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Frontiers in Pharmacology 2023The benefits and risks of starting anticoagulation therapy, such as direct oral anticoagulations (DOACs) or warfarin, in atrial fibrillation (AF) patients with a... (Review)
Review
The benefits and risks of starting anticoagulation therapy, such as direct oral anticoagulations (DOACs) or warfarin, in atrial fibrillation (AF) patients with a history of intracranial hemorrhage (ICH) remain controversial. We performed a systematic review and meta-analysis to compare the safety and efficacy of starting oral anticoagulation (OAC) and non-oral anticoagulation in these patients. PubMed, Cochrane Library, and Embase were searched from inception to 01 May 2022 for randomized controlled trials and cohort studies, reporting effectiveness and safety outcomes for anticoagulation therapy in atrial fibrillation patients with intracranial hemorrhage. The Newcastle-Ottawa Scale (NOS) and the Cochrane Collaboration tool were used to evaluate bias risks for all randomized controlled trials (RCTs) and cohort studies. An effects model was applied to calculate adjusted hazard ratios (aHRs) for randomized controlled trials and cohort studies. We analyzed data from two randomized controlled trials (304 patients) and seven Cohort studies (17,477 patients). Compared to non-oral anticoagulation, starting oral anticoagulation therapy reduced the risk of Ischemic Stroke/Systemic Embolism (SE) (aHR: 0.64, 95% CI: 0.55-0.57) and all-cause death (aHR: 0.53, 95% CI: 0.35-0.80) in atrial fibrillation patients and a prior history intracranial hemorrhage. Starting oral anticoagulation therapy did not increase the risk of recurrent intracranial hemorrhage (aHR: 1.07, 95% CI: 0.66-1.74), but increased the risk of major bleeding (aHR: 1.38, 95% CI: 1.00-1.91) than no oral anticoagulation therapy. The DOACs had a lower risk of Ischemic Stroke/SE (aHR: 0.84, 95% CI: 0.70-1.00), recurrent intracranial hemorrhage (aHR: 0.63, 95% CI: 0.49-0.82), and all-cause death (aHR: 0.65, 95% CI: 0.48-0.88) compared to warfarin. According to subgroup analyses, starting oral anticoagulation therapy have a higher risk of recurrent intracranial hemorrhage than non-oral anticoagulation therapy (aHR: 1.57, 95% CI: 1.36-1.81) for Asians. After intracranial hemorrhage in atrial fibrillation patients, restarting or initiating oral anticoagulation therapy decreased the risk of Ischemic Stroke/SE and all-cause death but did not increase the risk for recurrent intracranial hemorrhage. Direct oral anticoagulations have better efficacy and safety than warfarin if oral anticoagulation therapy is started. However, starting oral anticoagulation increases the risk for recurrent intracranial hemorrhage in the Asian region.
PubMed: 36969833
DOI: 10.3389/fphar.2023.1122564 -
Journal of the American College of... Oct 2022To provide recent population-based estimates of transthoracic needle biopsy (TTNB) complications and risk factors associated with these complications.
OBJECTIVE
To provide recent population-based estimates of transthoracic needle biopsy (TTNB) complications and risk factors associated with these complications.
METHODS
This retrospective cohort analysis included adults from a nationally representative longitudinal insurance claims data set who underwent TTNB in 2017 or 2018. Complications that were evaluated included pneumothorax, hemorrhage, and air embolism. Separate logistic regression models estimated the association of pneumothorax or hemorrhage with the setting of care (ie, inpatient or outpatient) and selected baseline patient demographic and clinical characteristics including age, gender, history of chronic obstructive pulmonary disease, diagnosis of pleural effusion, tobacco use, use of oral anticoagulants and antiplatelet agents, prior lung cancer screening, previous bronchoscopy within 1 year, and Elixhauser comorbidity index.
RESULTS
Among 16,971 patients who underwent TTNB, 25.8% experienced a complication within 3 days of the procedure (pneumothorax 23.3%, hemorrhage 3.6%, and air embolism 0.02%). Among patients who experienced pneumothorax, 31.9% required chest tube drainage. Among patients undergoing an outpatient TTNB (n = 12,443), 6.9% were hospitalized within 7 days. Biopsy in an inpatient setting, chronic obstructive pulmonary disease diagnosis, and prior bronchoscopy were associated with higher rates of both pneumothorax and hemorrhage. Prior lung cancer screening was associated with an increased risk of pneumothorax, and prior use of oral anticoagulants or antiplatelets was associated with higher rates of hemorrhage.
CONCLUSION
This contemporary population-based cohort study demonstrated that approximately one-quarter of patients undergoing TTNB experienced a complication. Pneumothorax was the most frequent complication, and hemorrhage and air embolism were rare. Among outpatients, complications from TTNB are an important cause of hospitalization.
Topics: Adult; Anticoagulants; Biopsy, Needle; Cohort Studies; Early Detection of Cancer; Embolism, Air; Hemorrhage; Humans; Image-Guided Biopsy; Lung; Lung Neoplasms; Multiple Pulmonary Nodules; Platelet Aggregation Inhibitors; Pneumothorax; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; Risk Factors
PubMed: 35738412
DOI: 10.1016/j.jacr.2022.04.010 -
Hamostaseologie Dec 2023For life-threatening or uncontrollable bleeding in association with the thrombin inhibitor dabigatran, the monoclonal antibody fragment idarucizumab is available, and...
BACKGROUND
For life-threatening or uncontrollable bleeding in association with the thrombin inhibitor dabigatran, the monoclonal antibody fragment idarucizumab is available, and for bleeding in association with the direct factor Xa inhibitors rivaroxaban or apixaban, the modified recombinant FXa protein andexanet is available for reversal. These antidotes represent emergency drugs that are typically used only after performing guideline-compliant multimodal measures.
METHODS
An interdisciplinary group of experienced experts in the fields of angiology, hematology, internal medicine, clinical pharmacology, laboratory medicine, transfusion medicine, anesthesiology, intensive care, and hemostaseology developed recommendations relevant to daily clinical practice based on the current scientific evidence.
RESULTS
Reversal of oral anticoagulants should be considered for severe bleeding in the following situations: (1) life-threatening bleeding or refractory hemorrhagic shock, (2) intracerebral bleeding, or (3) endoscopically unstoppable gastrointestinal bleeding. After successful hemostasis, anticoagulation (e.g., direct oral anticoagulant, vitamin K antagonist, and heparin) should be resumed promptly, taking into account individual bleeding and thromboembolic risk.
DISCUSSION
This article aims to facilitate the management of patients with andexanet by all medical disciplines involved, thereby ensuring optimal care of patients during bleeding episodes.
Topics: Humans; Anticoagulants; Hemorrhage; Rivaroxaban; Heparin; Recombinant Proteins; Factor Xa Inhibitors; Administration, Oral
PubMed: 37813368
DOI: 10.1055/a-2136-2391 -
International Journal of Molecular... Nov 2022Novel oral anticoagulants (NOACs) are drugs approved for the prevention and treatment of many thromboembolic cardiovascular conditions as a safer alternative to... (Review)
Review
Novel oral anticoagulants (NOACs) are drugs approved for the prevention and treatment of many thromboembolic cardiovascular conditions as a safer alternative to warfarin. We reviewed studies published in PubMed, UpToDate, Web of Science, and Cochrane about NOACs' risks and benefits in patients requiring anticoagulation, with a focus on gastrointestinal bleeding and on molecular and pathophysiological mechanisms underlying the risk of bleeding in patients treated with them. Apixaban resulted in a lower rate of gastrointestinal bleeding compared to dabigatran and rivaroxaban. However, data reported that gastrointestinal bleeding in patients treated with NOACs was less severe compared to warfarin. Studies show promising results on the increased and widespread use of NOACs in patients who require anticoagulation (for example-in case of atrial fibrillation or high risk of venous thromboembolism), reporting an overall lower risk of major bleeding events. The profile of NOACs was more effective and secure compared to warfarin, but a more careful medical prescription is required in patients who are at high risk of gastrointestinal bleeding.
Topics: Humans; Anticoagulants; Warfarin; Administration, Oral; Dabigatran; Gastrointestinal Hemorrhage
PubMed: 36430433
DOI: 10.3390/ijms232213955 -
Hamostaseologie Feb 2023The use of direct oral anticoagulants (DOACs) is increasing in patients needing treatment of venous thromboembolism (VTE) and stroke prevention in atrial fibrillation...
The use of direct oral anticoagulants (DOACs) is increasing in patients needing treatment of venous thromboembolism (VTE) and stroke prevention in atrial fibrillation (SPAF). This is due to the net clinical benefit in comparison to vitamin K antagonists (VKAs). The rise in DOAC use is accompanied by a remarkable reduction in heparin and VKA prescriptions. However, this rapid change in anticoagulation patterns brought new challenges to patients, prescribers, laboratories, and emergency physicians. Patients have new liberties concerning nutritional habits and comedication and no longer need frequent monitoring or dose adjustments. Still, they have to comprehend that DOACs are potent anticoagulants that may cause or contribute to bleeding. Challenges for the prescriber include decision pathways for choosing the right anticoagulant and dosage for a specific patient and to change bridging practice in case of invasive procedures. Laboratory personnel are challenged by DOAC due to limited 24/7 availability of specific DOAC quantification tests and by the impact of DOAC on routine coagulation assays and thrombophilia tests. Challenges for the emergency physician result from the increasing age of DOAC anticoagulated patients, the difficulties to establish last intake of DOAC type and dosage, to interpret coagulation test results in emergency situations, and to make decisions for or against DOAC reversal strategies in acute bleeding or urgent surgery. In conclusion, although DOACs make long-term anticoagulation safer and more convenient for patients, DOACs pose challenge to all healthcare providers involved in anticoagulation decisions. The key to correct patient management and optimal outcome therefore lies in education.
Topics: Humans; Antidotes; Laboratories; Anticoagulants; Heparin; Venous Thromboembolism; Hemorrhage; Atrial Fibrillation; Administration, Oral; Vitamin K
PubMed: 36807818
DOI: 10.1055/a-1987-3559 -
Erythema multiforme-like lip presentation in pemphigus vulgaris patients: a multicenter case series.BMC Oral Health Dec 2023Pemphigus vulgaris (PV) is a chronic autoimmune mucocutaneous blistering disease. Autoantibodies are directed against desmogleins, leading to the formation of...
Pemphigus vulgaris (PV) is a chronic autoimmune mucocutaneous blistering disease. Autoantibodies are directed against desmogleins, leading to the formation of intraepithelial bullae. PV, as with other autoimmune mucocutaneous disorders of the oral cavity, presents diagnostic and therapeutic challenges. Approximately 50-70% of cases present first with oral lesions. The lesions commonly start as vesicles or bullae that rapidly rupture, leading to erosions and ulcerations. The palatal, gingival, buccal, and labial mucosa are the most commonly affected sites. Oral PV can mimic several other diseases that cause mucosal erosions and/or ulcerations, including erythema multiforme (EM). EM is an acute, immune-mediated, self-limited hypersensitivity condition primarily associated with herpes simplex infection. Oral lesions can be variable, but a very characteristic presentation with labial hemorrhagic erosions, ulcerations and crusting is commonly seen. In this case series, we present six cases of PV: one male patient and five female patients whose ages ranged from 34 to 65 years old. All patients presented with hemorrhage and crusting of the lips in addition to multiple intraoral erosions and ulcerations. Three patients presented with oral and skin lesions. All patients underwent biopsies, and a diagnosis of PV was confirmed. All patients were treated with steroids (topical and systemic) and variable steroid-sparing agents. This case series emphasizes that oral PV may be misdiagnosed as EM in a subgroup of patients who present with persistent lip hemorrhage and crusting. Therefore, a comprehensive history, clinical examination and incisional biopsies should be considered in such patients.
Topics: Humans; Male; Female; Adult; Middle Aged; Aged; Pemphigus; Blister; Lip; Erythema Multiforme; Oral Ulcer; Chronic Disease; Hemorrhage
PubMed: 38041037
DOI: 10.1186/s12903-023-03665-w -
Trauma Surgery & Acute Care Open 2020Anticoagulant-associated traumatic intracranial hemorrhage (tICrH) is a devastating injury with high morbidity and mortality. For survivors, treating clinicians face the... (Review)
Review
Anticoagulant-associated traumatic intracranial hemorrhage (tICrH) is a devastating injury with high morbidity and mortality. For survivors, treating clinicians face the dilemma of restarting oral anticoagulation with scarce evidence to guide them. Thromboembolic risk is high from the bleeding event, patients' high baseline risks, that is, the pre-existing indication for anticoagulation, and the risk of immobility after the bleeding episode. This must be balanced with potentially devastating hematoma expansion or new hemorrhagic lesions. Retrospective evidence and expert opinion support restarting oral anticoagulants in most patients with tICrH, but timing is uncertain. Researchers have failed to make clear distinctions between tICrH and spontaneous intracranial hemorrhage (sICrH), which have differing natural histories. While both appear to benefit from restarting, sICrH has a higher rebleeding risk and similar or lower thrombotic risk. Clinical equipoise on restarting is also divergent. In sICrH, equipoise is centered on whether to restart. In tICrH, it is centered on when. Several prospective randomized clinical trials are ongoing or about to start to examine the risk-benefit of restarting. Most of them are restricted to patients with sICrH, with antiplatelet control groups. Most are also restricted to direct oral anticoagulants (DOACs), as they are associated with a lower overall risk of ICrH. There is some overlap with tICrH via subdural hematoma, and one trial is specific to restart timing with DOACs in only traumatic cases. This is a narrative review of the current evidence for restarting anticoagulation and restart timing after tICrH along with a summary of the ongoing and planned clinical trials.
PubMed: 33313417
DOI: 10.1136/tsaco-2020-000605 -
Heart (British Cardiac Society) Mar 2022To assess the risk of stroke/systemic embolism (SE) and major bleeding associated with the use of oral anticoagulants in elderly patients with atrial fibrillation (AF)...
OBJECTIVES
To assess the risk of stroke/systemic embolism (SE) and major bleeding associated with the use of oral anticoagulants in elderly patients with atrial fibrillation (AF) in a real-world population.
METHODS
We identified all anticoagulant-naive initiators of warfarin, dabigatran, rivaroxaban and apixaban for the indication AF in Norway between January 2013 and December 2017. Multivariate competing risk regression was used to calculate subhazard ratios (SHRs) describing associations between non-vitamin K antagonist oral anticoagulants (NOACs) compared with warfarin for risk of stroke/SE and major bleeding.
RESULTS
Among 30 401 patients ≥75 years identified (median age 82 years, 53% women, mean CHADS-VaSc score 4.5), 3857 initiated dabigatran, 6108 rivaroxaban, 13 786 apixaban and 6650 warfarin. Reduced dose was initiated in 11 559 (49%) of the NOAC-treated patients. For stroke, the SHRs for standard dose NOAC against warfarin were 0.80 (95% CI 0.57 to 1.13) for dabigatran; 1.07 (95% CI 0.89 to 1.30) for rivaroxaban and 0.95 (95% CI 0.78 to 1.15) for apixaban. For major bleeding, the SHRs against warfarin were 0.75 (95% CI 0.52 to 1.08) for dabigatran; 0.96 (95% CI 0.78 to 1.16) for rivaroxaban and 0.74 (95% CI 0.60 to 0.91) for apixaban. Comparing reduced doses of NOACs with warfarin yielded similar results. Sensitivity analyses were in accordance with the main results.
CONCLUSION
In this nationwide cohort study of patients ≥75 years initiating oral anticoagulation for AF, standard and reduced dose NOACs were associated with similar risks of stroke/SE as warfarin and lower or similar risks of bleeding. The NOACs seem to be a safe option also in elderly patients.
Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Dabigatran; Embolism; Female; Hemorrhage; Humans; Male; Rivaroxaban; Stroke; Warfarin
PubMed: 33975877
DOI: 10.1136/heartjnl-2020-318753 -
Kardiologia Polska 2023Atrial fibrillation is associated with significant morbidity and mortality, and its incidence is increasing globally. The primary complication of atrial fibrillation is... (Review)
Review
Atrial fibrillation is associated with significant morbidity and mortality, and its incidence is increasing globally. The primary complication of atrial fibrillation is ischemic stroke, whose risk may be reduced with oral anticoagulant agents, i.e., either vitamin K antagonists or direct oral anticoagulants. Patients with atrial fibrillation often have concomitant hepatic impairment, particularly because of increasing rates of non-alcoholic liver disease. However, anticoagulation in patients with liver disease is challenging due to the pathophysiological changes of the coagulation cascade and, as a result, an increased risk of major bleeding in such individuals. Furthermore, monitoring of the degree of anticoagulation is complicated in patients with liver disease due to issues such as spontaneous international normalized ratio (INR) elevation, changes in hepatic drug elimination, and thrombocytopenia. We review the current evidence on atrial fibrillation and anticoagulation in patients with liver disease. We suggest having a strong focus on risk factor management and argue that the risk of ischemic stroke often outweighs the risk of hemorrhagic events in this setting.
Topics: Humans; Atrial Fibrillation; Stroke; Anticoagulants; Hemorrhage; Risk Factors; Liver Diseases; Ischemic Stroke; Administration, Oral
PubMed: 37823759
DOI: 10.33963/v.kp.97812 -
BMC Oral Health Aug 2022Vitamin D deficiency has been associated with autoimmune diseases and oral health. Knowledge about the association between vitamin D status and oral conditions in JIA is...
BACKGROUND
Vitamin D deficiency has been associated with autoimmune diseases and oral health. Knowledge about the association between vitamin D status and oral conditions in JIA is limited. We aimed to investigate vitamin D status in a cohort of Norwegian children and adolescents with JIA and possible associations between serum vitamin D levels, clinical indicators of oral health, and JIA disease characteristics.
METHODS
This multi-center, cross-sectional study, included individuals with JIA aged 4-16 years from three geographically spread regions in Norway. Demographic data, age at disease onset, disease duration, JIA category, disease status, medication, and vitamin D intake were registered. One blood sample per individual was analyzed for 25(OH) vitamin D, and the level of insufficiency was defined as < 50 nmol/L. A clinical oral examination was performed applying commonly used indices in epidemiological studies of dental caries, dental erosion, enamel defects, gingival bleeding, and oral hygiene. Serum vitamin D was used as exposure variable in multivariable regression analyses to estimate the associations between insufficient vitamin D level, JIA disease status, and oral conditions, with adjustments for age, sex, geographical region, BMI, seasonal blood sampling, and parental education.
RESULTS
Among the 223 participants with JIA, 97.3% were Caucasians, 59.2% were girls, and median age was 12.6 years. Median disease duration was 4.6 years, and 44.4% had oligoarticular JIA. Mean serum vitamin D level was 61.4 nmol/L and 29.6% had insufficient levels. Vitamin D levels did not differ between sexes, but between regions, iso-BMI categories, age groups, and seasons for blood sampling. Insufficient vitamin D levels were associated with dentin caries (adjusted OR 2.89, 95% CI 1.43-5.86) and gingival bleeding (adjusted OR 2.36, 95% CI 1.10-5.01). No associations were found with active JIA disease or more severe disease characteristics.
CONCLUSION
In our study, nearly 30% had vitamin D insufficiency, with a particularly high prevalence among adolescents. Vitamin D insufficiency was associated with dentin caries and gingival bleeding, but not with JIA disease activity. These results point to the need for a multidisciplinary approach in the follow-up of children with JIA, including an increased focus on vitamin D status and oral health.
Topics: Adolescent; Arthritis, Juvenile; Child; Cross-Sectional Studies; Dental Caries; Female; Gingival Hemorrhage; Humans; Male; Oral Health; Vitamin D; Vitamin D Deficiency
PubMed: 35941635
DOI: 10.1186/s12903-022-02349-1