Impact of ABO blood groups on residual pulmonary vascular obstruction in patients with unprovoked pulmonary embolism

BackgroundAfter completing anticoagulant therapy for acute pulmonary embolism (PE), patients may have persistent thrombotic materials in the lung, causing residual pulmonary vascular obstruction (RPVO). Detectable by imaging, RPVO is associated with an increased risk of recurrent events and chronic complications. Identifying RPVO risk factors has become a recent focus, yet no genetic determinants have been established. This study specifically investigates the association between genetically determined ABO blood groups and RPVO in patients with unprovoked-PE. MethodsThis work relies on two French cohorts of patients with unprovoked-PE, EDITH and PADIS-PE, and a Canadian one, REVERSE-I, where RPVO was measured with the same protocol. In each study, five ABO polymorphisms were used to infer ABO blood groups: rs8176719-delG, rs41302905-T, rs2519093-T, rs1053878-A and rs8176743-T alleles tagging for O1, O2, A1, A2 and B, respectively. Associations between ABO blood groups and RPVO were assessed in each study using a Compound Poisson Gamma model, which accounts for the semi-continuous RPVO distribution. Study-specific results were then combined through meta-analysis. ResultsThe meta-analysis included 586 patients with unprovoked-PE, providing sufficient power (>80%), as confirmed by simulations, to detect moderate genetic effects (1.3-fold increased risk) of common variants (allele frequency [≥]0.05). Despite this, no significant association was observed between ABO blood groups and RPVO, and no consistent effect was seen across the three studies. InterpretationABO blood groups are unlikely to be major risk factors for RPVO. Nevertheless, this study provides an important foundation for future large-scale genetic investigations aimed at identifying the molecular determinants of RPVO.