rivaroxaban and Emergencies

Novel oral anticoagulants (NOACs) have emerged as a good alternative to warfarin in the prevention of stroke for patients with atrial fibrillation. NOAC use is increasing rapidly; therefore, greater understanding of their use in the perioperative period is important for optimal care. Studies and reviews that reported on the use of NOACs were identified, with particular focus on the perioperative period. PubMed was searched for relevant articles published between January 2000 and August 2015. The inevitable rise in the use of NOACs such as rivaroxaban (Xarelto™), apixaban (Eliquis™), edoxaban (Lixiana™) and dabigatran (Pradaxa™) may present a simplified approach to perioperative anticoagulant management due to fewer drug interactions, rapidity of onset of action and relatively short half-lives. Coagulation status, however, cannot reliably be monitored and no antidotes are currently available. When planning for discontinuation of NOACs, special consideration of renal function is required. Advice regarding the management of bleeding complications is provided for consideration in emergency surgery. In extreme circumstances, haemodialysis may be considered for bleeding with the use of dabigatran. NOACs will increasingly affect operative planning in plastic surgery. In order to reduce the incidence of complications associated with anticoagulation, the management of NOACs in the perioperative period requires knowledge of the time of last dose, renal function and the bleeding risk of the planned procedure. Consideration of these factors will allow appropriate interpretation of the current guidelines.

Topics: Administration, Oral; Algorithms; Anticoagulants; Dabigatran; Elective Surgical Procedures; Emergencies; Humans; Kidney; Liver; Perioperative Care; Plastic Surgery Procedures; Postoperative Hemorrhage; Practice Guidelines as Topic; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles

Patients taking direct oral anticoagulants (DOACs) who then need an emergency invasive procedure require specialized management strategies. Appropriate patient evaluation includes assessment of the current anticoagulation state, including timing of the last dose. DOACs require particular coagulation assays to measure anticoagulation levels accurately, although standard coagulation screening tests may provide qualitative guidance. Specialty societies have endorsed general recommendations for patient management to promote hemostasis in anticoagulated patients requiring surgery or other invasive procedures. These include general stopping rules (such as ≥24 hours for low-risk procedures and ≥48 hours for high-risk surgery with normal renal function) for elective procedures. Bridging therapy when oral anticoagulant treatment is interrupted has recently been questioned, depending on the clinical scenario. Novel agents for the reversal of DOAC-induced anticoagulation have recently been developed. Idarucizumab, a humanized monoclonal antibody fragment that selectively binds dabigatran, was recently approved for clinical use in patients with life-threatening or uncontrolled bleeding, and for patients requiring emergency interventions. Idarucizumab can streamline the pre- and periprocedural anticoagulation management of dabigatran-treated patients, as it provides fast, complete, and sustainable reversibility. Andexanet alfa is an inactive, decoy factor Xa (FXa) molecule that binds FXa inhibitors, and ciraparantag is a synthetic molecule designed to bind fractionated and unfractionated heparins, and each of the currently approved DOACs. As clinical development of the additional anti-FXa-specific anticoagulant reversal agents proceeds, the respective role of each in the management of emergency bleeding events and invasive procedures will be better defined, and it is hoped they will make important contributions to patient care.

Topics: Antibodies, Monoclonal, Humanized; Anticoagulants; Antidotes; Antithrombins; Arginine; Dabigatran; Deprescriptions; Emergencies; Factor Xa; Factor Xa Inhibitors; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Piperazines; Prothrombin Time; Pyrazoles; Pyridones; Recombinant Proteins; Rivaroxaban; Surgical Procedures, Operative

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; Dabigatran; Elective Surgical Procedures; Emergencies; Factor Xa Inhibitors; Hemorrhage; Humans; Kidney Diseases; Morpholines; Orthopedic Procedures; Postoperative Complications; Premedication; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Risk; Rivaroxaban; Thiophenes; Thrombophilia; Vitamin K

Topics: Anticoagulants; Antidotes; Benzimidazoles; beta-Alanine; Dabigatran; Emergencies; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Surgical Procedures, Operative; Thiophenes; Wounds and Injuries

New direct oral anticoagulants (NOAC), inhibitors of factor IIa or Xa, are expected to be widely used for the treatment of venous thromboembolic disease, or in case of atrial fibrillation. Such anticoagulant treatments are known to be associated with haemorrhagic complications. Moreover, it is likely that such patients on long-term treatment with NOAC will be exposed to emergency surgery or invasive procedures. Due to the present lack of experience in such conditions, we cannot make recommendations, but only propose management for optimal safety as regards the risk of bleeding in such emergency conditions. In this article, only dabigatran and rivaroxaban were discussed. For emergency surgery at risk of bleeding, we propose to dose the plasmatic concentration of drug. Levels inferior or equal to 30ng/mL for both dabigatran and rivaroxaban, should enable the realization of a high bleeding risk surgery. For higher concentration, it was proposed to postpone surgery by monitoring the evolution of the drug concentration. Action is then defined by the kind of NOAC and its concentration. If the dosage of the drug is not immediately available, proposals only based on the usual tests, PT and aPTT, also are presented. However, these tests do not really assess drug concentration or bleeding risk. In case of severe haemorrhage in a critical organ, it is proposed to reduce the effect of anticoagulant therapy using a nonspecific procoagulant drug (activated prothrombin concentrate, FEIBA, 30-50U/kg, or non-activated 4-factors prothrombin concentrates 50U/kg). For any other type of severe haemorrhage, the administration of such a procoagulant drug, potentially thrombogenic in these patients, will be discussed regarding concentration of NACO and possibilities for mechanical haemostasis.

Topics: Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Emergencies; Emergency Medical Services; Factor Xa Inhibitors; Hemorrhage; Hemostasis; Humans; Morpholines; Perioperative Care; Rivaroxaban; Surgical Procedures, Operative; Thiophenes; Thrombin

Topics: Anticoagulants; Aspirin; Benzimidazoles; Clopidogrel; Dabigatran; Emergencies; Enoxaparin; Fondaparinux; Heparin; Humans; Morpholines; Platelet Aggregation Inhibitors; Platelet Transfusion; Polysaccharides; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Surgical Procedures, Operative; Thiophenes; Ticlopidine; Warfarin

Dabigatran and rivaroxaban are novel anticoagulants that have been approved for the prevention of thromboembolic events in atrial fibrillation. These medications are attractive to both patients and clinicians, as, unlike warfarin, they do not require laboratory monitoring or dietary restrictions. However, they carry bleeding risks similar to that of warfarin and are without a reliable reversal agent.. The objectives of this article are to 1) summarize the pivotal trials leading to the U.S. Food and Drug Administration approvals of dabigatran (Pradaxa; Boehringer Ingelheim, Ridgefield, CT) and rivaroxaban (Xarelto; Janssen Pharmaceuticals, Inc., Titusville, NJ); 2) present the limited data available regarding the management of bleeding patients on these agents; and 3) provide suggestions to guide emergency providers given the limited data.. Dabigatran and rivaroxaban were approved based on large, non-inferiority trials comparing the new agents to warfarin with stroke or systemic embolism as the primary outcome. Traditional coagulation studies cannot be used to determine the degree of anti-coagulation produced by these agents. Fresh frozen plasma is unlikely to be effective in patients on these drugs who are acutely bleeding. Prothrombin complex concentrate can be considered in patients on rivaroxaban. Dabigatran is renally cleared, so dabigatran could be removed by hemodialysis. Theoretically, DDAVP (Sanofi-Aventis U.S. LLC, Bridgewater, NJ), aminocaproic acid, tranexamic acid, or recombinant activated factor VII could also be used in an attempt to control bleeding.. There is a need for assays for the degree of anticoagulation produced by drugs such as dabigatran and rivaroxaban. Additionally, studies are needed to evaluate reversal agents that could be effective in the setting of acute bleeding.

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Drug Approval; Emergencies; Hemorrhage; Humans; Morpholines; Rivaroxaban; Stroke; Thiophenes; United States; United States Food and Drug Administration; Warfarin

An accurate point-of-care test for detecting effective anticoagulation by direct oral anticoagulants (DOACs) in emergencies is an unmet need. We investigated the accuracy of a urinary qualitative strip test (DOAC Dipstick) to detect relevant DOAC exposure in patients who presented to an emergency department. In this prospective single-center cohort-type cross-sectional study, adults on DOAC treatment were enrolled. We assessed clinical sensitivity and specificity of DOAC Dipstick factor Xa and thrombin inhibitor pads to detect DOAC plasma levels ≥30 ng/mL using urine samples as the testing matrix. Liquid chromatography coupled with tandem-mass spectrometry was used as the reference standard method for plasma and urine measurement of DOAC concentrations. Of 293 patients enrolled, 265 patients were included in the analysis, of whom 92 were treated with rivaroxaban, 65 with apixaban, 77 with edoxaban, and 31 with dabigatran. The clinical sensitivity and specificity of the dipstick on urine samples to detect ≥30 ng/mL dabigatran plasma levels were 100% (95% confidence interval [CI]: 87-100%) and 98% (95% CI: 95-99%), respectively. The sensitivity and specificity of the dipstick to detect ≥30 ng/mL factor Xa inhibitor plasma levels were 97% (95% CI: 94-99%) and 69% (95% CI: 56-79%), respectively. The DOAC Dipstick sensitively identified effective thrombin and factor Xa inhibition in a real-world cohort of patients presenting at an emergency department. Therefore, the dipstick might provide a valuable test to detect relevant DOAC exposure in emergencies, although further studies will be needed to confirm these findings.

Topics: Administration, Oral; Anticoagulants; Cross-Sectional Studies; Dabigatran; Emergencies; Emergency Service, Hospital; Factor Xa; Factor Xa Inhibitors; Humans; Point-of-Care Systems; Point-of-Care Testing; Prospective Studies; Pyridones; Rivaroxaban; Thrombin

Patients treated with direct Xa inhibitors may require urgent surgery. Administration of prothrombin complex concentrate (PCC) in this setting is common; however, it is based on limited experience in healthy volunteers.. To characterize the population receiving PCC for apixaban/rivaroxaban reversal prior to an urgent surgery and evaluate its efficacy and safety.. This was a retrospective study in 2 tertiary hospitals. Bleeding was evaluated based on surgical reports, hemoglobin drop, and the use of blood products or additional PCC during 48 h. Safety measures were thrombotic complications and 30-day mortality.. Sixty-two patients aged 80.7 ± 9 years, treated with apixaban (39.63%) or rivaroxaban (23.37%), received PCC before an urgent surgery/procedure. Most underwent abdominal operation (61%), orthopedic surgery (13%), or transhepatic cholecystostomy insertion (10%). Bleeding during surgery was reported in 3 patients (5%), no patient required additional PCC, and 16 patients (26%) received packed cells (median: 1 unit, range: 1-5). The 30-day mortality and thrombosis rates were 21% (n = 13) and 3% (n = 2), respectively. The cause of death was related to the primary disease, most commonly sepsis. No patient died due to bleeding/thrombosis.. Our results support the use of PCC to achieve hemostasis in patients treated with Xa inhibitors prior to an urgent surgery.

Topics: Academic Medical Centers; Aged; Aged, 80 and over; Atrial Fibrillation; Blood Coagulation Factors; Blood Component Transfusion; Blood Loss, Surgical; Emergencies; Factor Xa Inhibitors; Female; Hemostatics; Humans; Male; Postoperative Hemorrhage; Preoperative Care; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Surgical Procedures, Operative; Tertiary Care Centers; Thrombophilia; Thrombosis; Tranexamic Acid

Controversy exists regarding first-line use of the recently approved reversal agent andexanet alfa due to limitations of the ANEXXA-4 study, thrombotic risks, and high medication acquisition cost. The purpose of this study was to evaluate the safety and effectiveness of 4F-PCC for the reversal of emergent oral fXa inhibitor-related bleeding. Furthermore, we aimed to evaluate a subgroup using strict ANNEXA-4 patient selection criteria.. This was a retrospective study conducted utilizing chart review of adult patients that received 4F-PCC for oral fXa inhibitor-related bleeding. The primary endpoint was the rate of clinical success defined as achieving excellent or good hemostatic effectiveness following the administration of 4F-PCC. Secondary endpoints included in-hospital mortality and arterial/venous thromboembolism, and cost compared with andexanet alfa.. A total of 119 patients were included, with 83 patients in the ANNEXA-4 criteria subgroup. Eighty-five of the 119 patients (71%) required reversal due to intracranial bleeding. Prior to reversal, 70 patients (59%) were taking apixaban and 49 patients (41%) were taking rivaroxaban. Clinical success was achieved in 106 of 119 patients (89%) and 74 of 83 patients (90%) in the strict criteria subgroup. Three of 119 patients (2.5%) had a thrombotic event during hospital stay and the overall mortality rate was 13%. The average cost increase of andexanet alfa compared to 4F-PCC would have been $29,500 per patient.. Administration of 4F-PCC for the reversal of oral fXa inhibitors was effective with relatively low thrombotic risk. Further direct prospective comparison of 4F-PCC to andexanet alfa is warranted.

Topics: Aged; Aged, 80 and over; Antidotes; Blood Coagulation Factors; Drug Costs; Emergencies; Factor Xa; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Hemorrhage; Hospital Mortality; Humans; Intracranial Hemorrhages; Male; Pyrazoles; Pyridones; Recombinant Proteins; Rivaroxaban; Thromboembolism; Treatment Outcome

The purpose of this study was to analyze the results of Cytosorb (CytoSorbents, Monmouth Junction, NJ) adsorption during emergency open heart operations in patients at high risk of bleeding due to treatment with coagulation-active substances.. We investigated 55 consecutive patients (median age 70 years; interquartile range: 60 to 77) who underwent emergency cardiac surgery at our institution between June 2016 and June 2018. All patients were receiving therapy with either ticagrelor (n = 43) or rivaroxaban (n = 12). In 39 of 55 cases, we routinely installed standardized Cytosorb adsorption into the heart-lung machine. Bleeding complications during and after surgery were analyzed in detail and compared with 16 patients without adsorption.. In the Cytosorb adsorption group, no rethoracotomies had to be performed. Drainage volumes in 24 hours were only 350 mL (interquartile range: 300 to 450 mL) after ticagrelor administration and 390 mL (interquartile range: 310 to 430 mL) after rivaroxaban therapy. In the majority of patients, transfusions of blood products were not needed. Compared with that group, among the group of patients without adsorption, multiple bleeding complications occurred. These were associated with longer total operation (p = 0.0042), higher drainage volumes (p = 0.0037), more transfusions of red blood cells (p = 0.0119) and platelets (p = 0.0475), a significantly higher rethoracotomy rate (p = 0.0003), significantly prolonged stay in the intensive care unit (p = 0.0141), and a longer hospital stay (p = 0.0244).. The intraoperative use of Cytosorb adsorption of ticagrelor and rivaroxaban in emergency open heart operations is reported for the first time. The data show that the strategy is safe and is an effective method to reduce bleeding complications. We recommend the use for safety in patients with ticagrelor or rivaroxaban undergoing emergency cardiac surgery.

Topics: Aged; Aged, 80 and over; Cardiac Surgical Procedures; Emergencies; Female; Hemadsorption; Humans; Male; Middle Aged; Postoperative Hemorrhage; Rivaroxaban; Ticagrelor

Direct oral anticoagulants are commonly used instead of vitamin K antagonists in patients needing long-term anticoagulant treatment. As their use has become more popular, there is an increase possibility to perform a major surgery on an urgent or emergency basis on patients under nonvitamin-K antagonist oral anticoagulants.. We report a case of a ruptured abdominal aortic aneurysm on a male patient under rivaroxaban and clopidogrel. Emergency open repair of the aneurysm was performed. No anti-Xa antidote was administered. The patient had an uneventful recovery.. An open repair of a ruptured abdominal aortic aneurysm under rivaroxaban is feasible. However, an antidote should be available in cases of uncontrolled diffused bleeding. To the best of our knowledge, this is the first reported case of successful open repair of a ruptured abdominal aortic aneurysm on a patient under rivaroxaban and clopidogrel.

Topics: Aortic Aneurysm, Abdominal; Aortic Rupture; Aortography; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Clopidogrel; Computed Tomography Angiography; Drug Administration Schedule; Emergencies; Factor Xa Inhibitors; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Rivaroxaban; Treatment Outcome

The increasing incidence of venous thromboembolism (VTE) in paediatric population has stimulated the development of liquid anticoagulant formulations. Thus our goal is to formulate a liquid formulation of poorly-water soluble anticoagulant, rivaroxaban (RIVA), for paediatric use and to assess the possibility of its intravenous administration in emergencies. Self-nanoemulsifying drug delivery systems (SNEDDSs) were developed and characterized. SNEDDS constituents were estimated from the saturated solubility study followed by plotting the corresponding ternary phase diagrams to determine the best self-emulsified systems. Thermodynamic stability, emulsification, dispersibility, robustness to dilution tests,

Topics: Animals; Anticoagulants; Biological Availability; Chemistry, Pharmaceutical; Drug Liberation; Drug Stability; Emergencies; Emulsions; Humans; Models, Animal; Nanocapsules; Particle Size; Polyethylene Glycols; Polymers; Polysorbates; Propylene Glycols; Rats; Rheology; Rivaroxaban; Solubility; Surface Properties; Venous Thromboembolism; Water

Topics: Antidotes; Blood Coagulation Factors; Blood Component Transfusion; Blood Loss, Surgical; Cerebral Hemorrhage; Drug Administration Schedule; Emergencies; Factor Xa; Factor Xa Inhibitors; Hemorrhage; Humans; Intraoperative Care; Premedication; Preoperative Care; Pyrazoles; Pyridones; Recombinant Proteins; Rivaroxaban; Wounds and Injuries

In patients receiving direct oral anticoagulants (DOACs), emergency treatment like thrombolysis for acute ischemic stroke is complicated by insufficient availability of DOAC-specific coagulation tests. Conflicting recommendations have been published concerning the use of global coagulation assays for ruling out relevant DOAC-induced anticoagulation.. Four hundred eighty-one samples from 96 DOAC-treated patients were tested using prothrombin time (PT), activated partial thromboplastin time (aPTT) and thrombin time (TT), DOAC-specific assays (anti-Xa activity, diluted TT), and liquid chromatography-tandem mass spectrometry. Sensitivity and specificity of test results to identify DOAC concentrations <30 ng/mL were calculated. Receiver operating characteristic analyses were used to define reagent-specific cutoff values.. Normal PT and aPTT provide insufficient specificity to safely identify DOAC concentrations <30 ng/mL (rivaroxaban/PT: specificity, 77%/sensitivity, 94%; apixaban/PT: specificity, 13%/sensitivity, 94%, dabigatran/aPTT: specificity, 49%/sensitivity, 91%). Normal TT was 100% specific for dabigatran, but sensitivity was 26%. In contrast, reagent-specific PT and aPTT cutoffs provided >95% specificity and a specific TT cutoff enhanced sensitivity for dabigatran to 84%. For apixaban, no cutoffs could be established.. Even if highly DOAC-reactive reagents are used, normal results of global coagulation tests are not suited to guide emergency treatment: whereas normal PT and aPTT lack specificity to rule out DOAC-induced anticoagulation, the low sensitivity of normal TT excludes the majority of eligible patients from treatment. However, reagent-specific cutoffs for global coagulation tests ensure high specificity and optimize sensitivity for safe emergency decision making in rivaroxaban- and dabigatran-treated patients.. URL: http://www.clinicaltrials.gov. Unique identifiers: NCT02371044 and NCT02371070.

Topics: Aged; Aged, 80 and over; Antithrombins; Blood Coagulation Disorders; Blood Coagulation Tests; Dabigatran; Emergencies; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Partial Thromboplastin Time; Point-of-Care Testing; Prothrombin Time; Pyrazoles; Pyridones; Rivaroxaban; Sensitivity and Specificity; Stroke; Thrombin Time; Thrombolytic Therapy

Topics: Adult; Aerospace Medicine; Collateral Circulation; Combined Modality Therapy; Edema; Emergencies; Female; Heparin; Humans; Leg; Livedo Reticularis; Low Back Pain; Mobility Limitation; Phlebography; Rivaroxaban; Stockings, Compression; Tachycardia, Sinus; Thrombectomy; Thrombolytic Therapy; Tissue Plasminogen Activator; Tomography, X-Ray Computed; Ultrasonography, Doppler; Vena Cava, Inferior; Venous Thrombosis

Topics: Administration, Oral; Antibodies, Monoclonal, Humanized; Antithrombins; Blood Loss, Surgical; Cerebral Hemorrhage; Clinical Trials as Topic; Dabigatran; Drug Approval; Emergencies; Factor Xa; Factor Xa Inhibitors; Hemorrhage; Humans; Pyrazoles; Pyridines; Pyridones; Recombinant Proteins; Rivaroxaban; Thiazoles; United States; United States Food and Drug Administration

Previous trials investigating usage of four-factor prothrombin complex concentrate (4F-PCC) excluded patients with various thrombotic risk factors. The objective of this study was to evaluate the safety and effectiveness of 4F-PCC in a real-world setting based on an institutional protocol that does not have strict exclusion criteria.. This was a retrospective study of adult patients who received 4F-PCC. The primary outcome was a confirmed thromboembolism within 14 days after 4F-PCC administration. Secondary outcomes included international normalized ratio (INR) correction to <1.5 at first draw and incidence of INR rebound for patients undergoing reversal of warfarin and hemostatic effectiveness for patients experiencing a bleed.. Ninety-three patients received 4F-PCC. Sixty-three (67.7%) were reversed for bleeding and 30 (32.3%) for surgery. Eleven patients (11.8%) developed a thromboembolism within 14 days. The median (interquartile range) time to event was 5 (2-7) days. Significant risk factors were heparin-induced thrombocytopenia (P= .01) and major surgery within 14 days (P= .02), as well as the presence of >6 thrombotic risk factors (P= .01). For patients post-warfarin reversal, 45/63 (71.4%) achieved INR correction at first draw, 55/63 (87.3%) achieved INR correction within 24 hours, and 14/55 (25.5%) experienced INR rebound. Of these 14 patients, 8 (57.1%) did not receive concomitant vitamin K.. 4F-PCC was associated with a notable thromboembolic risk. All patient-specific risk factors should be considered prior to administration. 4F-PCC remains a useful agent for warfarin reversal. Lack of concomitant vitamin K may contribute to INR rebound.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Factors; Cardiac Surgical Procedures; Dabigatran; Emergencies; Female; Gastrointestinal Hemorrhage; Heart Transplantation; Hemorrhage; Hemostatics; Heparin; Humans; Incidence; International Normalized Ratio; Intracranial Hemorrhages; Laparotomy; Male; Middle Aged; Preoperative Care; Pyrazoles; Pyridones; Retrospective Studies; Risk Factors; Rivaroxaban; Surgical Procedures, Operative; Thrombocytopenia; Thromboembolism; Vitamin K; Warfarin

Topics: Administration, Oral; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Emergencies; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Treatment Outcome

Rivaroxaban is a once-daily oral anticoagulant currently indicated for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. It is also indicated for the prevention and treatment of venous or pulmonary thromboembolism. Despite the known advantages of rivaroxaban over standard therapy, this treatment is not exempt from bleeding. We present the case of a 51-year-old woman with arterial hypertension and paroxysmal atrial fibrillation anticoagulated with rivaroxaban 20 mg o.d. Patient was admitted to the emergency department because of intense abdominal pain, high temperature, hypotension, tachycardia and a big tumor in the right abdominal area. The ultrasonic exam showed a big collection in the thoracic and abdominal area, compatible with hematoma. Due to clinical instability, urgent surgery was required. Based on the results of coagulation parameters (PT: 17.5 s), the time from the last rivaroxaban dose was taken, and the patient weight, nonactivated prothrombin complex concentrate at a single dose of 1000 IU was administrated intravenously 1 h before the surgery. PT value decreased to normal value (13.5 s), and surgery was performed without any bleeding complication. The management of patients treated with rivaroxaban who require urgent surgery is discussed in this report.

Topics: Abdomen; Administration, Oral; Atrial Fibrillation; Blood Coagulation; Blood Coagulation Factors; Drug Administration Schedule; Embolism; Emergencies; Factor Xa Inhibitors; Female; Hematoma; Humans; Injections, Intravenous; Middle Aged; Rivaroxaban; Tachycardia, Paroxysmal; Tomography, X-Ray Computed; Ultrasonography

New oral anticoagulants (NOACs) offer an alternative to warfarin for preventing stroke in patients with atrial fibrillation. NOACs are expected to replace warfarin and other vitamin K antagonists for most of their indications in the future. Knowledge of the use of NOACs in the perioperative period is important for optimal care.. Studies that reported on the use of NOACs were identified, focusing on evidence-based guidance relating to the perioperative period. PubMed was searched for relevant articles published between January 2000 and January 2014.. The anticipated expanded clinical use of NOACs such as rivaroxaban (Xarelto™), apixaban (Eliquis™) and dabigatran (Pradaxa™) has the potential to simplify perioperative anticoagulant management because of fewer drug-drug interactions, rapid onset of action, predictable pharmacokinetics and relatively short half-lives. However, coagulation status cannot be monitored by international normalized ratio and no antidotes are currently available. In elective surgery, it is important to discontinue the use of NOACs, with special consideration of renal function as route of elimination. Guidelines for the management of bleeding complications in patients on NOACs are provided, and may be considered for trauma and emergency surgery. Haemodialysis could be considered for bleeding with use of dabigatran. Better options for reversal of the effects of NOACs when bleeding occurs may follow with novel drugs.. Management of NOACs in elective and emergency conditions requires knowledge of time of last intake of drug, current renal function and the planned procedure in order to assess the overall risk of bleeding. Currently no antidote exists to reverse the effects of these drugs.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Biological Availability; Clinical Trials as Topic; Dabigatran; Drug Monitoring; Elective Surgical Procedures; Emergencies; Half-Life; Hemorrhage; Humans; Medication Adherence; Morpholines; Preoperative Care; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Thiophenes; Time Factors; Warfarin

New oral anticoagulants (NOAC) are becoming available as alternatives to warfarin to prevent systemic embolism in patients with non-valvular atrial fibrillation and for the treatment and prevention of venous thromboembolism. An in-depth understanding of their pharmacology is invaluable for appropriate prescription and optimal management of patients receiving these drugs should unexpected complications (such as bleeding) occur, or the patient requires urgent surgery. The Australasian Society of Thrombosis and Haemostasis has set out to inform physicians on the use of the different NOAC based on current available evidence focusing on: (i) selection of the most suitable patient groups to receive NOAC, (ii) laboratory measurements of NOAC in appropriate circumstances and (iii) management of patients taking NOAC in the perioperative period, and strategies to manage bleeding complications or 'reverse' the anticoagulant effects for urgent invasive procedures.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Blood Coagulation Tests; Blood Loss, Surgical; Contraindications; Dabigatran; Drug Interactions; Drug Monitoring; Drug Substitution; Elective Surgical Procedures; Emergencies; Hematoma, Epidural, Spinal; Hemorrhage; Humans; Kidney Diseases; Liver Diseases; Morpholines; Patient Selection; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Thrombophilia

To describe the pharmacologic agents and strategies used for urgent reversal of warfarin and the target-specific oral anticoagulants dabigatran, rivaroxaban, and apixaban.. To reverse the anticoagulant effects of warfarin in patients who are bleeding or need surgery, exogenous vitamin K (phytonadione) may be used in combination with another, shorter-acting intervention, such as fresh frozen plasma (FFP), prothrombin complex concentrate (PCC), recombinant factor VIIa, or activated PCC (aPCC). Three-factor PCC contains factors II, IX, and X in an inactivated form, and four-factor PCC also includes factor VII in an inactivated form. No four-factor PCC products are available in the United States, but aPCC, which contains the same four factors with factor VII provided in an activated form, is available. The intervention depends on the International Normalized Ratio, presence of bleeding, and need for and timing of surgery. Research suggests that clotting factor concentrates are more effective than FFP alone for warfarin reversal. These products also may be useful for reversing the effects of target-specific oral anticoagulants, but limited efficacy and safety data are available to support their use. The risks and benefits associated with these products need to be weighed before their use for reversal of dabigatran, rivaroxaban, or apixaban. Additional clinical data are needed to clearly define the role of concentrated clotting factor products in reversal and to determine the optimal clotting factor concentrate product and dose for urgent reversal of oral anticoagulation.. Phytonadione and clotting factor concentrates appear to have a role for reversal of warfarin, and limited evidence suggests that clotting factor concentrates could have a role in reversal of target-specific oral anticoagulants in an emergency situation.

Topics: Administration, Oral; Anticoagulants; Antifibrinolytic Agents; Antithrombins; Benzimidazoles; beta-Alanine; Blood Coagulation Factors; Blood Loss, Surgical; Dabigatran; Drug Therapy, Combination; Emergencies; Hemorrhage; Humans; International Normalized Ratio; Morpholines; Plasma; Pyrazoles; Pyridones; Rivaroxaban; Surgical Procedures, Operative; Thiophenes; Thromboembolism; Treatment Outcome; Vitamin K 1; Warfarin

Thromboprophylaxis with oral anticoagulants (OACs) is an important but underused element of atrial fibrillation (AF) treatment. Reduction of stroke risk with anticoagulants comes at the price of increased bleeding risk. Patients with AF receiving anticoagulants require heightened attention with transition from one care setting to another. Patients presenting for emergency care of anticoagulant-related bleeding should be triaged for the severity and source of the bleeding using appropriate measures, such as discontinuing the OAC, administering vitamin K, when appropriate, to reverse warfarin-induced bleeding, or administering clotting factors for emergent bleeding. Reversal of OACs in patients admitted to the hospital for surgery can be managed similarly to patients with bleeding, depending on the urgency of the surgical procedure. Patients with AF who are admitted for conditions unrelated to AF should be assessed for adequacy of stroke risk prophylaxis and bleeding risk. Newly diagnosed AF should be treated in nearly all patients with either warfarin or a newer anticoagulant. Patient education is critically important with all anticoagulants. Close adherence to the prescribed regimen, regular international normalized ratio testing for warfarin, and understanding the stroke risk conferred by both AF and aging are goals for all patients receiving OACs. Detailed handoff from the hospitalist to the patient's primary care physician is required for good continuity of care. Monitoring by an anticoagulation clinic is the best arrangement for most patients. The elderly, or particularly frail or debilitated patients who are transferring to long-term care, need a detailed transfer of information between settings, education for the patient and family, and medication reconciliation. Communication and coordination of care among outpatient, emergency, inpatient, and long-term care settings are vital for patients with AF who are receiving anticoagulants to balance stroke prevention and bleeding risk.

Topics: Administration, Oral; Aftercare; Aged; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Continuity of Patient Care; Dabigatran; Drug Monitoring; Drug Substitution; Emergencies; Hemorrhage; Humans; Morpholines; Patient Education as Topic; Rivaroxaban; Stroke; Thiophenes; Warfarin