Diagnosis of deep vein thrombosis with D-dimer adjusted to clinical probability: Prospective diagnostic management study

Clive Kearon; Kerstin De Wit; Sameer Parpia; Sam Schulman; Frederick A. Spencer; Sangita Sharma; Marc Afilalo; Susan R. Kahn; Gregoire Le Gal; Sudeep Shivakumar; Shannon M. Bates; Cynthia Wu; Alejandro Lazo-Langner; Frédérick D'Aragon; Jean François Deshaies; Luciana Spadafora; Jim A. Julian

doi:10.1136/bmj-2021-067378

Diagnosis of deep vein thrombosis with D-dimer adjusted to clinical probability: Prospective diagnostic management study

Clive Kearon, Kerstin De Wit, Sameer Parpia, Sam Schulman, Frederick A. Spencer, Sangita Sharma, Marc Afilalo, Susan R. Kahn, Gregoire Le Gal, Sudeep Shivakumar, Shannon M. Bates, Cynthia Wu, Alejandro Lazo-Langner, Frédérick D'Aragon, Jean François Deshaies, Luciana Spadafora, Jim A. Julian

Medicine

Research output: Contribution to journal › Article › peer-review

20 Citations (Scopus)

Abstract

AbstractObjective To evaluate the safety and efficiency of a diagnostic algorithm for deep vein thrombosis (DVT) that uses clinical pretest probability based D-dimer thresholds to exclude DVT. Design Prospective diagnostic management study. Setting University based emergency departments or outpatient clinics in Canada. Participants Patients with symptoms or signs of DVT. Intervention DVT was considered excluded without further testing by Wells low clinical pretest probability and D-dimer <1000 ng/mL or Wells moderate clinical pretest probability and D-dimer <500 ng/mL. All other patients had proximal ultrasound imaging. Repeat proximal ultrasonography was restricted to patients with initially negative ultrasonography, low or moderate clinical pretest probability, and D-dimer >3000 ng/mL or high clinical pretest probability and D-dimer >1500 ng/mL. If DVT was not diagnosed, patients did not receive anticoagulant treatment. Main outcome measure Symptomatic venous thromboembolism at three months. Results 1508 patients were enrolled and analysed, of whom 173 (11.5%) had DVT on scheduled diagnostic testing. Of the 1275 patients with no proximal DVT on scheduled testing who did not receive anticoagulant treatment, eight (0.6%, 95% confidence interval 0.3% to 1.2%) were found to have venous thromboembolism during follow-up. Compared with a traditional DVT testing strategy, this diagnostic approach reduced the need for ultrasonography from a mean of 1.36 scans/patient to 0.72 scans/patient (difference -0.64, 95% confidence interval -0.68 to -0.60), corresponding to a relative reduction of 47%. Conclusions The diagnostic strategy using a combination of clinical pretest probability and D-dimer identified a group of patients at low risk for DVT during follow-up while substantially reducing the need for ultrasound imaging. Registration ClinicalTrials.gov NCT02038530.

Original language	English
Article number	e067378
Journal	The BMJ
Volume	376
DOIs	https://doi.org/10.1136/bmj-2021-067378
Publication status	Published - Feb 15 2022

Bibliographical note

Funding Information:
Funding: The 4D study was supported by grants from the Canadian Institutes of Health Research (MOP-125951) and was endorsed by the Canadian Venous Thromboembolism Clinical Research (CanVECTOR) Network. The funding source had no role in the collection, analysis, or interpretation of the data; the writing of the report; or the decision to submit for publication. CK (deceased) was supported by an investigator award from the Heart and Stroke Foundation of Canada and the Jack Hirsh Professorship in Thromboembolism (McMaster University). KdW is supported by investigator awards from Physician Services Incorporated and the Hamilton Health Sciences Foundation. SRK is supported by a Tier 1 Canada Research Chair. GLG is supported by an Early Researcher Award from the Province of Ontario, a Heart and Stroke Foundation Ontario Mid-Career Investigator award, and a research chair on the diagnosis of venous thromboembolism, Department of Medicine, University of Ottawa. SMB is supported by the Eli Lilly Canada/May Cohen Chair in Women’s Health. FDA is supported by the Fonds de Recherche du Québec-Santé. Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: the study was funded by the Canadian Institutes of Health Research; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. Ethical approval: The study was approved by the Hamilton Integrated Research Ethics Board (# 13-844) and research ethics boards of participating institutions. All participants gave informed consent. Data sharing: A complete de-identified patient level dataset will be made available to researchers for the purpose of meta-analysis or a newly proposed study. Data will be made available following submission of a maximum two page proposal by the requestor. The trial Steering Committee will review and, if acceptable, provide approval of the request. A signed data sharing access agreement will be required. Data will become available one year after publication of the initial study results. Data availability will end four years after publication of the initial study results. Data requests should be sent to parpia@mcmaster.ca.

Publisher Copyright:
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ASJC Scopus Subject Areas

General Medicine

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10.1136/bmj-2021-067378

Cite this

Kearon, C., De Wit, K., Parpia, S., Schulman, S., Spencer, F. A., Sharma, S., Afilalo, M., Kahn, S. R., Le Gal, G., Shivakumar, S., Bates, S. M., Wu, C., Lazo-Langner, A., D'Aragon, F., Deshaies, J. F., Spadafora, L., & Julian, J. A. (2022). Diagnosis of deep vein thrombosis with D-dimer adjusted to clinical probability: Prospective diagnostic management study. The BMJ, 376, Article e067378. https://doi.org/10.1136/bmj-2021-067378

Kearon, C, De Wit, K, Parpia, S, Schulman, S, Spencer, FA, Sharma, S, Afilalo, M, Kahn, SR, Le Gal, G, Shivakumar, S, Bates, SM, Wu, C, Lazo-Langner, A, D'Aragon, F, Deshaies, JF, Spadafora, L & Julian, JA 2022, 'Diagnosis of deep vein thrombosis with D-dimer adjusted to clinical probability: Prospective diagnostic management study', The BMJ, vol. 376, e067378. https://doi.org/10.1136/bmj-2021-067378

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abstract = "AbstractObjective To evaluate the safety and efficiency of a diagnostic algorithm for deep vein thrombosis (DVT) that uses clinical pretest probability based D-dimer thresholds to exclude DVT. Design Prospective diagnostic management study. Setting University based emergency departments or outpatient clinics in Canada. Participants Patients with symptoms or signs of DVT. Intervention DVT was considered excluded without further testing by Wells low clinical pretest probability and D-dimer <1000 ng/mL or Wells moderate clinical pretest probability and D-dimer <500 ng/mL. All other patients had proximal ultrasound imaging. Repeat proximal ultrasonography was restricted to patients with initially negative ultrasonography, low or moderate clinical pretest probability, and D-dimer >3000 ng/mL or high clinical pretest probability and D-dimer >1500 ng/mL. If DVT was not diagnosed, patients did not receive anticoagulant treatment. Main outcome measure Symptomatic venous thromboembolism at three months. Results 1508 patients were enrolled and analysed, of whom 173 (11.5%) had DVT on scheduled diagnostic testing. Of the 1275 patients with no proximal DVT on scheduled testing who did not receive anticoagulant treatment, eight (0.6%, 95% confidence interval 0.3% to 1.2%) were found to have venous thromboembolism during follow-up. Compared with a traditional DVT testing strategy, this diagnostic approach reduced the need for ultrasonography from a mean of 1.36 scans/patient to 0.72 scans/patient (difference -0.64, 95% confidence interval -0.68 to -0.60), corresponding to a relative reduction of 47%. Conclusions The diagnostic strategy using a combination of clinical pretest probability and D-dimer identified a group of patients at low risk for DVT during follow-up while substantially reducing the need for ultrasound imaging. Registration ClinicalTrials.gov NCT02038530. ",

author = "Clive Kearon and {De Wit}, Kerstin and Sameer Parpia and Sam Schulman and Spencer, {Frederick A.} and Sangita Sharma and Marc Afilalo and Kahn, {Susan R.} and {Le Gal}, Gregoire and Sudeep Shivakumar and Bates, {Shannon M.} and Cynthia Wu and Alejandro Lazo-Langner and Fr{\'e}d{\'e}rick D'Aragon and Deshaies, {Jean Fran{\c c}ois} and Luciana Spadafora and Julian, {Jim A.}",

note = "Funding Information: Funding: The 4D study was supported by grants from the Canadian Institutes of Health Research (MOP-125951) and was endorsed by the Canadian Venous Thromboembolism Clinical Research (CanVECTOR) Network. The funding source had no role in the collection, analysis, or interpretation of the data; the writing of the report; or the decision to submit for publication. CK (deceased) was supported by an investigator award from the Heart and Stroke Foundation of Canada and the Jack Hirsh Professorship in Thromboembolism (McMaster University). KdW is supported by investigator awards from Physician Services Incorporated and the Hamilton Health Sciences Foundation. SRK is supported by a Tier 1 Canada Research Chair. GLG is supported by an Early Researcher Award from the Province of Ontario, a Heart and Stroke Foundation Ontario Mid-Career Investigator award, and a research chair on the diagnosis of venous thromboembolism, Department of Medicine, University of Ottawa. SMB is supported by the Eli Lilly Canada/May Cohen Chair in Women{\textquoteright}s Health. FDA is supported by the Fonds de Recherche du Qu{\'e}bec-Sant{\'e}. Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: the study was funded by the Canadian Institutes of Health Research; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. Ethical approval: The study was approved by the Hamilton Integrated Research Ethics Board (# 13-844) and research ethics boards of participating institutions. All participants gave informed consent. Data sharing: A complete de-identified patient level dataset will be made available to researchers for the purpose of meta-analysis or a newly proposed study. Data will be made available following submission of a maximum two page proposal by the requestor. The trial Steering Committee will review and, if acceptable, provide approval of the request. A signed data sharing access agreement will be required. Data will become available one year after publication of the initial study results. Data availability will end four years after publication of the initial study results. Data requests should be sent to parpia@mcmaster.ca. Publisher Copyright: {\textcopyright} ",

year = "2022",

month = feb,

day = "15",

doi = "10.1136/bmj-2021-067378",

language = "English",

volume = "376",

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TY - JOUR

T1 - Diagnosis of deep vein thrombosis with D-dimer adjusted to clinical probability

T2 - Prospective diagnostic management study

AU - Kearon, Clive

AU - De Wit, Kerstin

AU - Parpia, Sameer

AU - Schulman, Sam

AU - Spencer, Frederick A.

AU - Sharma, Sangita

AU - Afilalo, Marc

AU - Kahn, Susan R.

AU - Le Gal, Gregoire

AU - Shivakumar, Sudeep

AU - Bates, Shannon M.

AU - Wu, Cynthia

AU - Lazo-Langner, Alejandro

AU - D'Aragon, Frédérick

AU - Deshaies, Jean François

AU - Spadafora, Luciana

AU - Julian, Jim A.

N1 - Funding Information: Funding: The 4D study was supported by grants from the Canadian Institutes of Health Research (MOP-125951) and was endorsed by the Canadian Venous Thromboembolism Clinical Research (CanVECTOR) Network. The funding source had no role in the collection, analysis, or interpretation of the data; the writing of the report; or the decision to submit for publication. CK (deceased) was supported by an investigator award from the Heart and Stroke Foundation of Canada and the Jack Hirsh Professorship in Thromboembolism (McMaster University). KdW is supported by investigator awards from Physician Services Incorporated and the Hamilton Health Sciences Foundation. SRK is supported by a Tier 1 Canada Research Chair. GLG is supported by an Early Researcher Award from the Province of Ontario, a Heart and Stroke Foundation Ontario Mid-Career Investigator award, and a research chair on the diagnosis of venous thromboembolism, Department of Medicine, University of Ottawa. SMB is supported by the Eli Lilly Canada/May Cohen Chair in Women’s Health. FDA is supported by the Fonds de Recherche du Québec-Santé. Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: the study was funded by the Canadian Institutes of Health Research; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. Ethical approval: The study was approved by the Hamilton Integrated Research Ethics Board (# 13-844) and research ethics boards of participating institutions. All participants gave informed consent. Data sharing: A complete de-identified patient level dataset will be made available to researchers for the purpose of meta-analysis or a newly proposed study. Data will be made available following submission of a maximum two page proposal by the requestor. The trial Steering Committee will review and, if acceptable, provide approval of the request. A signed data sharing access agreement will be required. Data will become available one year after publication of the initial study results. Data availability will end four years after publication of the initial study results. Data requests should be sent to parpia@mcmaster.ca. Publisher Copyright: ©

PY - 2022/2/15

Y1 - 2022/2/15

N2 - AbstractObjective To evaluate the safety and efficiency of a diagnostic algorithm for deep vein thrombosis (DVT) that uses clinical pretest probability based D-dimer thresholds to exclude DVT. Design Prospective diagnostic management study. Setting University based emergency departments or outpatient clinics in Canada. Participants Patients with symptoms or signs of DVT. Intervention DVT was considered excluded without further testing by Wells low clinical pretest probability and D-dimer <1000 ng/mL or Wells moderate clinical pretest probability and D-dimer <500 ng/mL. All other patients had proximal ultrasound imaging. Repeat proximal ultrasonography was restricted to patients with initially negative ultrasonography, low or moderate clinical pretest probability, and D-dimer >3000 ng/mL or high clinical pretest probability and D-dimer >1500 ng/mL. If DVT was not diagnosed, patients did not receive anticoagulant treatment. Main outcome measure Symptomatic venous thromboembolism at three months. Results 1508 patients were enrolled and analysed, of whom 173 (11.5%) had DVT on scheduled diagnostic testing. Of the 1275 patients with no proximal DVT on scheduled testing who did not receive anticoagulant treatment, eight (0.6%, 95% confidence interval 0.3% to 1.2%) were found to have venous thromboembolism during follow-up. Compared with a traditional DVT testing strategy, this diagnostic approach reduced the need for ultrasonography from a mean of 1.36 scans/patient to 0.72 scans/patient (difference -0.64, 95% confidence interval -0.68 to -0.60), corresponding to a relative reduction of 47%. Conclusions The diagnostic strategy using a combination of clinical pretest probability and D-dimer identified a group of patients at low risk for DVT during follow-up while substantially reducing the need for ultrasound imaging. Registration ClinicalTrials.gov NCT02038530.

AB - AbstractObjective To evaluate the safety and efficiency of a diagnostic algorithm for deep vein thrombosis (DVT) that uses clinical pretest probability based D-dimer thresholds to exclude DVT. Design Prospective diagnostic management study. Setting University based emergency departments or outpatient clinics in Canada. Participants Patients with symptoms or signs of DVT. Intervention DVT was considered excluded without further testing by Wells low clinical pretest probability and D-dimer <1000 ng/mL or Wells moderate clinical pretest probability and D-dimer <500 ng/mL. All other patients had proximal ultrasound imaging. Repeat proximal ultrasonography was restricted to patients with initially negative ultrasonography, low or moderate clinical pretest probability, and D-dimer >3000 ng/mL or high clinical pretest probability and D-dimer >1500 ng/mL. If DVT was not diagnosed, patients did not receive anticoagulant treatment. Main outcome measure Symptomatic venous thromboembolism at three months. Results 1508 patients were enrolled and analysed, of whom 173 (11.5%) had DVT on scheduled diagnostic testing. Of the 1275 patients with no proximal DVT on scheduled testing who did not receive anticoagulant treatment, eight (0.6%, 95% confidence interval 0.3% to 1.2%) were found to have venous thromboembolism during follow-up. Compared with a traditional DVT testing strategy, this diagnostic approach reduced the need for ultrasonography from a mean of 1.36 scans/patient to 0.72 scans/patient (difference -0.64, 95% confidence interval -0.68 to -0.60), corresponding to a relative reduction of 47%. Conclusions The diagnostic strategy using a combination of clinical pretest probability and D-dimer identified a group of patients at low risk for DVT during follow-up while substantially reducing the need for ultrasound imaging. Registration ClinicalTrials.gov NCT02038530.

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Diagnosis of deep vein thrombosis with D-dimer adjusted to clinical probability: Prospective diagnostic management study

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