Hypercoagulability in Prader-Willi Syndrome: A case-control study exploring coagulation profiles and thrombotic risk

Prader-Willi syndrome (PWS) is a complex imprinting disorder associated with severe obesity and endocrine dysfunction, both contributing to increased cardiovascular morbidity. Emerging data suggest a disproportionately high incidence of thromboembolic events in PWS, potentially implicating an intrinsic hypercoagulable state.

We conducted a cross-sectional, case-control study including 49 genetically confirmed PWS patients (22 pediatric and 27 adult) and 85 age-, sex-, and body-mass-index-matched controls. Participants underwent comprehensive hemostatic assessment including standard coagulation tests, thrombophilia screening, and factor VIII and von Willebrand factor (vWF: Ag) and platelet function analysis. Thrombin generation test and thromboelastography in PWS were also explored.

Routine coagulation and thrombophilia parameters were largely normal across groups. Thrombin generation test and platelet function analysis were unremarkable. However, D-dimer and vWF: Ag levels were significantly elevated in both pediatric and adult PWS groups with no association to obesity or inflammatory markers. Thromboelastography showed a hypercoagulable pattern in 89.76% of PWS participants, independent of body mass index or metabolic status.

This study identifies a distinct hypercoagulable profile in individuals with PWS not attributable solely to obesity and likely linked to endothelial dysfunction rather than conventional thrombophilic mechanisms. This may justify personalized thrombotic risk assessment in PWS and further investigation into preventive strategies.