospital Prognostic Indicator in Acute Pulmonary Embolism: Evidence From a Registry Study and Genetic Analyses

ABSTRACT Background and Objective As a well‐established inflammatory biomarker, leukocyte count is associated with higher mortality in acute pulmonary embolism (PE). We aimed to confirm the prognostic utility of leukocyte count and its integration with simplified Pulmonary Embolism Severity Index (sPESI) for predicting all‐cause hospital mortality in acute PE. Methods Data derived from a national, multicentre and prospective registry including patients with acute PE were analysed to develop and validate an in‐hospital mortality prediction model incorporating leukocyte count and sPESI. Mendelian Randomisation (MR) was performed to assess the relationship between leukocyte count and mortality. Results A total of 7312 PE patients were stratified into three groups based on admission leukocyte count: < 4 × 10 9 /L ( n = 301, 4.1%), (4–10) × 10 9 /L ( n = 5074, 69.4%) and > 10 × 10 9 /L ( n = 1937, 26.5%). Patients with leukocytosis exhibited a higher prevalence of anaemia, thrombocytopenia, hypoxemia, cardiac and renal injury, as well as haemodynamic instability. The in‐hospital all‐cause mortality was 3.0%, 2.3% and 6.4% ( p < 0.001) across the three groups, respectively. The area under the curve (AUC) of sPESI was 0.719 (95% CI 0.681–0.756, p < 0.001), increasing to 0.738 (95% CI 0.701–0.775, p < 0.001) when combined with leukocyte count groups. The prognostic value of leukocyte count and its combination with sPESI was validated in a cohort with 7660 PE patients. MR analysis demonstrated that elevated leukocyte counts increased mortality risk (OR = 1.11, 95% CI 1.00–1.24, p = 0.047). Conclusion Admission leukocyte count enhances the prognostic accuracy of sPESI for in‐hospital all‐cause mortality in PE. Leukocyte count could serve as a potential biomarker for identifying PE patients at increased mortality risk.