Background: Hemophilic arthropathy (HA) caused by recurrent joint bleedings leads to major morbidity. Non-steroidal anti-inflammatory drugs (NSAIDs) are effective for musculoskeletal related pain and may also have anti-inflammatory and thus joint-protective effects. However, fear for increased bleeding risk during the use of non-selective cyclooxygenase (COX) inhibitors and cardiovascular events in COX-2 inhibitors restrains prescription within this population.

Aims: This systematic review aimed to give a complete overview of all publications reporting on safety of NSAIDs in patients with hemophilia (PWH).

Methods: A systematic search in PubMed, EMBASE and Cochrane till March 2021 was performed, including conference abstract from 2017 to search date. Two authors reviewed all studies independently on title/abstract and included studies reporting about adverse bleeding or cardiovascular events in PWH on NSAIDs.

Articles in non-English, in vitro/animal experiments only, expert opinions, case reports (n < 3) and articles without full-text availability were excluded.

Results: Our search resulted in 1476 studies of which 19 studies could be included for this review. Selective COX-2 inhibitors showed no evident risk for adverse bleeding events or increased factor use. Also, no thrombotic cardiovascular events were reported. Most of the studies reporting about traditional NSAIDs showed no statistically significant differences in hemorrhages compared to placebo. However, patients with comorbidity (e.g. hepatic decompensation, H.pylori presence) may have risk for additional bleeding episodes.

Conclusion(s): Use of NSAIDs in PWH is safe based on the current literature. However, most studies are of low quality with a high risk of bias, included specific or small patient populations or used self-reported registrations. Causality is difficult to examine as there are several other factors that can influence bleeding tendency in PWH and follow-up is relatively short. Future (randomized controlled trial) studies with longitudinal follow-up in large patient populations should be performed to confirm safe use of these cheap, easily accessible and potentially joint protective drugs.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/safety-of-non-steroidal-anti-inflammatory-drugs-in-hemophilia-a-systematic-review-reporting-on-adverse-bleeding-and-cardiovascular-events/