Coagulation assays and direct oral anticoagulant levels among patients having an elective surgery or procedure.


Journal

Journal of thrombosis and haemostasis : JTH
ISSN: 1538-7836
Titre abrégé: J Thromb Haemost
Pays: England
ID NLM: 101170508

Informations de publication

Date de publication:
12 2022
Historique:
revised: 27 09 2022
received: 06 07 2022
accepted: 29 09 2022
pubmed: 7 10 2022
medline: 16 11 2022
entrez: 6 10 2022
Statut: ppublish

Résumé

The Perioperative Anticoagulation Use for Surgery Evaluation study prospectively evaluated a prespecified periprocedural interruption strategy of direct oral anticoagulants (DOACs) among patients with atrial fibrillation. Coagulation testing is widely available and frequently requested prior to invasive procedures. Coagulation assays display poor sensitivity to clinically relevant DOAC concentrations. Determine the utility of routinely available coagulation testing at predicting a DOAC concentration of <30 ng/ml among patients in the preprocedural setting. We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive and negative likelihood ratio (LR+ and LR-) of a normal coagulation assay result for identifying patients with a preprocedural DOAC level < 30 ng/ml. We identified weak or very weak correlations between coagulation assay results and DOAC levels in the preprocedural setting, except for a moderate correlation between the thrombin time (TT) and dabigatran concentrations (ρ = 0.68; p < .001). The prothrombin time (PT) and activated partial thromboplastin time (APTT) demonstrated modest sensitivity (78.9% to 88.2%) and PPVs (76.4% to 93.1%) but poor specificity (13.2% to 53.3%) and NPVs (16.3% to 30.2%) across all three DOACs. A normal TT was associated with 100% specificity and PPV values for a dabigatran level < 30 ng/ml. A normal APTT among patients on dabigatran was associated with an LR+ of 1.671 (95% confidence interval [CI] 1.297, 2.154) and an LR- of 0.395 (95% CI 0.207, 0.751) for levels <30 ng/ml. The PT and APTT perform poorly at safely identifying patients with negligible DOAC levels in the preprocedural setting.

Sections du résumé

BACKGROUND
The Perioperative Anticoagulation Use for Surgery Evaluation study prospectively evaluated a prespecified periprocedural interruption strategy of direct oral anticoagulants (DOACs) among patients with atrial fibrillation. Coagulation testing is widely available and frequently requested prior to invasive procedures. Coagulation assays display poor sensitivity to clinically relevant DOAC concentrations.
OBJECTIVES
Determine the utility of routinely available coagulation testing at predicting a DOAC concentration of <30 ng/ml among patients in the preprocedural setting.
METHODS
We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive and negative likelihood ratio (LR+ and LR-) of a normal coagulation assay result for identifying patients with a preprocedural DOAC level < 30 ng/ml.
RESULTS
We identified weak or very weak correlations between coagulation assay results and DOAC levels in the preprocedural setting, except for a moderate correlation between the thrombin time (TT) and dabigatran concentrations (ρ = 0.68; p < .001). The prothrombin time (PT) and activated partial thromboplastin time (APTT) demonstrated modest sensitivity (78.9% to 88.2%) and PPVs (76.4% to 93.1%) but poor specificity (13.2% to 53.3%) and NPVs (16.3% to 30.2%) across all three DOACs. A normal TT was associated with 100% specificity and PPV values for a dabigatran level < 30 ng/ml. A normal APTT among patients on dabigatran was associated with an LR+ of 1.671 (95% confidence interval [CI] 1.297, 2.154) and an LR- of 0.395 (95% CI 0.207, 0.751) for levels <30 ng/ml.
CONCLUSIONS
The PT and APTT perform poorly at safely identifying patients with negligible DOAC levels in the preprocedural setting.

Identifiants

pubmed: 36200348
doi: 10.1111/jth.15901
pii: S1538-7836(22)18386-8
doi:

Substances chimiques

Dabigatran I0VM4M70GC
Rivaroxaban 9NDF7JZ4M3
Pyridones 0
Pyrazoles 0
Anticoagulants 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2953-2963

Subventions

Organisme : CIHR
ID : CDT-142654
Pays : Canada

Informations de copyright

© 2022 International Society on Thrombosis and Haemostasis.

Références

Troy A, Anderson T. National Trends in use of and spending on Oral anticoagulants among US Medicare beneficiaries from 2011 to 2019. JAMA Health Forum. 2021;2:e211693.
Yu AYX, Malo S, Svenson LW, Wilton SB, Hill MD. Temporal trends in the use and comparative effectiveness of direct Oral anticoagulant agents versus warfarin for nonvalvular atrial fibrillation: A Canadian Population-Based Study. J Am Heart Assoc. 2017;6:e007129. doi:10.1161/JAHA.117.007129
Douketis JD, Spyropoulos AC, Kaatz S, et al. Perioperative bridging anticoagulation in patients with atrial fibrillation. N Engl J Med. 2015;373:823-833. doi:10.1056/NEJMoa1501035
Spyropoulos AC, Brohi K, Caprini J, et al. Scientific and standardization committee communication: guidance document on the periprocedural management of patients on chronic oral anticoagulant therapy: recommendations for standardized reporting of procedural/surgical bleed risk and patient-specific thromboembolic risk. J Thromb Haemost. 2019;17:1966-1972. doi:10.1111/jth.14598
Tripodi A. To measure or not to measure direct oral anticoagulants before surgery or invasive procedures. J Thromb Haemost. 2016;14:1325-1327. doi:10.1111/jth.13344
Spyropoulos AC, Al-Badri A, Sherwood MW, et al. To measure or not to measure direct oral anticoagulants before surgery or invasive procedures: comment. J Thromb Haemost. 2016;14:2556-2559. doi:10.1111/jth.13505
Douketis JD, Spyropoulos AC, Duncan J, et al. Perioperative Management of Patients with Atrial Fibrillation Receiving a direct Oral anticoagulant. JAMA Intern Med. 2019;179:1469-1478. doi:10.1001/jamainternmed.2019.2431
Douketis JD, Spyropoulos AC, Murad MH, et al. Perioperative Management of Antithrombotic Therapy: an American College of Chest Physicians Clinical Practice Guideline. Chest. 2022;S0012-3692(22)01364-2 (online ahead of print). doi:10.1016/j.chest.2022.07.025
Shaw JR, Castellucci L, Siegal D, et al. Management of direct oral anticoagulant associated bleeding: results of a multinational survey. Thromb Res. 2018;163:19-21. doi:10.1016/j.thromres.2018.01.008
Douxfils J, Ageno W, Samama CM, et al. Laboratory testing in patients treated with direct oral anticoagulants: a practical guide for clinicians. J Thromb Haemost. 2018;16:209-219. doi:10.1111/jth.13912
Samuelson BT, Cuker A, Siegal DM, Crowther M, Garcia DA. Laboratory assessment of the anticoagulant activity of direct Oral anticoagulants: a systematic review. Chest. 2017;151:127-138. doi:10.1016/j.chest.2016.08.1462
Gosselin R, Grant RP, Adcock DM. Comparison of the effect of the anti-Xa direct oral anticoagulants apixaban, edoxaban, and rivaroxaban on coagulation assays. Int J Lab Hematol. 2016;38:505-513. doi:10.1111/ijlh.12528
Dager WE, Gosselin RC, Kitchen S, Dwyre D. Dabigatran effects on the international normalized ratio, activated partial thromboplastin time, thrombin time, and fibrinogen: a multicenter, in vitro study. Ann Pharmacother. 2012;46:1627-1636. doi:10.1345/aph.1R179
Douxfils J, Mullier F, Robert S, Chatelain C, Chatelain B, Dogné JM. Impact of dabigatran on a large panel of routine or specific coagulation assays. Laboratory recommendations for monitoring of dabigatran etexilate. Thromb Haemost. 2012;107:985-997. doi:10.1160/TH11-11-0804
Douketis JD, Spyropoulos AC, Anderson JM, et al. The perioperative anticoagulant use for surgery evaluation (PAUSE) study for patients on a direct Oral anticoagulant who need an elective surgery or procedure: design and rationale. Thromb Haemost. 2017;117:2415-2424. doi:10.1160/TH17-08-0553
Pernod G, Albaladejo P, Godier A, et al. Management of major bleeding complications and emergency surgery in patients on long-term treatment with direct oral anticoagulants, thrombin or factor-Xa inhibitors: proposals of the working group on perioperative haemostasis (GIHP) - march 2013. Arch Cardiovasc Dis. 2013;106:382-393. doi:10.1016/j.acvd.2013.04.009
Godier A, Martin AC, Leblanc I, et al. Peri-procedural management of dabigatran and rivaroxaban: duration of anticoagulant discontinuation and drug concentrations. Thromb Res. 2015;136:763-768. doi:10.1016/j.thromres.2015.08.006
Tafur A, Li N, Clark N, et al. Predictors of bleeding in the perioperative anticoagulant use for surgery evaluation (PAUSE). Study. 2019;134:710.
Godier A, Dincq AS, Martin AC, et al. Predictors of pre-procedural concentrations of direct oral anticoagulants: a prospective multicentre study. Eur Heart J. 2017;38:2431-2439. doi:10.1093/eurheartj/ehx403
Sarode R. Direct oral anticoagulant monitoring: what laboratory tests are available to guide us? Hematology Am Soc Hematol Educ Program. 2019;2019:194-197. doi:10.1182/hematology.2019000027
Brakta C, Stepanian A, Elayeb R et al. Prediction of apixaban or rivaroxaban concentrations based on low molecular weight heparin anti-Xa activity using nomograms: a useful tool in emergency clinical situations like thrombolysis in stroke [abstract]. https://abstracts.isth.org/abstract/prediction-of-apixaban-or-rivaroxaban-concentrations-based-on-low-molecular-weight-heparin-anti-xa-activity-using-nomograms-a-useful-tool-in-emergency-clinical-situations-like-thrombolysis-in-stroke/. Accessed September 11, 2022.
Mithoowani S, Moffat KA, Gupta A, Carlino SA, Crowther MA. Low molecular weight heparin anti-Xa assays can identify patients with clinically important apixaban and rivaroxaban drug levels. Thromb Res. 2022;215:1-4. doi:10.1016/j.thromres.2022.05.005
Levy JH, Ageno W, Chan NC, et al. When and how to use antidotes for the reversal of direct oral anticoagulants: guidance from the SSC of the ISTH. J Thromb Haemost. 2016;14:623-627. doi:10.1111/jth.13227
Testa S, Legnani C, Antonucci E, et al. Drug levels and bleeding complications in atrial fibrillation patients treated with direct oral anticoagulants. J Thromb Haemost. 2019;17:1064-1072. doi:10.1111/jth.14457
Tafur AJ, Clark NP, Spyropoulos AC, et al. Predictors of bleeding in the perioperative anticoagulant use for surgery evaluation study. J Am Heart Assoc. 2020;9:e017316. doi:10.1161/JAHA.120.017316
Douxfils J, Chatelain C, Chatelain B, Dogné JM, Mullier F. Impact of apixaban on routine and specific coagulation assays: a practical laboratory guide. Thromb Haemost. 2013;110:283-294. doi:10.1160/TH12-12-0898
Douxfils J, Mullier F, Loosen C, Chatelain C, Chatelain B, Dogné JM. Assessment of the impact of rivaroxaban on coagulation assays: laboratory recommendations for the monitoring of rivaroxaban and review of the literature. Thromb Res. 2012;130:956-966. doi:10.1016/j.thromres.2012.09.004
Evrard J, Hardy M, Dogné JM, et al. Are the DOAC plasma level thresholds appropriate for clinical decision-making? A reappraisal using thrombin generation testing. Int J Lab Hematol. 2021;43:e48-e51. doi:10.1111/ijlh.13356
Barrett YC, Wang Z, Frost C, Shenker A. Clinical laboratory measurement of direct factor Xa inhibitors: anti-Xa assay is preferable to prothrombin time assay. Thromb Haemost. 2010;104:1263-1271. doi:10.1160/TH10-05-0328
Van Blerk M, Bailleul E, Chatelain B, et al. Influence of dabigatran and rivaroxaban on routine coagulation assays. A Nationwide Belgian Survey Thromb Haemost. 2015;113:154-164. doi:10.1160/TH14-02-0161
Samama MM, Martinoli JL, LeFlem L, et al. Assessment of laboratory assays to measure rivaroxaban--an oral, direct factor Xa inhibitor. Thromb Haemost. 2010;103:815-825. doi:10.1160/TH09-03-0176

Auteurs

Joseph R Shaw (JR)

Department of Medicine, University of Ottawa, and the Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.

Na Li (N)

Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.
Department of Computing and Software, McMaster University, Hamilton, Ontario, Canada.

Joanne Nixon (J)

Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

Karen A Moffat (KA)

Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Hamilton Regional Laboratory Medicine Program, Hamilton, Ontario, Canada.

Alex C Spyropoulos (AC)

The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Department of Medicine, Northwell Health at Lenox Hill Hospital, New York, New York, USA.

Sam Schulman (S)

Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Department of Obstetrics and Gynecology, I.M. Schenov First Moscow State Medical University, Moscow, Russia.

James D Douketis (JD)

Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH