PB1063 - Safety assessment of Prothromplex®, a 4-factor prothrombin complex concentrate, focused on heparin-related adverse events

Background: Prothromplex® is a 4-factor prothrombin complex concentrate containing balanced levels of prothrombin complex factors (coagulation factors FII, FVII, FIX and FX), as well as protein C and protein S. Prothromplex® acts to restore depleted levels of these factors in the treatment of bleeding and perioperative prophylaxis of bleeding resulting from anticoagulation therapy or congenital deficiency. Per ISTH SSC recommendations, Prothromplex® also contains heparin to reduce thrombogenicity.

Aims: To evaluate the safety of Prothromplex® and the risks associated with heparin-related adverse events.

Methods: We reviewed worldwide safety data on Prothromplex® use (including reported events from clinical trials, spontaneous use, post-marketing studies, scientific literature and health authority data) from January 1, 1900 to July 31, 2023, using search criteria specific for the following heparin-related adverse events, heparin-induced thrombocytopenia (HIT), hypersensitivity, lack of effect and thrombotic events. Event reporting rates were calculated based on cumulative IU of Prothromplex® sold. The formulation of Prothromplex® remained unchanged during the review time frame, although a second pathogen removal step (nanofiltration) was introduced during manufacture. This study was funded by Takeda.

Results: Based on a cumulative number of 2,937,615,196 IU of Prothromplex®, no cases of HIT were reported. Overall reporting rates for other search criteria were: hypersensitivity, 13.3 events per billion IU (16 cases); lack of effect, 3.1 events per billion IU (9 cases); and thrombotic events, 14.3 events per billion IU (41 cases). The most commonly reported events in these categories were ischemic stroke (n=13), deep vein thrombosis (n=11), bronchospasm (n=6), erythema (n=5) and drug ineffective (n=5). The majority of reported events had limited medical data available or were confounded by advanced age (≥65 years), cardiovascular risk factors and/or alternative etiologies.

Conclusion(s): Overall, no trends or new safety signals were identified. Prothromplex® use was associated with a low incidence of heparin-related adverse events, including no reported cases of HIT.