Thrombin generation in PNH patients treated sequentially with Eculizumab and Ravulizumab: a paired analysis

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder characterized by complement-mediated hemolysis and a high thrombotic risk. The introduction of complement inhibitors has markedly reduced thromboembolic events. Eculizumab, the first approved C5 inhibitor, requires biweekly infusions, while ravulizumab, with a prolonged half-life, allows administration every eight weeks. To compare their effects on coagulation dynamics, we retrospectively analyzed paired plasma samples from nine PNH patients sequentially treated with both agents using the Thrombin Generation Assay TGA. TGA parameters were largely comparable between treatments, with a significantly shorter start-tail time observed during ravulizumab therapy (p = 0.04). This data indicating a shorter duration of thrombin generation is consistent with the known more sustained complement inhibition during ravulizumab. No significant differences were found in hemolysis markers, PNH clone size, or blood counts. Despite the small sample size and retrospective design, this study provides the first evidence that ravulizumab and eculizumab exert similar effects on thrombin generation, supporting the equivalent efficacy of long-acting C5 inhibition in maintaining hemostatic balance in PNH.