Direct (new) oral anticoagulants (DOACs): Drawbacks, bleeding and reversal

2021 ◽  
Vol 19 ◽  
Author(s):  
Ozgur Karcioglu ◽  
Sehmus Zengin ◽  
Bilgen Ozkaya ◽  
Eylem Ersan ◽  
Sarper Yilmaz ◽  
...  
Keyword(s):  
Oral Anticoagulants ◽  
Fresh Frozen Plasma ◽  
New Oral Anticoagulants ◽  
Coagulation Cascade ◽  
Thrombin Inhibitor ◽  
Severe Bleeding ◽  
Prothrombin Complex Concentrates ◽  
Clinical Scenarios ◽  
Fresh Frozen ◽  
Frozen Plasma

Background and Objective: Direct (new) Oral Anticoagulants (DOACs) have emerged as a contemporary and promising option in the treatment of thromboses and VTE, while protecting the coagulation cascade against untoward bleeding events. They are used in the management and prophylaxis of Venous Thromboembolism (VTE) and other thrombotic diseases. The most prominent complication of these agents is bleeding. These agents have similar or lower rates of major intracranial hemorrhages, while they had a higher risk of major gastrointestinal bleeding when compared to warfarin. This manuscript is aimed to revise and update the literature findings to outline the side effects of DOACs in various clinical scenarios. Methods: A narrative review of currently published studies was performed. Online database searches were performed for clinical trials published before July 2021, on the efficacy and adverse effects attributed to the anticoagulant treatment, especially DOACs. A literature search via electronic databases was carried out, beginning with the usage of the agents in the Western Languages papers. The search terms initially included direct (new) oral anticoagulants, dabigatran, rivaroxaban, apixaban, edoxaban, idarucizumab, andexanet, prothrombin complex concentrates, and fresh frozen plasma. Papers were examined for methodological soundness before being included. Results: Severe bleeding episodes require aggressive interventions for successful management. Therefore, bleeding should be evaluated in special regard to the location and rate of hemorrhage, and total volume of blood loss. Patient's age, weight and organ dysfunctions (e.g., kidney/liver failure or chronic respiratory diseases) directly affect the clinical course of overdose. Conclusion: Management recommendations for hemorrhage associated with DOAC use vary, depending on the class of the culprit agent (direct thrombin inhibitor vs. FXa inhibitor), the clinical status of the patient (mild/ moderate vs. severe/life-threatening), and capabilities of the institution. Specific reversal agents (i.e., idarucizumab and andexanet alfa) can be used if available, while prothrombin complex concentrates, fresh frozen plasma and/ or tranexamic acid can also be employed as nonspecific replacement agents in the management of DOAC-related bleeding diathesis.

Using Plasma and Prothrombin Complex Concentrates

2019 ◽  
Vol 46 (01) ◽  
pp. 032-037
Author(s):  
Jerrold H. Levy ◽  
Kamrouz Ghadimi ◽  
Nathan H. Waldron ◽  
Jean M. Connors
Keyword(s):  
Multimodal Therapy ◽  
Oral Anticoagulants ◽  
Traumatic Injury ◽  
Fresh Frozen Plasma ◽  
Prothrombin Complex Concentrates ◽  
Multiple Risks ◽  
Fresh Frozen ◽  
Circulatory Overload ◽  
Frozen Plasma ◽  
Management Algorithms

AbstractSurgical patients, following procedural interventions or traumatic injury, often bleed due to ongoing blood loss or coagulopathy. Volume resuscitation and transfusion management are critical for the massively bleeding patient. While transfusions may correct coagulopathy, they carry multiple risks including circulatory overload and transfusion-related acute lung injury. Factor concentrates, specifically prothrombin complex concentrates (PCCs), are often used as part of multimodal therapy for bleeding along with laboratory testing to rapidly assess underlying coagulopathy. Although they are commonly used as part of management algorithms, studies evaluating their efficacy against fresh frozen plasma (FFP) or other potential therapies are needed. Further, PCCs are indicated to treat the coagulopathy associated with non-vitamin K oral anticoagulants in the perioperative setting. The focus of this commentary will be the perioperative use of PCCs, plasma, and FFP.

scholarly journals Management of the Bleeding Patient Receiving New Oral Anticoagulants: A Role for Prothrombin Complex Concentrates

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Lisa M. Baumann Kreuziger ◽  
Joseph C. Keenan ◽  
Colleen T. Morton ◽  
David J. Dries
Keyword(s):  
Recombinant Factor Viia ◽  
Factor Viia ◽  
Oral Anticoagulants ◽  
New Oral Anticoagulants ◽  
Coagulation Cascade ◽  
Clotting Factors ◽  
Prothrombin Complex Concentrates ◽  
Clotting System ◽  
Clinical Trial Evidence

Ease of dosing and simplicity of monitoring make new oral anticoagulants an attractive therapy in a growing range of clinical conditions. However, newer oral anticoagulants interact with the coagulation cascade in different ways than traditional warfarin therapy. Replacement of clotting factors will not reverse the effects of dabigatran, rivaroxaban, or apixaban. Currently, antidotes for these drugs are not widely available. Fortunately, withholding the anticoagulant and dialysis are freqnently effective treatments, particularly with rivaroxaban and dabigatran. Emergent bleeding, however, requires utilization of Prothrombin Complex Concentrates (PCCs). PCCs, in addition to recombinant factor VIIa, are used to activate the clotting system to reverse the effects of the new oral anticoagulants. In cases of refractory or emergent bleeding, the recommended factor concentrate in our protocols differs between the new oral anticoagulants. In patients taking dabigatran, we administer an activated PCC (aPCC) [FELBA] due to reported benefit in human in vitro studies. Based on human clinical trial evidence, the 4-factor PCC (Kcentra) is suggested for patients with refractory rivaroxaban- or apixaban-associated hemorrhage. If bleeding continues, recombinant factor VIIa may be employed. With all of these new procoagulant agents, the risk of thrombosis associated with administration of factor concentrates must be weighed against the relative risk of hemorrhage.

Prothrombin Complex Concentrates are Superior to Fresh Frozen Plasma for Emergency Reversal of Vitamin K Antagonists: A Meta-Analysis in 2606 Subjects

Drugs ◽  
2019 ◽  
Vol 79 (14) ◽  
pp. 1557-1565 ◽  
Author(s):  
Robert Hill ◽  
Thang S. Han ◽  
Irina Lubomirova ◽  
Nikhil Math ◽  
Paul Bentley ◽  
...  
Keyword(s):  
Vitamin K ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Fresh Frozen Plasma ◽  
Prothrombin Complex Concentrates ◽  
Fresh Frozen ◽  
Frozen Plasma

Anticoagulants and antithrombotics in critical illness

2016 ◽  
Author(s):  
Vickie McDonald ◽  
Marie Scully
Keyword(s):  
Platelet Count ◽  
Critical Illness ◽  
Prothrombin Complex Concentrate ◽  
Oral Anticoagulants ◽  
Fresh Frozen Plasma ◽  
Heparin Therapy ◽  
Heparin Induced Thrombocytopenia ◽  
Routine Monitoring ◽  
Fresh Frozen ◽  
Frozen Plasma

Coagulation is best thought of using the cell-based model of coagulation. Patients commenced on heparin therapy should have their platelet count monitored early because of the risk of heparin-induced thrombocytopenia, which can occur on any type or dose of heparin. Emergency reversal of warfarin should be with prothrombin complex concentrate (containing factors II, VII, IX, and X) and not fresh frozen plasma. New oral anticoagulants have the advantage of predictable pharmacokinetics and do not require routine monitoring, but optimal reversal strategies for these agents are not clear. Thrombolytic agents lead to variable degrees of systemic lysis, which may cause haemorrhage, including intracerebral haemorrhage

Prophylactic correction of the international normalized ratio in neurosurgery: a brief review of a brief literature

2011 ◽  
Vol 114 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Kelly L. West ◽  
Cory Adamson ◽  
Maureane Hoffman
Keyword(s):  
Bleeding Risk ◽  
International Normalized Ratio ◽  
Fresh Frozen Plasma ◽  
Coagulation Cascade ◽  
Bleeding Tendency ◽  
Invasive Procedures ◽  
Clinical Tool ◽  
Clotting Factors ◽  
Fresh Frozen ◽  
Frozen Plasma

Prophylactic fresh-frozen plasma (FFP) transfusion is often undertaken in hemodynamically stable patients with a minimally elevated international normalized ratio (INR) prior to invasive procedures, despite little evidence in support of this practice. The authors review the current literature in an attempt to clarify best clinical practice with regard to this issue. Although the activated partial thromboplastin time and prothrombin time–INR are useful laboratory tests to measure specific clotting factors in the coagulation cascade, in the absence of active bleeding or a preexisting coagulopathy, their utility as predictors of overall bleeding risk is limited. Several studies have shown an imperfect correlation between mild elevations in the INR and subsequent bleeding tendency. Furthermore, FFP transfusion is not always sufficient to achieve normal INR values in patients who have mild elevations (< 2) to begin with. Finally, there are risks associated with FFP transfusion, including potential transfusion-associated [disease] exposures as well as the time delay imposed by laboratory testing and transfusion administration prior to initiation of procedures. The authors propose that the current concept of a “normal” INR value warrants redefinition to make it a more meaningful clinical tool. Based on their review of the literature, the authors suggest that in a hemodynamically stable patient population there is a range of mildly prolonged INR values for which FFP transfusion is not beneficial, and is potentially harmful.

scholarly journals Evaluation of Thromboelastometry in Sepsis in Correlation With Bleeding During Invasive Procedures

2017 ◽  
Vol 24 (6) ◽  
pp. 993-997 ◽  
Author(s):  
Pavel Lukas ◽  
Miroslav Durila ◽  
Jakub Jonas ◽  
Tomas Vymazal
Keyword(s):  
Venous Catheter ◽  
International Normalized Ratio ◽  
Fresh Frozen Plasma ◽  
University Hospital ◽  
Severe Bleeding ◽  
Invasive Procedures ◽  
Extrinsic Pathway ◽  
Fresh Frozen ◽  
Assigned Number ◽  
Frozen Plasma

Prolongation of prothrombin time (PT) is often encountered in patients with sepsis. On the other hand, thromboelastometry as a global coagulation test might yield normal results. The aim of our study was to evaluate whether prolonged PT in the presence of normal thromboelastometry parameters is associated with severe bleeding in patients with sepsis undergoing invasive procedures. In patients with sepsis undergoing low-risk bleeding invasive procedures (central venous catheter placement, dialysis catheter insertion, drain insertion, and so on) or high-risk bleeding invasive procedures (surgical tracheostomy, surgical laparotomy, thoracotomy, and so on), coagulation was assessed by thromboelastometry using EXTEM test (test for evaluation of the extrinsic pathway of coagulation, contains activator of extrinsic pathway) and with PT. For period of years 2013 to 2016, we assessed occurrence of severe bleeding during those procedures and 24 hours later in patients with prolonged PT and normal thromboelastometry results. This retrospective study was performed at Department of Anaesthesiology and Intensive Care Medicine of Motol University Hospital in Prague. Data from 76 patients with sepsis were analyzed. Median value of international normalized ratio (INR) was 1.59 (min—1.3 and max—2.56), and median value of prothrombin ratio (PR) was 1.5 (min—1.23 and max—2.55) with normal thromboelastometry finding. Despite prolonged INR/PR, no severe bleeding was observed during invasive procedures. Our data show that sepsis may be accompanied by normal thromboelastometry results, despite prolonged values of PT, and invasive procedures were performed without severe bleeding. This approach to coagulation assessment in sepsis may reduce administration of fresh frozen plasma to the patients. The study was registered at Clinical Trials.gov with assigned number NCT02971111.

scholarly journals Spontaneous Sublingual Haematoma in a 90-year Old Patient: A Complication of Direct Oral Anticoagulants

2020 ◽  
Vol 6 (2) ◽  
pp. 111-114
Author(s):  
Johannes Daniël Cnossen ◽  
Jeannette Fenna Schoonderbeek ◽  
Maaike Muller
Keyword(s):  
Rare Complication ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Upper Airway ◽  
Chronic Atrial Fibrillation ◽  
Fresh Frozen Plasma ◽  
Nasal Intubation ◽  
Fresh Frozen ◽  
Life Threatening ◽  
Frozen Plasma

AbstractSublingual haematoma is a rare complication of anticoagulants and can be life-threatening. As the number of prescribed anticoagulants is increasing, the incidence of complications of these drugs will continue to increase. A report of a sublingual haematoma in an elderly patient with chronic atrial fibrillation treated with edoxban (Lixiana ©, Daiichi Sankyo Europe GmbH, München, Germany) is reported. A 90-year male presented at the emergency department with an obstructed upper airway due to a sublingual haematoma. The patient received tranexamic acid, prothrombin complex, and fresh frozen plasma. After fiberoptic nasal intubation, the patient was monitored in the intensive care unit. After four days, the patient was extubated, and after six days, the swelling resolved completely. Complications of anticoagulants are rare but can be life-threatening. Recognition of an endangered airway and reversing the effects of the anticoagulant are essential. Surgical evacuation of the haematoma could be considered but is not necessary.

scholarly journals Pathogenesis, diagnosis, prevention and treatment of disseminated intravascular coagulation syndrome in COVID-19 infection

2020 ◽  
Vol 92 (11) ◽  
pp. 51-56
Author(s):  
P. A. Vorobyev ◽  
A. P. Momot ◽  
L. S. Krasnova ◽  
A. P. Vorobiev ◽  
A. K. Talipov
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Fresh Frozen Plasma ◽  
Clotting Factors ◽  
Intravascular Coagulation ◽  
Prevention And Treatment ◽  
Fresh Frozen ◽  
Direct Anticoagulants ◽  
Frozen Plasma

Aim. Clinical characteristics of disseminated intravascular coagulation (DIC) in COVID-19 infection and assessment of the effectiveness of complex therapy for this syndrome at the stages of prevention and treatment of various complications. Materials and methods. The study of publications was carried out through search engines on the Internet using keywords. To diagnose the infection, the COVID-19 program was used on the MeDiCase platform, which is publicly available on www.medicase.pro, which suggests a diagnosis with a sensitivity of 89.47%. The study included 85 patients with acute COVID-19 with mild to moderate disease, aged 11 to 81 years. The presence of the pathogen was confirmed immunologically in 12% of patients; in other cases, the diagnosis was based on the results of an automated survey in the MeDiCase system. All patients, according to the MGNOT recommendations, were prescribed one of the oral direct anticoagulants - Eliquis at a dose of 5 mg 2 times a day, Ksarelto at a dose of 10 mg 2 times a day or Pradax at a dose of 110 mg 2 times a day for at least 2 weeks. All other drugs with antiviral, immunomodulatory effects, antibiotics were canceled. Results. The presence of DIC is substantiated by the morphological picture of changes in organs and tissues, clinical (hematoma-petechial type of bleeding in combination with thromboembolic syndrome and the presence of thrombovasculitis) and laboratory changes: an increase in the level of soluble fibrin-monomer complexes, D-dimer, hyperfibrinogenaemia, less often - thrombocytopenia, violation of fibrinolytic activity. The phenomenon of consumption of clotting factors and profuse bleeding are rare. Direct anticoagulants, fresh frozen plasma transfusions and plasmapheresis are used in the treatment of disseminated intravascular coagulation. The paper presents its own positive results of early prescription at the outpatient stage of direct oral anticoagulants in prophylactic doses (no case of disease progression), individual cases of the use of fresh frozen plasma and plasapheresis. Conclusion. DIC syndrome with the development of thrombovasculitis is the most important pathogenetic mechanism for the development of microthrombotic and hemorrhagic disorders in organs during infection with COVID-19, leading to dysfunction of the lungs, brain and other nerve tissues, kidneys, thromboembolic complications, etc. Many symptoms of the disease may be associated with a violation of the nervous regulation of the functions of organs and systems. Prevention of thrombovasculitis is effective already at the stage of the first manifestation of the disease with the outpatient use of direct anticoagulants (oral, low molecular weight heparins). In case of more severe manifestations (complications) of the disease, additional use of freshly frozen plasma and plasmapheresis is effective.

scholarly journals An Institutional Survey of Warfarin Reversal in the Setting of Life-Threatening Bleeds

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4981-4981
Author(s):  
Ian Garrahy ◽  
Tushar Pawar ◽  
Anthony Donato ◽  
Amber Stevenson ◽  
Daniel Forman
Keyword(s):  
Conflicts Of Interest ◽  
Factor Viia ◽  
Fresh Frozen Plasma ◽  
P Value ◽  
Anticoagulation Management ◽  
Clinical Scenarios ◽  
Fresh Frozen ◽  
Life Threatening ◽  
Warfarin Reversal ◽  
Frozen Plasma

Introduction: The bleeding risk of warfarin is well known. Therapeutic options for warfarin reversal in life-threatening bleeds include fresh frozen plasma (FFP), recombinant factor VIIa (rFVIIa), and prothrombin complex concentrate (PCC). Despite the theoretical advantage and clinical evidence supporting PCC, it is not widely used in the US. Methods: An online anonymous questionnaire was sent to all providers in the Tower Health System asking them about their practice, specialty, degree, years in practice, and basic questions regarding their comfort and frequency of prescribing anticoagulants. The questionnaire also asked the providers how they would manage ten various clinical scenarios related to anticoagulation management. One question specifically addressed the management of warfarin reversal in an 85-year-old presenting with hemorrhagic shock. Analysis of variance was used to compare the scoring means between groups while linear regression and Pearson's correlation coefficient measured the relationship between years of practice and test scores. Results: Out of 404 responders, 232 (57.4%) selected an incorrect answer and 212 (52.5%) incorrectly selected fresh frozen plasma as the answer to the question (see uploaded image) that addressed warfarin reversal in the setting of major bleeding. Those providers who answered this question correctly and those who answered it incorrectly had mean scores of 68.26% and 52.16% respectively on the overall survey (p value 0.000). Conclusion: As compared to FFP, the use of PCC for warfarin reversal is associated with a significant reduction in all-cause mortality. This project demonstrates a professional practice gap and serves to highlight an area in medicine where many providers are not practicing in accordance with evidence-based practice. Furthermore, this particular question from the survey discovered that providers who performed better on the survey were more likely to answer questions regarding anticoagulation reversal correctly. Figure Disclosures No relevant conflicts of interest to declare.

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