The effect of routine preoperative interruption of dabigatran therapy on coagulation parameters and dabigatran plasma levels in a mixed surgical population

Summary Dabigatran is an oral anticoagulant used for atrial fibrillation and venous thromboembolism. While an effective antibody reversal agent is available, its cost precludes routine use and the mainstay of preoperative management is timely dabigatran interruption. Unlike warfarin, there are no universally accepted protocols for interruption of dabigatran in the preoperative period and there is uncertainty around the interpretation of standard coagulation tests in the presence of dabigatran. We performed a prospective, observational pilot study in patients presenting for elective surgery to examine: 1) the preoperative plasma dabigatran concentrations on day of surgery associated with the local dabigatran interruption protocol, 2) the potential utility of dabigatran concentrations on day of surgery, and 3) the utility of standard coagulation tests in determining whether dabigatran concentrations were below a ‘safe’ threshold for surgery. We recruited patients presenting to pre-admission clinics for elective surgery. Dabigatran concentrations below 30 µg/L were considered adequate for proceeding with surgery. Data were obtained and analysed from 21 patients with a median (range) age of 70 (20–86) years. Median (range) dabigatran concentrations on the day of surgery were 5 (0–59) µg/L. Two patients had day of surgery concentrations exceeding 30 µg/L. Of the standard coagulation tests examined, only the thrombin clotting time (TCT) was abnormal for these two patients. Our interruption protocol was associated with safe dabigatran concentrations in most patients on the day of surgery. A minority of patients had dabigatran concentrations above the safe threshold, which were detectable by abnormal TCT results.

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The preoperative management of dabigatran and its specific antidote idarucizumab in patients with nonvalvular atrial fibrillation: Case reports

Arhiv za farmaciju ◽

10.5937/arhfarm2005310t ◽

2020 ◽

Vol 70 (5) ◽

pp. 310-318

Author(s):

Milan Tomić

Keyword(s):

Atrial Fibrillation ◽

Anticoagulant Activity ◽

Case Reports ◽

Oral Anticoagulants ◽

Antibody Fragment ◽

Bleeding Risk ◽

Ease Of Use ◽

Preoperative Management ◽

Nonvalvular Atrial Fibrillation ◽

Reversal Agent

Dabigatran is a novel oral anticoagulant preferred due to its ease of use, favorable pharmacokinetics, decreased potential for drug-drug interactions, and the lack of monitoring requirements. With the growing use of dabigatran, it is important to highlight that dabigatran increases the risk of hemorrhage after some procedures. Therefore, when dabigatran is used before the elective or urgent procedures, it is necessary to compare the thromboembolic event risk with the relative risk of bleeding. Before the approval of a reversal agent, the lack of specific antidotes had been the major limitation against the widespread utilization of dabigatran. In October 2015, idarucizumab, a humanized monoclonal antigen-binding antibody fragment capable of reversing the anticoagulant activity of dabigatran, has been introduced into the market to be used in lifethreatening bleeding or urgent surgery. In this manuscript, the preoperative management of dabigatran and the initial experience of using idarucizumab in a patient with nonvalvular atrial fibrillation were described. We propose that the option of dabigatran reversal needs to be considered in patients with nonvalvular atrial fibrillation. However, additional research is needed to define optimal perioperative management of dabigatran and other novel oral anticoagulants, especially in high bleeding risk patients, and to determine whether pre-procedure coagulation testing should be performed.

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Investigation of pathological haemorrhage in Maine Coon cats

Veterinary Record ◽

10.1136/vr.105503 ◽

2020 ◽

Vol 187 (9) ◽

pp. e75-e75

Author(s):

Conor O'Halloran ◽

Petra Cerna ◽

Craig Breheny ◽

Nicki Reed ◽

Kerry Rolph ◽

...

Keyword(s):

Elective Surgery ◽

Activated Partial Thromboplastin Time ◽

Clotting Time ◽

Blood Samples ◽

Coagulation Tests ◽

Group 3 ◽

Group 2 ◽

Hereditary Condition ◽

Edta Anticoagulated Blood ◽

Group 1

ObjectiveAfibrinogenaemic haemorrhage was previously reported in a Maine Coon cat. Two littermates subsequently died from surgical non-haemostasis, suggesting a hereditable coagulopathy.MethodsWe prospectively recruited cats which were: a) Maine Coons with pathological haemorrhage (group 1, n=8), b) healthy familial relatives of group 1 (group 2, n=13) and c) healthy Maine Coons unrelated to groups 1 and 2 (group 3, n=12). Coagulation tests: prothrombin time, activated partial thromboplastin time and thrombin clotting time (TCT) were performed on citrated plasma along with quantification of fibrinogen. Routine haematological examination was performed on EDTA-anticoagulated blood collected contemporaneously.ResultsThirty-three blood samples were analysed. Fibrinogen concentrations were significantly reduced in groups 1 (P<0.01) and 2 (P<0.01) compared with group 3. Similarly, TCT was found to be significantly extended in group 1 (P<0.01) and group 2 (P=0.02) with respect to group 3.ConclusionsDysfibrinogenaemia was identified in clinical cases and their healthy relatives, suggesting that this may represent a hereditary condition of Maine Coon cats. Clinicians should be aware of the increased potential for non-haemostasis in this cat breed and consider assessing clotting function before (elective) surgery.

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Faculty Opinions recommendation of Comparative effectiveness of warfarin and new oral anticoagulants for the management of atrial fibrillation and venous thromboembolism: a systematic review.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717955123.793462606 ◽

2012 ◽

Author(s):

Jack Kron ◽

Eric Stecker

Keyword(s):

Atrial Fibrillation ◽

Systematic Review ◽

Venous Thromboembolism ◽

Comparative Effectiveness ◽

Oral Anticoagulants ◽

New Oral Anticoagulants

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Faculty Opinions recommendation of Efficacy and Harms of Direct Oral Anticoagulants in the Elderly for Stroke Prevention in Atrial Fibrillation and Secondary Prevention of Venous Thromboembolism: Systematic Review and Meta-Analysis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725514028.793512947 ◽

2016 ◽

Author(s):

Nanette Wenger

Keyword(s):

Atrial Fibrillation ◽

Systematic Review ◽

Venous Thromboembolism ◽

Secondary Prevention ◽

Stroke Prevention ◽

Meta Analysis ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

The Elderly

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Faculty Opinions recommendation of Edoxaban: A comprehensive review of the pharmacology and clinical data for the management of atrial fibrillation and venous thromboembolism.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726196940.793521400 ◽

2016 ◽

Author(s):

D John Doyle

Keyword(s):

Atrial Fibrillation ◽

Venous Thromboembolism ◽

Clinical Data ◽

Comprehensive Review

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Perioperative Management of Patients Receiving New Anticoagulants

Current Pharmaceutical Design ◽

10.2174/1381612825666190709220449 ◽

2019 ◽

Vol 25 (19) ◽

pp. 2149-2157 ◽

Cited By ~ 1

Author(s):

Massimo Lamperti ◽

Andrey Khozenko ◽

Arun Kumar

Keyword(s):

Vitamin K ◽

Elective Surgery ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Oral Intake ◽

Bleeding Risk ◽

Dietary Vitamin ◽

Reversal Agent ◽

Onset Of Action ◽

Reversal Agents

There is an increased use of oral anticoagulants for the prevention of venous and arterial thrombosis. Vitamin-K antagonists have been used for decades as the main oral anticoagulants but they have the draback a complex therapeutic management, slow onset of action and by a different oral intake caused by dietary vitamin K intake. New non-vitamin K antagonist oral anticoagulants (NOACs) have been developed to overcome the limitations of warfarin. Their management is easier as it requires a fixed daily dose without coagulation monitoring. Although their therapeutic profile is safe, proper attention should be paid in case of unexpected need for the reversal of their coagulation effect and in case a patient needs to have a scheduled surgery. For non-acute cardiac surgery, discontinuation of NOACs should start at least 48 hours prior surgery. Intracranial bleedings associated with NOACs are less dangerous comparing to those warfarin-induced. NOACs need to be stopped ≥24 hours in case of elective surgery for low bleeding-risk procedures and ≥48 hours for high bleeding-risk surgery in patients with normal renal function and 72 hours in case of reduced CrCl < 80. The therapy with NOACs should be resumed from 48 to 72 hours after the procedure depending on the perceived bleeding, type of surgery and thrombotic risks. There are some available NOAC reversal agents acting within 5 to 20 minutes. In case of lack of reversal agent, adequate diuresis, renal replacement therapy and activated charcoal in case of recent ingestion should be considered.

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Edoxaban: A Comprehensive Review of the Pharmacology and Clinical Data for the Management of Atrial Fibrillation and Venous Thromboembolism

Cardiology and Therapy ◽

10.1007/s40119-016-0058-2 ◽

2016 ◽

Vol 5 (1) ◽

pp. 1-18 ◽

Cited By ~ 35

Author(s):

Zachary A. Stacy ◽

William B. Call ◽

Aaron P. Hartmann ◽

Golden L. Peters ◽

Sara K. Richter

Keyword(s):

Atrial Fibrillation ◽

Venous Thromboembolism ◽

Clinical Data ◽

Comprehensive Review

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THE EFFECT OF EARLY BLOOD TRANSFUSION ON THE OUTCOME OF GASTROINTESTINAL HAEMORRHAGE

10.1055/s-0038-1644157 ◽

1987 ◽

Author(s):

S D Blair ◽

S B Javanvrin ◽

C N McCollum ◽

R M Greenhalgh

Keyword(s):

Blood Transfusion ◽

Blood Coagulation ◽

Whole Blood ◽

Randomised Trial ◽

Gastrointestinal Haemorrhage ◽

Clotting Time ◽

Prospective Randomised Trial ◽

Coagulation Tests ◽

To Receive ◽

Upper Gastrointestinal

It has been suggested that mortality due to upper gastrointestinal haemorrhage may be reduced by restricting blood transfusion [1], We have assessed whether this is due to an anticoagulant effect in a prospective randomised trial.One hundred patients with severe, acute gastrointestinal haemorrhage were randomised to receive either at least 2 units of blood during the first 24 hours of admission, or no blood unless their haemaglobin was lessthan 8g/dl or they were shocked. Minor bleeds and varices were excluded As hypercoagulation cannot be measured using conventional coagulation tests, fresh whole blood coagulation was measured by the Biobridge Impedance Clotting Time (ICT). Coagulation was assessed at 24 hour intervals and compared to age matched controls with the results expressed as mean ± sem.The ICT on admission for the transfusion group (n=50) was 3.2±0.2 mins compared to 10±0.2 mins in controls. This hyper-coagulable state was partially reversed to 6.4±0.3 mins at 24 hours (p<0.001). The 50 allocated to receive no blood had a similar ICT on admission of 4.4±0.4 mins but the hypercoagulable state was maintained with ICT at 24 hours of 4.320.4 mins. Only 2 patients not transfused rebled compared to 15 in the early transfusion group (p<0.001). Five patients died, and they were all in the early transfusion group.These findings show there is a hypercoagulable response to haemorrhage which is partially reversed by blood transfusion leading to rebleeding

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Atrial fibrillation associated with increased risk of venous thromboembolism

Thrombosis and Haemostasis ◽

10.1160/th14-05-0405 ◽

2015 ◽

Vol 113 (01) ◽

pp. 185-192 ◽

Cited By ~ 23

Author(s):

Chun-Cheng Wang ◽

Cheng-Li Lin ◽

Guei-Jane Wang ◽

Chiz-Tzung Chang ◽

Fung-Chang Sung ◽

...

Keyword(s):

Atrial Fibrillation ◽

Venous Thromboembolism ◽

Incidence Rates ◽

Vein Thrombosis ◽

Kaplan Meier ◽

Increased Risk ◽

Long Term Follow Up ◽

Deep Vein

SummaryWhether atrial fibrillation (AF) is associated with an increased risk of venous thromboembolism (VTE) remains controversial. From Longitudinal Health Insurance Database 2000 (LHID2000), we identified 11,458 patients newly diagnosed with AF. The comparison group comprised 45,637 patients without AF. Both cohorts were followed up to measure the incidence of deep-vein thrombosis (DVT) and pulmonary embolism (PE). Univariable and multivariable competing-risks regression model and Kaplan-Meier analyses with the use of Aelon-Johansen estimator were used to measure the differences of cumulative incidences of DVT and PE, respectively. The overall incidence rates (per 1,000 person-years) of DVT and PE between the AF group and non-AF groups were 2.69 vs 1.12 (crude hazard ratio [HR] = 1.92; 95 % confidence interval [CI] = 1.54-2.39), 1.55 vs 0.46 (crude HR = 2.68; 95 % CI = 1.97-3.64), respectively. The baseline demographics indicated that the members of the AF group demonstrated a significantly older age and higher proportions of comorbidities than non-AF group. After adjusting for age, sex, and comorbidities, the risks of DVT and PE remained significantly elevated in the AF group compared with the non-AF group (adjusted HR = 1.74; 95 %CI = 1.36-2.24, adjusted HR = 2.18; 95 %CI = 1.51-3.15, respectively). The Kaplan-Meier curve with the use of Aelon-Johansen estimator indicated that the cumulative incidences of DVT and PE were both more significantly elevated in the AF group than in the non-AF group after a long-term follow-up period (p<0.01). In conclusion, the presence of AF is associated with increased risk of VTE after a long-term follow-up period.

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