Clinical presentation and course of bleeding events in patients with venous thromboembolism, treated with apixaban or enoxaparin and warfarin

SummaryApixaban, a direct acting oral anticoagulant (DOAC), was found to be non-inferior to and safer as enoxaparin followed by warfarin for treatment of venous thromboembolism (VTE) in the AMPLIFY trial. Information is needed on how bleeding events with DOACs present and develop. In this post-hoc analysis, the clinical presentation and course of all major and clinically relevant non major (CRNM) bleeding events in the AMPLIFY trial were blindly classified by three investigators, using predesigned classification schemes containing four categories. Odds ratios (OR) for classifying as category three or four (representing a more severe clinical presentation and course) were calculated between apixaban and enoxaparin/warfarin. In total, 63 major and 311 CRNM bleeding events were classified. Of the major bleeds, a more severe clinical presentation occurred in 28.5% of apixaban versus 44.9% of enoxaparin/warfarin related recipients (OR 0.49, 95% confidence interval [CI] 0.14–1.78). A severe clinical course was observed in 14.3% and in 12.2%, respectively (OR 1.19, 95%CI 0.21–6.69). Of the CRNM bleeding events, a more severe clinical presentation and extent of clinical care was found in 25% of apixaban recipients compared to 22.7% in the enoxaparin/warfarin group (OR 1.13, 95%CI 0.65–1.97). The clinical presentation and course of major and CRNM bleeds were similar in apixaban and enoxaparin/warfarin treated patients. This finding should reassure physicians and patients that even in the absence of a specific reversal agent, apixaban is a convenient and safe choice for VTE.

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Abnormal vaginal bleeding in women with venous thromboembolism treated with apixaban or warfarin

Thrombosis and Haemostasis ◽

10.1160/th16-11-0874 ◽

2017 ◽

Vol 117 (04) ◽

pp. 809-815 ◽

Cited By ~ 29

Author(s):

Suzanne Bleker ◽

Barbara Hutten ◽

Anne Timmermans ◽

Harry Büller ◽

Saskia Middeldorp ◽

...

Keyword(s):

Venous Thromboembolism ◽

Diagnostic Tests ◽

Vaginal Bleeding ◽

Clinical Presentation ◽

Diagnostic Procedures ◽

Absolute Number ◽

Bleeding Events ◽

Warfarin Group ◽

Bleeding Episodes ◽

Abnormal Vaginal Bleeding

SummaryAbnormal vaginal bleeding can complicate direct oral anticoagulant (DOAC) treatment. We aimed to investigate the characteristics of abnormal vaginal bleeding in patients with venous thromboembolism (VTE) receiving apixaban or enoxaparin/warfarin. Data were derived from the AMPLIFY trial. We compared the incidence of abnormal vaginal bleeding between patients in both treatment arms and collected information on clinical presentation, diagnostic procedures, management and outcomes. In the AMPLIFY trial, 1122 women were treated with apixaban and 1106 received enoxaparin/warfarin. A clinically relevant non-major (CRNM) vaginal bleeding occurred in 28 (2.5 %) apixaban and 24 (2.1 %) enoxaparin/warfarin recipients (odds ratio [OR] 1.2, 95 % confidence interval [CI] 0.7–2.0). Of all CRNM bleeds, 28 of 62 (45 %) and 24 of 120 (20 %) were of vaginal origin in the apixaban and enoxaparin/warfarin group, respectively (OR 3.4; 95 % CI 1.8–6.7). Premenopausal vaginal bleeds on apixaban were characterised by more prolonged bleeding (OR 2.3; 95 %CI 0.5–11). In both pre- and postmenopausal vaginal bleeds, diagnostic tests were performed in six (21 %) and in seven (29 %) apixaban and enoxaparin/ warfarin treated patients, respectively. Medical treatment was deemed not necessary in 16 (57 %) apixaban and 16 (67 %) enoxaparin/warfarin recipients. The severity of clinical presentation and course of the bleeds was mild in 75 % of the cases in both groups. In conclusion, although the absolute number of vaginal bleeding events is comparable between apixaban and enoxaparin/warfarin recipients, the relative occurrence of vaginal bleeds is higher in apixaban-treated women. The characteristics and severity of bleeding episodes were comparable in both treatment arms.

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Deep venous thrombosis in the clinical course of pulmonary embolism

Phlebology The Journal of Venous Disease ◽

10.1177/0268355518819510 ◽

2018 ◽

Vol 34 (7) ◽

pp. 453-458

Author(s):

Natalia Stoeva ◽

Milena Staneva ◽

Galina Kirova ◽

Rumiana Bakalova

Keyword(s):

Pulmonary Embolism ◽

Mortality Rate ◽

Pulmonary Artery ◽

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Clinical Presentation ◽

Clinical Course ◽

Clinical Signs ◽

Arterial Blood ◽

Severe Clinical Presentation

Objectives The aim of the study is to find how concomitant deep venous thrombosis (DVT) changes the clinical course of pulmonary embolism. Methods Three hundred and five patients with pulmonary embolism were examined and grouped into DVT and non-DVT groups. Both groups were compared with regard to demography, predisposing factors, clinical signs, thrombotic burden, and one-month mortality rate. Results The patients with DVT had a more severe clinical presentation: higher heart rate (94.80 ± 18.66 beats per minute versus 87.9 ± 13.90 in the non-DVT group, p = 0.00033), more hemodynamic instability (11.35% versus 3.05% in the non-DVT group, p = 0.005), and less pCO2 in arterial blood gases (30.81 ± 7.94 mmHg versus 32.59 ± 7.35 mmHg in the non-DVT group, p = 0.049). The DVT group had heavier thrombotic burden in pulmonary artery, measured by Mastora score. The one-month mortality rate did not differ statistically between groups. Conclusions Patients with symptomatic pulmonary embolism and concomitant DVT have heavier thrombotic burden in the pulmonary artery and more severe clinical presentation compared to those without DVT, but a similar one-month mortality rate.

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Clinical Impact and Course of Anticoagulant-Related Major Bleeding in Cancer Patients

Blood ◽

10.1182/blood.v128.22.2611.2611 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2611-2611 ◽

Cited By ~ 1

Author(s):

Noémie Kraaijpoel ◽

Nick van Es ◽

Suzanne M Bleker ◽

Marjolein P Brekelmans ◽

Elise S Eerenberg ◽

...

Keyword(s):

Venous Thromboembolism ◽

Board Of Directors ◽

Cancer Patients ◽

Major Bleeding ◽

Clinical Presentation ◽

Clinical Course ◽

Vitamin K Antagonists ◽

Phase Iii ◽

Anticoagulant Treatment ◽

Advisory Committees

Abstract Background Venous thromboembolism (VTE), comprising deep vein thrombosis and pulmonary embolism, is a frequent complication in cancer patients. During anticoagulant treatment for VTE, the risk of major bleeding events (MBE) is 2- to 6-fold higher in cancer patients than in those without cancer. It is unknown whether the clinical presentation and course of anticoagulant-related MBE in cancer patients differ from patients without cancer. Methods Individual patient data from 4 randomized controlled phase III trials in which factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban) were compared with vitamin K antagonists for the treatment of VTE were used for the present analysis. The severity of the clinical presentation and clinical course of anticoagulant-related MBE were compared between patients with and without cancer. Using predefined criteria, the severity of the clinical presentation and course of MBE were classified into four categories by independent adjudicators, who were blinded to treatment allocation. Category 1 indicates a mild clinical presentation or course, while category 4 indicates a severe presentation or course (Table 1). A one-stage meta-analysis was used to estimate crude odds ratios (ORs) and ORs adjusted for age, sex, and type of anticoagulant treatment with 95% confidence intervals (CIs) for the effect of cancer on the severity of the clinical presentation and course. For this analysis categories 3 and 4 were combined. We also explored the cause and site of bleeding in these patients. Results The study group comprised 290 patients with MBE, of whom 50 (17%) had active cancer or were diagnosed with cancer during follow-up. The clinical presentation was judged to be severe (category 3 or 4) in 38% of patients with cancer and 44% of patients without cancer (adjusted OR 0.90, 95% CI 0.47-1.72). Clinical course was judged to be severe in 20% and 25% of patients with and without cancer, respectively (adjusted OR 0.75, 95% CI 0.35-1.61) (Table 2). The bleeding pattern varied significantly between the two groups (p=0.002); cancer patients more often had gastrointestinal (52% vs. 35%) and vaginal (14% vs. 6%) MBE, whereas intracranial (19% vs. 6% and retroperitoneal (5% vs. 0%) MBE occurred more often in patients without cancer (Table 3). MBE was related to the tumor site in 40% of cancer patients. Conclusion The findings of the present study indicate that the clinical presentation and course of anticoagulant-related MBE are not more severe in cancer patients than in patients without cancer, which is reassuring for physicians who treat cancer-associated VTE. Disclosures Eerenberg: Sanquin: Consultancy; CSL Behring: Consultancy; Baxter: Consultancy. Middeldorp:Aspen: Consultancy, Honoraria; Boehringer Ingelheim: Consultancy; Daiichi Sankyo: Consultancy, Honoraria; Bayer: Consultancy; Sanquin: Consultancy; GSK: Consultancy, Honoraria; BMS/Pfizer: Consultancy, Honoraria. Cohen:Takeda: Consultancy; Leo Pharma: Consultancy; GlaxoSmithKline: Consultancy, Speakers Bureau; Daiichi Sankyo: Consultancy, Honoraria, Speakers Bureau; Bayer: Consultancy, Honoraria, Speakers Bureau; Department of Health: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Honoraria, Speakers Bureau; Medscape: Speakers Bureau; UK Government Health Select Committee: Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Consultancy, Speakers Bureau; Colation to Prevent Venous Thromboembolism: Other: Founder; NHS: Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Aspen: Consultancy, Speakers Bureau; ONO: Consultancy, Honoraria; XO1: Consultancy, Honoraria; Portola: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy; Lifeblood: Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria.

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Real-life data of direct anticoagulant use, bleeding risk and venous thromboembolism recurrence in chronic thromboembolic pulmonary hypertension patients: an observational retrospective study

Pulmonary Circulation ◽

10.1177/2045894019873545 ◽

2020 ◽

Vol 10 (1) ◽

pp. 204589401987354 ◽

Cited By ~ 3

Author(s):

Sert Sena ◽

Mutlu Bulent ◽

Kocakaya Derya ◽

Kaptan Deniz ◽

Ataş Halil ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Venous Thromboembolism ◽

Anticoagulant Therapy ◽

Major Bleeding ◽

Real Life ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Bleeding Events ◽

Warfarin Group ◽

Thromboembolic Pulmonary Hypertension ◽

Recurrent Vte

Introduction Lifelong anticoagulation is the cornerstone of the chronic thromboembolic pulmonary hypertension (CTEPH) treatment regardless of the additional pulmonary endarterectomy, balloon pulmonary angioplasty, or medical treatment alone. Aim of this study was to evaluate the rate of oral anticoagulant preferences and document direct oral anticoagulants’ (DOACs’) safety, efficacy in the CTEPH population. Methods Patients’ demographic data obtained from database between September 2011 and April 2018. In-hospital events, death, venous thromboembolism (VTE) recurrence, bleeding events and anticoagulant therapy transition were recorded. Results We reviewed 501 CTEPH patients who observed 9.0 ± 8.5 years. All-cause death, all bleeding, recurrent VTE was observed in 15.6%, 31% and 12%. Forty-one patients (8.2%) were diagnosed as inoperable. Of all, 15.2% of operable patients remained as residual. All-cause mortality rates were 13.8% (57 pts.) in the warfarin group as compared with 9.7% (13 pts.) in rivaroxaban group (HR: 1.61, 95% CI, 0.89–2.99; p: 0.11). Higher bleeding events occurred with warfarin group (27.1%) as compared with rivaroxaban (24.6%; HR: 1.28, 95% CI, 0.86–1.88; p: 0.22). Major bleeding was significantly higher with warfarin group (HR: 1.94, 95% CI, 1.05–3.62; p: 0.03). Subgroup analysis of all-cause death revealed that this significance dominated by the rate of death according to bleeding events; warfarin versus those seen with rivaroxaban (4.85% vs. 2.2%; HR: 4.75, 95% CI: 1.12–20.16; p = 0.03). The rate of recurrent VTE was found 8.9% in the rivaroxaban group, 10.9% in warfarin group (HR: 1.21, 95% CI, 0.64–2.23; p: 0.55). Conclusion DOACs could be a safe and effective alternative for lifelong anticoagulant therapy in CTEPH patients. Rivaroxaban produced similar rates of thromboembolism and non-relevant bleeding compared to those associated with warfarin. The main difference was found with major bleeding that it was mainly associated with the death rate according to major bleeding. Using DOACs might be a more reasonable way to prevent bleeding events without increasing thromboembolic risk.

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Clinical impact and course of major bleeding with edoxaban versus vitamin K antagonists

Thrombosis and Haemostasis ◽

10.1160/th15-11-0892 ◽

2016 ◽

Vol 116 (07) ◽

pp. 155-161 ◽

Cited By ~ 11

Author(s):

Marjolein Brekelmans ◽

Suzanne Bleker ◽

Rupert Bauersachs ◽

Zoltan Boda ◽

Harry Büller ◽

...

Keyword(s):

Vitamin K ◽

Major Bleeding ◽

Clinical Presentation ◽

Clinical Course ◽

Vitamin K Antagonists ◽

Bleeding Events ◽

Vein Thrombosis ◽

Recurrent Deep Vein Thrombosis ◽

Major Bleeding Events ◽

Deep Vein

SummaryEdoxaban is a once-daily direct oral anticoagulant (DOAC). The Hokusai-VTE study revealed that, after initial treatment with heparin, edoxaban was non-inferior to and safer than vitamin K antagonists (VKA) in the prevention of recurrent deep-vein thrombosis and pulmonary embolism. This is the first report on the clinical relevance and management of bleeding events with edoxaban. All major bleeding events were classified blindly by three study-independent adjudicators. Predefined criteria were used to classify severity of clinical presentation and, separately, the clinical course and outcome into four categories. Major bleeding occurred in 56 patients treated with edoxaban and 65 patients treated with VKA. The severest categories (3 or 4) of the clinical presentation were assigned to 46 % of the major bleeding episodes in edoxaban recipients versus 58 % of the major bleeds in VKA recipients (odds ratio [OR] 0.62, 95 % confidence interval [CI] 0.30–1.27, p = 0.19). Clinical course was classified as severe (category 3 or 4) in 23 % of the edoxaban and 29 % of the VKA associated bleeds (OR 0.73, 95 % CI 0.32–1.66, p = 0.46). In conclusion, edoxaban associated major bleeding events have a comparable clinical presentation and course to major bleeds with VKA in patients treated for venous thromboembolism in the Hokusai-VTE study. These results may assure physicians that it is safe to prescribe this medication. If a major bleeding during edoxaban treatment occurs, its clinical presentation and clinical course are not worse than in VKA-treated patients.

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Clinical impact of major bleeding in patients with venous thromboembolism treated with factor Xa inhibitors or vitamin K antagonists

Thrombosis and Haemostasis ◽

10.1160/th16-12-0946 ◽

2017 ◽

Vol 117 (10) ◽

pp. 1944-1951 ◽

Cited By ~ 20

Author(s):

Elise Eerenberg ◽

Alexander Cohen ◽

Saskia Middeldorp ◽

Gary Raskob ◽

Harry Büller ◽

...

Keyword(s):

Venous Thromboembolism ◽

Vitamin K ◽

Major Bleeding ◽

Clinical Presentation ◽

Vitamin K Antagonists ◽

Factor Xa ◽

Bleeding Events ◽

Different Types ◽

Fxa Inhibitor ◽

Major Bleeding Events

SummaryFactor Xa (fXa)-inhibitors are as effective and safer than vitamin-K–antagonists (VKA) in the treatment of venous thromboembolism (VTE). We previously classified the severity of clinical presentation and course of all major bleeding events from the EINSTEIN, AMPLIFY and HOKUSAI-VTE trials separately. The current aim was to combine these findings in order to increase precision, assess a class effect and analyse presentation and course for different types of bleeding, i. e. intracranial, gastro-intestinal, and other. We classified the clinical presentation and course of all major bleeding events using pre-defined criteria. Both classifications comprised four categories; one being the mildest, and four the most severe. Odds ratios (OR) were calculated for all events classified as category three or four between fXa-inhibitors and VKA recipients. Also, ORs were computed for different types of bleeding. Major bleeding occurred in 111 fXa-inhibitor recipients and in 187 LMWH/VKA recipients. The clinical presentation was classified as category three or four in 35% and 48% of the major bleeds in fXa inhibitor and VKA recipients, respectively (OR 0.59, 95% CI 0.36–0.97). For intracranial, gastro-intestinal and other bleeding a trend towards a less severe presentation was observed for patients treated with fXa inhibitors. Clinical course was classified as severe in 22% of the fXa inhibitor and 25% of the VKA associated bleeds (OR 0.83, 95% CI 0.47–1.46). In conclusion, FXa inhibitor associated major bleeding events had a significantly less severe presentation and a similar course compared to VKA. This finding was consistent for different types of bleeding.

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Cardiovascular involvement in alpha-n-acetyl neuraminidase deficiency syndromes (sialidosis type I and II)

Cardiology in the Young ◽

10.1017/s1047951120004953 ◽

2021 ◽

pp. 1-3

Author(s):

Priyanka Prasanna ◽

Chenni S. Sriram ◽

Sarah H. Rodriguez ◽

Utkarsh Kohli

Keyword(s):

Autosomal Recessive ◽

Ventricular Dysfunction ◽

Clinical Presentation ◽

Clinical Course ◽

Rare Condition ◽

Autosomal Recessive Disorder ◽

Left Ventricular ◽

Type I ◽

Neonatal Onset ◽

Cardiovascular Involvement

Abstract Sialidosis, a rare autosomal recessive disorder, is caused by a deficiency of NEU1 encoded enzyme alpha-N-acetyl neuraminidase. We report a premature male with neonatal-onset type II sialidosis which was associated with left ventricular dysfunction. The clinical presentation and subsequent progression which culminated in his untimely death at 16 months of age are succinctly described. Early-onset cardiovascular involvement as noted in this patient is not well characterised. The case report is supplemented by a comprehensive review of the determinants, characteristics, and the clinical course of cardiovascular involvement in this rare condition.

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Fondaparinux Pre-, Peri-, and/or Postpartum for the Prophylaxis/Treatment of Venous Thromboembolism (FondaPPP)

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/10760296211014575 ◽

2021 ◽

Vol 27 ◽

pp. 107602962110145

Author(s):

Carl-Erik Dempfle ◽

Jürgen Koscielny ◽

Edelgard Lindhoff-Last ◽

Birgit Linnemann ◽

Irene Bux-Gewehr ◽

...

Keyword(s):

Venous Thromboembolism ◽

Adverse Events ◽

Drug Hypersensitivity ◽

Low Molecular Weight ◽

Premature Births ◽

First Line ◽

Bleeding Events ◽

Heparin Induced Thrombocytopenia ◽

First Line Therapy ◽

Heparin Allergy

We analyzed data for women who received fondaparinux for ≥7 days during pregnancy. The study retrospectively included women who received fondaparinux pre-, peri- and/or postpartum for ≥7 days for prophylaxis/venous thromboembolism (VTE) treatment at German specialist centers (2004-2010). Data on pregnancy, VTE risk factors, anticoagulant treatment, pregnancy outcome and adverse events were extracted from medical records. 120 women (mean age 31.5 years) were included. Among 84 women with prior pregnancies, 41.0% had ≥1 abortion. Anticoagulation was indicated for prophylaxis in 92.5% cases, including 82.5% women with an elevated VTE risk (82.8% thrombophilia, 34.2% VTE history). All women received low-molecular-weight heparin (LMWH) as first-line therapy; 3 also unfractionated heparin. Treatment changed to fondaparinux, due to heparin allergy (41.7%) or heparin-induced thrombocytopenia (10.0%). Fondaparinux was generally well tolerated. Adverse events included bleeding events (n = 5), abortion (n = 2), premature births (n = 2), stillbirth (n = 1), arrested labors (n = 2), injection site erythema (n = 4) and unspecified drug hypersensitivity (n = 6). No VTE events or increased liver enzymes occurred during treatment. In this retrospective study, fondaparinux was effective and well tolerated. Trial registration: ClinicalTrials.gov NCT01004939.

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