scholarly journals Cervical and intracranial artery dissections

2021 ◽  
Vol 14 ◽  
pp. 175628642110372
Author(s):  
Stefan T. Engelter ◽  
Philippe Lyrer ◽  
Christopher Traenka
Keyword(s):  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Intravenous Thrombolysis ◽  
Future Research ◽  
Artery Dissection ◽  
Intracranial Artery ◽  
Antithrombotic Agent ◽  
Vessel Occlusion ◽  
Randomized Controlled

This review summarizes recent therapeutic advances in cervical (CeAD) and intracranial artery dissection (IAD) research. Despite unproven benefits, but in the absence of any signal of harm, in patients, with acute ischemic stroke attributable to CeAD, intravenous thrombolysis and, in case of large-vessel occlusion, endovascular revascularization should be considered. Future research will clarify which patients benefit most from either treatment modality. For stroke prevention, the recently published randomized controlled TREAT-CAD study showed that, against the initial hypothesis, aspirin was not shown non-inferior to anticoagulation with vitamin K antagonists (VKAs). With the results of two randomized controlled trials (CADISS and TREAT-CAD) available now, the evidence to consider aspirin as the standard therapy of CeAD is weak. Further analyses might clarify whether the assumption supports, in particular, that patients presenting with cerebral ischemia, clinical or subclinical with magnetic resonance imaging surrogates, might benefit most from VKA treatment. In turn, it remains to be shown, whether in CeAD patients presenting with pure local symptoms and without hemodynamic compromise, antiplatelets are sufficient, and whether a dual antiplatelet therapy during the first weeks of treatment is recommendable. The observation that ischemic strokes occurred (or recurred) very early after CeAD diagnosis, consistently across randomized and observational studies, supports the recommendation to start antithrombotic treatment immediately, whatever antithrombotic agent is chosen in each individual case. The lack of a license for the use in CeAD patients and the paucity of data are still arguments against the use of direct oral anticoagulants in CeAD. Nevertheless, due to their beneficial safety and efficacy profile proven in atrial fibrillation, these agents are a worthwhile treatment option to be tested in further CeAD treatment trials. In IAD, the experience with the use of antithrombotic agents is limited. As the risk of suffering intracranial hemorrhage is higher in IAD than in CeAD, the use of antithrombotic therapy in IAD remains controversial.

Direct Oral Anticoagulant Plasma Levels for the Management of Acute Ischemic Stroke

2019 ◽  
Vol 48 (1-2) ◽  
pp. 17-25 ◽  
Author(s):  
Armin Marsch ◽  
Kosmas Macha ◽  
Gabriela Siedler ◽  
Lorenz Breuer ◽  
Erwin F. Strasser ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Plasma Level ◽  
Acute Ischemic Stroke ◽  
Plasma Levels ◽  
Emergency Treatment ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Complications ◽  
Vessel Occlusion

Introduction: The management of acute ischemic stroke in patients on direct oral anticoagulants (DOACs) is challenging. However, the substance-specific plasma level could guide treatment decisions on recanalization therapies. We present a plasma-level-based protocol for emergency treatment of stroke patients on oral anticoagulants. Bleeding complications and clinical outcome for patients on DOACs are reported and compared to patients on vitamin K antagonists (VKAs). Methods: In patients with acute ischemic stroke and suspected use of DOACs within 48 h prior to hospital admission, plasma levels were measured using the calibrated Xa-activity (apixaban, edoxaban, rivaroxaban) or the Hemoclot®-assay (dabigatran). Levels <50 ng/mL were supportive for thrombolysis, while high values >100 ng/mL excluded patients from recombinant tissue plasminogen activator use. For patients on VKAs, the cutoff was set at international normalized ratio of 1.7. Endovascular thrombectomy of a large vessel occlusion was performed independently from coagulation testing. Consecutive patients were included in an observational registry. Results: Five hundred and twenty-two patients (261 on VKAs and 261 on DOACs) were included. Thirty patients (11.5%) on VKAs and 24 (9.2%) on DOACs received thrombolysis, followed by mechanical thrombectomy in 10 and 14 patients, respectively. Seventeen patients in each group received thrombectomy only. Symptomatic intracranial hemorrhage associated with thrombolysis occurred in 1 patient on VKA (3.3%) and 1 on DOAC (4.2%; p = 0.872). The turnaround time of specific assays did not show a significant delay in comparison to standard coagulation parameters. Conclusion: DOAC plasma levels could support decisions on emergency treatment of ischemic stroke. Systemic thrombolysis below suggested thresholds appears preliminary feasible and safe without an excess in bleeding complications.

scholarly journals Recanalisation therapies for acute ischaemic stroke in patients on direct oral anticoagulants

2021 ◽  
Vol 92 (5) ◽  
pp. 534-541
Author(s):  
David J Seiffge ◽  
Thomas Meinel ◽  
Jan Christoph Purrucker ◽  
Johannes Kaesmacher ◽  
Urs Fischer ◽  
...  
Keyword(s):  
Ischaemic Stroke ◽  
Mechanical Thrombectomy ◽  
Current Knowledge ◽  
Anticoagulant Activity ◽  
Therapeutic Option ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Intravenous Thrombolysis ◽  
Vessel Occlusion ◽  
Reversal Agents

Direct oral anticoagulants (DOACs) have emerged as primary therapeutic option for stroke prevention in patients with atrial fibrillation. However, patients may have ischaemic stroke despite DOAC therapy and there is uncertainty whether those patients can safely receive intravenous thrombolysis or mechanical thrombectomy. In this review, we summarise and discuss current knowledge about different approaches to select patient. Time since last DOAC intake—as a surrogate for anticoagulant activity—is easy to use but limited by interindividual variability of drug pharmacokinetics and long cut-offs (>48 hours). Measuring anticoagulant activity using drug-specific coagulation assays showed promising safety results. Large proportion of patients at low anticoagulant activity seem to be potentially treatable but there remains uncertainty about exact safe cut-off values and limited assay availability. The use of specific reversal agents (ie, idarucizumab or andexanet alfa) prior to thrombolysis is a new emerging option with first data reporting safety but issues including health economics need to be elucidated. Mechanical thrombectomy appears to be safe without any specific selection criteria applied. In patients on DOAC therapy with large vessel occlusion, decision for intravenous thrombolysis should not delay thrombectomy (eg, direct thrombectomy or immediate transfer to a thrombectomy-capable centre recommended). Precision medicine using a tailored approach combining clinicoradiological information (ie, penumbra and vessel status), anticoagulant activity and use of specific reversal agents only if necessary seems a reasonable choice.

scholarly journals Non-valvular Atrial Fibrillation in CKD: Role of Vitamin K Antagonists and Direct Oral Anticoagulants. A Narrative Review

2021 ◽  
Vol 8 ◽  
Author(s):  
Aleix Cases ◽  
Pablo Gomez ◽  
Jose Jesus Broseta ◽  
Elisa Perez Bernat ◽  
Juan de Dios Arjona Barrionuevo ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Randomized Controlled Trials ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Controlled Trials ◽  
Thromboembolic Events ◽  
Randomized Controlled ◽  
Valvular Calcification

Atrial fibrillation (AF) is the most common arrhythmia in chronic kidney disease (CKD), with a close bidirectional relationship between the two entities. The presence of CKD in AF increases the risk of thromboembolic events, mortality and bleeding. Vitamin K antagonists (VKA) have been the mainstay of treatment for the prevention of thromboembolic events in AF until recently, with confirmed benefits in AF patients with stage 3 CKD. However, the risk-benefit profile of VKA in patients with AF and stages 4–5 CKD is controversial due to the lack of evidence from randomized controlled trials. Treatment with VKA in CKD patients has been associated with conditions such as poorer anticoagulation quality, increased risk of bleeding, faster progression of vascular/valvular calcification and higher risk of calciphylaxis. Direct oral anticoagulants (DOACs) have shown equal or greater efficacy in stroke/systemic embolism prevention, and a better safety profile than VKA in post-hoc analysis of the pivotal randomized controlled trials in patients with non-valvular AF and stage 3 CKD, yet evidence of its risk-benefit profile in more advanced stages of CKD is scarce. Observational studies associate DOACs with a good safety/effectiveness profile compared to VKA in non-dialysis CKD patients. Further, DOACs have been associated with a lower risk of acute kidney injury and CKD development/progression than VKA. This narrative review summarizes the evidence of the efficacy and safety of warfarin and DOACs in patients with AF at different CKD stages, as well as their effects on renal function, vascular/valvular calcification and bone health.

scholarly journals Cerebral Ischemia in Patients on Direct Oral Anticoagulants

Stroke ◽  
2019 ◽  
Vol 50 (4) ◽  
pp. 873-879 ◽  
Author(s):  
Kosmas Macha ◽  
Armin Marsch ◽  
Gabriela Siedler ◽  
Lorenz Breuer ◽  
Erwin F. Strasser ◽  
...  
Keyword(s):  
Vitamin K ◽  
Plasma Levels ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
International Normalized Ratio ◽  
Large Vessel ◽  
Stroke Severity ◽  
Large Vessel Occlusion ◽  
Vessel Occlusion

Background and Purpose— In patients with ischemic stroke on therapy with vitamin K antagonists, stroke severity and clinical course are affected by the quality of anticoagulation at the time of stroke onset, but clinical data for patients using direct oral anticoagulants (DOACs) are limited. Methods— Data from our registry including all patients admitted with acute cerebral ischemia while taking oral anticoagulants for atrial fibrillation between November 2014 and October 2017 were investigated. The activity of vitamin K antagonists was assessed using the international normalized ratio on admission and categorized according to a threshold of 1.7. DOAC plasma levels were measured using the calibrated Xa-activity (apixaban, rivaroxaban, and edoxaban) or the Hemoclot-assay (dabigatran) and categorized into low (<50 ng/mL), intermediate (50–100 ng/mL), or high (>100 ng/mL). Primary objective was the association between anticoagulant activity and clinical and imaging characteristics. Results— Four hundred sixty patients were included (49% on vitamin K antagonists and 51% on DOAC). Patients on vitamin K antagonists with low international normalized ratio values had higher scores on the National Institutes of Health Stroke Scale and a higher risk of large vessel occlusion on admission. For patients on DOAC, plasma levels were available in 75.6% and found to be low in 49 (27.7%), intermediate in 41 (23.2%), and high in 87 patients (49.2%). Low plasma levels were associated with higher National Institutes of Health Stroke Scale scores on admission (low: 8 [interquartile range, 3–15] versus intermediate: 4 [1–11] versus high: 3 [0–8]; P <0.001) and higher risk of persisting neurological deficits or cerebral infarction on imaging (85.7% versus 75.6% versus 54.0%; P <0.001). Low DOAC plasma levels were an independent predictor of large vessel occlusion (odds ratio, 3.84 [95% CI, 1.80–8.20]; P =0.001). Conclusions— The activity of anticoagulation measured by specific DOAC plasma levels on admission is associated with stroke severity and presence of large vessel occlusion.

scholarly journals Recent Advances in Anticoagulant Treatment of Immune Thrombosis: A Focus on Direct Oral Anticoagulants in Heparin-Induced Thrombocytopenia and Anti-Phospholipid Syndrome

2021 ◽  
Vol 23 (1) ◽  
pp. 93
Author(s):  
Julie Carré ◽  
Georges Jourdi ◽  
Nicolas Gendron ◽  
Dominique Helley ◽  
Pascale Gaussem ◽  
...  
Keyword(s):  
Retrospective Studies ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Current Treatment ◽  
Prothrombotic State ◽  
Heparin Induced Thrombocytopenia ◽  
Need For Treatment ◽  
Randomized Controlled ◽  
Anti Phospholipid Syndrome

For more than 10 years, direct oral anticoagulants (DOACs) have been increasingly prescribed for the prevention and treatment of thrombotic events. However, their use in immunothrombotic disorders, namely heparin-induced thrombocytopenia (HIT) and antiphospholipid syndrome (APS), is still under investigation. The prothrombotic state resulting from the autoimmune mechanism, multicellular activation, and platelet count decrease, constitutes similarities between HIT and APS. Moreover, they both share the complexity of the biological diagnosis. Current treatment of HIT firstly relies on parenteral non-heparin therapies, but DOACs have been included in American and French guidelines for a few years, providing the advantage of limiting the need for treatment monitoring. In APS, vitamin K antagonists are conversely the main treatment (+/- anti-platelet agents), and the use of DOACs is either subject to precautionary recommendations or is not recommended in severe APS. While some randomized controlled trials have been conducted regarding the use of DOACs in APS, only retrospective studies have examined HIT. In addition, vaccine-induced immune thrombotic thrombocytopenia (VITT) is now a part of immunothrombotic disorders, and guidelines have been created concerning an anticoagulant strategy in this case. This literature review aims to summarize available data on HIT, APS, and VITT treatments and define the use of DOACs in therapeutic strategies.

scholarly journals Applied Nanotechnologies in Anticoagulant Therapy: From Anticoagulants to Coagulation Test Performance of Drug Delivery Systems

Applied Nano ◽  
2021 ◽  
Vol 2 (2) ◽  
pp. 98-117
Author(s):  
Yuri B. G. Patriota ◽  
Luíse L. Chaves ◽  
Evren H. Gocke ◽  
Patricia Severino ◽  
Mônica F. R. Soares ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Anticoagulant Therapy ◽  
Test Performance ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Delivery Systems ◽  
Reversal Agent ◽  
Laboratory Assessment ◽  
Administration Routes

Heparin-based delivery systems have been explored to improve their therapeutic efficacy and to reduce toxicity for different administration routes. Regardless of the applied drug delivery system (DDS), the evaluation of anticoagulant performance is instrumental for the development of a suitable DDS. The understanding of the range of anticoagulant assays, together with their key applications and limitations, is essential both within the context of scientific research and for clinical usage. This review provides an overview of the current anticoagulant therapy and discusses the advantages and limitations of currently available anticoagulant assays. We also discuss studies involving low-molecular-weight heparin (LMWH)-based nanocarriers with emphasis on their anticoagulation performance. Conventional anticoagulants have been used for decades for the treatment of many diseases. Direct oral anticoagulants have overcome some limitations of heparins and vitamin K antagonists. However, the lack of an accurate laboratory assessment, as well as the lack of a factor “xaban” (Xa) inhibitor reversal agent, remains a major problem associated with these anticoagulants. LMWHs represent anticoagulant agents with noteworthy efficacy and safety, and they have been explored to improve their outcomes with various nanocarriers through several administration routes. The main problems related to LMWHs have been surmounted, and improved efficiency may be achieved through the use of DDSs.

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