Hemorrhagic events in patients receiving heparin or enoxaparin in combination with Oral antithrombotics, NSAIDs, and antiplatelet medications: A multi-center case-series study

Hemorrhagic events are amongst the major adverse effects of injectable anticoagulants such as heparin and enoxaparin. This necessitates close monitoring of their use for clinically relevant drug-drug interactions.

To study the rate of hemorrhagic events, the anatomical site, and the severity of the hemorrhage in patients receiving heparin or enoxaparin in combination with clopidogrel, non-steroidal anti-inflammatory drugs (NSAIDs), and warfarin.

A prospective, multi-center, case-series study was designed. Patients admitted to two teaching hospitals who received either an NSAID, and/ or warfarin, and/or clopidogrel were evaluated. Yellow Card Scheme was applied to record any hemorrhagic events. Naranjo scale was utilized for causality assessment.

123 patients were eligible for inclusion between November 2014 and April 2015. Sixty-five patients (52.5%) received heparin and 58 patients (47.2%) received enoxaparin. Of 123 patients 115 (93.5%) patients received aspirin, 69 (56.1%) patients received warfarin, 34 (27.6%) patients received an antiplatelet medication, and 121 (98.4%) patients received NSAIDS in combination with heparin or enoxaparin. Overall, 26 (21.1%) cases of hemorrhagic incident were reported of which six (4.9%) cases were categorized as major bleeding. Patients receiving heparin constituted the largest proportion among all 26 haemorrhagic incidents (57.7%). All patients with hemorrhagic incident had aspirin in their medication regimen while 19 (73.0%) patients were concomitantly receiving warfarin as well. Hematuria (46.2%), hematoma in injection site (38.5%) and hematoma (34.6%) were the top three types of the hemorrhagic events. In Naranjo scale analysis, 19 patients scored more than 9 points, indicating a definite ADR causality. Moreover, seven patients scored 5 to 8 affirming a probable association with ADR.

The risk of hemorrhagic events 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 are recommended.