The New Direct Oral Anticoagulants in Special Indications: Rationale and Preliminary Data in Cancer, Mechanical Heart Valves, Anti-phospholipid Syndrome, and Heparin-Induced Thrombocytopenia and Beyond

2014 ◽  
Vol 51 (2) ◽  
pp. 152-156 ◽  
Author(s):  
Lorenzo Alberio
Keyword(s):  
Preliminary Data ◽  
Heart Valves ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Mechanical Heart Valves ◽  
Heparin Induced Thrombocytopenia ◽  
Anti Phospholipid Syndrome

scholarly journals Heparin is more effective than apixaban in inhibiting in vitro contact activated coagulation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M.M Engelen ◽  
C Van Laer ◽  
M Jacquemin ◽  
C Vandenbriele ◽  
K Peerlinck ◽  
...  
Keyword(s):  
Thrombin Generation ◽  
Heart Valves ◽  
Thrombus Formation ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Coagulation Factor ◽  
Mechanical Heart Valves ◽  
Contact Activation

Abstract Introduction Contact of blood with artificial surfaces such as mechanical support devices, catheters, and mechanical heart valves activates the contact activation (CA) pathway of coagulation. Furthermore, recent animal data and clinical studies suggest a more important contribution of CA in pathological thrombus formation in other cardiovascular diseases. Direct oral anticoagulants (DOACs) are recommended as first-line treatment in most patients who require long-term anticoagulation. However, because DOACs directly inhibit a single downstream coagulation factor (thrombin (fXIIa) or factor Xa (fXa)), it has been suggested that their efficacy could be reduced in the presence of strong activation of the CA pathway as compared to anticoagulants that target multiple, more upstream located coagulation factors. Purpose To compare the efficacy of a DOAC (apixaban) and heparin to suppress thrombin generation in the presence of strong CA pathway activation. Methods Pooled platelet-poor plasma was spiked with either apixaban (dissolved in DMSO and PBS) or unfractionated heparin to achieve therapeutic plasma levels. SynthASil, a commercially available mixture of phospholipids and silica, was used to stimulate the CA pathway in two different dilutions (1–80 and 5–80). Downstream coagulation was accessed by Thrombin Generation Test using Thrombinoscope by Stago and associated Thrombin Calibrator (activity 640 nM). The endogenous thrombin potential (area under the thrombin generation curve; ETP), peak thrombin generation (PTG), time to peak (ttPeak) and time to start (ttStart) were accessed. Results With decreasing concentrations of apixaban, stimulation with the lower dose SynthASil reveals an increasing ETP and PTG. As expected, ttPeak and ttStart decreased. Even supratherapeutic levels of apixaban (i.e. 1120 ng/mL) could not inhibit thrombin from being generated, in striking contrast with UFH where no thrombin was formed. Using a five times higher dose of SynthASil showed comparable ETP for all concentrations of apixaban, allocated around the control value. PTG, however, slightly increased with decreasing concentrations of apixaban. ttPeak and ttStart slightly decreased. Except for the subtherapeutic UFH concentration of 0,114 IU/mL, no thrombin was generated with UFH. Conclusion UFH is more effective in inhibiting downstream thrombin generation compared to apixaban as a response to activation of the CA pathway in vitro. These findings could help explain why direct inhibitors were not able to show non-inferiority in patients with mechanical heart valves and support the development of specific CA pathway inhibitors for patients with conditions that activate the CA pathway. Thrombin generation curves Funding Acknowledgement Type of funding source: None

scholarly journals Potentially inappropriate prescribing of DOACs to patients with mechanical heart valves: a federated analysis of 57.9 million patients' primary care records in situ using OpenSAFELY

2021 ◽  
Author(s):  
◽  
Louis Fisher ◽  
Victoria Speed ◽  
Helen J Curtis ◽  
Christopher T Rentsch ◽  
...  
Keyword(s):  
Heart Valve ◽  
Heart Valves ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Inappropriate Prescribing ◽  
Mechanical Heart Valve ◽  
Mechanical Heart Valves ◽  
Audit And Feedback ◽  
National Guidance

National guidance was issued during the COVID-19 pandemic to switch patients on warfarin to direct oral anticoagulants (DOACs) where appropriate as these require less frequent blood testing. DOACs are not recommended for patients with mechanical heart valves. We conducted a retrospective cohort study of DOAC prescribing in people with a record of a mechanical heart valve between September 2019 and May 2021, and describe the characteristics of this population. We identified 15,457 individuals with a mechanical heart valve recorded in their records, of whom 1058 (6.8%) had been prescribed a DOAC during the study period. 767 individuals with a record of a mechanical heart valve were currently prescribed a DOAC as of May 31st 2020. This is suggestive of inappropriate prescribing of DOACs in individuals with mechanical heart valves. Direct alerts have been issued to clinicians through their EHR software informing the issue. We show that the OpenSAFELY platform can be used for rapid audit and feedback to mitigate the indirect health impacts of COVID-19 on the NHS. We will monitor changes in prescribing for this risk group over the following months.

scholarly journals Recent Advances in Anticoagulant Treatment of Immune Thrombosis: A Focus on Direct Oral Anticoagulants in Heparin-Induced Thrombocytopenia and Anti-Phospholipid Syndrome

2021 ◽  
Vol 23 (1) ◽  
pp. 93
Author(s):  
Julie Carré ◽  
Georges Jourdi ◽  
Nicolas Gendron ◽  
Dominique Helley ◽  
Pascale Gaussem ◽  
...  
Keyword(s):  
Retrospective Studies ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Current Treatment ◽  
Prothrombotic State ◽  
Heparin Induced Thrombocytopenia ◽  
Need For Treatment ◽  
Randomized Controlled ◽  
Anti Phospholipid Syndrome

For more than 10 years, direct oral anticoagulants (DOACs) have been increasingly prescribed for the prevention and treatment of thrombotic events. However, their use in immunothrombotic disorders, namely heparin-induced thrombocytopenia (HIT) and antiphospholipid syndrome (APS), is still under investigation. The prothrombotic state resulting from the autoimmune mechanism, multicellular activation, and platelet count decrease, constitutes similarities between HIT and APS. Moreover, they both share the complexity of the biological diagnosis. Current treatment of HIT firstly relies on parenteral non-heparin therapies, but DOACs have been included in American and French guidelines for a few years, providing the advantage of limiting the need for treatment monitoring. In APS, vitamin K antagonists are conversely the main treatment (+/- anti-platelet agents), and the use of DOACs is either subject to precautionary recommendations or is not recommended in severe APS. While some randomized controlled trials have been conducted regarding the use of DOACs in APS, only retrospective studies have examined HIT. In addition, vaccine-induced immune thrombotic thrombocytopenia (VITT) is now a part of immunothrombotic disorders, and guidelines have been created concerning an anticoagulant strategy in this case. This literature review aims to summarize available data on HIT, APS, and VITT treatments and define the use of DOACs in therapeutic strategies.

scholarly journals Changes in Prescribing Antithrombotic Therapy in Patients with Atrial Fibrillation in the Multidisciplinary Hospital in Volgograd from 2012 to 2020

2022 ◽  
Vol 17 (6) ◽  
pp. 831-836
Author(s):  
A. S. Gerasimenko ◽  
O. V. Shatalova ◽  
V. S. Gorbatenko ◽  
V. I. Petrov
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Practice ◽  
Clinical Guidelines ◽  
Antithrombotic Therapy ◽  
Heart Valves ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
International Normalized Ratio ◽  
Prosthetic Heart Valves ◽  
Discharge From Hospital

Aim. To study the frequency of prescribing antithrombotic agents in patients with non-valvular atrial fibrillation (AF) in real clinical practice, to evaluate changes of prescriptions from 2012 till 2020.Material and methods. The medical records of inpatients (Form 003/y) with the diagnosis AF, hospitalized in the cardiological department were analyzed. According to the inclusion criteria, the patients were over 18 years of age, established diagnosis of non-valvular AF. There were two exclusion criteria: congenital and acquired valvular heart disease and prosthetic heart valves. In retrospective analysis we have included 263 case histories in 2012, 502 ones in 2016 and 524 in 2020. CHA2DS2-VASc score was used for individual stroke risk assessment in AF. The rational use of the antithrombotic therapy was evaluated according with current clinical practice guidelines at analyzing moment.Results. During period of observation the frequency of antiplatelet therapy significantly decreased from 25,5% to 5,5% (р<0.001), decreased the frequency of administration of warfarin from 71,9% to 18,3% (р<0.001). The frequency of use of direct oral anticoagulants increased in 2020 compared to 2016 (р<0.001). For patients with a high risk of stroke anticoagulant therapy was administered in 71.8% of cases in 2012, 88.5% in 2016 and 92.5% in 2020. Before discharge from hospital majority of patients (72%) achieved a desired minimum international normalized ratio (INR) from 2.0 to 3.0 in 2012. In 2016 and 2020 an only 33% and 40.6% of patients achieved INR (2.0-3.0).Conclusion. Doctors have become more committed to following clinical guidelines during the period of the investigation. In 2020 antithrombotic therapy for atrial fibrillation was suitable according to current clinical guidelines.

Heparin induced thrombocytopenia

2015 ◽  
Vol 35 (04) ◽  
pp. 372-375 ◽  
Author(s):  
N. A. Viniou ◽  
P. Diamantopoulos ◽  
J. Barbetseas ◽  
E. A. Sanidas
Keyword(s):  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Treatment Options ◽  
Factor Xa ◽  
Additional Treatment ◽  
Thrombin Inhibitors ◽  
Factor Xa Inhibitors ◽  
Clinical Aspects ◽  
Heparin Induced Thrombocytopenia

SummaryHeparin induced thrombocytopenia (HIT) is a prothrombotic syndrome initiated by platelet-activating auto-antibodies with potentially devastating complications. Once the diagnosis of HIT is suspected, discontinuation of heparin and treatment with an alternative anticoagulant are mandatory. While established drugs for HIT are no longer available, parenteral factor Xa inhibitors, thrombin inhibitors and perhaps the direct oral anticoagulants provide additional treatment options. The aim of this review was to highlight the current clinical aspects regarding HIT focusing on the role of novel medications.

scholarly journals Off-label Use of Direct Oral Anticoagulants in Patients Receiving Surgical Mechanical and Bioprosthetic Heart Valves

2021 ◽  
Vol 4 (3) ◽  
pp. e211259
Author(s):  
Ankur Kalra ◽  
Sajjad Raza ◽  
Baqir Hasan Jafry ◽  
Harley E. King ◽  
Joseph A. Lahorra ◽  
...  
Keyword(s):  
Heart Valves ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Off Label Use ◽  
Bioprosthetic Heart Valves ◽  
Off Label ◽  
Label Use

Factor Xa Inhibitors for Patients after Mechanical Heart Valve Replacement?

2021 ◽  
Author(s):  
Stephen Gerfer ◽  
Maria Grandoch ◽  
Thorsten C.W. Wahlers ◽  
Elmar W. Kuhn
Keyword(s):  
Heart Valve ◽  
Heart Valves ◽  
Oral Anticoagulants ◽  
Mechanical Heart Valve ◽  
Factor Xa ◽  
Mechanical Heart Valves ◽  
Factor Xa Inhibitors ◽  
Current Evidence ◽  
Small Scale ◽  
Number Of Patients

AbstractPatients with a mechanical heart valve need a lifelong anticoagulation due to the increased risk of valve thrombosis and thrombo-embolism. Currently, vitamin K antagonists (VKA) are the only approved class of oral anticoagulants, but relevant interactions and side effects lead to a large number of patients not achieving the optimal therapeutic target international normalized ration (INR). Therefore, steady measurements of the INR are imperative to ensure potent anticoagulation within a distinctive range. Direct oral anticoagulants (DOACs) with newer agents could serve as a possible alternative to VKAs in this patient cohort. DOACs are approved for several indications, e.g., atrial fibrillation (AF). They only have a minor interaction potential, which is why monitoring is not needed. Thereby, DOACs improve the livability of patients in need of chronical anticoagulation compared with VKAs. In contrast to dual platelet inhibition using aspirin in combination with an ADP receptor antagonist and the direct thrombin inhibitor dabigatran, the oral factor Xa inhibitors apixaban and rivaroxaban show promising results according to current evidence. In small-scale studies, factor Xa inhibitors were able to prevent thrombosis and thrombo-embolic events in patients with mechanical heart valves. Finally, DOACs seem to represent a feasible treatment option in patients with mechanical heart valves, but further studies are needed to evaluate clinical safety. In addition to the ongoing PROACT Xa trial with apixaban in patients after aortic On-X valve implantation, studies in an all-comer collective with rivaroxaban could be promising.

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