hemorrhagic events in patients receiving heparin or enoxaparin in combination with oral antithrombotics, nsaids, and antiplatelet medications: a multi-center case-series study

Background: hemorrhagic events are amongst the significant adverse effects of injectableanticoagulants such as heparin and enoxaparin. this undesirable effect needs close monitoringof their use for clinically relevant drug-drug interactions.objectives: to study the rate of hemorrhagic events, the anatomical site, and the severityof the bleeding in patients receiving heparin or enoxaparin in combination with clopidogrel,non-steroidal anti-inflammatory drugs (nsaids), and warfarin.methods: we designed a prospective, multi-center, case-series study. patients admitted to twoteaching hospitals who received either an nsaid, or warfarin, or clopidogrel were evaluated.any hemorrhagic event was recorded by yellow card scheme. also, the naranjo scale wasutilized for causality assessment.results: a total of 123 patients were eligible for inclusion. they were admitted between november2014 and april 2015. sixty-five patients (52.5%) received heparin and 58 patients (47.2%)received enoxaparin. of 123 patients, 115 patients (93.5%) received aspirin, 69 (56.1%) warfarin,34 (27.6%) an antiplatelet medication, and 121 (98.4%) nsaids in combination with heparinor enoxaparin. overall, 26 cases (21.1%) of the hemorrhagic incident were reported, of whomsix cases (4.9%) were categorized as major bleeding. patients receiving heparin constituted thelargest proportion among all 26 hemorrhagic incidents (57.7%). all patients with the hemorrhagicincident had aspirin in their medication regimen, while 19 patients (73.0%) were concomitantlyreceiving warfarin as well. hematuria (46.2%), hematoma in the injection site (38.5%), andhematoma (34.6%) were the top three types of hemorrhagic events. in naranjo scale analysis, 19patients scored more than 9 points, indicating a definite adverse drug reaction (adr) causality.moreover, seven patients scored 5 to 8, affirming a possible association with adr.conclusion: the risk of hemorrhagic can be influenced by undesirable drug-drug interactions.close monitoring of high-risk patients is advised to prevent adverse hemorrhagic reactions.further studies to detect the explanatory factors associated with the hemorrhagic events arerecommended.