Management of combined oral antithrombotic therapy by an antithrombotic stewardship program: a prospective study

Aims: Given the complexity of antithrombotic therapy guidelines especially in patients with combined antithrombotic therapy, there is a risk of inappropriate prescribing and medication errors. In order to prevent this, a multidisciplinary antithrombotic stewardship (ASP) is implemented in our hospital. The primary aim of this study is to determine the efficacy of this ASP by assessing the number of patients on combined antithrombotic therapy for whom one or more interventions are needed. Methods: A prospective cohort study in a large teaching hospital is conducted. Hospitalized patients who received combined antithrombotic therapy in which an oral anticoagulant was combined with one (double therapy) or two (triple therapy) platelet aggregation inhibitors were included. The ASP proactively evaluated the appropriateness of this combined antithrombotic therapy. If needed, ASP improved the concerned therapy. Each improvement measurement by ASP was counted as one intervention. Results: A total of 460 patients were included over a period of 12 months. 251 (54.6%) patients required at least one intervention from the ASP. The most common intervention was to define and document a maximum duration of the combined antithrombotic therapy (65.5%) instead of lifetime use of the combination, to discontinue antithrombotic therapy (19.4%) as the proper indication was lacking and to adjust the dosage (8.1%). Conclusion: As intervention was needed in more than half of the patients on combined antithrombotic therapy, it seems essential to implement an ASP that dedicated evaluates antithrombotic therapy to improve and ensure optimal use and medication safety.

699Are we treating our older generations appropriately?

Background This study aims to understand the disease burden of Atrial Fibrillation (AF) and how it is treated among older Australian women. Methods Data from the oldest cohort (born 1921-26) of the Australian Longitudinal Study of Women’s Health were linked to state based hospital data to identify AF and to Pharmaceutical Benefit Scheme data for medication details. Yearly prevalence and incidence of AF was calculated, followed by calculation of proportions for different medications received. Results A total of 6671 women were eligible for the analysis. About 1827 women from were identified as having AF between 2000-2015. Despite steady incidence, prevalence of AF increased from 2.7% (95%CI=1.6%-3.8%) when women were aged 74-79 years to 24.8% (95%CI=23.2%-26.4%) in 2015 when women were 89-94 years. About 10% of women with AF did not receive any treatment for AF and another 60% did not receive any prophylaxis for thromboembolism within 3 years of AF onset. More than three quarters of women with AF received a combination of medications. Rate control with Vitamin K Inhibitors and Rate control with Platelet Aggregation Inhibitors were the most common combinations. Conclusions Older women have high prevalence of AF. These women are undertreated for the prevention of the most common and disabling complication of AF, stroke. Key messages Prevalence of AF is increasing and women receive inadequate treatment rendering them at risk of serious complications like stroke. This results in reduced quality of life for patients as well as burdens the health care system.

Use of antithrombotics at the end of life: an in-depth chart review study

Background Antithrombotics are frequently prescribed for patients with a limited life expectancy. In the last phase of life, when treatment is primarily focused on optimizing patients’ quality of life, the use of antithrombotics should be reconsidered. Methods We performed a secondary analysis of a retrospective review of 180 medical records of patients who had died of a malignant or non-malignant disease, at home, in a hospice or in a hospital, in the Netherlands. All medication prescriptions and clinical notes of patients using antithrombotics in the last three months of life were reviewed manually. We subsequently developed case vignettes based on a purposive sample, with variation in setting, age, gender, type of medication, and underlying disease. Results In total 60% (n=108) of patients had used antithrombotics in the last three months of life. Of all patients using antithrombotics 33.3 % died at home, 21.3 % in a hospice and 45.4 % in a hospital. In total, 157 antithrombotic prescriptions were registered; 30 prescriptions of vitamin K antagonists, 60 of heparins, and 66 of platelet aggregation inhibitors. Of 51 patients using heparins, 32 only received a prophylactic dose. In 75.9 % of patients antithrombotics were continued until the last week before death. Case vignettes suggest that inability to swallow, bleeding complications or the dying phase were important factors in making decisions about the use of antithrombotics. Conclusions Antithrombotics in patients with a life limiting disease are often continued until shortly before death. Clinical guidance may support physicians to reconsider (dis)continuation of antithrombotics and discuss this with the patient.

AB0723 JUVENILE BEHCET’S DISEASE: WHICH PARTICULARITIES?

Background:Behcet’s disease (BD) is a systemic vasculitis that affects young adults aged between 20 and 30 years old. It is rare in childhood.Objectives:This work aims to analyze the clinical features of this form by comparing it with adult BD.Methods:Through a retrospective study including 192 cases with BD seen in The Internal Medicine Department at Tahar Sfar Hospital Mahdia TUNISA, we report 8 cases of juvenile BD (4.2%) that occurred under the age of 16 years.Results:There were 8 male. The average age of BD onset was 14 years [11, 16 years]. Genital aphthosis was noted in 5 patients. Ophthalmologic damage was observed in 4 patients, dominated by uveitis (75% of cases). No cases of blindness were observed. Joint damage was seen in 5 patients and vascular and neurological damage in 2 patients respectively. All patients received colchicine in addition to a platelet aggregation inhibitors at the moment of BD diagnosis. When comparing juvenile BD group with that of adults, we have noticied, the frequency of cutaneo-mucous and articular manifestations, the rarity of neurological damage and the absence of cardiac and digestive damage in the juvenile BD group.Conclusion:Juvenile BD is a rare form, with a male predominance. The younger age is not a poor prognostic factor. Early diagnosis and treatment can reduce the disease’s complications.References:[1]doi: 10.1007/s00296-018-4208-9Disclosure of Interests:None declared

Influence of Oral Anticoagulation and Antiplatelet Drugs on Outcome of Elderly Severely Injured Patients

Introduction: Severely injured elderly patients have a poorer prognosis and higher mortality rates after severe trauma compared with younger patients. The aim of this study was to correlate the influence of pre-existing oral anticoagulation (OAC) and antiplatelet drugs (PAI) on the outcome of severely injured elderly patients. Methods: Using a prospective cohort study model over an 11-year period, severely injured elderly patients (≥65 years and ISS ≥ 16) were divided into two groups (no anticoagulation/platelet inhibitors: nAP and OAC/PAI). A comparison of the groups was conducted regarding injury frequency, trauma mechanism, severity of head injuries, and medication-related mortality. Results: In total, 254 out of 301 patients were analyzed (nAP: n = 145; OAC/PAI: n = 109, unknown data: n = 47). The most relevant injury was falling from low heights (<3 m), which led to a significantly higher number of severe injuries in patients with OAC/PAI. Patients with pre-existing OAC/PAI showed a significantly higher overall mortality rate compared to the group without (38.5% vs. 24.8%; p = 0.019). The severity of head injuries in OAC/PAI was also higher on average (AIS 3.7 ± 1.6 vs. 2.8 ± 1.9; p = 0.000). Conclusion: Pre-existing oral anticoagulation and/or platelet aggregation inhibitors are related to a higher mortality rate in elderly polytrauma patients. Low-energy trauma can lead to even more severe head injuries due to pre-existing medication than is already the case in elderly patients without OAC/PAI.

Identifying and Characterizing Serious Adverse Drug Reactions Associated With Drug-Drug Interactions in a Spontaneous Reporting Database

Background: Drug-drug interactions (DDIs) are an important cause of adverse drug reactions (ADRs). In literature most of studies focus only on potential DDIs, while detailed data on serious ADRs associated with DDIs are limited. Our aim is to identify and characterize serious ADRs caused by DDIs using a spontaneous reporting database.Methods: All serious ADR reports, not related to vaccines and with a “definite”, “probable” or “possible” causality assessment, inserted into the National Pharmacovigilance database from Veneto Region (January 1, 2015 to May 31, 2020) were analyzed. A list of drug pairs was created by selecting the reports containing at least two suspected or concomitant drugs. We verified which drug pairs potentially interacted according to the online version of DRUGDEX® system. For each potential DDI we controlled whether the ADR description in the report corresponded to the interaction effect as described in Micromedex. A detailed characterization of all serious reports containing an occurring DDI was performed.Results: In the study period a total of 31,604 reports of suspected ADRs from the Veneto Region were identified, of which 2,195 serious reports (6.9% of all ADR reports) containing at least two suspected or concomitant drugs were analyzed. We identified 1,208 ADR reports with at least one potential DDI (55.0% of 2,195) and 381 reports (17.4% of 2,195 reports) with an occurring ADR associated with a DDI. The median age of patients and the number of contraindicated or major DDIs were significantly higher in reports with an occurring DDI. Warfarin was the most frequently reported interacting drug and the most common ADRs were gastrointestinal or cerebral hemorrhagic events. The proton pump inhibitors/warfarin, followed by platelet aggregation inhibitors/warfarin were the drug-drug combinations most frequently involved in ADRs caused by DDIs. The highest proportion of fatal reports was observed with platelet aggregation inhibitors/warfarin and antidepressants/warfarin.Conclusion: Our findings showed that about one-third of patients exposed to a potential DDI actually experienced a serious ADR. Furthermore, our study confirms that a spontaneous reporting database could be a valuable resource for identifying and characterizing ADRs caused by DDIs and the drugs leading to serious ADRs and deaths.

De novo assembled salivary gland transcriptome and expression pattern analyses for Rhipicephalus evertsi evertsi Neuman, 1897 male and female ticks

Ticks secrete proteins in their saliva that change over the course of feeding to modulate the host inflammation, immune responses, haemostasis or may cause paralysis. RNA next generation sequencing technologies can reveal the complex dynamics of tick salivary glands as generated from various tick life stages and/or males and females. The current study represents 15,115 Illumina sequenced contigs of the salivary gland transcriptome from male and female Rhipicephalus evertsi evertsi ticks of early, mid and late feeding stages from 1320 separate assemblies using three short read assemblers. The housekeeping functional class contributed to the majority of the composition of the transcriptome (80%) but with lower expression (51%), while the secretory protein functional class represented only 14% of the transcriptome but 46% of the total coverage. Six percent had an unknown status contributing 3% of the overall expression in the salivary glands. Platelet aggregation inhibitors, blood clotting inhibitors and immune-modulators orthologous to the ancestral tick lineages were confirmed in the transcriptome and their differential expression during feeding in both genders observed. This transcriptome contributes data of importance to salivary gland biology and blood feeding physiology of non-model organisms.

Platelet Aggregation Inhibitors and Anticoagulants Delay Surgery for Hip Fractures

Background: we aimed to analyze the influence of antithrombotic medication in delaying surgery for fragility hip fractures; Method: a total of 312 consecutive hip fracture cases over 55 years who underwent surgery in our Orthopedic Clinic; Results: of these, 90 patients received chronic antithrombotic medication. There were no differences between the medicated group and controls (n = 222) regarding age, gender, type of fracture and haemoglobin at admittance. However, median time to surgery was significantly longer in the medicated group: 4(3–6) days compared to 2(1–4) (p < 0.0001). By type of medication, time to surgery was: 3(1–4) days for acetylsalicylic acid (n = 44), 6(5.25–7.75) days for clopidogrel (n = 15), 4.5(4–7) days for acenocoumarin (n = 18) and 5(4–7.25) days for novel direct oral anticoagulants (n = 13). The Charlson comorbidity index was significantly higher in the medicated group: 5 [4–5] versus 4 [3–5]. There were no differences in transfusions except for fresh frozen plasma, which was administered more in the medicated patients; Conclusions: the prevalence of platelet aggregation inhibitors and anticoagulant use among fragility hip fracture patients is high, with almost a third using some form of antithrombotic medication. This may significantly lengthen time to surgery.

Multiplate® Platelet Aggregation Findings Are Dependent on Platelet Count but Can Be Corrected by Use of a Ratio

Impedance aggregometry (Multiplate®) detects the effects of platelet aggregation inhibitors and can predict thrombotic complications after coronary and cerebrovascular stent interventions. The bedside method uses whole blood samples not corrected for platelet count. It is claimed but not proved that the findings are unrelated to platelet count in the physiological range. We therefore investigated in the experimental study: (1) whether impedance aggregometry findings and platelet count are correlated and (2) whether the aggregation/platelet count ratio expresses platelet function independent of platelet count. Following ethics committee approval, platelet-rich plasma from healthy probands was diluted with platelet-poor plasma to obtain different platelet counts. Thereafter, platelet count was measured and samples were subjected to impedance aggregometry using thrombin receptor activating peptide (TRAP) for platelet activation. In all probands, impedance aggregometry findings and platelet count were highly correlated (r = 0.88 to 0.94; p < 0.05). The combination of all experiments revealed the proportionality between impedance aggregometry findings and platelet count (n = 31, r = 0.78, p = 0.0001). In contrast, the ratio of impedance aggregometry findings and platelet count was not significantly correlated with platelet count (r = 0.017; p = 0.3) and thus constitutes a specific measure for platelet function. In conclusion, impedance aggregometry findings subsequent to the activation with TRAP are dependent on both platelet function and platelet count. Normalization of impedance aggregometry findings for platelet count can be achieved by a ratio resulting in more specific results.