Direct Oral Anticoagulants in Patients with Paroxysmal Nocturnal Hemoglobinuria: A Scoping Review

Background & aims

Paroxysmal nocturnal hemoglobinuria (PNH) is a hematological disorder with an increased risk of thrombosis. For patients with PNH, thrombosis is the main cause of death. Thrombosis in patients with PNH typically occurs in unusual locations such as mesenteric, cerebral, or cutaneous veins; arterial occurrences are less frequent. Most patients with thrombosis are treated with anticoagulation such as heparin, low molecular weight heparin, and warfarin. There is no significant data regarding the treatment of thrombotic events in patients with PNH with direct oral anticoagulants (DOACs) like apixaban rivaroxaban. Particularly as the duration of treatment for thrombosis is not well defined and can be lifelong. This scoping systematic review aims to investigate the current literature on the use of DOAC in patients with PNH.

Materials and methods

Following the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines, PubMed, Scopus, and Google Scholar databases were searched for published articles up to 20 June 2024. The search included retrospective, prospective studies, reviews, case series, and case reports. The inclusion criteria were English literature with PNH patients above 18 years who developed thrombotic events. Studies in languages other than English and articles lacking sufficient information were excluded, and pregnant patients were excluded. Search terms were (Paroxysmal nocturnal hemoglobinuria) AND (rivaroxaban) OR (apixaban) OR (Edoxaban) (dabigatran). The included studies were subjected to two eligibility checks. After completing the screening of titles and abstracts, the full texts of the publications that met the inclusion criteria were obtained.

Results

After removing the duplicate, a total of 790 articles were screened, and only 30 articles met the inclusion criteria. The vast majority of patients had received the standard therapy with heparin, low molecular weight heparin, and warfarin. Only two cases of PNH with thrombotic events have been treated with DOAC, namely rivaroxaban.

Discussion and Conclusion

PNH is a highly thrombotic condition. There is scarce data about the use of DOAC in patients with PNH. Our review showed that most patients were not treated with DOAC. Moreover, the lack of a well-defined duration of anticoagulation therapy in patients with PNH makes the use of vitamin K antagonists more concerning. Therefore, DOAC use needs to be investigated for treating PNH patients who are well-controlled with a complement inhibitor. The limitations of Vitamin K antagonist use include a limited therapeutic window necessitating regular monitoring of the international normalized ratio, interactions with foods rich in vitamin K, and pharmacological interactions with a variety of drugs. DOACs require less monitoring compared to Vitamin K antagonists, which can significantly improve the quality of life for patients with PNH. The reduced need for frequent blood tests and dose adjustments means patients can experience greater convenience and less disruption to their daily lives. This ease of management can lead to better adherence to treatment, reduced stress, and an overall enhanced sense of well-being. Additionally, the predictable pharmacokinetics of DOACs allow for more consistent anticoagulation, further contributing to improved patient outcomes. Large-scale studies are required to gather data on the efficacy and safety of using DOACs in patients with PNH.

No relevant conflicts of interest to declare.