Publications by authors named "Jan Beyer-Westendorf"

153 Publications

The prognostic value of respiratory symptoms and performance status in ambulatory cancer patients and unsuspected pulmonary embolism; analysis of an international, prospective, observational cohort study.

J Thromb Haemost 2021 Sep 16. Epub 2021 Sep 16.

Department of Medicine and Ageing Sciences, University G. D'Annunzio, Chieti, Italy.

Background: Optimal risk stratification of unsuspected pulmonary embolism (UPE) in ambulatory cancer patients (ACPs) remains unclear. Existing clinical predictive rules (CPRs) are derived from retrospective databases and have limitations. The UPE registry is a prospective international registry with pre-specified characteristics of ACPs with a recent UPE. The aim of this study was to assess the utility of risk factors captured in the UPE registry in predicting proximate (30-, 90- and 180-day) mortality and how they performed when applied to an existing CPR.

Objectives: To evaluate risk factors for proximate mortality, overall survival, recurrent venous thromboembolism and major bleeding, in the patients enrolled in the UPE registry cohort.

Methods: Data from the 695 ACPs in this registry were subjected to multivariate logistic regression analyses to identify predictors independently associated with proximate mortality and overall survival. The most consistent predictors were applied to the Hull CPR, an existing 5-point prediction rule.

Results: The most consistent predictors of mortality were patient-reported respiratory symptoms within 14 days before, and ECOG performance status at the time of UPE. These predictors applied to the Hull-CPR produced a consistent correlation with proximate mortality and overall survival (area under the curve [AUC] = 0.70 [95% CI 0.63, 077], AUC = 0.65 [95% CI 0.60, 070], AUC = 0.64 [95% CI 0.59, 068], and AUC = 0.61, 95% CI 0.57, 0.65, respectively).

Conclusion: In ACPs with UPE, ECOG performance status logged contemporaneously to the UPE diagnosis and respiratory symptoms prior to UPE diagnosis can stratify mortality risk. When applied to the HULL-CPR these risk predictors confirmed the risk stratification clusters of low-intermediate and high-risk for proximate mortality as seen in the original derivation cohort.
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http://dx.doi.org/10.1111/jth.15489DOI Listing
September 2021

The Importance of Appropriate Dosing of Nonvitamin K Antagonist Oral Anticoagulants for Stroke Prevention in Patients with Atrial Fibrillation.

TH Open 2021 Jul 23;5(3):e353-e362. Epub 2021 Aug 23.

Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, Montfermeil, France.

Preventing thromboembolic events, while minimizing bleeding risks, remains challenging when managing patients with atrial fibrillation (AF). Several factors contribute to current dosing patterns of nonvitamin K antagonist oral anticoagulants (NOACs), including patient characteristics, comorbidities, and physician judgment. Application of NOAC doses inconsistent with the drug labels may cause patients to receive either subtherapeutic (increasing stroke risk) or supratherapeutic (increasing bleeding risk) anticoagulant levels. In clinical practice, under- or over-dosing of NOACs in patients with AF is not uncommon. This analysis of prospective and retrospective registry and database studies on NOAC use in patients with AF (with at least 250 patients in each treatment arm) showed that under-dosing may be associated with reduced effectiveness for stroke prevention, with similar or even increased bleeding than with the standard dose. This may reflect underlying conditions and patient factors that increase bleeding despite NOAC dose reduction. Such factors could drive the observed overuse of reduced NOAC dosages, often making the prescription of reduced-dose NOAC an intentional label deviation. In contrast, over-dosing more likely occurs accidentally; instead of providing benefits, it may be associated with worse safety outcomes than the standard dose, including increased bleeding risk and higher all-cause mortality rates. This review summarizes the main findings on NOAC doses usually prescribed to patients with AF in clinical practice.
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http://dx.doi.org/10.1055/s-0041-1731777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382498PMC
July 2021

Secondary Immune Thrombocytopenia (ITP) Associated with ChAdOx1 Covid-19 Vaccination - A Case Report.

TH Open 2021 Jul 30;5(3):e315-e318. Epub 2021 Jul 30.

Department of Medicine, Hematology Division, University Hospital Carl Gustav Carus, Dresden, Germany.

Novel mRNA and vector-based covid-19 vaccinations have shown high efficacy in preventing symptomatic COVID-19 infections. Compared with the number of performed vaccinations, rates of severe side effects seem low. Rare prothrombotic coagulation disorders with suspected association to ChAdOx1 nCoV-19 (AstraZeneca) have been reported. These cases have gathered considerable media attention and caused a temporary pause of usage of the AstraZeneca vaccine in Europe and several other countries and are currently discussed as vaccine-induced immune thrombotic thrombocytopenia (VITT). However, hemorrhagic complications from ChAdOx1 nCoV-19 vaccination have also been reported but, so far, received less public attention despite considerable potential for life-threatening complications. Here we present a case of severe immune thrombocytopenia after ChAdOx1 covid-19 vaccination and its successful primary management.
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http://dx.doi.org/10.1055/s-0041-1731774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324423PMC
July 2021

Patient-reported outcomes associated with changing to rivaroxaban for the treatment of cancer-associated venous thromboembolism - The COSIMO study.

Thromb Res 2021 Oct 2;206:1-4. Epub 2021 Jul 2.

CESP-Center for Public Health Research, University of Milan Bicocca, Monza, Italy; IRCCS Multimedica, Sesto San Giovanni, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.thromres.2021.06.021DOI Listing
October 2021

Every 6 seconds in Europe.

Thromb Res 2021 Jul 21. Epub 2021 Jul 21.

Division of Hematology, Dresden University Hospital, Dresden, Germany.

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http://dx.doi.org/10.1016/j.thromres.2021.07.012DOI Listing
July 2021

Quality of life in patients with pulmonary embolism treated with edoxaban versus warfarin.

Res Pract Thromb Haemost 2021 Jul 14;5(5):e12566. Epub 2021 Jul 14.

Daiichi Sankyo Pharma Development Basking Ridge NJ USA.

Background: Long-term sequelae of acute pulmonary embolism (PE) include decreased quality of life (QoL). Evidence suggests that adequacy of initial anticoagulant treatment in the acute phase of venous thrombosis has a key impact on late postthrombotic complications. We hypothesize that patients with acute PE treated with edoxaban for acute PE experience have improved QoL compared to those treated with warfarin.

Methods: Patients with PE who participated in the Hokusai-VTE trial were contacted between June 2017 and September 2020 for a single long-term follow-up visit. Main outcomes were the generic and disease-specific QoL measured by the 36-Item Short Form Health Survey (SF-36) and Pulmonary Embolism Quality of Life questionnaire.

Results: We included 251 patients from 26 centers in eight countries, of which 129 (51%) had been assigned to edoxaban and 122 (49%) to warfarin. Patient- and thrombus-specific characteristics were similar in both groups. Mean time since randomization in the Hokusai-VTE trial was 7.0 years (standard deviation, 1.0). No relevant or statistical differences were observed in the QoL for patients treated with edoxaban compared to patients treated with warfarin. The mean difference between patients treated with edoxaban and patients with PE treated with warfarin was 0.8 (95% confidence interval [CI]. -1.6 to 3.2) for the SF-36 summary mental score and 1.6 (95% CI, -0.9 to 4.1) for summary physical score.

Conclusion: Our findings indicate that patients with an index PE treated with edoxaban or warfarin have a similar long-term QoL. Since our study was a follow-up study from a well-controlled clinical trial setting, future studies should be designed in a daily clinical practice setting. We suggest a longitudinal design for investigation of changes in QoL over time.
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http://dx.doi.org/10.1002/rth2.12566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279124PMC
July 2021

Use of direct oral anticoagulants in patients with obesity for treatment and prevention of venous thromboembolism: Updated communication from the ISTH SSC Subcommittee on Control of Anticoagulation.

J Thromb Haemost 2021 08 14;19(8):1874-1882. Epub 2021 Jul 14.

Division of Hematology, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA.

Although direct-acting oral anticoagulants (DOACs) have widespread first-line use for treatment and prevention of venous thromboembolism (VTE), uncertainty remains regarding their efficacy and safety in patients with obesity. We reviewed available data for use of DOACs for VTE treatment and prevention in patients with obesity, including phase 3, phase 4, meta-analyses, and pharmacokinetic and pharmacodynamics studies. In addition, we reviewed available data regarding DOACs in bariatric surgery. We provide updated guidance recommendations on using DOACs in patients with obesity for treatment and prevention of VTE, as well as following bariatric surgery.
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http://dx.doi.org/10.1111/jth.15358DOI Listing
August 2021

Pharmacokinetics of direct oral anticoagulants in emergency situations - Results of the prospective observational RADOA-registry.

Thromb Haemost 2021 Jul 13. Epub 2021 Jul 13.

Med. Klinik III, Johann-Wolfgang-Goethe-Universitätsklinik Frankfurt, Frankfurt, Germany.

Background Direct oral anticoagulants (DOAC) are increasingly used worldwide. Little is known so far about their pharmacokinetics in emergency situations. Methods A prospective, observational registry was performed to determine the clinical course in consecutive patients with major bleeding or urgent surgery treated with DOACs. In back-up blood samples from routine care DOAC drug concentrations were measured using UPLC-MS/MS. Anticoagulant intensity at first presentation and drug half-life (t1/2), tested in repeat samples, were evaluated. Results 140 patients were prospectively included. Pharmacokinetic data were available in 94% (132/140) of patients. 67% (89/132) experienced life-threatening bleeding and 33% (43/132) needed an urgent surgery. For pharmacokinetic analysis a total of 605 blood samples was available. Median concentration on admission was 205 ng/mL for rivaroxaban and 108 ng/mL for apixaban. All treatment groups showed a high variation of drug concentrations at baseline. In rivaroxaban treated patients t½ was 17.3 hours (95% CI: 15.4 - 19.7) without significant difference in both groups (major bleeding: t½ 16.7 hours, 95% CI: 14.7 - 19.3; urgent surgery: t½ 19.7 hours, 95% CI 15.2 - 27.9; p=0.292). In apixaban treated patients t½ was 25.0 hours (95% CI: 22.9 - 27.6) with a longer t½ after urgent surgery (t1/2: 30.8 hours; 95% CI: 26.9 - 36.4) compared to severe bleeding (t1/2: 20.8 hours; 95% CI: 18.8 - 23.2; p<0.001). Conclusions Emergency patients under DOAC treatment show a high variation of anticoagulant concentrations at baseline. Compared with rivaroxaban, apixaban showed a lower median concentration on admission and a longer t½.
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http://dx.doi.org/10.1055/a-1549-6556DOI Listing
July 2021

Reproductive issues in women on direct oral anticoagulants.

Res Pract Thromb Haemost 2021 May 3;5(4):e12512. Epub 2021 May 3.

Thrombosis Research Unit Department of Medicine I Division Haematology University Hospital "Carl Gustav Carus" Dresden Dresden Germany.

Direct oral anticoagulants (DOACs) are replacing warfarin and other vitamin K antagonists for a wide range of indications. Advantages of DOAC therapy are fewer food and drug interactions and fixed dosing without routine laboratory monitoring, making DOACs the perfect choice especially for younger patients, in whom the main indication for anticoagulation is prevention and treatment of venous thromboembolism (VTE). Although DOACs are safer and much more convenient than other anticoagulant alternatives, their profile may have drawbacks, especially for younger female patients in whom reproductive issues need special considerations. These may include the issue of heavy menstrual bleeding (HMB) during anticoagulant therapy, the embryotoxicity risk from inadvertent DOAC exposure during pregnancy, and the prevention or planning of pregnancies during DOAC therapy. This review summarizes the most relevant evidence in this increasingly important field of women's health.
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http://dx.doi.org/10.1002/rth2.12512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105156PMC
May 2021

Venous Thromboembolism Therapy with Apixaban in Daily Care Patients: Results from the Dresden NOAC Registry.

TH Open 2021 Apr 4;5(2):e143-e151. Epub 2021 May 4.

Thrombosis Research Unit, Division Hematology, Department of Medicine I, University Hospital "Carl Gustav Carus" Dresden, Dresden, Germany.

The effectiveness and safety of venous thromboembolism (VTE) treatment with apixaban, demonstrated in phase III trials, need to be confirmed in daily care. Using data from the prospective, noninterventional cross-indication we evaluated rates of VTE recurrence and bleeding complications during apixaban treatment of VTE patients. For this analysis, we only included patients with acute VTE who started apixaban within 14 days after diagnosis and who were enrolled within these 14 days. Patient characteristics, treatment persistence, and clinical outcomes were assessed. Between August 1st, 2014 and October 31, 2018, 352 patients with apixaban treatment for acute VTE were enrolled. During treatment (median exposure 13.7 ± 9.8 months; median follow-up 21.7 ± 6.1 months) rates of recurrent VTE and International Society on Thrombosis and Haemostasis major bleeding were 1.3/100 pt.years (95% confidence interval or CI 0.4-3.0) and 1.5/100 pt.years (0.6-3.3), respectively. At 6 months. 68.6% of patients were still taking apixaban, 23.9% had a scheduled end of treatment, 6.3% were switched to other anticoagulants, and the remaining 2.3% had unplanned complete discontinuation of anticoagulation. Of the 188 patients stopping apixaban, 12 (6.4%) experienced a recurrent VTE (six pulmonary embolisms ± deep vein thrombosis, six deep vein thrombosis; mean time between stopping anticoagulation and VTE recurrence 5.2 ± 4.1 months [range 14-417 days]). Our findings suggest that, in daily care, apixaban demonstrated high effectiveness, safety, and persistence in the treatment of acute VTE with low rates of unplanned discontinuation.
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http://dx.doi.org/10.1055/s-0041-1728675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096533PMC
April 2021

Homoarginine and methylarginines independently predict long-term outcome in patients presenting with suspicion of venous thromboembolism.

Sci Rep 2021 May 5;11(1):9569. Epub 2021 May 5.

Department of Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany.

Endogenous arginine derivatives homoarginine, asymmetric dimethylarginine (ADMA) and symmetric dimethyarginine (SDMA) are independent mortality predictors in atherosclerotic cardiovascular disease (CVD). Our study reports the first analysis, whether homoarginine, ADMA and SDMA predict venous thromboembolism (VTE) recurrence and overall mortality in patients with suspected acute VTE. We assessed serum levels of homoarginine, ADMA and SDMA by LC-MS/MS in 865 individuals from a prospective consecutive cohort of patients with clinical suspicion of VTE. The median follow-up time for mortality was 1196 days. VTE was confirmed by imaging in 418 patients and excluded in 447 patients. Low levels of homoarginine and high levels of ADMA or SDMA independently predicted all-cause mortality after adjustment for sex, age, oral anticoagulants, body mass index, arterial hypertension, diabetes mellitus, smoking, dyslipidemia, chronic heart failure, history of stroke, creatinine and cancer both in patients with VTE and without VTE. Interestingly, none of those parameters was predictive for VTE recurrence. We provide the first report that low circulating levels of homoarginine and high circulating levels of ADMA and SDMA independently predict all-cause mortality in patients with suspected VTE. These parameters might serve as markers of "frailty" and should be considered for future risk stratification approaches in this clinical population. Taking into account that homoarginine supplementation is protective in animal models of CVD and safe in healthy human volunteers, our study provides the basis for future homoarginine supplementation studies in patients with suspected VTE to investigate possible direct protective effects of homoarginine in this population.
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http://dx.doi.org/10.1038/s41598-021-88986-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100302PMC
May 2021

SARS-CoV-2 Vaccine and Thrombosis: An Expert Consensus on Vaccine-Induced Immune Thrombotic Thrombocytopenia.

Thromb Haemost 2021 Aug 4;121(8):982-991. Epub 2021 May 4.

Department of Internal Medicine and Clinical Immunology, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Centre de Référence des Maladies Auto-Immunes Systémiques Rares, Centre de Référence des Maladies Auto-Inflammatoires et de l'Amylose inflammatoire, Paris, France.

Historically, the vaccination strategies developed in the second half of the 20th century have facilitated the eradication of infectious diseases. From the onset of COVID-19 pandemic to the end of April 2021, more than 150 million cases and 3 million deaths were documented worldwide with disruption of the economic and social activity, and with devastating material, physical, and psychological consequences. Reports of unusual and severe thrombotic events, including cerebral and splanchnic venous thrombosis and other autoimmune adverse reactions, such as immune thrombocytopenia or thrombotic microangiopathies in connection with some of the SARS-CoV-2 vaccines, have caused a great deal of concern within the population and the medical community. This report is intended to provide practical answers following an overview of our knowledge on these thrombotic events that are extremely rare but have serious consequences. Vaccine hesitancy threatens to reverse the progress made in controlling vaccine-preventable diseases. These adverse events must be put into perspective with an objective analysis of the facts and the issues of the vaccination strategy during this SARS-CoV-2 pandemic. Health care professionals remain the most pertinent advisors and influencers regarding vaccination decisions; they have to be supported to provide reliable and credible information on vaccines. We need to inform, reassure, and support our patients when the prescription is made. Facing these challenges and observations, a panel of experts express their insights and propose a tracking algorithm for vaccinated patients based on a 10-point guideline for decision-making on what to do and not to do.
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http://dx.doi.org/10.1055/a-1499-0119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322589PMC
August 2021

[Persistent dyspnea after COVID-19: Suggestions for follow-up care].

MMW Fortschr Med 2021 04;163(8):52-55

Fachkrankenhaus Coswig und Universitätsklinikum Dresden, Coswig, Deutschland.

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http://dx.doi.org/10.1007/s15006-021-9842-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075707PMC
April 2021

Definition of haemostatic effectiveness in interventions used to treat major bleeding: Communication from the ISTH SSC Subcommittee on Control of Anticoagulation.

J Thromb Haemost 2021 04;19(4):1112-1115

Department of Hematology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

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http://dx.doi.org/10.1111/jth.15222DOI Listing
April 2021

Checkpoint inhibitors and thrombosis: what's up?

Blood 2021 03;137(12):1569-1570

University Hospital "Carl Gustav Carus".

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http://dx.doi.org/10.1182/blood.2020009480DOI Listing
March 2021

Heavy menstrual bleeding in women on anticoagulant treatment for venous thromboembolism: Comparison of high- and low-dose rivaroxaban with aspirin.

Res Pract Thromb Haemost 2021 Feb 17;5(2):308-313. Epub 2021 Feb 17.

Department of Medicine McMaster University Hamilton ON Canada.

Background: Rivaroxaban may induce heavy menstrual bleeding. It is unknown if this effect is dose related or if rivaroxaban is associated with more menstrual bleeding than aspirin.

Objectives: To demonstrate and compare menstrual patterns and actions taken among women receiving aspirin and two doses of rivaroxaban.

Methods: The EINSTEIN-CHOICE trial compared once-daily rivaroxaban 20 mg, rivaroxaban 10 mg, and aspirin 100 mg for extended treatment of venous thromboembolism in patients who had completed 6 to 12 months of anticoagulant therapy. In 362 women with menstrual cycles, menstrual flow duration and intensity assessed at days 30, 90, 180, and 360 were compared with those before starting anticoagulant therapy.

Results: Menstrual flow duration increased in 12%-18% of the 134 women given 20-mg rivaroxaban, in 6% to 12% of 120 women given 10-mg rivaroxaban, and in 9% to 12% of 108 women given aspirin. Corresponding increases in flow intensity were 19% to 24%, 14% to 21%, and 13% to 20%. The odds ratios (ORs) for increased menstrual flow duration were 1.36 (95% confidence interval [CI], 0.62-2.96) for rivaroxaban 20 mg versus aspirin, 0.77 (95% CI, 0.33-1.81) for rivaroxaban 10 mg versus aspirin, and 0.57 (95% CI, 0.26-1.25) for rivaroxaban 10 mg versus 20 mg. The ORs for increased menstrual flow intensity were 1.41 (95% CI, 0.67-2.99), 1.07 (95% CI, 0.49-2.34), and 0.76 (95% CI, 0.37- 1.57), respectively.

Conclusions: There were no statistically significant differences in menstrual hemorrhage patterns between women treated with 10 or 20 mg of rivaroxaban and aspirin. Compared with 10-mg rivaroxaban or aspirin, 20-mg rivaroxaban showed numerically more often increased menstrual flow duration and intensity.
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http://dx.doi.org/10.1002/rth2.12474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938616PMC
February 2021

5-year outcomes from rivaroxaban therapy in atrial fibrillation: Results from the Dresden NOAC Registry.

Thromb Res 2021 06 8;202:24-30. Epub 2021 Mar 8.

Department of Medicine I, Division of Hematology and Hemostaseology, University Hospital "Carl Gustav Carus" Dresden, Technical University, Fetscherstrasse 74, D-01307 Dresden, Germany. Electronic address:

Introduction: Following successful phase-III trials, direct oral anticoagulants such as rivaroxaban have largely replaced warfarin for stroke prevention in atrial fibrillation (SPAF). However, data from randomized trials should be confirmed in unselected cohorts.

Materials And Methods: Prospective registries can provide such data but often limit follow-up to short periods only. Extending our previously reported follow-up of 2.2 years in 1204 SPAF patients receiving rivaroxaban in the non-interventional DRESDEN NOAC REGISTRY, we now provide prospectively collected 5 years data (mean follow-up 5.5 ± 2.3 years) for this cohort.

Results: Between 1 October 2011 and 31 December 2019, the combined endpoint of stroke/transient ischemic attack/systemic embolism occurred at a rate of 2.3/100 patient-years in the intention-to-treat analysis (95% confidence interval [CI] 1.9-2.7) and at 1.6/100 patient-years in the on-treatment analysis (events within 3 days after last drug intake). On-treatment rates for major or clinically relevant non-major bleeding were 3.1 and 19.6/100 patient-years, respectively. Rivaroxaban treatment discontinuation occurred in a total of 574 patients during follow-up (11.0/100 patient-years in Kaplan-Meier analysis) and 426 patient died (all-cause mortality 6.3/100 pt. years; mean time from enrolment 3.6 ± 2.1 years), of which the causes of death were reported as arterial or venous embolism for 32 patients (21 occurring after treatment discontinuation and 11 during active treatment) and as bleeding for 24 patients.

Conclusions: Our data provide reassuring long-term outcome data for an elderly, co-morbid SPAF population, especially with regard to the low rate of fatal thromboembolic and bleeding complications.
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http://dx.doi.org/10.1016/j.thromres.2021.03.004DOI Listing
June 2021

Restart of Anticoagulant Therapy and Risk of Thrombosis, Rebleeding, and Death after Factor Xa Inhibitor Reversal in Major Bleeding Patients.

Thromb Haemost 2021 Aug 25;121(8):1097-1106. Epub 2021 Feb 25.

Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada.

Background:  Lack of data on balancing bleeding and thrombosis risk causes uncertainty about restarting anticoagulants after major bleeding. Anticoagulant reversal trials offer prospectively gathered data after major bleeding with well-documented safety events and restarting behavior.

Objectives:  To examine the relationship of restarting anticoagulation with thrombosis, rebleeding, and death.

Methods:  This is a posthoc analysis of a prospective factor Xa inhibitor reversal study at 63 centers in North America and Europe. We compared outcomes of restarted patients with those not restarted using landmark and time-dependent Cox proportional hazards models. Outcomes included thrombotic and bleeding events and death and a composite of all three.

Results:  Of 352 patients enrolled, oral anticoagulation was restarted in 100 (28%) during 30-day follow-up. Thirty-four (9.7%) had thrombotic events, 15 (4.3%) had bleeding events (after day 3), and 49 (14%) died. In the landmark analysis comparing patients restarted within 14 days to those not, restarting was associated with decreased thrombotic events (hazard ratio [HR] = 0.112; 95% confidence interval [CI]: 0.001-0.944;  = 0.043) and increased rebleeding (HR = 8.39; 95% CI: 1.13-62.29;  = 0.037). The time-dependent Cox model showed evidence for a reduction in a composite (thrombotic events, bleeding, and death) attempting to capture net benefit (HR = 0.384; 95% CI: 0.161-0.915;  = 0.031).

Conclusion:  This analysis provides modest evidence that restarting anticoagulation in factor Xa inhibitor-associated major bleeding patients is correlated with reduced risk of thrombotic events and increased risk of rebleeding. There is low-level evidence of net benefit for restarting. A randomized trial of restarting would be appropriate.
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http://dx.doi.org/10.1055/a-1400-6159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322590PMC
August 2021

Hormonal Contraception. Guideline of the DGGG, OEGGG and SGGG (S3 Level, AWMF Registry Number 015/015, January 2020).

Geburtshilfe Frauenheilkd 2021 Feb 8;81(2):152-182. Epub 2021 Feb 8.

Klinik für Kardiologie und Angiologie, Marienhaus Klinikum Eifel, Klinikstandort Bitburg, Bitburg, Germany.

This is an official interdisciplinary guideline published and coordinated by the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (OEGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The guideline was developed for use in German-speaking regions and is backed by numerous professional societies and organizations. The aim of this guideline is to provide an evidence- and consensus-based overview of the diagnostic approach and the management of hormonal contraception based on a systematic evaluation of the relevant literature. To compile this S3-guideline, a systematic search for evidence was carried out in PubMed and the Cochrane Library to adapt existing guidelines and identify relevant reviews and meta-analyses. A structured evaluation of the evidence was subsequently carried out on behalf of the Guidelines Commission of the DGGG, and a structured consensus was achieved based on consensus conferences attended by representative members from the different specialist societies and professions. Evidence-based recommendations about the advice given to women requesting contraception were compiled. The guideline particularly focuses on prescribing contraceptives which are appropriate to women's individual needs, take account of her personal circumstances, and have few or no side effects.
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http://dx.doi.org/10.1055/a-1259-1609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895491PMC
February 2021

Direct Oral Anticoagulants in Atrial Fibrillation: Practical Considerations and Remaining Issues.

Hamostaseologie 2021 Feb 15;41(1):35-41. Epub 2021 Feb 15.

Thrombosis Research Unit, Department of Medicine I, Division Hematology, University Hospital "Carl Gustav Carus" Dresden, Dresden, Germany.

Preventing thromboembolic events, while minimizing bleeding risks, remains challenging when managing patients with atrial fibrillation. Despite large and successful trial programs, several clinical concerns remain which commonly relate to fears of over- or underexposure to drugs and unfavorable outcomes. After a short summary of the main phase III trial findings, this short review discusses the evidence and clinical relevance of common clinical concerns (correct direct oral anticoagulant [DOAC] dosing; DOAC in moderate-to-severe renal impairment; and the relevance of fasting, nasogastric tube feeding, or high body mass index) on DOAC plasma levels. Finally, the need for specific DOAC antidotes will be addressed.
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http://dx.doi.org/10.1055/a-1329-2430DOI Listing
February 2021

Clinical history of cancer-associated splanchnic vein thrombosis.

J Thromb Haemost 2021 04 24;19(4):983-991. Epub 2021 Feb 24.

Department of Medicine and Surgery, University of Insubria, Varese, Italy.

Background: Cancer represents a risk factor for splanchnic vein thrombosis (SVT) and usual site venous thromboembolism (VTE).

Objectives: To compare characteristics and outcomes of patients with cancer-associated SVT and usual site VTE.

Patients/methods: Patients with solid cancer and SVT were enrolled in an international, prospective registry between May 2008 and January 2012. The comparison cohort included (1:1 ratio) patients with solid cancer and usual site VTE treated at two thrombosis centers who had a minimum of 12 months follow-up at December 2019 or experienced one of the outcomes within 12 months follow-up. Recurrent VTE, major bleeding, and all-cause mortality were evaluated at 12-month follow-up.

Results: A total of 264 patients (132 in each cohort) were enrolled. Patients with SVT were less likely to have metastatic disease (36.1% vs 72.5%) or receive cancer therapy at thrombosis diagnosis (29.6% vs 64.9%). The most frequent cancer types were hepatobiliary and pancreatic in the SVT cohort and gastrointestinal in the usual site VTE cohort. Fewer patients with SVT received anticoagulation (68.9% vs 99.2%), and treatment duration was shorter (6.0 vs 11.0 months). The cumulative incidence of major bleeding (2.3% vs 4.7%) was nonsignificantly lower in the SVT cohort, whereas recurrent thrombosis (4.7% vs 5.5%) and all-cause mortality (41.7% vs 39.4%) were comparable between the two cohorts.

Conclusions: The risk of recurrent thrombosis and bleeding appears to be similar in cancer patients with SVT and cancer patients with usual site VTE, despite some differences in baseline characteristics and anticoagulant treatment. Further prospective studies are warranted to confirm these findings.
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http://dx.doi.org/10.1111/jth.15214DOI Listing
April 2021

[Thromboembolic Complications in COVID-19].

Dtsch Med Wochenschr 2020 12 30;145(24):1728-1734. Epub 2020 Nov 30.

Medizinische Klinik 1, Bereich Hämatologie und Hämostaseologie, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden.

COVID-19 represents a clinical situation that lacks precedence and clinical experience. It introduces a number of pitfalls in well-established clinical routines and poses unique challenges to diagnostic pathways. This review discusses the current evidence on the thromboembolic risk of COVID-19 patients, the recommendations for thromboprophylaxis and the relevance of abnormal coagulation tests. Pathophysiological concepts are discussed and practical solutions and current guidance recommendations are presented.
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http://dx.doi.org/10.1055/a-1198-3639DOI Listing
December 2020

Treatment of cancer-associated thrombosis: The evolution of anticoagulant choice and clinical insights into practical management.

Crit Rev Oncol Hematol 2021 Jan 20;157:103125. Epub 2020 Oct 20.

Hull York Medical School and Hull University Teaching Hospitals NHS Trust, Hull, United Kingdom.

Low-molecular-weight heparin (LMWH) therapy is recommended over vitamin K antagonists (VKAs) for the treatment of cancer-associated thrombosis (CAT) and extended therapy is recommended in those with active cancer to prevent recurrent thrombosis. However, the inconvenience of daily subcutaneous injections and the cost of LMWH therapy hinder long-term use. Observational data demonstrate that persistence with LMWH therapy is low in clinical practice and that many patients are switched to oral alternatives - namely VKAs and direct oral anticoagulants (DOACs). Recently, the efficacy and safety of apixaban, edoxaban, and rivaroxaban versus LMWH therapy for the treatment of CAT have been demonstrated in randomized trials. This review provides a critical evaluation of studies with DOACs in this setting and an update on the guidance regarding anticoagulant use for the treatment of CAT. In recognition of the heterogeneity of patients with cancer and the challenges of CAT, patient cases with expert clinical perspectives are presented.
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http://dx.doi.org/10.1016/j.critrevonc.2020.103125DOI Listing
January 2021

Safety of direct oral anticoagulant exposure during pregnancy: a retrospective cohort study.

Lancet Haematol 2020 Dec;7(12):e884-e891

Department of Medicine I, Division of Haematology and Haemostaseology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

Background: Direct oral anticoagulants (DOACs) have largely replaced vitamin K antagonists in many indications for anticoagulation. Prescribed to millions of patients, including women of reproductive age, exposure to DOACs in early pregnancy is not uncommon, but data on the embryotoxic risks are scarce. We aimed to assess the risk of DOAC embryotoxicity in a large sample of reported cases.

Methods: In this retrospective cohort study, we collected individual case reports of DOAC exposure in pregnancy from gynaecologists, haematologists, and vascular specialists starting from May, 2015. We obtained exports in April and October, 2017, August, 2018, and December, 2019, from the pharmacovigilance databases of the DOAC manufacturers, the European Medicines Agency (EMA), the German drug authority, and searched the homepage of the US Food and Drug Administration (FDA) for pregnancy exposure reports. Data from the International Society of Thrombosis and Haemostasis (ISTH) registry were obtained in August, 2018, and on July 21, 2020; data from the Teratology Information Service in Ulm, Germany, were received July 22, 2020. We also ran a systematic literature search on July 22, 2020, for cases of DOAC exposure. These data were compiled with those from our 2016 risk assessment and duplicate reports were excluded. Fetal or neonatal abnormalities were classified as a major birth defect according to the European Concerted Action on Congenital Anomalies and Twins (EUROCAT) classification and adjudicated into four categories: relation to DOAC exposure likely, possible, unlikely, or unrelated.

Findings: We identified 1193 reports of DOAC exposure during pregnancy: 49 from physicians, 48 from the ISTH registry, 29 from the Teratology Information Service, 62 from the German drug authority, 536 from Bayer (extracted from the Bayer pharmacovigilance system, the WHO VigiBase, and from the FDA Adverse Event Reporting System), 87 from Boehringer Ingelheim, 16 from Daiichi Sankyo, 98 from the literature search, two from the FDA homepage search, ten from the Risk Evaluation and Mitigation Strategy Review, and 256 from the EMA reports. After excluding potential duplicates, we identified 614 unique cases of DOAC exposure in pregnancy occurring between Feb 1, 2007, and July 9, 2020, that consisted of rivaroxaban in 505 (82%) pregnancies, dabigatran in 36 (6%), apixaban in 50 (8%), and edoxaban in 23 (4%). The median duration of DOAC exposure was 5·3 weeks (IQR 4·0-7·0) into pregnancy. Information on pregnancy outcome was available in 336 (55%) of 614 pregnancies: 188 (56%) livebirths, 74 (22%) miscarriages, and 74 (22%) elective pregnancy terminations. 21 (6%; 95% CI 4-9) of 336 showed fetal abnormalities, of which 12 (4%; 2-6) were adjudicated as major birth defects potentially related to DOAC exposure.

Interpretation: Although reports of pregnancy outcomes after DOAC exposure are missing important details and predominantly describe rivaroxaban exposures, the available data do not suggest that DOAC exposure in pregnancy carries a high risk of embryopathy. The 2016 ISTH guidance against elective pregnancy termination for fear of DOAC embryotoxicity and the recommendation in favour of close pregnancy surveillance is still valid. Pregnancy outcome data are inconsistently captured in pharmacovigilance databases, indicating a strong need for a more robust system of reporting.

Funding: None.
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http://dx.doi.org/10.1016/S2352-3026(20)30327-6DOI Listing
December 2020

Rivaroxaban Versus Warfarin for Management of Obese African Americans With Non-Valvular Atrial Fibrillation or Venous Thromboembolism: A Retrospective Cohort Analysis.

Clin Appl Thromb Hemost 2020 Jan-Dec;26:1076029620954910

Department of Pharmacy Practice, University of Connecticut School of Pharmacy, Storrs, CT, USA.

African Americans (AAs) and obese individuals have increased thrombotic risk. This study evaluated the effectiveness and safety of rivaroxaban versus warfarin in obese, AAs with nonvalvular atrial fibrillation (NVAF) or venous thromboembolism (VTE). Optum® De-Identified Electronic Health Record (EHR) data was used to perform separate propensity-score matched analyses of adult, oral anticoagulant (OAC)-naïve AAs with NVAF or acute VTE, respectively; who had a body mass index≥30kg/m and ≥12-months EHR activity with ≥1-encounter before OAC initiation. Cox regression was performed and reported as hazard ratios (HRs) with 95% confidence intervals (CIs). For the NVAF analysis, 1,969 rivaroxaban- and 1,969 warfarin-users were matched. Rivaroxaban was not associated with a difference in stroke/systemic embolism versus warfarin (HR = 0.88, 95%CI = 0.60-1.28), but less major bleeding (HR = 0.68, 95%CI = 0.50-0.94) was observed. Among 683 rivaroxaban-users with VTE, 1:1 matched to warfarin-users, rivaroxaban did not alter recurrent VTE (HR = 1.36, 95%CI = 0.79-2.34) or major bleeding (HR = 0.80, 95%CI = 0.37-1.71) risk versus warfarin at 6-months (similar findings observed at 3- and 12-months). Rivaroxaban appeared to be associated with similar thrombotic, and similar or lower major bleeding risk versus warfarin in these obese, AA cohorts.
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http://dx.doi.org/10.1177/1076029620954910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588768PMC
July 2021

Anticoagulation Treatment in Cancer-Associated Venous Thromboembolism: Assessment of Patient Preferences Using a Discrete Choice Experiment (COSIMO Study).

Thromb Haemost 2021 Feb 2;121(2):206-215. Epub 2020 Sep 2.

Real World and Advanced Analytics, Ingress-Health HWM GmbH, Wismar, Germany.

Introduction:  Clinical guidelines recommend anticoagulation therapy for the treatment of cancer-associated venous thromboembolism (VTE), but little is known about preferences. Therefore, the objective of this discrete choice experiment (DCE) was to elucidate patient preferences regarding anticoagulation convenience attributes.

Methods:  Adult patients with cancer-associated VTE who switched to direct oral anticoagulants were included in a single-arm study (COSIMO). Patients were asked to decide between hypothetical treatment options based on a combination of the following attributes: route of administration (injection/tablet), frequency of intake (once/twice daily), need for regular controls of the international normalized ratio (INR) at least every 3 to 4 weeks (yes/no), interactions with food/alcohol (yes/no), and distance to treating physician (1 vs. 20 km) as an additional neutral attribute. DCE data were collected by structured telephone interviews and analyzed based on a conditional logit regression.

Results:  Overall, 163 patients (mean age 63.7 years, 49.1% female) were included. They strongly preferred oral administration compared with self-injections (importance of this attribute for overall treatment decisions: 73.8%), and a treatment without dietary restrictions (11.8%). Even if these attributes were less important (7.2% and 6.5%, respectively), patients indicated a preference for a shorter distance to the treating physician and once-daily dosing compared with twice-daily intake. "Need for regular controls of INR at least every 3 to 4 weeks" showed no significant impact on the treatment decision (0.7%).

Conclusion:  This study showed that treatment-related decision making in cancer-associated VTE, assuming comparable effectiveness and safety of anticoagulant treatments, is predominantly driven by "route of administration," with patients strongly preferring oral administration.
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http://dx.doi.org/10.1055/s-0040-1714739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850882PMC
February 2021

Survival and quality of life after early discharge in low-risk pulmonary embolism.

Eur Respir J 2021 02 4;57(2). Epub 2021 Feb 4.

Emergency Dept, Clinico San Carlos Hospital, IdISSC, Madrid, Spain.

Introduction: Early discharge of patients with acute low-risk pulmonary embolism requires validation by prospective trials with clinical and quality-of-life outcomes.

Methods: The multinational Home Treatment of Patients with Low-Risk Pulmonary Embolism with the Oral Factor Xa Inhibitor Rivaroxaban (HoT-PE) single-arm management trial investigated early discharge followed by ambulatory treatment with rivaroxaban. The study was stopped for efficacy after the positive results of the predefined interim analysis at 50% of the planned population. The present analysis includes the entire trial population (576 patients). In addition to 3-month recurrence (primary outcome) and 1-year overall mortality, we analysed self-reported disease-specific (Pulmonary Embolism Quality of Life (PEmb-QoL) questionnaire) and generic (five-level five-dimension EuroQoL (EQ-5D-5L) scale) quality of life as well as treatment satisfaction (Anti-Clot Treatment Scale (ACTS)) after pulmonary embolism.

Results: The primary efficacy outcome occurred in three (0.5%, one-sided upper 95% CI 1.3%) patients. The 1-year mortality was 2.4%. The mean±sd PEmb-QoL decreased from 28.9±20.6% at 3 weeks to 19.9±15.4% at 3 months, a mean change (improvement) of -9.1% (p<0.0001). Improvement was consistent across all PEmb-QoL dimensions. The EQ-5D-5L was 0.89±0.12 at 3 weeks after enrolment and improved to 0.91±0.12 at 3 months (p<0.0001). Female sex and cardiopulmonary disease were associated with poorer disease-specific and generic quality of life; older age was associated with faster worsening of generic quality of life. The ACTS burden score improved from 40.5±6.6 points at 3 weeks to 42.5±5.9 points at 3 months (p<0.0001).

Conclusions: Our results further support early discharge and ambulatory oral anticoagulation for selected patients with low-risk pulmonary embolism. Targeted strategies may be necessary to further improve quality of life in specific patient subgroups.
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http://dx.doi.org/10.1183/13993003.02368-2020DOI Listing
February 2021

Definition of major bleeding: Prognostic classification.

J Thromb Haemost 2020 11 11;18(11):2852-2860. Epub 2020 Sep 11.

Vascular and Emergency Medicine-Stroke Unit, University of Perugia, Perugia, Italy.

Background: In patients on anticoagulant treatment, the major bleeding (MB) definition released by the International Society of Thrombosis and Haemostasis (ISTH) is widely accepted. However, this definition identifies MBs with highly variable short-term risk of death.

Objectives: The study aims were to derive and validate a classification of ISTH-defined MBs for the risk of short-term death.

Methods: Consecutive patients admitted for ISTH-defined MB occurring while on treatment with oral anticoagulants were included in the study and divided into a derivation and a validation cohort. Death within 30 days was the primary study outcome.

Results: Among 1077 patients with MB, 64/517 and 63/560 patients in the derivation and validation cohort died, respectively. In the derivation cohort, Glasgow coma scale (GCS) <14 and shock were predictors of death; critical site bleeding and hemoglobin decrease ≥2 g/dL, or transfusion ≥ 2 units were not. GCS <14 (hazard ratio [HR], 8.67; 95% confidence interval [CI], 3.93-19.13) was predictor of death in intracranial hemorrhage (ICH) and shock at admission (HR, 4.84; 95% CI, 2.01-11.70) and pericardial bleeding (HR, 11.37; 95% CI, 1.33-97.31) in non-ICH MBs. The predictive value of GCS <14 in ICH and shock and pericardial bleeding in non-ICH MBs was confirmed in the validation cohort. None of the patients with isolated ocular or articular bleeding died. A prognostic classification of ISTH-defined MBs for the risk of short-term death is proposed as "serious," "severe," and "life-threatening" (ICH with GCS <14 or non-ICH with shock) MBs.

Conclusion: According to our study, ISTH-defined MBs can be stratified for the risk of death within 30 days.
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http://dx.doi.org/10.1111/jth.15048DOI Listing
November 2020

Systematic Literature Review of Randomized Trials Comparing Antithrombotic Therapy Following Revascularization Procedures in Patients With Peripheral Artery Disease.

Angiology 2020 10 8;71(9):773-790. Epub 2020 Jul 8.

1670Bayer AG, Berlin, Germany.

A systematic literature review was conducted to identify and summarize the clinical efficacy and safety of available antithrombotic therapies after peripheral endovascular or surgical revascularization in patients with peripheral artery disease (PAD). Five databases were searched using free-text and Emtree/Mesh terms for PAD, randomized controlled trials (RCTs), and antithrombotic therapies of interest (ie, single antiplatelet therapy, dual antiplatelet therapy, and vitamin K antagonists). Randomized controlled trials were eligible for inclusion if they assessed the risk of thrombotic events (ie, myocardial infarction, ischemic stroke, cardiovascular death, limb ischemia, or limb amputation) or safety profile (ie, minor, moderate, major, or fatal bleeding events) after revascularization. In total, 16 RCTs were identified. Only a few studies reported on treatment effects of the investigated therapies. Myocardial infarction, ischemic stroke, cardiovascular death, and amputation were reported in up to 2.3%, 2.3%, 5.6%, and 7.3% of patients, respectively. Bleeding events were observed in up to 8.4% (major) and 1.5% (fatal) of patients. Despite available treatments, patients with PAD undergoing revascularization remain at risk of thrombotic events. There is a need for new treatments that will help to optimize care for patients with symptomatic PAD undergoing revascularization.
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http://dx.doi.org/10.1177/0003319720936505DOI Listing
October 2020

Anticoagulant therapy for splanchnic vein thrombosis: ISTH SSC Subcommittee Control of Anticoagulation.

J Thromb Haemost 2020 07;18(7):1562-1568

Department of Medicine and Surgery, University of Insubria, Varese, Italy.

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http://dx.doi.org/10.1111/jth.14836DOI Listing
July 2020
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