scholarly journals Emergency Cardiac Surgery in Patients on Oral Anticoagulants

2021 ◽  
Author(s):  
Rami Akhrass ◽  
A. Marc Gillinov ◽  
Faisal Bakaeen ◽  
Scott Cameron ◽  
Jay Bishop ◽  
...  
Keyword(s):  
Circulatory Arrest ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Difficult Patient ◽  
Disseminated Intravascular Coagulopathy ◽  
Reversal Agents ◽  
Coagulation Profile ◽  
Intravascular Coagulopathy ◽  
Time To Onset ◽  
Case Basis

Emergency surgery, blood transfusion, and reoperation for bleeding have been associated with increased morbidity and mortality. Every effort is made to optimize patients preoperatively including cessation of oral anticoagulants in an attempt to normalize the coagulation profile. The recent explosive use of direct oral anticoagulants (DOACs) and antiplatelet medications has made the above more difficult. Cardiopulmonary bypass (CPB), with its associated fibrinolysis and platelet consumption, may exacerbate a pre-existing coagulopathy. In addition, the underlying surgical pathology, such as endocarditis accompanied by sepsis and disseminated intravascular coagulopathy (DIC) or aortic dissection requiring hypothermia and circulatory arrest, can aggravate an already challenged hematological profile. Ensuring a dry operative field upon entry by correcting the coagulopathy is offset by the concern of potentially hindering efforts to anticoagulate the patient in preparation for CPB, in addition to possibly creating a hypercoagulable state that could increase the risk of thromboembolic events. Management is challenging and decisions are typically made on a case-by-case basis. Surgery is delayed when possible and less invasive percutaneous options should be considered if feasible. If surgery is unavoidable, attention is paid to exercising meticulous techniques, avoiding excessive hypothermia, treating coexisting issues such as sepsis and correcting the coagulopathy with antidotes, reversal agents and blood products, with the understanding that a normal coagulation profile does not necessarily translate into hemostasis or the absence of thrombosis. Proper knowledge of the mechanism of action of the oral anticoagulants, available antidotes and their time to onset are essential in properly treating this difficult patient population.

scholarly journals Emergency Cardiac Surgery in Patients on Oral Anticoagulants and Antiplatelet Medications

2021 ◽  
Author(s):  
Rami Akhrass ◽  
A. Marc Gillinov ◽  
Faisal Bakaeen ◽  
Deena Akras ◽  
Scott Cameron ◽  
...  
Keyword(s):  
Prothrombin Complex Concentrate ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Operative Field ◽  
Operative Morbidity ◽  
Bleeding Management ◽  
Reversal Agents ◽  
Risk Of Bleeding ◽  
Heparin Resistance ◽  
Case Basis

Emergency surgery, blood transfusion, and reoperation for bleeding have been associated with increased operative morbidity and mortality. The recent increased use of direct oral anticoagulants and antiplatelet medications have made the above more challenging. In addition, cardiopulmonary bypass (CPB) with its associated hemodilution, fibrinolysis and platelet consumption may exacerbate the pre-existing coagulopathy and increase the risk of bleeding. Management decisions are typically made on a case-by-case basis. Surgery is delayed when possible and less invasive percutaneous options should be considered if feasible. Attention is paid to exercising meticulous techniques, avoiding excessive hypothermia and treating coexisting issues such as sepsis. Ensuring a dry operative field upon entry by correcting the coagulopathy with reversal agents is offset by the concern of potentially hindering efforts to anticoagulate the patient (heparin resistance) in preparation for CPB, in addition to possibly increasing the risk of thromboembolism. Proper knowledge of the anticoagulants, their reversal agents, and the usefulness of laboratory testing are all essential. Platelet transfusion remains mainstay for antiplatelet medications. Four-factor prothrombin complex concentrate is considered in patients on oral anticoagulants if CPB needs to be instituted quickly. Specific reversal agents such as idarucizumab and andexanet alfa can be considered if significant tissue dissection is anticipated such as redo sternotomy, but are costly and may lead to heparin resistance and anticoagulant rebound.

A Review on the Use of Reversal Agents of Direct Oral Anticogulant Drugs in Case of Gastrointestinal Bleeding

2020 ◽  
Vol 15 ◽  
Author(s):  
Veronica Ojetti ◽  
Angela Saviano ◽  
Mattia Brigida ◽  
Luisa Saviano ◽  
Alessio Migneco ◽  
...  
Keyword(s):  
Gastrointestinal Bleeding ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Medical Emergency ◽  
Management Approach ◽  
Emergency Setting ◽  
Reversal Agents ◽  
Life Threatening ◽  
Andexanet Alfa

Background : Major bleeding is a life-threatening condition and a medical emergency with high mortality risk. It is often the complication of anticoagulant’s intake. Anticoagulants are commonly used for the prevention and the treatment of thrombotic events. The standard therapy with vitamin K antagonist (warfarin) has been frequently replaced by direct oral anticoagulants (DOACs). The latter agents (rivaroxaban, apixaban, edoxaban, dabigatran, betrixaban) showed a better efficacy and safety compared to standard warfarin treatment and they are recommended for the reduction of ischemic stroke. Literature data reported a high risk of gastrointestinal bleeding with DOACs, in particular with dabigatran and rivaroxaban. In case of life-threatening gastrointestinal bleeding, these patients could benefit from the use of reversal agents. Methods: We performed an electronic search on PUBMED of the literature concerning reversal agents for DOACs and gastrointestinal bleeding in the Emergency Department from 2004 to 2020. AIM: This review summarizes the current evidences about three reversal agents idarucizumab, andexanet alfa and ciraparantag, and the use of the first two in the emergency setting in patients with an active major bleeding or who need urgent surgery to offer physicians indications for a better management approach in order to increase patient’s safety. Conclusion: Although these agents have been marketed for five years (idarucizumab) and two years (andexanet alfa) respectively, and despite guidelines considering antidotes as first-line agents in treating life-threatening hemorrhage when available, these antidotes seem to gain access very slowly in the clinical practice. Cost, logistical aspects and need for plasma level determination of DOAC for an accurate therapeutic use probably have an impact on this phenomenon.. An expert multidisciplinary bleeding team should be established so as to implement international guidelines based on local resources and organization.

scholarly journals Reversal Strategies for Intracranial Hemorrhage Related to Direct Oral Anticoagulant Medications

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Alok Dabi ◽  
Aristides P. Koutrouvelis
Keyword(s):  
Side Effects ◽  
Intracranial Hemorrhage ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Coagulation Cascade ◽  
Reversal Agents ◽  
United States Food ◽  
Life Threatening

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.

scholarly journals Assessing and Reversing the Effect of Direct Oral Anticoagulants on Coagulation

2020 ◽  
Vol 133 (1) ◽  
pp. 223-232
Author(s):  
Arielle Langer ◽  
Jean M. Connors
Keyword(s):  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Reversal Agents

This article presents a focused review of the available tests to assess the effect of direct oral anticoagulants on coagulation and the use of reversal agents in the perioperative setting for practicing anesthesiologists.

Abstract MP38: Intracerebral Hemorrhage Across the United States: Incidence and Mortality Trends From 1990 to 2017

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Augustin DeLago ◽  
Harpreet Singh ◽  
Arashdeep Rupal ◽  
Chinmay Jani ◽  
Arshi Parvez ◽  
...  
Keyword(s):  
United States ◽  
Intracerebral Hemorrhage ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
The United States ◽  
Mortality Trends ◽  
Reversal Agents ◽  
Incidence And Mortality ◽  
The Us

Background: Intracerebral Hemorrhage (ICH) accounts for 10% of strokes annually in the United States (US). Up-to-date trends in disease burden and regional variation remain unknown; especially after a dramatic increase in the use of direct oral anticoagulants (DOACs) since 2010. Our study reports updated incidence, mortality and mortality to incidence ratio (MIR) data related to ICH across the US. Methods: This observational study utilized the Global Burden of Disease database to determine age-standardized incidence (ASIR), death (ASDR) and MIR rates for ICH overall and for each state in the US from 1990-2017. All analyses were stratified by sex. Trends were analyzed using Joinpoint regression analysis, with presentation of estimated annual percentage changes (EAPCs) in ASIRs, ASDRs and MIRs over the observation period. Results: We observed an overall decrease in ASIRs, ASDRs and MIRs in both genders from 1990-2017, apart from female ASIRs and ASDRs in West Virginia and Kentucky. In 2017, the mean ASIR per 100,000 population for men was 25.67 and 19.17 for women. The 2017 mean ASDRs per 100,000 population for men and women were 13.96 and 11.35, respectively. The District of Columbia had the greatest decreases in ASIR EAPCs for males at -41.25% and females at -40.58%, and the greatest decreases in ASDR EAPCs for both males and females at -55.38% and -48.51%, respectively. The overall MIR during the study period decreased in males by -12.12% and females by -7.43%. However, MIR increased in males from 2014-2017 (EAPC +2.2% [95% CI +0.9%-+3.5%]) and in females from 2011-2017 (EAPC +1.0% [CI +0.7%-+1.4%]). Conclusion: This report reveals overall decreasing trends in incidence, mortality and MIR from 1990-2017. Notably, no significant change in mortality was found in the last 6 years of the study period, and MIR worsened in males from 2014-2017 and in females from 2011-2017, suggesting decreased ICH related survival lately. The substitution of vitamin K antagonists with DOACs is one possible explanation for a downtrend in incidence despite an aging population and increased use of anticoagulants. Limited access to reversal agents for DOACs is a potential reason for increase in MIR, however concrete deductions cannot be made owing to the observational nature of the study.

Anticoagulation in Acute Neurological Disease

2021 ◽  
Vol 41 (05) ◽  
pp. 530-540
Author(s):  
Cina Sasannejad ◽  
Kevin N. Sheth
Keyword(s):  
Intracerebral Hemorrhage ◽  
Neurological Disease ◽  
Sinus Thrombosis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Cerebral Venous Sinus Thrombosis ◽  
Metabolic Complications ◽  
Reversal Agents ◽  
Clinical Scenarios ◽  
Patients At Risk

AbstractWhile anticoagulation and its reversal have been of clinical relevance for decades, recent academic and technological advances have expanded the repertoire of its application in neurological disease. The advent of direct oral anticoagulants provides effective, mechanistically elegant, and relatively safer therapeutic options than warfarin for eligible patients at risk for neurological sequelae of prothrombotic states, particularly given the recent availability of corresponding reversal agents. In this review, we examine the provenance, indications, safety, and reversal tools for anticoagulant medications in the context of neurological disease, with specific attention to acute ischemic stroke, cerebral venous sinus thrombosis, and intracerebral hemorrhage. We will use specific clinical scenarios to illustrate the complex factors that must be considered in the use of anticoagulation, including intracranial pathology such as intracerebral hemorrhage, traumatic brain injury, or malignancy; metabolic complications such as chronic kidney disease; pregnancy; and advanced age.

scholarly journals Difficult Intraoperative Heparinization Following Andexanet Alfa Administration

2019 ◽  
Vol 3 (4) ◽  
pp. 390-394 ◽  
Author(s):  
C. James Watson ◽  
Sara Zettervall ◽  
Matthew Hall ◽  
Michael Ganetsky
Keyword(s):  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Hemodynamic Instability ◽  
The United States ◽  
Major Hemorrhage ◽  
Reversal Agents ◽  
Abdominal Aortic ◽  
United States Food ◽  
Andexanet Alfa

Direct oral anticoagulants are now commonplace, and reversal agents are recently becoming available. Andexanet alfa (AnXa), approved by the United States Food and Drug Administration in 2018, is a novel decoy molecule that reverses factor Xa inhibitors in patients with major hemorrhage. We present a case of a 70-year-old man taking rivaroxaban with hemodynamic instability from a ruptured abdominal aortic aneurysm. He received AnXa prior to endovascular surgery, and intraoperatively he could not be heparinized for graft placement. Consideration should be given to the risks and benefits of AnXa administration in patients who require anticoagulation after hemorrhage has been controlled.

scholarly journals Reversal of direct oral anticoagulants: a practical approach

Hematology ◽  
2016 ◽  
Vol 2016 (1) ◽  
pp. 612-619 ◽  
Author(s):  
Andrew W. Shih ◽  
Mark A. Crowther
Keyword(s):  
Phase 1 ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Antibody Fragment ◽  
Factor Xa ◽  
Factor Xa Inhibitors ◽  
Severe Bleeding ◽  
Thrombin Time ◽  
Ancillary Benefits ◽  
Reversal Agents

Abstract Direct oral anticoagulants (DOACs) have at least noninferior efficacy compared with other oral anticoagulants and have ancillary benefits, including overall better safety profiles, lack of the need for routine monitoring, rapid onset of action, and ease of administration. Reversal of these agents may be indicated in certain situations such as severe bleeding and for perioperative management. DOAC-associated bleeding should be risk stratified: patients with moderate or severe bleeding should have the DOAC discontinued and reversal strategies should be considered. Laboratory testing has limited utility in the acute management of bleeding; thrombin time and activated partial thromboplastin time may be useful for excluding clinically relevant levels of dabigatran. Prothrombin time is potentially useful for rivaroxaban and edoxaban, but calibrated anti-Xa assays are optimal for determining clinically relevant levels of factor Xa inhibitors. Because specific reversal agents are not widely available, supportive care and interventions for local hemostasis remain the cornerstones of therapy in the patient with DOAC-associated bleeding. Nonspecific reversal agents should be considered only in the event of severe bleeding because their efficacy is unknown, and they are associated with risk of thrombosis. Recent results from phase 3/4 studies demonstrate efficacy for an antidote to dabigatran (idarucizumab, a monoclonal antibody fragment with specificity for dabigatran) and an antidote to factor Xa inhibitors (andexanet alfa, a recombinant and inactive form of factor Xa that binds inhibitors). A universal reversal agent (ciraparantag) for many anticoagulants, including the DOACs, shows promise in results from phase 1 and 2 studies.

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