Problemas Relacionados à Trombocitopenia em Pacientes com Fibrilação Atrial Concomitante que Necessitam de Prevenção Antitrombótica: Um Estudo de Coorte Retrospectivo / Thrombocytopenia-Related Problems in Patients with Concomitant Atrial Fibrillation Requiring Antithrombotic Prevention: A Retrospective Cohort Study

Resumo Baixas doses de edoxabana e enoxaparina sódica foram objeto de uma comparação retrospectiva implementada com a técnica do escore de propensão a fim de mitigar os efeitos das diferenças nas características clínicas basais de duas coortes e minimizar o risco de viés. Posteriormente, usando um modelo de riscos proporcionais de Cox, avaliou-se a associação de cada tipo de terapia com o risco do composto de morte por todas as causas, acidente vascular cerebral/ataque isquêmico transitório, hospitalizações e ocorrência de sangramentos maiores. Para essa análise, um valor de p < 0,05 foi considerado estatisticamente significante. A terapia com enoxaparina e cirrose hepática como causadora de trombocitopenia estiveram associadas ao aumento do risco do endpoint composto (enoxaparina: hazard ratio (HR): 3,31; IC 95%: 1,54 a 7,13; p = 0,0023; cirrose hepática, HR: 1,04; 95% CI: 1,002 a 1,089; p = 0,0410). Por outro lado, a terapia com edoxabana mostrou-se significativamente associada à diminuição do risco do endpoint composto (HR: 0,071; 95% CI: 0,013 a 0,373; p = 0,0019). Com base nessa análise retrospectiva, o edoxaban em doses baixas seria uma ferramenta farmacológica segura e eficaz para a profilaxia de eventos cardioembólicos em pacientes com FA e trombocitopenia.

Abstract Low-dose edoxaban and enoxaparin sodium have been the subject of a retrospective comparison implemented with the propensity score technique in order to mitigate the effects of the differences in the basal clinical features of two cohorts and minimize the risk of bias. Subsequently, using a Cox proportional-hazards model, the association of each type of therapy with the risk of the composite of all-cause death, stroke/transient ischemic attack, hospitalizations and major bleeding events was assessed. For this analysis, a p-value < 0.05 was considered statistically significant. Therapy with enoxaparin and liver cirrhosis as causing thrombocytopenia were associated with increased risk of the composite endpoint (enoxaparin: hazard ratio (HR): 3.31; 95% CI: 1.54 to 7.13; p = 0.0023; liver cirrhosis, HR: 1.04; 95% CI: 1.002 to 1.089; p = 0.0410). Conversely, edoxaban therapy was significantly associated with decreased risk of the composite endpoint (HR: 0.071; 95% CI: 0.013 to 0.373; p = 0.0019). Based on this retrospective analysis, edoxaban at low doses would appear as an effective and safe pharmacological tool for the prophylaxis of cardioembolic events in patients with AF and thrombocytopenia.

Rapid change of estrogen levels induce reversible cerebral vasoconstriction syndrome and cerebral venous sinus thrombosis: A report of two cases

@#Reversible cerebral vasoconstriction syndrome (RCVS) presents with characteristic clinical, brain imaging, and angiographic findings. The most common clinical feature of RCVS is a severe acute headache, which is often referred to as a thunderclap headache owing to the nature of its presentation. It may occur spontaneously or may be provoked by various precipitating factors. We present two cases of RCVS concomitant with cerebral venous sinus thrombosis (CVST). Patient 1 was a 42-yearold woman admitted to our hospital with severe headache radiating to the neck, with associated vomitting. She had a history of ovarian cancer and underwent an operation for resection of the tumor a month prior to presentation. After resection, her estradiol (E2) levels were reduced from 288 pg/ ml to 31 pg/ml (normal range, 0-49 pg/ml). Initial imaging upon admission to our hospital revealed left posterior convexity subarachnoid hemorrhage. Magnetic resonance angiography (MRA) showed findings consistent with RCVS affecting the left posterior cerebral artery. Magnetic resonance venography (MRV) showed CVST of the left transverse and sigmoid sinuses. Single photon emission computed tomography (SPECT) showed a left posterior ischemic lesion. These findings improved following treatment with nimodipine and anticoagulant. Patient 2 was a 39-year-old woman presented with holocranial headache associated with vomiting. She was diagnosed with an ovarian tumor. She underwent an operation three months prior to presentation. After tumor resection, her E2 level decrease from 193 pg/ml to 19 pg/ml (normal range, 0-49 pg/ml). MRA confirmed the presence of a vasospasm involving the right anterior cerebral artery. MRV confirmed the presence of thrombosis involving the superior sagittal sinus. She was discharged on postpartum day 31 without neurological deficits after treatment with anticoagulants. At 3 month follow-up, both MRA and MRV were within the normal limits. In conclusion, this is the first report of two women diagnosed with RCVS with concomitant CVST following ovarian tumor resection. The rapid change of perioperative E2 levels may have contributed to the development of CVST and RCVS.

Non-Vitamin K Oral Anticoagulants Associated Bleeding and Its Antidotes / 대한뇌졸중학회지

Oral anticoagulant-associated intracerebral hemorrhage (OAC-ICH) accounts for nearly 20% of all ICH. The number of patients with an indication for oral anticoagulant therapy (OAT) increases with increasing age. OAT became less complicate with the introduction of non-vitamin K oral anticoagulants (NOAC) OAT because of easier handling, favorable risk-benefit profile, reduced rates of ICH compared to vitamin K antagonists and no need for routine coagulation testing. Consequently, despite a better safety profile of NOAC the number of patients with OAC-ICH will increase. The mortality and complication rates of OAC-ICH are high and therefore they are the most feared complication of OAT. Immediate normalization of coagulation is the main goal and therefore knowledge of pharmacodynamics and coagulation status is essential. Laboratory measurements of anticoagulant activity in NOAC patients is challenging as specific tests are not widely available. More accessible tests such as the prothrombin time and activated partial thromboplastin time have important limitations. In dabigatran-associated ICH 5 g Idarucizumab should be administered. In rivaroxaban and apixaban-associated ICHs administration of andexanet alpha should be considered. Prothrombin complex concentrate may be considered if andexanet alpha is not available or in case of an ICH associated with edoxaban.

Risk Factors of Gastrointestinal Bleeding in Patients Receiving New Oral Anticoagulants / 대한Helicobacter연구학회지

New oral anticoagulants (NOACs) are now widely used for the prevention and treatment of venous thrombosis, and for the prevention of stroke and systemic embolism in patients with atrial fibrillation. As compared with warfarin, NOACs have the advantage of rapid onset of action and less drug interaction. However, they carry a higher risk of gastrointestinal (GI) bleeding than warfarin. The risk of GI bleeding in patients using NOACs varies according to the type and dose of the drug. By contrast, apixaban and edoxaban are reported to carry similar risks as warfarin, and the risks with dabigatran and rivaroxaban are higher than that with warfarin. In patients using NOACs, old age, impaired renal function, impaired liver function, concurrent use of antiplatelet agents, and nonsteroidal anti-inflammatory drugs are considered major risk factors of GI bleeding, and gastroprotective agents such as histamine-2 receptor antagonist and proton pump inhibitor have preventive effects. To prevent GI bleeding associated with NOACs, the characteristics of each NOAC and the risk factors of bleeding should be recognized.

Direct Oral Anticoagulant for the Treatment of Venous Thromboembolism in Japanese Patients with Cancer

<p>Background/Aim: There is almost no study on direct oral anticoagulant (DOAC) for the treatment of venous thromboembolism (VTE) in Japanese patients with advanced cancer. The aim of this study was to evaluate the efficacy of DOAC for the treatment of VTE in Japanese patients with advanced cancer. Methods: We retrospectively reviewed patients with active cancer who had new-onset proximal deep vein thrombosis and/or pulmonary embolism at our hospital. We compared two DOACs, edoxaban and apixaban, with warfarin and evaluated the incidence of VTE recurrence and bleeding in a period of 3 months. The recurrence was diagnosed based on computed tomography or echography findings. Results: The number of patients treated with edoxaban, apixaban, and warfarin was 47, 31, and 30, respectively. In the warfarin group, the mean international normalized ratio of prothrombin time (2SD) after 3 months was 2.11 (0.42). There was no incidence of major bleeding. Non-major bleeding occurred in 17%, 10%, and 27% of the patients treated with edoxaban, apixaban, and warfarin, respectively (edoxaban vs. warfarin, risk ratio [RR]: 0.64, 95% confidence interval [CI]: 0.27–1.52; apixaban vs. warfarin, RR: 0.38, 95% CI: 0.11–1.28). All bleeding episodes occurred in 30%, 26%, 57% of patients treated with edoxaban, apixaban, and warfarin, respectively (edoxaban vs. warfarin, RR: 0.53, 95% CI: 0.31–0.90; apixaban vs. warfarin, RR: 0.46, 95% CI: 0.23–0.89). Recurrent VTE in edoxaban, apixaban, and warfarin groups occurred in 8%, 3%, and 16% of the patients, respectively (edoxaban vs. warfarin, RR: 0.52, 95% CI: 0.18–2.18; apixaban vs. warfarin, RR: 0.22, 95% CI: 0.03–1.80). Fisher’s exact test was used for statistical analysis. Conclusion: Our study suggests that the DOAC groups are relatively at a lower risk of VTE recurrence, non-major bleeding, as well as all bleeding episodes, as compared with the warfarin group. Therefore, DOAC might be useful in the treatment of VTE in Japanese patients with advanced cancer.</p>

Meta-analysis of Stroke Efficacy and Bleeding Risk of Edoxaban versus Warfarin in the Prevention of Pa-tients with Atrial Fibrillation / 中国药房

OBJECTIVE:To systematically review the effect of stroke efficacy and bleeding risk of edoxaban versus warfarin in the prevention of patients with atrial fibrillation,and provide evidence-based reference for clinical treatment. METHODS:Re-trieved from Cochrane Library,Medline,EMBase,CJFD,Wangfang Database and VIP Database,randomized controlled trials (RCT)about the stroke efficacy and bleeding risk of edoxaban versus warfarin in patients with atrial fibrillation were collected. Me-ta-analysis was performed for the incidences of stoke and excessive hemorrhage by using Rev Man 5.3 software after data extract. RESULTS:Totally 13 RCTs were included,involving 24 950 patients. Results of Meta-analysis showed,compared with warfarin group,there were no significant differences in the incidences of stoke [RR=0.97,95%CI(0.88,1.08),P=0.60] and excessive hem-orrhage [RR=0.84,95%CI(0.59,1.19),P=0.33] in edoxaban group. But the subgroup analysis showed,when daily dose of edoxa-ban was more than 30 mg,the incidence of stroke in edoxaban group was significantly lower than warfarin group [RR=0.84,95%CI(0.72,0.97),P=0.02];when it was 30 mg,the incidence of excessive bleeding in edoxaban group was significantly lower than warfarin group [RR=0.46,95%CI(0.35,0.61),P30 mg/d)of edoxaban can more effectively prevent the occurrence of stroke and low doses(30 mg/d) can reduce the risk of excessive bleeding.

Perioperative venous thromboembolic disease and the emerging role of the novel oral anticoagulants: An analysis of the implications for perioperative management.

Venous thromboembolism includes 2 inter-related conditions: Deep venous thrombosis and pulmonary embolism. Heparin and low-molecular-weight heparin followed by oral anticoagulation with vitamin K agonists is the first line and current accepted standard therapy with good efficacy. However, this therapeutic strategy has many limitations including the significant risk of bleeding and drug, food and disease interactions that require frequent monitoring. Dabigatran, rivaroxaban, apixaban, and edoxaban are the novel oral anticoagulants that are available for use in stroke prevention in atrial fibrillation and for the treatment and prevention of venous thromboembolism (HYPERLINK\l "1). Recent prospective randomized trials comparing the NOACs with warfarin have shown similar efficacy between the treatment strategies but fewer bleeding episodes with the NOACs. This paper presents an evidence-based review describing the efficacy and safety of the new anticoagulants compared to warfarin.

Application of New Oral Anticoagulants: Prevention of Stroke in Patients with Nonvalvular Atrial Fibrillation / 대한내과학회지

Only anticoagulation has been shown to reduce atrial fibrillation-related deaths. Vitamin K antagonists are difficult to use due to their narrow therapeutic range, unpredictable response, requirement for frequent coagulation monitoring, frequent dose adjustment, slow onset-offset, and numerous drug-drug and drug-food interactions. New oral anticoagulants (NOACs), such as dabigatran, rivaroxaban, and apixaban have been developed and are available in Korea, and edoxaban was shown to be effective and safe, also. NOACs showed better pharmacodynamics with predictable serum concentrations and effects, and no requirement for coagulation monitoring. These drugs have been shown to be more effective and safer than warfarin for prevention of stroke and systemic thromboembolism in patients with nonvalvular atrial fibrillation. Broad, appropriate, and aggressive use of NOACs would improve the results of treatment in patients with nonvalvular atrial fibrillation in Korea.