Neurosurgical complications of direct thrombin inhibitors—catastrophic hemorrhage after mild traumatic brain injury in a patient receiving dabigatran

2012 ◽  
Vol 116 (5) ◽  
pp. 1093-1096 ◽  
Author(s):  
Sarah T. Garber ◽  
Walavan Sivakumar ◽  
Richard H. Schmidt
Keyword(s):  
Atrial Fibrillation ◽  
Randomized Clinical Trials ◽  
Dabigatran Etexilate ◽  
Ground Level ◽  
Thrombin Inhibitors ◽  
Thrombin Inhibitor ◽  
Direct Thrombin Inhibitors ◽  
Systemic Embolism ◽  
Nonvalvular Atrial Fibrillation ◽  
Reversal Agent

Dabigatran etexilate is an oral anticoagulant that acts as a direct, competitive thrombin inhibitor. Large randomized clinical trials have shown higher doses of dabigatran (150 mg taken twice daily) to be superior to warfarin in terms of stroke and systemic embolism rates in patients with nonvalvular atrial fibrillation. As a result, in 2010 the US FDA approved the use of dabigatran for the prevention of stroke and systemic embolism in patients with atrial fibrillation. Dabigatran is especially attractive in the outpatient setting because patients do not require routine monitoring with prothrombin times or international normalized ratios. To date, no effective reversal agent for dabigatran in the event of catastrophic hemorrhage has been identified. The authors report a case of an elderly patient, being treated with dabigatran for atrial fibrillation, who presented with a rapidly expanding intracranial hemorrhage after a ground-level fall. This case highlights an impending neurosurgical quandary of complications secondary to this new anticoagulation agent and suggests potential options for management.

scholarly journals Antithrombotic Medication for Cardioembolic Stroke Prevention

2011 ◽  
Vol 2011 ◽  
pp. 1-23 ◽  
Author(s):  
M. Àngels Font ◽  
Jerzy Krupinski ◽  
Adrià Arboix
Keyword(s):  
Atrial Fibrillation ◽  
Dabigatran Etexilate ◽  
Cardioembolic Stroke ◽  
Thrombin Inhibitors ◽  
Dose Titration ◽  
Modern World ◽  
Direct Thrombin Inhibitors ◽  
Nonvalvular Atrial Fibrillation ◽  
Increased Risk ◽  
Clinically Significant

Embolism of cardiac origin accounts for about 20% of ischemic strokes. Nonvalvular atrial fibrillation is the most frequent cause of cardioembolic stroke. Approximately 1% of population is affected by atrial fibrillation, and its prevalence is growing with ageing in the modern world. Strokes due to cardioembolism are in general severe and prone to early recurrence and have a higher long-term risk of recurrence and mortality. Despite its enormous preventive potential, continuous oral anticoagulation is prescribed for less than half of patients with atrial fibrillation who have risk factors for cardioembolism and no contraindications for anticoagulation. Available evidence does not support routine immediate anticoagulation of acute cardioembolic stroke. Anticoagulation therapy's associated risk of hemorrhage and monitoring requirements have encouraged the investigation of alternative therapies for individuals with atrial fibrillation. New anticoagulants being tested for prevention of stroke are low-molecular-weight heparins (LMWH), unfractionated heparin, factor Xa inhibitors, or direct thrombin inhibitors like dabigatran etexilate and rivaroxaban. The later exhibit stable pharmacokinetics obviating the need for coagulation monitoring or dose titration, and they lack clinically significant food or drug interaction. Moreover, they offer another potential that includes fixed dosing, oral administration, and rapid onset of action. There are several concerns regarding potential harm, including an increased risk for hepatotoxicity, clinically significant bleeding, and acute coronary events. Therefore, additional trials and postmarketing surveillance will be needed.

scholarly journals The Risk of Myocardial Infarction in Patients with Atrial Fibrillation Taking a Direct Thrombin Inhibitor: Myths and Reality

2020 ◽  
Vol 16 (2) ◽  
pp. 301-306
Author(s):  
B. A. Tatarsky ◽  
N. V. Kazennova ◽  
D. A. Napalkov
Keyword(s):  
Myocardial Infarction ◽  
Atrial Fibrillation ◽  
Observational Studies ◽  
Randomized Clinical Trials ◽  
Dabigatran Etexilate ◽  
Vascular Complications ◽  
Thrombin Inhibitor ◽  
Definitive Answer ◽  
Increased Risk ◽  
Meta Analyses

The purpose of this review is to analyze the results of randomized clinical trials, meta-analyses of cohort and observational studies in real clinical practice on the influence of dabigatran etexilate on the risk of myocardial infarction in patients with atrial fibrillation. A pivotal RE-LY study on dabigatran use in patients with atrial fibrillation did not show statistically significant differences in the frequency of myocardial infarction between any of the doses of dabigatran and warfarin, and the risk of coronary events did not depend on the presence of coronary heart disease or myocardial infarction in the patient's history. Subsequently, a number of meta-analyses have reported an increased risk of myocardial infarction when dabigatran was administered to patients with atrial fibrillation. In general, these studies were characterized by conflicting data, which did not allow to draw any definite conclusions regarding the use of dabigatran in relation to the risk of myocardial infarction. Two FDA cohort observational studies were published in 2014 and 2017, and the former was significantly criticized by experts, and the results of the second study did not provide a definitive answer to the question about the importance of the effect of dabigatran on the development of myocardial infarction in patients with atrial fibrillation. Even more "confusing" the problem arose after the publication of meta-analyses of randomized trials, which showed that the risk of myocardial infarction was increased in patients treated with direct oral anticoagulants compared to patients treated with warfarin. This review provides high quality evidence for the efficacy of dabigatran in preventing myocardial infarction and other vascular complications in patients with atrial fibrillation.

Approved Uses of Dabigatran Etexilate as an Anticoagulant

2011 ◽  
Vol 27 (6) ◽  
pp. 258-265
Author(s):  
Joshua B Darnell ◽  
Erika L Kleppinger
Keyword(s):  
Atrial Fibrillation ◽  
Data Extraction ◽  
Dabigatran Etexilate ◽  
Anticoagulation Therapy ◽  
Minor Bleeding ◽  
Systemic Embolism ◽  
Nonvalvular Atrial Fibrillation ◽  
Phase 3 ◽  
Study Selection ◽  
Life Threatening

Objective: To review, analyze, and critique dabigatran etexilate's approved uses as an anticoagulant. Data Sources: Literature searches were performed via MEDLINE, International Pharmaceutical Abstracts, and Google Scholar through February 2011, using the term dabigatran. Additional data were obtained from tertiary sources and prescribing information. Study Selection and Data Extraction: All published Phase 3 anticoagulation trials investigating dabigatran for currently approved indications were selected. Information from other anticoagulation trials investigating dabigatran was used for critiquing Phase 3 studies. Data Synthesis: Dabigatran etexilate has been evaluated in multiple clinical trials as an alternative to enoxaparin for prevention of venous thromboembolism in total hip and knee replacement surgeries. It has also been evaluated as an alternative to warfarin in stroke and systemic embolism prevention in patients with atrial fibrillation. Results have generally been positive, with few exceptions. The standard adult dose of dabigatran 150 mg twice daily, approved for use in the US for stroke prevention in nonvalvular atrial fibrillation, was found to be superior to warfarin in regard to occurrence rates of stroke or systemic embolism and hemorrhagic stroke. The occurrence rates of intracranial bleeding, life-threatening bleeding, and major or minor bleeding were lower with dabigatran 150 mg twice daily than with warfarin; however, the occurrence of gastrointestinal bleeding was significantly higher. Conclusions: With its numerous benefits, and despite its drawbacks, dabigatran remains a promising option for oral anticoagulation therapy.

The Direct Thrombin Inhibitors Dabigatran and Lepirudin Inhibit GPIbα-Mediated Platelet Aggregation

2019 ◽  
Vol 119 (06) ◽  
pp. 916-929 ◽  
Author(s):  
Katharina Trabold ◽  
Stephanie Makhoul ◽  
Stepan Gambaryan ◽  
Joanne van Ryn ◽  
Ulrich Walter ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Platelet Aggregation ◽  
Soluble Guanylate Cyclase ◽  
Adenosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Thrombin Inhibitors ◽  
Thrombin Inhibitor ◽  
Direct Thrombin Inhibitors ◽  
Platelet Receptor ◽  
Induced Aggregation

AbstractThe direct thrombin inhibitor (DTI) dabigatran is a non-vitamin K antagonist oral anticoagulant for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation. In addition to its anti-thrombotic efficacy, dabigatran has been suggested to exert some pro-thrombotic effect due to fostering the ligation of thrombin to its high affinity platelet receptor glycoprotein (GP) Ibα in patients with atrial fibrillation. On the other hand, we provided evidence that a member of another class of DTIs, lepirudin, stimulates the inhibitory cyclic guanosine monophosphate (cGMP)/soluble guanylate cyclase pathway in human platelets. Here, we investigated the effect of lepirudin and dabigatran spiked to platelets from healthy volunteers on GPIbα-mediated platelet aggregation and agglutination. Ristocetin/von Willebrand factor (vWF)-induced aggregation of platelets in the presence or absence of plasma was significantly inhibited by lepirudin, dabigatran and D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone (PPACK). However, ristocetin/vWF-mediated platelet agglutination and binding of vWF to platelets were not affected by the DTIs. The anti-aggregatory effect was confirmed by using the GPIbα-specific agonist echicetin beads for human and murine platelets. DTIs diminished echicetin beads-induced Syk Y352 phosphorylation (used here as readout for an early signal occurring during echicetin-induced platelet aggregation), but did not inhibit adenosine diphosphate- or thromboxane A2-induced platelet aggregation. Thrombin was not generated in response to ristocetin/vWF or echicetin beads and therefore did not explain the inhibitory effect of the DTIs. Therapeutic concentration of lepirudin and dabigatran did not affect significantly platelet vasodilator-stimulated phosphoprotein S239 phosphorylation or cGMP and cyclic adenosine monophosphate levels. These data suggest that the DTIs, lepirudin and dabigatran, impair platelet activation measured during platelet aggregation induced by ristocetin/vWF or echicetin beads.

scholarly journals A REVIEW ON A COMPARATIVE STUDY ON EFFECTIVENESS AND SAFETY OF NOVEL ORAL ANTICOAGULANTS IN PATIENTS WITH ATRIAL FIBRILLATION

2019 ◽  
Vol 7 (2) ◽  
Author(s):  
Priyanka P K ◽  
Mathew George ◽  
Lincy Joseph
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Therapeutic Option ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Novel Oral Anticoagulants ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Systemic Embolism ◽  
Anticoagulant Drugs

Atrial fibrillation (AF) is characterized as an extremely rapid and disorganized atrial activation. These irregular heartbeats will cause blood to collect within the heart and potentially form a clot, which can travel to a person’s brain and cause a stroke. AF increases stroke risk by 3 to 5 fold. Vitamin K antagonists (VKAs) are highly effective for the prevention of stroke, mainly of ischemic origin, in patients with AF. For this reason, VKAs are currently recommended in all AF patients at moderate to high risk for stroke or systemic embolism (SSE). VKAs have significant limitations, particularly their unpredictable anticoagulant response and numerous food and drug interactions, mandating regular laboratory monitoring. These limitations make treatment with VKAs problematic for many patients; as a result, only about half of all potentially eligible AF patients are treated with VKAs. Over the last several years, novel oral anticoagulant drugs (NOACs), including direct thrombin inhibitors (dabigatran) and factor Xa inhibitors (apixaban & rivaroxaban), have been developed. New orally administered anticoagulant drugs have emerged as potential alternatives to VKAs for the prevention of ischaemic stroke or systemic embolism in patients with chronic atrial fibrillation. Novel oral anticoagulants (NOACs), due to their a lot of predictable therapeutic result and more favorable haemorrhagic risk profile, represent a particularly attractive therapeutic option in AF patients. Keywords:  Novel oral anticoagulants (NOACs), Vitamin K antagonist (VKAs), Atrial fibrillation, Apixaban, Dabigatran, Rivaroxaban.

scholarly journals Dabigatran for Stroke Prevention in Nonvalvular Atrial Fibrillation: Answers to Challenging “Real-World” Questions

Thrombosis ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Jorge Ferreira ◽  
Daniel Ferreira ◽  
Miguel Viana-Baptista ◽  
Paulo Bettencourt ◽  
Rui Cernadas ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Real World ◽  
Stroke Prevention ◽  
Oral Anticoagulant ◽  
Dabigatran Etexilate ◽  
Direct Thrombin Inhibitor ◽  
Thrombin Inhibitor ◽  
Joint Effort ◽  
Nonvalvular Atrial Fibrillation ◽  
New Oral Anticoagulant

Dabigatran etexilate is a novel, oral, reversible, direct thrombin inhibitor that constitutes a major breakthrough for stroke prevention in patients with nonvalvular atrial fibrillation (AF). Dabigatran was the first new oral anticoagulant approved in Europe and became available in Portugal, for stroke prevention in nonvalvular AF, earlier than in most European countries. This paper is the joint effort of a panel of experts from different specialties and provides information on the use of dabigatran, in anticipation of the challenges that will come with increased usage.

Dabigatran Use in the Real World

2013 ◽  
Vol 27 (4) ◽  
pp. 384-388 ◽  
Author(s):  
Lauren A. Kimmons ◽  
Rajesh Kabra ◽  
McLisa Davis ◽  
Beth V. Segars ◽  
Carrie S. Oliphant
Keyword(s):  
Atrial Fibrillation ◽  
Dabigatran Etexilate ◽  
Retrospective Chart Review ◽  
Bleeding Risk ◽  
Drug Approval ◽  
Bleeding Complications ◽  
Thrombin Inhibitor ◽  
Nonvalvular Atrial Fibrillation ◽  
Randomized Evaluation ◽  
Starting Dose

Dabigatran etexilate, an oral direct thrombin inhibitor, was approved by the Food and Drug Administration to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation based on the outcomes of the Randomized Evaluation of Long-term anticoagulant therapY (RE-LY) study. Although this study provides robust data on the efficacy and safety of dabigatran, there may be differences in the drug use and outcomes in routine clinical practice following drug approval. In this retrospective chart review study, we describe the use of dabigatran in 160 patients in 4 adult hospitals (1 academic and 3 community), including appropriate prescribing for indication, starting dose, concomitant anticoagulant and antiplatelet use, and clinical outcomes such as bleeding, myocardial infarction, and stroke. The study revealed appropriate indication of nonvalvular atrial fibrillation in 145 (91%) of the 160 patients. The dose of dabigatran was appropriate in 90% of the patients, with the most common cause of inappropriate dosing due to perceived bleeding risk. Over a follow-up period of 6 months, bleeding complications were noted in 6 patients still taking dabigatran, 5 of which were gastrointestinal bleeding. Our study underscores the importance of prescriber education regarding the appropriate indication, dosage, and safety of dabigatran with active participation of pharmacists in this process.

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