scholarly journals Late Pulmonary Embolism after COVID-19 Pneumonia despite Adequate Rivaroxaban Treatment

2020 ◽  
Author(s):  
Giuseppe Di Tano ◽  
Luigi Moschini ◽  
Marco Loffi ◽  
Gianluca Galeazzi ◽  
Sophie Testa ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Acute Infection ◽  
Chronic Atrial Fibrillation ◽  
Drug Plasma ◽  
Thrombotic Complications ◽  
Underlying Mechanisms ◽  
Drug Plasma Levels

Introduction: SARS-CoV-2 infection may predispose patients to thrombotic disease. Patients with COVID-19 pneumonia who are receiving non-vitamin K antagonists or direct oral anticoagulants for chronic disease are usually switched to heparin treatment during hospitalization. However, information about the most appropriate antithrombotic therapy after the acute infection phase is lacking. Case Description: We report the case of a patient with chronic atrial fibrillation who was recently hospitalized for severe COVID-19 pneumonia. Four weeks after discharge he experienced an episode of an acute pulmonary embolism while on rivaroxaban therapy with adequate drug plasma levels, and in the absence of strong predisposing risk factors. Conclusion: This case highlights the risk of thrombotic complications after COVID-19 infection, raises some concern about their underlying mechanisms, and supports the use of effective anti-thrombotic therapy.

scholarly journals Bleeding and thrombotic complications during treatment with direct oral anticoagulants or vitamin K antagonists in venous thromboembolic patients included in the prospective, observational START2-register

BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e040449
Author(s):  
Gualtiero Palareti ◽  
Emilia Antonucci ◽  
Cristina Legnani ◽  
Daniela Mastroiacovo ◽  
Daniela Poli ◽  
...  
Keyword(s):  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Efficacy Rate ◽  
Bleeding Events ◽  
Venous Thromboembolic ◽  
Thrombotic Complications ◽  
The Difference

ObjectiveThe proportion and characteristics of Italian patients affected by venous thromboembolism (VTE) treated with direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs), and complications occurring during follow-up.DesignA prospective cohort of 2728 VTE patients included in the Survey on anticoagulaTed pAtients RegisTer (START2-Register) from January 2014 to June 2018 was investigated. Characteristics of patients, type of treatment and complications occurring during 2962 years of follow-up were analysed.SettingAbout 60 Italian anticoagulation and thrombosis centres participated in the observational START2-RegisterParticipants2728 adult patients with VTE of a lower limb and/or pulmonary embolism (PE), with a follow-up after the initial phase treatment.InterventionsPatients could receive DOACs or VKAs; both prescribed by the National and Regional Health Systems for patients with VTE.Outcomes measuresEfficacy: rate of VTE recurrence (all thrombotic complications were also recorded). Safety: the rate of major and clinically relevant non-major bleeding events.ResultsAlmost 80% of patients were treated with DOACs. The prevalence of symptomatic PE and impaired renal function was higher in patients receiving VKAs. Duration of anticoagulation was >180 days in approximately 70% of patients. Bleeding events were similar in both treatment groups. The overall eventuality of recurrence was significantly higher in DOAC cohorts versus VKA cohorts (HR 2.15 (1.14–4.06), p=0.018); the difference was almost completely due to recurrences occurring during extended treatment (2.73% DOAC vs 0.49% VKA, p<0.0001). All-cause mortality was higher in VKA-treated (5.9%) than in DOAC-treated patients (2.6%, p<0.001).ConclusionItalian centres treat most patients with VTE with DOACs and prefer VKA for those with more serious clinical conditions. Recurrences were significantly more frequent in DOAC-treated patients due to increased incidence after 180 days of treatment, probably due to reduced adherence to treatment. These results underline the importance of structured surveillance of DOAC-treated patients with VTE to strengthen treatment adherence during extended therapy.

Point-of-Care Coagulation Tests Monitoring of Direct Oral Anticoagulants and Their Reversal Therapy: State of the Art

2017 ◽  
Vol 43 (04) ◽  
pp. 423-432 ◽  
Author(s):  
Paolo Bianchi ◽  
Marco Ranucci ◽  
Ekaterina Baryshnikova ◽  
Giacomo Iapichino
Keyword(s):  
Point Of Care ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Plasma Concentrations ◽  
Urgent Surgery ◽  
Drug Plasma Concentrations ◽  
Drug Plasma ◽  
Coagulation Tests ◽  
Before And After

AbstractDirect oral anticoagulants (DOACs) exert similar anticoagulant effects to vitamin K antagonists and are increasingly used worldwide. Nevertheless, an evidence-based approach to patients receiving DOACs when any unplanned urgent surgery or bleeding (either spontaneous or traumatic) occurs is still missing. In this review, we investigate the role of point-of-care coagulation tests when other, more specific tests are not available. Indeed, thromboelastography and activated clotting time can detect dabigatran-induced coagulopathy, while their accuracy is limited for apixaban and rivaroxaban, mostly in cases of low drug plasma concentrations. These tests can also be used to guide the reversal of DOAC-induced coagulopathy providing a quick, before-and-after picture in case of therapeutic use of hemostatic compounds.

scholarly journals Novel Anticoagulant Treatment for Pulmonary Embolism with Direct Oral Anticoagulants Phase 3 Trials and Clinical Practice

2018 ◽  
Vol 35 (02) ◽  
pp. 83-91 ◽  
Author(s):  
Liselotte van der Pol ◽  
Albert Mairuhu ◽  
Christophe Leroyer ◽  
Francis Couturaud ◽  
Menno Huisman ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Clinical Practice ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Similar Efficacy ◽  
Ease Of Use ◽  
Therapeutic Management ◽  
Published Data ◽  
Phase 3

AbstractAnticoagulant therapy is the cornerstone of therapeutic management in acute venous thromboembolism (VTE), consisting of pulmonary embolism and deep vein thrombosis. Direct oral anticoagulants (DOACs) have become the standard of care because of their good safety profile and ease of use in clinical practice. Indeed, phase 3 randomized trials (AMPLIFY, EINSTEIN, RECOVER, and HOKUSAI studies) showed that DOACs provided a similar efficacy and a better safety than conventional treatment with parenteral heparin with overlapping loading dose of vitamin K antagonists in acute VTE therapeutic management. The results of published data from real-world registries confirm the safety and efficacy of DOACs demonstrated in the phase 3 trials.

scholarly journals Viral Coagulopathy in Patients With COVID-19: Treatment and Care

2020 ◽  
Vol 26 ◽  
pp. 107602962093677 ◽  
Author(s):  
Nickolas Kipshidze ◽  
George Dangas ◽  
Christopher J. White ◽  
Nodar Kipshidze ◽  
Fakiha Siddiqui ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Antiplatelet Agents ◽  
Endothelial Damage ◽  
Cellular Mechanisms ◽  
Catheter Directed Thrombolysis ◽  
Organ Systems ◽  
Thrombotic Complications ◽  
Novel Coronavirus

COVID-19 has proven to be particularly challenging given the complex pathogenesis of SARS-CoV-2. Early data have demonstrated how the host response to this novel coronavirus leads to the proliferation of pro-inflammatory cytokines, massive endothelial damage, and generalized vascular manifestations. While SARS-CoV-2 primarily targets the upper and lower respiratory tract, other organ systems are also affected. SARS-CoV-2 relies on 2 host cell receptors for successful attachment: angiotensin-converting enzyme 2 and transmembrane protease serine 2. Clinicopathologic reports have demonstrated associations between severe COVID-19 and viral coagulopathy, resulting in pulmonary embolism; venous, arterial, and microvascular thrombosis; lung endothelial injury; and associated thrombotic complications leading to acute respiratory distress syndrome. Viral coagulopathy is not novel given similar observations with SARS classic, including the consumption of platelets, generation of thrombin, and increased fibrin degradation product exhibiting overt disseminated intravascular coagulation–like syndrome. The specific mechanism(s) behind the thrombotic complications in COVID-19 patients has yet to be fully understood. Parenteral anticoagulants, such as heparin and low-molecular-weights heparins, are widely used in the management of COVID-19 patients. Beyond the primary (anticoagulant) effects of these agents, they may exhibit antiviral, anti-inflammatory, and cytoprotective effects. Direct oral anticoagulants and antiplatelet agents are also useful in the management of these patients. Tissue plasminogen activator and other fibrinolytic modalities may also be helpful in the overall management. Catheter-directed thrombolysis can be used in patients developing pulmonary embolism. Further investigations are required to understand the molecular and cellular mechanisms involved in the pathogenesis of COVID-19-associated thrombotic complications.

Medical Management Of Pulmonary Embolism

2018 ◽  
Author(s):  
Aaron B Waxman ◽  
Andrew J Schissler
Keyword(s):  
Pulmonary Embolism ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Pregnant Patient ◽  
Reperfusion Therapy ◽  
Medical Attention ◽  
Medium Risk ◽  
Evidenced Based ◽  
Acute Pe

Acute pulmonary embolism (PE) can be fatal and requires prompt medical attention. This chapter reviews the treatment of acute PE, including a detailed report of the acute- and long-term management of high-risk (“massive”), medium-risk (“submassive”), and low-risk thrombi. It summarizes the reperfusion therapies available in hemodynamically unstable patients with massive PEs such as thrombolysis, embolectomy, and percutaneous catheter-directed treatment. There is further in-depth examination of the various anticoagulants available including parenteral therapies, vitamin K antagonists, and direct oral anticoagulants. Recommendations on the treatment duration are discussed. Other considerations are described, including how management changes in the pregnant patient with acute PE, when venous filters should be considered and whether to initiate treatment before confirming a diagnosis. Overall this chapter serves as an excellent evidenced-based guide to better manage the various presentations of acute PE.   This review contains 3 figures, 5 tables and 47 references Key Words: anticoagulation, embolectomy, PE, pulmonary embolism, reperfusion therapy, thrombolysis, treatment

scholarly journals Modern position of anticoagulants in acute pulmonary embolism: achievements, limitations, prospects

2019 ◽  
Vol 27 (1) ◽  
pp. 93-106 ◽  
Author(s):  
Yuliya V. Terekhovskaya ◽  
Viktor G. Okorokov ◽  
Natal`ya N. Nikulina
Keyword(s):  
Pulmonary Embolism ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Evidence Base ◽  
Sufficient Evidence ◽  
Aim Analysis ◽  
The Russian Federation ◽  
Choice Of Therapy

Pulmonary embolism (PE) is the third most common cardiovascular disease after myocardial infarction and stroke, and one of the leading causes of death in Europe. Aim. Analysis of the modern scientific base concerning the possibilities and limitations of use of anticoagulant therapy (ACT) at different stages of medical care in PE depending on risk stratification. The article reflects the position of modern Clinical guidelines, the results of recent studies and some controversial and unresolved issues of the ACT for PE. Conclusion. Currently, a sufficient evidence base has been obtained in favor of the fact that the ACT increases the survival rate of patients with past PE even taking into account an increase in the frequency of hemorrhagic complications; the choice of therapy schemes for PE is based on the stratification of the risk of patients; the schemes of the ACT for the acute period, for the subsequent prevention of relapses of PE are developed, the evidence of the expediency of its further prolongation (a study of rivaroxaban at a dose of 10 mg for prolonged therapy) is obtained. Use of direct oral anticoagulants (DOAC) in patients with past PE has a more optimal efficacy/safety profile compared to vitamin K antagonists (VCA). However, not all the issues of the ACT for PE are solved, therefore the prospects for the study and application of the ACT in PE include: reasonability of obtaining substantiated data on use of DOAC after thrombolysis, in patients with reduced renal function, with antiphospholipid syndrome, with neoplastic diseases, and also for determination of exact periods of extended therapy. It is necessary to search for additional prognostic factors for PE, to study and register specific antidotes for DOAC (currently in the Russian Federation a specific antidote to dabigatran Idarucizumab-registered); to increase the share of DOAC in the ACT as drugs with a proven best profile efficacy/safety compared to VCA.

scholarly journals Do women with venous thromboembolism bleed more than men during anticoagulation? Data from the real-life, prospective START-Register

2021 ◽  
Vol 12 ◽  
pp. 204209862110629
Author(s):  
Gualtiero Palareti ◽  
Cristina Legnani ◽  
Emilia Antonucci ◽  
Benilde Cosmi ◽  
Anna Falanga ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Vaginal Bleeding ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Hormonal Contraception ◽  
Real Life ◽  
Renal Diseases ◽  
Bleeding Events ◽  
Risk Of Bleeding

Background: Venous thromboembolism (VTE) is a frequent and serious disease that requires immediate and long-term anticoagulant treatment, which is inevitably associated with a risk of bleeding complications. Some studies, though not all, reported a higher risk of bleeding in female patients treated with either old anticoagulants [vitamin k antagonists (VKAs)] or recent anticoagulants [direct oral anticoagulants (DOACs)]. Furthermore, analyses of clinical trials reported an abnormal vaginal bleeding in women of reproductive age treated with DOACs. This study aimed at comparing the risk of bleeding in an inception cohort of VTE women and men included in a prospective observational registry. Methods: Baseline characteristics and bleeding events occurring during anticoagulation in patients of both sexes, included in the START-Register after a first VTE, were analyzed. Results: In all, 1298 women were compared with 1290 men. Women were older and more often had renal diseases; their index events were often provoked (often by hormonal contraception and pregnancy), and more frequently presented as isolated pulmonary embolism (PE). The rate of bleeding was similar in women (2.9% patient-years) and men (2.1% patient-years), though it was higher when uterine bleeds were included (3.5% patient-years, p = 0.0141). More bleeds occurred in VKA- than DOAC-treated patients (6.4% versus 2.6%, respectively; p = 0.0013). At multivariate analysis, age ⩾ 75 years was associated with higher prevalence of bleeds. Conclusion: The occurrence of bleeding was not different between women and men during anticoagulation after VTE. Only after inclusion of vaginal/uterine bleeds, the rate of bleeding was higher in women. The incidence of bleeding was higher in women treated with VKAs. Plain Language Summary The risk of bleeding in women anticoagulated for deep vein thrombosis or pulmonary embolism is not higher than that in men, except for vaginal bleeding Background: The occurrence of a venous thromboembolic event (VTE, including deep vein thrombosis and pulmonary embolism) necessarily requires a period of at least 3–6 months of treatment with anticoagulant drugs [either vitamin k antagonists (VKA) or, more recently, direct oral anticoagulants (DOACs)]. Anticoagulation therapy, however, is associated with a risk of bleeding that is influenced by several factors. Sex is one of these factors as some authors have hypothesized that women are at higher risk than men. Furthermore, some studies have recently found more vaginal bleeding in VTE women treated with a DOAC compared with those who received VKAs. Methods: The present study aimed to compare the frequency of bleeds occurring in women and in men who were treated with DOACs or VKAs for a first VTE event and followed in real-life conditions. Since the beginning of their anticoagulant treatment, the patients were included in a prospective, multicenter, observational registry (the START-Register), and bleeding events were recorded. Results: A total of 1298 women were compared with 1290 men. Women were older and more often were affected by renal diseases; their VTE events were often associated with risk factors (especially hormonal contraception and pregnancy) and presented as isolated pulmonary embolism. The rate of all bleeding events (including major, non-major but clinically relevant, and minor bleeds) was higher in women (3.5% patient-years) than in men (2.1% patient-years, p = 0.0141); however, the difference was no longer statistically significant after exclusion of uterine bleeds (2.9% patient years). More bleeding occurred in women receiving VKA as anticoagulant drug compared with those treated with a DOAC (6.4% versus 2.6%, respectively; p = 0.0013). At multivariate analysis, age ⩾ 75 years was associated with higher prevalence of bleeds. Conclusion: In conclusion, we found that in real-life conditions, the rate of bleeding events occurring during anticoagulation after a VTE episode is not higher in women than in men. Only after inclusion of vaginal bleeds, the rate of bleeding was higher in women. More bleeds (including vaginal bleeding) occurred in women treated with VKA than DOACs.

Catastrophic antiphospholipid syndrome following the introduction of rivaroxaban

Lupus ◽  
2020 ◽  
Vol 29 (7) ◽  
pp. 787-790 ◽  
Author(s):  
Romain Stammler ◽  
Paul Legendre ◽  
Patrice Cacoub ◽  
Philippe Blanche ◽  
Jean -Charles Piette ◽  
...  
Keyword(s):  
Antiphospholipid Syndrome ◽  
Vitamin K ◽  
Antiphospholipid Antibodies ◽  
Multiorgan Failure ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Thrombotic Event ◽  
Catastrophic Antiphospholipid Syndrome ◽  
Thrombotic Complications

Summary Catastrophic antiphospholipid syndrome is the most severe complication of antiphospholipid syndrome. Vitamin K antagonists are the reference treatment for preventing relapsing thrombotic complications in patients with antiphospholipid syndrome. Direct oral anticoagulants are nonetheless sometimes used in this setting. We report two cases of women who were triple-positive for antiphospholipid antibodies and developed catastrophic antiphospholipid syndrome in the week after the introduction of rivaroxaban. The first patient, who had had a previous thrombotic event, had multiorgan failure 3 days after vitamin K antagonists was replaced by rivaroxaban, and the second developed a similar clinical presentation 7 days after introduction of the same treatment. Both catastrophic antiphospholipid syndrome episodes were successfully treated with heparin followed by vitamin K antagonists, corticosteroids, and plasmapheresis. These two cases highlight for the inefficacy of rivaroxaban preventing severe thrombotic events such as catastrophic antiphospholipid syndrome and thus provide further support for recommendations that vitamin K antagonists must remain the reference anticoagulant in patients with triple-positive antiphospholipid antibodies.

scholarly journals Initial and Long-Term Treatment of Pulmonary Embolism: Current Approach and Future Perspectives

2018 ◽  
Vol 38 (02) ◽  
pp. 75-86
Author(s):  
Walter Ageno ◽  
Marco Donadini
Keyword(s):  
Pulmonary Embolism ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Right Ventricular Dysfunction ◽  
Current Approach ◽  
Duration Of Treatment ◽  
Onset Of Action ◽  
Long Term Treatment ◽  
Risk Patients

AbstractPulmonary embolism is associated with variable risk of early mortality, ranging from less than 1% to more than 15%. Risk stratification, based on clinical variables and signs of right ventricular dysfunction, is crucial to decide the best management and treatment strategy. Home therapy may be an option for low-risk patients, whereas patients at intermediate risk need to be hospitalized and some of them, at intermediate high risk, may require more intensive monitoring to early detect signs of haemodynamic decompensation. The initial treatment is based on anticoagulants with rapid onset of action, either parenteral (heparin/fondaparinux) or oral (direct oral anticoagulants, DOACs). Thereafter, DOACs (or, if contraindicated, vitamin K antagonists) needs to be continued for at least 3 months. Beyond this period, an individual re-evaluation of the risk-to-benefit ratio of anticoagulation should be performed, based on several factors, including the type of index event, age, sex, D-dimer and residual venous obstruction. Possibly safer strategies can be offered to higher risk patients requiring extended duration of treatment, including the DOACs apixaban and rivaroxaban at reduced dose.

Direct oral anticoagulants in patients with cancer

2019 ◽  
Vol 76 (14) ◽  
pp. 1019-1027
Author(s):  
John B Bossaer ◽  
Kelly L Covert
Keyword(s):  
Atrial Fibrillation ◽  
Cancer Patients ◽  
Randomized Clinical Trials ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Safety Data ◽  
Standard Of Care ◽  
Patients With Cancer ◽  
Thrombotic Complications

AbstractPurposeThis review summarizes the available evidence concerning direct oral anticoagulant (DOAC) use to treat venous thromboembolism (VTE) in patients with cancer as well as pertinent safety data on the use of DOACs in patients with both cancer and atrial fibrillation.SummaryThe introduction of DOACs into clinical practice changed the way thrombotic complications are managed and prevented in diverse patient populations, including VTE and atrial fibrillation. Low-molecular-weight heparins have been the standard of care for treating VTE in cancer patients due to superiority over vitamin K antagonists in preventing recurrent VTE. Therefore, widespread DOAC use for VTE in patients with active cancer has not been adopted.ConclusionRecent randomized clinical trials (SELECT-D, Hokusai VTE Cancer) have provided evidence that DOACs may have a role in treating VTE in cancer patients.

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