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The primary care clinician faces many challenges and is often left to manage complex pathology because of resource constraints at higher levels of care. One of these complex conditions is the perioperative management of antithrombotic medication. This narrative review is focused on helping the clinician navigate the complex path and multiple guidelines related to the perioperative use of antithrombotic medication. Perioperative antithrombotic guidelines (American College of Chest Physicians, European Society of Regional Anaesthesia, and American Society of Regional Anesthesia) and relevant publications were identified by a PubMed search using the terms perioperative AND anticoagulants OR antithrombotics AND guideline. Issues relevant to clinical practice were identified, and attempts were made to explain any ambiguity that arose. Adhering to basic pharmacological principles and evidence-based guidelines allows for the safe usage of antithrombotics. Knowing when to stop, continue, bridge and restart antithrombotic medication prevents perioperative morbidity and mortality. Stopping antithrombotic medication too early can lead to thromboembolic complications associated with their primary disease process. Not stopping antithrombotic medication or stopping it too late can potentially cause life-threatening bleeding, haematomas and increased transfusion requirements.

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Background: Patients with multiple myeloma (MM) are at risk of venous thromboembolism (VTE), worsened by immunomodulatory drugs. Although antithrombotics are recommended for prophylaxis, existing guidelines are suboptimal and treatment outcomes remain unclear. Objectives: This study aimed to investigate adverse events, antithrombotic utilization, and their associations with survival outcomes in patients with MM initiating multi-drug immunomodulatory combinations. Design: A posthoc analysis of individual-participant level data (IPD). Methods: IPD from three daratumumab clinical trials (MAIA, POLLUX, and CASTOR) were pooled. Adverse events incidence and antithrombotic utilization were assessed. Logistic and Cox regression were utilized to examine associations between antithrombotics use with adverse events and survival outcomes at the baseline and 6-month landmark. Results: Among 1804 patients, VTE occurred in 10%, bleeding in 14%, ischemic heart disease in 4%, and stroke in 2%. Patients with these adverse events demonstrated elevated rates of any grade ⩾3 events. Antiplatelet (primarily aspirin) and anticoagulant (primarily LMWH and direct oral anticoagulants) prescriptions have seen an increase from baseline (25% and 14%, respectively) to 6 months (35% and 31%). The primary indication for their use was prophylaxis. Anticoagulant use within 6 months was associated with reduced VTE (OR (95% CI) = 0.45 (0.26-0.77), p = 0.004), while antiplatelet use showed no associations with any evaluated adverse events. Antithrombotics and survival outcomes had no significant associations. Conclusion: This study underscores the complexities of antithrombotic therapy and adverse events in MM and highlights the need for vigilant and proactive management due to increased grade ⩾3 adverse events. While anticoagulant use was associated with reduced VTE risk, further research is needed to optimize thromboprophylaxis guidelines and explore antithrombotic efficacy and safety in patients with MM. Trial registration: MAIA (NCT02252172), POLLUX (NCT02076009), CASTOR (NCT02136134).

Blood clot prevention drugs in multiple myeloma: usage and impact on patient outcomes Aims and Purpose of the Research This study aimed to understand how blood-thinning medications are used by patients with multiple myeloma, a type of blood cancer. Specifically, we wanted to find out how often these medications are used, what side effects they might cause, and whether they are linked with how long the patients live. Background of the Research This study is important because patients with multiple myeloma often have a higher risk of blood clots, especially when they are taking certain anticancer treatments. Blood-thinning drugs are usually recommended to prevent these clots, but it's not always clear how well these drugs work or what side effects they might cause. Methods and Research Design This study looked at data from three clinical trials involving a multiple myeloma drug called daratumumab. We looked at how often side effects occurred and how often blood-thinning drugs were used. Two groups of blood thinning drugs were investigated: antiplatelets and anticoagulants. We used two types of statistical methods, called logistic and Cox regression, to see if there was a connection between the use of these blood-thinning drugs and the occurrence of side effects or survival rates at the start of the study and after six months. Results and Importance The study found that the use of blood-thinning drugs increased over time and that using anticoagulants within the first six months was linked to a lower risk of blood clots. However, blood-thinning drugs were not linked with how long the patients lived. These results are important because they can help doctors better manage the use of blood-thinning drugs in patients with multiple myeloma. The key message is that more research is needed to improve guidelines for preventing blood clots and to better understand the safety and effectiveness of blood-thinning drugs in these patients.

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INTRODUCTION: The effect of antiplatelet and anticoagulant medications on the outcomes of sinus floor augmentation remains unclear. METHODS: This retrospective cohort study analyzed data from electronic medical records of consecutive patients undergoing sinus floor augmentation at a single medical center. Patients were categorized into three categories: patients under antiplatelet medications, patients under anticoagulation medications, and healthy individuals. Data collected included tobacco smoking, residual alveolar bone height, timing of implant placement, materials used, vertical bone gain, early implant failure (EIF), and complications such as Schneiderian membrane perforation and postoperative bleeding. Multivariable analysis was performed to assess risk factors for EIF. Statistical significance was considered below 5%. RESULTS: Among 110 patients with 305 implants, EIF occurred in 10% of patients and 4.65% of implants. No significant difference in postoperative bleeding or EIF was found between study groups. Univariate and multivariable analyses highlighted tobacco smoking (odds ratio [OR] = 7.92), lower residual alveolar ridge height (OR = 0.81), and staged implant placement (OR = 4.64) as significant EIF risk factors in this cohort. CONCLUSIONS: Anticoagulant and antiplatelet therapies do not significantly elevate the risk of EIF or postoperative bleeding following sinus floor augmentation. Tobacco smoking, residual alveolar ridge height and staged sinus floor augmentation were risk factors for EIF in patients using antiplatelet or anticoagulation medications undergoing sinus floor augmentation.

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The "holy grail" of preventing and treating thrombosis and thromboembolism would be a drug that was highly effective (preventing clots) and at the same time had a low risk of bleeding. From a hemostasiological perspective, the inhibition of factor XI represents a promising target because a reduced level of factor XI protects against thrombosis without significantly increasing the risk of spontaneous bleeding. Currently, three different classes of drugs of factor XI-inhibition are tested. These are (1) monoclonal antibodies (mAbs), (2) so-called synthetic, small molecules and (3) antisense oligonucleotides (ASOs). This article provides a narrative overview of the current status of studies on all three classes of drugs. Tests with mAbs have been conducted primarily in DVT prevention after knee replacement surgery. One large phase 3 study is testing the mAbs Abelacimab in patients with atrial fibrillation. The synthetic, small molecules Asundexian and Milvexian are tested in several phase 3 trials, mainly in patients with non-cardioembolic ischemic stroke. Results can be expected in the coming years. Clinical testing of ASOs to inhibit factor XI are still in their infancies.

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Background: Patients in palliative care are often treated with antithrombotics, even in the late stages of disease. Clear guidelines regarding deprescribing are lacking. Objective: The aims of this study were to investigate bleeding as a side effect of antithrombotic treatments the last year in life and map the timing of deprescribing. Methods: A retrospective cohort study was performed. All medical records were screened for deceased patients admitted to a palliative care unit in Stockholm, Sweden, over a 3-year period. Patients with antithrombotics were identified; data on bleeding, and on side effects due to deprescribing, were extracted from the medical records. Log-binomial models were used to explore factors associated with bleeding. Results: Of 1501 patients, 897 were treated with antithrombotics during the last year of life (mean age 75 years, 41% women). Of these, 56% continued treatment up until the last 3 days of life. Of the 897 patients, 144 (16%) had at least one bleeding during the treatment. The risk for bleeding was significantly higher for men with prostate cancer compared to other cancer forms, adjusted relative risk 1.9 (95% CI 1.1-3.2). No difference in risk for bleeding was found between sex, age groups, type of antithrombotics, or indication. Two patients (0.2%) developed strokes after antithrombotics were deprescribed. Conclusions: Treatment with antithrombotics during the last year of life is associated with a high risk of bleeding. In this cohort, men with prostate cancer seemed to have more side effects of bleeding than other groups. Few experienced side effects from deprescribing.

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Interventions in structural heart disease cover many catheter-based procedures for congenital and acquired conditions including valvular diseases, septal defects, arterial or venous obstructions, and fistulas. Among the available procedures, the most common are aortic valve implantation, mitral or tricuspid valve repair/implantation, left atrial appendage occlusion, and patent foramen ovale closure. Antithrombotic therapy for transcatheter structural heart disease interventions aims to prevent thromboembolic events and reduce the risk of short-term and long-term complications. The specific approach to antithrombotic therapy depends on the type of intervention and individual patient factors. In this review, we synopsize contemporary evidence on antithrombotic therapies for structural heart disease interventions and highlight the importance of a personalized approach. These recommendations may evolve over time as new evidence emerges and clinical guidelines are updated. Therefore, it's crucial for healthcare professionals to stay updated on the most recent guidelines and individualize therapy based on patient-specific factors and procedural considerations.

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Ischemic stroke is a devastating disease that causes morbidity and mortality. Malnutrition following ischemic stroke is common in stroke patients. During the rehabilitation, the death rates of stroke patients are significantly increased due to malnutrition. Nutritional supplements such as protein, vitamins, fish, fish oils, moderate wine or alcohol consumption, nuts, minerals, herbal products, food colorants, marine products, fiber, probiotics and Mediterranean diets have improved neurological functions in stroke patients as well as their quality of life. Platelets and their mediators contribute to the development of clots leading to stroke. Ischemic stroke patients are treated with thrombolytics, antiplatelets, and antithrombotic agents. Several systematic reviews, meta-analyses, and clinical trials recommended that consumption of these nutrients and diets mitigated the vascular, peripheral, and central complications associated with ischemic stroke (Fig. 2). Particularly, these nutraceuticals mitigated the platelet adhesion, activation, and aggregation that intended to reduce the risks of primary and secondary stroke. Although these nutraceuticals mitigate platelet dysfunction, there is a greater risk of bleeding if consumed excessively. Moreover, malnutrition must be evaluated and adequate amounts of nutrients must be provided to stroke patients during intensive care units and rehabilitation periods. In this review, we have summarized the importance of diet and nutraceuticals in ameliorating neurological complications and platelet dysfunction with an emphasis on primary and secondary prevention of ischemic stroke.

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BACKGROUND: This study sought to examine the effect of antithrombotic use on clinical outcomes in non-variceal upper gastrointestinal bleeding (UGIB). METHODS: Patients consecutively diagnosed with non-variceal UGIB between February 2019 and September 2020 were divided into two groups based on their antithrombotic use: users and non-users. Using propensity score matching (PSM) and multivariable regression analyses, the impact of antithrombotic use prior to UGIB presentation on clinical outcomes was examined. RESULTS: In the entire cohort, there were 210 and 260 patients in the antithrombotic user and non-user groups, respectively. Using PSM analysis with seven covariates, two matched groups of 157 patients were created at a 1:1 ratio. In the matched cohort, despite their longer hospital stays and a higher rate of intensive care unit admissions, the patients in the user group had lower 30- and 90-day mortality rates (4.5% vs. 14.0 %; p = 0.003 and 8.9% vs. 18.5 %; p = 0.014, respectively). In the entire cohort, multivariable analyses adjusted for confounding factors revealed that antithrombotic use was associated with lower risks of in-hospital (adjusted OR: 0.437; 95 % CI: 0.191-0.999), 30-day (adjusted OR: 0.261; 95 % CI: 0.099-0.689), and 90-day (adjusted OR: 0.386; 95 % CI: 0.182-0.821) mortality. CONCLUSION: Antithrombotic use prior to UGIB presentation was found to be an independent protective factor for all-cause mortality.

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Anti-amyloid immunotherapies have recently emerged as treatments for Alzheimer's disease. While these therapies have demonstrated efficacy in clearing amyloid-ß and slowing cognitive decline, they have also been associated with amyloid-related imaging abnormalities (ARIA) which include both edema (ARIA-E) and hemorrhage (ARIA-H). Given that ARIA have been associated with significant morbidity in cases of antithrombotic or thrombolytic therapy, an understanding of mechanisms of and risk factors for ARIA is of critical importance for stroke care. We discuss the latest data regarding mechanisms of ARIA, including the role of underlying cerebral amyloid angiopathy, and implications for ischemic stroke prevention and management.

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Diabetes mellitus is a significant risk factor for both ischaemic and haemorrhagic stroke, affecting up to a third of individuals with cerebrovascular diseases. Beyond being a risk factor for stroke, diabetes and hyperglycaemia have a negative impact on outcomes after ischaemic and haemorrhagic stroke. Hyperglycaemia during the acute ischaemic stroke phase is associated with a higher risk of haemorrhagic transformation and poor functional outcome, with evidence in favour of early intervention to limit and manage severe hyperglycaemia. Similarly, intensive glucose control nested in a broader bundle of care, including blood pressure, coagulation and temperature control, can provide substantial benefit for clinical outcomes after haemorrhagic stroke. As micro- and macrovascular complications are frequent in people with diabetes, cardiovascular prevention strategies also need to consider tailored treatment. In this regard, the broader availability of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists can allow tailored treatments, particularly for those with heart failure and chronic kidney disease as comorbidities. Here, we review the main concepts of hyperacute stroke management and CVD prevention among people with diabetes, capitalising on results from large studies and RCTs to inform clinicians on preferred treatments.

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Revolutionary advances in the treatment of hemophilia has led to a significant improvement in life expectancy. Associated with this has been an increase in age-related diseases especially atherosclerotic cardiovascular disease (CVD). While people with hemophilia (PWH) develop atherosclerosis at rates similar to those of the general population, rates of atherothrombosis and mortality related to CVD have been much lower, due to their hypocoagulable state. Changing treatment paradigms, aimed at reducing the risk of bleeding by improving hemostasis to levels approaching normality, has meant that the protection they are thought to have had may be lost. CVD risk factors are just as common in PWH as in the general population, but appear to be undertreated. In particular, primary prevention of CVD is vital in all individuals, but particularly in PWH as treatment of established CVD can be difficult. Active identification and management of CVD risk factors, such as obesity, physical inactivity, hypertension, and hypercholesterolemia, is required. In particular, statins have been shown to significantly reduce cardiovascular and all-cause mortality with few adverse events and no increased risk of bleeding in the general population, and their use needs urgent assessment in PWH. Further longitudinal research into preventing CVD in PWH, including accurate CVD risk assessment, is required to optimize prevention and management.

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Objective: This systematic review aims to investigate a potential correlation between the administration of antiplatelets (APs) or anticoagulants (ACs) and perioperative complications, with a particular focus on hemorrhagic events, in patients undergoing decompressive craniectomy (DC). Additionally, the secondary objective is to assess the neurological outcomes in patients undergoing DC while taking APs/ACs, comparing them to patients not on APs/ACs. Methods: The study utilized PubMed and Science Direct as primary online medical databases for the systematic review. Articles underwent screening based on title, abstract, and full-text review. Four studies meeting the inclusion criteria were selected for comprehensive analysis. Results: Our findings suggest that the administration of APs/ACs in patients undergoing DC does not significantly impact functional outcomes. Notably, the occurrence of rebleeding within 6 months and other complications, including infections, appears to be less frequent in patients taking APs compared to those not taking APs/ACs. Conclusion: Literature-derived data on the association between APs/ACs and DC presented considerable heterogeneity and insufficient volume for robust statistical analysis. Consequently, a definitive conclusion regarding the influence of suspending or continuing these therapies on complications and clinical outcomes cannot be confidently reached at present. To address this, a large-scale prospective study is warranted to gather substantial and precise data, facilitating a nuanced understanding of how to balance the risks and benefits associated with antiplatelet and anticoagulant agents in the context of decompressive craniectomy.

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PURPOSE: To investigate the effect of antithrombotics on the occurrence of maxillofacial haemorrhagic symptoms, and to determine if these haemorrhagic symptoms are predictors of maxillofacial fractures. METHOD: A prospective cohort study was conducted of consecutive patients with maxillofacial trauma who had been admitted to the emergency department of four hospitals in the Netherlands. This study compared five haemorrhagic symptoms (peri-orbital haematoma, raccoon eyes, epistaxis, subconjunctival ecchymosis, and intra-oral haematoma) between patients not-using (NUA) and using (UA) of antithrombotics, and whether these maxillofacial haemorrhagic symptoms served as predictors for maxillofacial fractures. RESULTS: Out of the 1005 patients, 812 (81%) belonged to the NUA group, and 193 (19%) to the UA group. UA patients exhibited higher frequencies of peri-orbital hematoma (54% vs. 39%, p < 0.001), raccoon eyes (10% vs. 5%, p = 0.01), and subconjunctival ecchymoses (16% vs. 7%, p < 0.001). In NUA, peri-orbital hematoma (OR = 2.5, p < 0.001), epistaxis (OR = 4.1, p < 0.001), subconjunctival ecchymosis (OR = 2.3, p = 0.02), and intra-oral hematoma (OR = 7.1, p < 0.001) were significant fracture predictors. Among UA, peri-orbital hematoma (OR = 2.2, p = 0.04), epistaxis (OR = 5.4, p < 0.001), subconjunctival ecchymosis (OR = 3.7, p = 0.008), and intra-oral hematoma (OR = 22.0, p < 0.001) were significant fracture predictors. CONCLUSION: Maxillofacial haemorrhagic symptoms were observed more frequently in the UA group than in the NUA group. However, in both groups, maxillofacial haemorrhagic symptoms appear to be predictors of maxillofacial fractures. Caution is warranted in attributing these symptoms solely to antithrombotic use during emergency department assessments.

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BACKGROUND AND PURPOSE: Demographics, clinical characteristics, stroke mechanisms and long-term outcomes were compared between acute ischaemic stroke (AIS) patients with active cancer (AC) versus non-cancer patients. METHODS: Using data from 2003 to 2021 in the Acute STroke Registry and Analysis of Lausanne, a retrospective cohort study was performed comparing patients with AC, including previously known and newly diagnosed cancers, with non-cancer patients. Patients with inactive cancer were excluded. Outcomes were the modified Rankin Scale (mRS) score at 3 months, death and cerebrovascular recurrences at 12 months before and after propensity score matching. RESULTS: Amongst 6686 patients with AIS, 1065 (15.9%) had a history of cancer. After excluding 700 (10.4%) patients with inactive cancer, there were 365 (5.5%) patients with AC and 5621 (84%) non-cancer AIS patients. Amongst AC patients, 154 (42.2%) strokes were classified as cancer related. In multivariable analysis, patients with AC were older (adjusted odds ratio [aOR] 1.02, 95% confidence interval [CI] 1.00-1.03), had fewer vascular risk factors and were 48% less likely to receive reperfusion therapies (aOR 0.52, 95% CI 0.35-0.76). Three-month mRS scores were not different in AC patients (aOR 2.18, 95% CI 0.96-5.00). At 12 months, death (adjusted hazard ratio 1.91, 95% CI 1.50-2.43) and risk of cerebrovascular recurrence (sub-distribution hazard ratio 1.68, 95% CI 1.22-2.31) before and after propensity score matching were higher in AC patients. CONCLUSIONS: In a large institutional registry spanning nearly two decades, AIS patients with AC had less past cerebrovascular disease but a higher 1-year risk of subsequent death and cerebrovascular recurrence compared to non-cancer patients. Antithrombotic medications at discharge may reduce this risk in AC patients.

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AIMS: Data on the optimal use of antithrombotic drugs and associated clinical outcomes in patients with atrial fibrillation (AF) and acute ischaemic stroke (IS) are limited. We investigated the prescription patterns of antithrombotics in community practice and long-term clinical prognosis according to early post-stroke antithrombotic therapy in patients with AF and acute IS. METHODS AND RESULTS: Patients with AF who were admitted for acute IS at a single tertiary hospital in 2010-2020 were retrospectively reviewed. Clinical profiles including the aetiology of stroke and prescription patterns of antithrombotics were identified. The net clinical outcome (NCO)-the composite of recurrent stroke, any bleeding, hospitalization or emergency department visits for cardiovascular (CV) events, and death-was compared according to the antithrombotic therapy at the first outpatient clinic visit [oral anticoagulation (OAC) alone vs. antiplatelet (APT) alone vs. OAC/APT(s)] following discharge. A total of 918 patients with AF and acute IS (mean age, 72.6 years; male, 59.3%; mean CHA2DS2-VASc score 3.3) were analysed. One-third (33.9%, n = 310) of patients were simultaneously diagnosed with AF and IS. The most common aetiology of IS was cardioembolism (71.2%), followed by undetermined aetiology (19.8%) and large artery atherosclerosis (6.0%). OAC, APT(s), and concomitant OAC and APT(s) were prescribed in 33.4%, 11.1%, and 53.4% of patients during admission that changed to 67.0%, 9.1%, and 21.7% at the first outpatient clinic, and were mostly continued up to one year after IS. Non-prescription of OAC was observed in 11.3% of post-stroke patients with AF. During a median follow-up of 2.1 years, the overall incidence rate of NCO per 100 patient-year (PY) was 20.14. APT(s) monotherapy presented the highest cumulative risk of NCO (adjusted hazard ratio 1.47, 95% confidence interval 1.08-2.00, P = 0.015; with reference to OAC monotherapy) mainly driven by the highest rates of recurrent stroke and any bleeding. OAC/APT(s) combination therapy was associated with a 1.62-fold significantly higher risk of recurrent stroke (P = 0.040) and marginally higher risk of any bleeding than OAC monotherapy. CONCLUSION: Approximately one-third of acute IS in AF have a distinctive mechanism from cardioembolism. Although APT was frequently prescribed in post-stroke patients with AF, no additive clinical benefit was observed. Adherence to OAC treatment is essential to prevent further CV adverse events in patients with AF and IS.

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INTRODUCTION: Insufficient withdrawal duration of antithrombotics leads to excessive bleeding after major surgery. We hypothesize that intraoperative hemoadsorption (HA) can reduce postoperative allogeneic transfusion requirements and excessive bleeding events (EBE), without an increase in ischemic/thromboembolic events (ITE) in patients who have taken antithrombotics and undergone nonelective cardiac surgery. METHODS: A total of 460 patients admitted to our hospital from 2018 to 2022 were included in this study and divided into two groups: HA and non-HA. Because of the risk of bias due to differences in antithrombotic type, withdrawal duration, or basic coagulation function, propensity score matching was used for analyses. RESULTS: Out of 154 cases in the HA group, 144 pairs were successfully matched. No HA safety events such as hemolysis, hypotension, or device failure occurred. After matching, the two groups were found to be comparable in preoperative antithrombotic type, withdrawal duration, platelets and coagulation function, and demographic and perioperative characteristics. Although the HA group did not have a reduced incidence of EBE, this group exhibited significant decreases in the transfusion rate and volume, the incidence of ITE, acute kidney injury, and central nervous system injury. CONCLUSIONS: For patients who have undergone nonelective cardiac surgery and taken antithrombotics, HA can simply and safely rebalance the postoperative coagulation system and have associations with reduced transfusion and postoperative ITE.

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The incidence of fatal adverse drug reactions (ADRs) in hospitals varies widely, and ADRs are often underreported. The impact of medical safety processes is not easily evaluated, and although medical practice changes constantly, little is known about ADR trends. This study concentrated on the current incidence and properties of fatal ADRs occurring in a university hospital and compared the results with two previous studies performed in the same hospital. We investigated retrospectively all 1236 deaths that occurred during 2019 in the Helsinki University Hospital. All the cases were evaluated by a team of experts, and the causality was assessed using the categories by World Health Organization and Uppsala monitoring centre. Suicides were excluded. Among death cases, we identified 65 certain or probable ADR cases (5.3%), representing 0.011% of all hospital admissions. Cytostatics and antithrombotics remained the largest drug classes, with neutropenia or sepsis and bleedings as the most common fatal ADRs. Compared with our earlier studies, warfarin caused less, and direct oral anticoagulants caused more fatal bleedings, reflecting the drug usage among the population. In contrast to earlier studies, contrast media and insulin did not cause any fatal ADRs, which may reflect an improvement in pharmacovigilance awareness among healthcare workers.

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