Influence of Coadministration of Antithrombotic Medicines, Warfarin, and NSAIDs on Heparin Safety: Data from a Prospective Observational Study

BACKGROUND: Utilization of heparins has been increasing in the last decade, thus, in-depth analysis is needed to assess heparins safety monitoring patterns, incidence rates of adverse drug reactions (ADR), and frequency of coadministration with other medicines. OBJECTIVES: To investigate the safety monitoring of heparin in hospitals and the influence of coadministration of nonsteroidal anti-inflammatory drugs (NSAIDs), antithrombotic medicines, and warfarin on heparin safety. METHODS: We reviewed hospital records of 339 patients who had orders for heparin or low molecular weight heparin from May 2009 to May 2010. IBM SPSS Statistics version 18.0 was used to perform statistical analysis. RESULTS: Dalteparin (n=238, 70.21%) was the most frequently prescribed heparin. The most frequent indications given were for prophylaxis of venous thrombosis (n=135, 39.82%) and treatment of unstable coronary artery disease and myocardial infarction (n=166, 48.97%). ADRs were reported for 75 patients (22.12%), including coagulation abnormalities in 25 patients (7.37%), renal dysfunctions in 24 patients (7.08%), and thrombocytopenia in 10 patients (2.95%). 256 patients (75.52%) had relative contraindications. ADRs were associated with the previously reported relative contraindications (Spearman’s rank correlation coefficient [rS]=0.261, Pearson’s chi-squared test [χ2]=45.5, P less than 0.0005) and with prolonged treatment with heparins (rS=0.279 and χ2=74.7, P less than 0.0005). ADRs were not related to heparin use but indicated increased risk for negative treatment outcomes. Coadministration of heparin with warfarin, acetylsalicylic acid, clopidogrel, ketorolac, and NSAIDs was associated with the increased risk of adverse drug reactions. The relationship was low but statistically significant. The strongest relationship was with coadministration of aspirin (rS=0.283, χ2=21.42, P less than 0.0005), while the coadministration of NSAIDs showed only a very weak relationship to the development of ADRs (rS=0.133, χ2=21.01, P less than 0.0005). For the development of thrombocytopenia, the strongest risk was calculated for coadministration of warfarin (rS=0.248, χ2=28.14, P less than 0.0005), while coadministration of medicines from the list did not have a relationship with the risk of thrombocytosis. CONCLUSIONS: Safety monitoring of heparin orders is essential, especially for patients with relative contraindications during long-term treatment and in case of coadministration of oral anticoagulants, platelet inhibitors, and NSAIDs.