scholarly journals Rivaroxaban-Induced Nontraumatic Spinal Subdural Hematoma: An Uncommon Yet Life-Threatening Complication

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Mazen Zaarour ◽  
Samer Hassan ◽  
Nishitha Thumallapally ◽  
Qun Dai

In the last decade, the desire for safer oral anticoagulants (OACs) led to the emergence of newer drugs. Available clinical trials demonstrated a lower risk of OACs-associated life-threatening bleeding events, including intracranial hemorrhage, compared to warfarin. Nontraumatic spinal hematoma is an uncommon yet life-threatening neurosurgical emergency that can be associated with the use of these agents. Rivaroxaban, one of the newly approved OACs, is a direct factor Xa inhibitor. To the best of our knowledge, to date, only two published cases report the incidence of rivaroxaban-induced nontraumatic spinal subdural hematoma (SSDH). Our case is the third one described and the first one to involve the cervicothoracic spine.

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Alba Colell ◽  
Adrià Arboix ◽  
Francesco Caiazzo ◽  
Elisenda Grivé

In the last decade, the clinical relevance for developing safer oral anticoagulants prompted the development of new classes of drugs that have shown a lower risk of life-threatening bleeding events as compared to standard warfarin. Nontraumatic spinal subdural hematoma is an uncommon urgent complication that can be associated with the use of these agents. An unusual case of spinal subdural hematoma related to apixaban treatment for nonrheumatic atrial fibrillation is reported here.


2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Alok Dabi ◽  
Aristides P. Koutrouvelis

Direct oral anticoagulants (DOACs) are a new class of anticoagulants that directly inhibit either thrombin or factor Xa in the coagulation cascade. They are being increasingly used instead of warfarin or other vitamin K antagonists (VKAs). Adverse side effects of DOACs may result in hemorrhagic complications, including life-threatening intracranial hemorrhage (ICH), though to a much lesser degree than VKAs. Currently there are relatively limited indications for DOACS but their usage is certain to expand with the availability of their respective specific reversal agents. Currently, only idarucizumab (antidote for dabigatran) has been United States Food and Drug Administration- (FDA-) approved, but others (andexanet-α and ciraparantag) may be approved in near future, and the development and availability of such reversal agents have the potential to dramatically change the current anticoagulant use by providing reversal of multiple oral anticoagulants. Until all the DOACs have FDA-approved reversal agents, the treatment of the dreaded side effects of bleeding is challenging. This article is an attempt to provide an overview of the management of hemorrhage, especially ICH, related to DOAC use.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3672-3672 ◽  
Author(s):  
Yimin Pearl Wang ◽  
Rohan Kehar ◽  
Alla Iansavitchene ◽  
Alejandro Lazo-Langner

Introduction: The standard oral anticoagulant therapy administered to non-valvular AF patients has typically been Vitamin K Antagonists (VKA) particularly warfarin. In recent years, Direct Oral Anticoagulants (DOACs) including Direct Thrombin Inhibitors (DTI) and Direct Factor Xa inhibitors (FXa inhibitors) have become an alternative to warfarin. Randomized trials comparing warfarin and DOACs showed comparable effectiveness without significant additional major bleeding risk. However, bleeding events in RCTs may differ from those in daily use due to the routine exclusion of patients with a higher risk of bleeding from many studies. We aimed to assess bleeding risk between DOACs and warfarin in AF patients in observational studies and we also sought to determine differences between patients that were experienced or naïve to oral anticoagulants. Methods: A systematic literature search was conducted in the OVID MEDLINE® and EMBASE® electronic databases. Observational studies and randomized control trials (RCT) from 1990 to January 2019 were retrieved and examined by two independent reviewers. A pooled effect hazard ratio (HR) was calculated using a random effects model using the generic inverse variance method. Subgroup analyses according to previous exposure to anticoagulants, study type, funding type and DOAC type were conducted. The primary outcome was major bleeding risk. The secondary outcome was clinically relevant non-major bleeding. All studies must have used an established or validated definition of major bleeding. Results: The initial literature search identified 3359 potentially eligible citations. After primary screening, 150 articles were eligible for full text review and there were 35 studies including 2,356,201 patients that met the inclusion criteria. Overall, patients on DOACs were less likely to experience a bleeding event compared to warfarin (HR 0.78, 95%CI 0.71, 0.85, P<0.001). The results were consistent when analyzing patients receiving DTIs or FXa inhibitors (DTI: HR 0.76, 95% CI 0.67,0.87; FXa inhibitors: HR 0.79, 95% CI 0.69,0.89). However, among patients receiving factor Xa inhibitors, there was a significant difference in the risk of bleeding according to individual drug. Among patients receiving rivaroxaban the risk of bleeding was similar to warfarin (HR 0.98, 95%CI 0.91,1.06, p=0.60) whereas in those receiving apixaban there was a 40% reduction in the risk of bleeding compared to warfarin (HR 0.60, 95%CI 0.50,0.71, p<0.001) (Figure 1). Three studies reported information according to previous anticoagulant exposure. The overall pooled hazard ratio was 0.68 (95% CI 0.55, 0.82 p<0.001) in favor of patients on DOACs. In the subgroup analysis of previous anticoagulant use, the risk of bleeding was lower for DOACs compared to warfarin in both the experienced population (HR 0.70, 95%CI 0.51, 0.96) and the naïve population (HR 0.64, 95% CI 0.47,0.87). However, heterogeneity was moderate to high among both subgroups. Conclusion: This review and meta-analysis of observational studies including over 2.3 million patients showed that overall DOACs have a lower risk of major bleeding and clinically relevant non-major bleeding compared to warfarin. Most importantly, although the pooled effect estimate did not differ between DTIs and FXa inhibitors, among patients receiving FXa inhibitors there was a significant difference between individual agents. Patients on apixaban had a significantly lower risk of bleeding compared to warfarin in contrast to patients on rivaroxaban who had a similar risk. Disclosures No relevant conflicts of interest to declare.


2020 ◽  
Vol 182 (12) ◽  
pp. 3052-3055
Author(s):  
Diana Carli ◽  
Andrea Gazzin ◽  
Maria Roberta Bongioanni ◽  
Mauro Bergui ◽  
Alessandro Mussa ◽  
...  

Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 247-250
Author(s):  
Meng Qi ◽  
Tao Huang ◽  
Lei Xu ◽  
Ning Wang ◽  
Peipei Zhang ◽  
...  

AbstractWe present a rare case of spinal subdural hematoma induced by guidewire-based lumbar drainage in a subarachnoid hemorrhage patient with a ruptured intracranial aneurysm. Decreased muscle strength and muscle tension of bilateral lower limbs were noted, and an MRI confirmed the spinal subdural hematoma from the sacral to the thoracic segments. The spinal subdural hematoma evacuation and spinal canal decompression were performed by laminectomy. However, the patient did not benefit from the surgery and developed lower limb muscle atrophy. The complication of the spinal subdural hematoma after lumbar drainage is extremely rare; only limited approaches are available for the treatment of spinal hematoma to improve the outcome and avoid severe consequences. Thus, the present case might suggest refraining from use of a guidewire during lumbar drainage for the prevention of spinal subdural hematoma and close observation of the related symptoms and signs for the early detection of spinal hematoma after the procedure. In addition, full decompression can be performed by complete hematoma evacuation and laminectomy of related segments for the treatment of spinal subdural hematoma induced by lumbar drainage.


2015 ◽  
Vol 9 (2) ◽  
pp. 122
Author(s):  
Pierre Amarenco ◽  
Werner Hacke ◽  
Bo Norrving ◽  
Natalia Rost ◽  
◽  
...  

In patients with atrial fibrillation (AF) the risk of stroke is substantially increased, especially in those who are elderly (over 75 years) or have risk factors such as previous stroke, heart failure or hypertension. Stroke outcomes are also generally much worse in those with AF. Current guidelines indicate that any patient with AF and risk factors for stroke should receive anticoagulant therapy to limit their stroke risk. Despite these established recommendations, only 50 % of patients at risk receive anticoagulation with a vitamin K antagonist (VKA) and only 50 % of those are within the therapeutic range, indicating lack of adherence to the guidelines. Withholding anticoagulant therapy is mainly left to an individual physician’s choice, as shown in the ongoing GARFIELD registry of AF stroke prevention practice. Many physicians fear the risk of intracranial haemorrhage (ICH) for which outcomes remain poor. Recent clinical studies have shown that the non-VKA oral anticoagulants (NOACs) (apixaban, rivaroxaban, dabigatran and edoxaban) significantly reduce the risk of ICH and other bleeding events, while having non-inferior stroke prevention to warfarin. Use of these drugs, limiting exposure to aspirin and alcohol and controlling blood pressure have been shown to minimise ICH risk in large clinical trials and meta-analyses. Recent data from the Effective aNticoaGulation with factor xA next GEneration in Atrial Fibrillation (ENGAGE AF)-TIMI 48 study showed that the factor Xa inhibitor edoxaban was non-inferior to well-managed warfarin for reducing all stroke risk, and significantly reduced haemorrhagic stroke, major bleeding, ICH and death. These findings further support the case for using NOAC therapy for stroke prevention in patients with AF and risk factors for stroke.


2020 ◽  
pp. 28-43
Author(s):  
O. O. Shakhmatova

Edoxaban is a selective direct factor Xa inhibitor. Edoxaban in a dose of 60 mg per day is an effective and safe option in the prevention of thromboembolic complications in patients with nonvalvular atrial fibrillation, including in combination therapy in patients after percutaneous coronary interventions. ENGAGE AF-TIMI 48 is currently the most extensive study comparing direct oral anticoagulants and warfarin in patients with atrial fibrillation, both in terms of number of participants and duration of observation. For edoxaban, an adequate approach to dose reduction has been developed in patients with alikely increase in plasma concentration due to renal impairment, low body weight or inter-drug interactions. Such dose reduction does notlead to an increase in the frequency of ischemic complications.Edoxaban is characterized by an optimal safety profile in patients with chronic moderate kidney disease, a small number of drug interactions and a convenient mode of administration. In patients with atrial fibrillation and concomitant ischemic heart disease, the use of Edoxaban is associated with a decrease in the frequency of myocardial infarctions, as well as strokes and episodes of systemic thromboembolism in comparison with warfarin. The drug can be successfully used as anticoagulant support for cardioversion and catheter ablation for atrial fibrillation.Edoxaban intake does not require routinelaboratory control. In case of unexpected situations (life-threatening bleeding, urgent surgical intervention) in patients receiving edoxaban, to assess the degree of anticoagulation should use the determination of anti-Xa activity. Clinical studies of a specific antidote of edoxaban - andexanet alfa are ongoing. Before approval of the specific antidote in severe andlife-threatening bleedings against the background of edoxaban administration, the use of prothrombin complex concentrate should be considered. Data on the effective and safe use of edoxaban in routine clinical practice have been accumulated.


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
G.Y.H Lip ◽  
A Keshishian ◽  
A Kang ◽  
X Luo ◽  
N Atreja ◽  
...  

Abstract Background Patients with non-valvular atrial fibrillation (NVAF) use oral anticoagulants such as warfarin or non-vitamin K antagonist oral anticoagulants (NOACs) for the prevention of stroke. However, the effectiveness and safety of warfarin and NOACs can be influenced by pre-existing patient comorbidities, such as a history of bleeding, and limited evidence are available to inform the choice of the most appropriate anticoagulant treatment for NVAF patients with bleeding history. Purpose This study used five United States insurance claims databases to evaluate the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) among NVAF patients with prior bleeding events who were prescribed NOACs versus warfarin. Methods This retrospective observational study used data from 5 databases (CMS Medicare and four commercial databases, covering >180 million beneficiaries) to select adult NVAF patients who were treated with apixaban, dabigatran, rivaroxaban, or warfarin (01JAN2013–30JUN2019). Patients were required to have a prior bleeding event, defined as a hospitalization with a diagnosis for intracranial hemorrhage (ICH), gastrointestinal (GI) bleeding or bleeding at other key sites prior to or during the index treatment episode. In each database, three 1:1 NOAC-warfarin propensity-score-matched (PSM) cohorts were created before pooling the results. Outcome measures were time to first stroke/SE, (ischemic stroke, hemorrhagic stroke, and SE), and time to first MB (gastrointestinal bleeding, intracranial hemorrhage, and MB at other key sites), and were measured from the index treatment episode to treatment discontinuation or switch, death, health plan disenrollment, or end of study period. Hazard ratios of S/SE and MB were calculated using Cox proportional hazards models. Results Among the eligible NVAF population, 8.2% of patients had a prior bleeding event (ICH: 12.3%; GI: 60.7%; Other: 27.0%). After PSM, a total of 43,092 apixaban-warfarin, 11,295 dabigatran-warfarin, and 32,723 rivaroxaban-warfarin patient pairs with prior bleeding were selected with a mean follow-up of 8–9 months. Apixaban and rivaroxaban were associated with a lower risk of S/SE, and dabigatran was associated with a similar risk of S/SE when compared to warfarin. Apixaban and dabigatran were associated with a lower risk of MB, and rivaroxaban was associated with a similar risk of MB, compared to warfarin (Figure). Conclusion Among NVAF patients with prior bleeding events, NOACs were associated with varying risks of S/SE and MB compared to warfarin. These results can help inform healthcare providers concerning the impact of OAC treatment in NVAF patients with history of bleeding. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bristol-Myers Squibb Company and Pfizer, Inc.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
L Dominguez Rodriguez ◽  
S Raposeiras Roubin ◽  
D Alonso Rodriguez ◽  
S J Camacho Freire ◽  
E Abuassi ◽  
...  

Abstract Introduction Embolic prevention with oral anticoagulation is the cornerstone for the management of patients with atrial fibrillation (AF). However, data about the efficacy and safety of oral anticoagulation in nonagenarian patients are limited. We aimed to analyze the impact of oral anticoagulation in mortality, embolic and hemorrhagic events, in patients ≥90 years with non-valvular AF. Methods We used data from a multicentric registry of 1,750 consecutive nonagenarian patients diagnosed of AF between 2013 and 2018. A propensity-matched analysis was performed to match the baseline characteristics of patients treated or not with oral anticoagulants, and for those treated with vitamin K antagonists (VKAs) vs direct oral anticoagulants (DOACs). The impact of oral anticoagulation in the embolic and hemorrhagic risk was assessed by a competitive risk analysis, using a Fine and Gray regression model, with death being the competitive event. For embolic risk, we have considered a stroke, pulmonary or peripheral embolism. For bleeding risk, we have considered any bleeding requiring hospital admission. Results The mean of CHA2DS2-VASC and HASBLED scores was 4.5±1.3 and 2.8±1.0 points, respectively. Most of patients were anticoagulated (70.1%; n=1,256). DOACs were used in 709 patients, and VKAs in 517 patients. During a median follow-up of 25.2 months (IQR 12.2–44.3 months), 988 patients died (56.5%), 180 presented embolic events (10.3%), 186 had bleeding events (10.6%), and 29 had intracranial hemorrhage (ICH, 1.7%). After propensity-score matching, anticoagulation (versus non anticoagulation) was associated with lower mortality rate (HR 0.73, 95% CI 0.60–0.89; p=0.002), less mortality and embolic events (HR 0.77, 95% CI 0.64–0.92; p=0.005), but more bleeding events (HR 2.05, 95% CI 1.25–3.35; p=0.004). In comparison with VKAs, DOACs showed similar risk of mortality and embolic events (HR 1.14, 95% CI 0.88–1.47; p=0.337), and similar risk of bleeding events (HR 0.75, 95% CI 0.43–1.28; p=0.287), although a trend to lower risk of ICH was found (HR 0.17, 95% CI 0.02–1.39; p=0.097). Conclusions Among nonagenarian patients with AF, oral anticoagulation was associated with lower all-cause mortality. Although survival free of embolic events was significantly higher in patients with anticoagulation, the risk of major bleeding was twice than in non-anticoagulated patients. There was not differences between VKAs and DOACs in terms of embolic events and total major bleeding. However, compared with VKAs, DOACs were showed a trend to lower risk of ICH.


Hematology ◽  
2014 ◽  
Vol 2014 (1) ◽  
pp. 518-523 ◽  
Author(s):  
Maureane Hoffman ◽  
Dougald M. Monroe

Abstract Dabigatran, rivaroxaban, and apixaban are orally active anticoagulants that are approved in many countries. Dabigatran inhibits thrombin, whereas rivaroxaban and apixaban are factor Xa inhibitors. In clinical trials, these novel oral anticoagulants were at least as effective as warfarin for preventing stroke in patients with atrial fibrillation, but with a lower rate of serious bleeding. However, the lack of true antidotes for these agents has caused concern when patients suffer life-threatening bleeding or trauma or require emergent invasive procedures. True antidotes are under development for all of these agents. In the meantime, activated and nonactivated prothrombin complex concentrates have been used as reversal agents. Factor VIIa may also be effective for reversal of the factor Xa inhibitors. Reversal of novel oral anticoagulants by these hemostatic agents has not been studied in bleeding human patients, so their true efficacy and appropriate dosing are not known.


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