Prophylaxis and management of thromboembolism in pnh patients: an italian survey

Abstract

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal hematopoietic stem cell disorder characterized by uncontrolled complement-mediated intravascular hemolysis and a disproportionately high thromboembolic risk. Although terminal complement inhibition (CIT) has substantially modified the disease course, reducing thromboembolic events (TE), the residual risk remains elevated and evidence-based anticoagulation guidelines are lacking. To characterize real- world practice, we conducted a nationwide, cross-sectional survey involving 24 Italian Centers caring for 291 patients, evaluating strategies for primary antithrombotic prophylaxis (PAP), secondary prophylaxis (SAP), and management of breakthrough hemolysis (BTH). Marked heterogeneity emerged. PAP prior to CIT was routinely employed in only one-third of Centers, whereas an equal proportion did not use it; the remainder adopted risk-based approaches integrating thrombophilia traits or clone size. SAP was universally administered after TE, with 75% of Centers maintaining indefinite anticoagulation regardless of CIT response. Anticoagulation during BTH was likewise variable, with LMWH as the preferred agent and duration largely dictated by biochemical resolution. These findings demonstrate substantial inter-center variability, underscoring the lack of harmonized national frameworks. The results highlight the need for structured expert consensus and standardized clinical algorithms to optimize thrombosis prevention and management in PNH in the era of complement inhibition.