Review ArticleClinical Decision Rules and D-dimer in Venous Thromboembolism: Current controversies and future research priorities
Introduction
Venous thromboembolism (VTE), comprising both deep vein thrombosis (DVT) and pulmonary embolism (PE), are common, potentially lethal yet treatable clinical conditions [1]. Clinical Decision Rules (CDRs) are decision making tools, using combinations of simple available clinical predictors to define an outcome in the present, in other words a diagnosis (or a probability of disease), or an outcome in the future, in other words a prognosis (or probability of an outcome), either of which leads to a diagnostic course of action or a therapeutic course of action [2]. CDRs and/or D-dimer have a crucial place in the diagnostic and therapeutic management of VTE. These tools permit us to judiciously and safely use diagnostic imaging for VTE diagnosis, select the right treatment setting for initial therapeutic management of VTE (intensive care unit, ward or home) and select which patients will derive net benefit from anticoagulant therapies.
The focus of this narrative review will be to review current controversies in the use of clinical decision rules and/or D-dimer in the diagnostic and therapeutic management of VTE. We will highlight wide international practice variations, even among experts in thrombosis, and also highlight challenges in knowledge translation for most clinicians that impact putting research findings into routine clinical practice. These challenges are largely reflective of the absence of level IA evidence to guide practice in these areas and the need to develop and validate simple and widely available tools that are easy to adopt in routine clinical practice.
Section snippets
Methodologic Standards for Clinical Predictors
High quality evidence to support routine use of CDRs, and other clinical prediction tools, requires that they are developed and validated strictly following methodologic guidelines (see Table 1). Standards for their development and validation were first published more than 20 years ago [3], were updated and which have formed the basis for a quality assessment framework we should consider before adopting CDRs in our daily practice [2]. These standards require adherence to methodologic guidelines
Challenges and Controversies in VTE Diagnosis: Pretest Probability Assessment for Diagnostic Management of DVT or PE: Simplified Rules or The Original Rules?
The original Wells DVT CDR and the Wells PE CDR in addition to the Geneva CDR for PE, have been well evaluated in clinical research over the last 2 decades [4]. Nonetheless it is evident from published practice patterns that clinicians often do not use these rules [5]. The risk of this underuse is either over or under diagnosis of VTE [5]. Some of the knowledge translation barriers that have been highlighted include 1) the need to recall more than 7 items with each of these rules, 2) the need
Challenges and Controversies in VTE Diagnosis: Traditional or Age-Adjusted D-Dimer Cut Off for DVT or Pulmonary Embolism Diagnostic Management?
After pre-test probability assessment, clinicians can use D-dimer as a next step to determine if imaging is required or VTE is excluded. Epidemiologic research has demonstrated that in the CT scan era, the diagnosis of PE is increasing in frequency with a reduction in case fatality rate without a change in pulmonary embolism mortality pointing to over-diagnosis by CT scan [7]. There are also concerns with CT scan radiation leading to cancer and other CT complications. It is felt that improved
Challenges and Controversies in VTE Diagnosis: VTE Diagnosis and Pregnancy: Use of D-Dimer and Clinical Decision Rules
While clinical assessment using clinical decision rules has been demonstrated to be very useful in assigning pre-test probability for DVT [14] and PE [15], [16] outside of pregnancy, the studies deriving and validating these CDRs model did not include pregnant patients. The proportion of confirmed VTE is usually lower among pregnant women with suspected VTE. Moreover, it is very likely that the distribution of physical findings (e.g. left leg swelling) and risk factors (e.g. trauma,
Challenges and Controversies in VTE Prediction: Therapeutic Management of VTE: Duration of Anticoagulation
In unprovoked VTE patients the duration of anticoagulation is one of the most important unanswered questions clinicians face on a daily basis. Clinicians and patients must balance the long-term risks of recurrent VTE off anticoagulants with the long-term risk of major bleeding to come to a treatment decision regarding the duration of anticoagulation. In unselected unprovoked VTE patients, these long term risks are closely balanced [22]. Attention has turned towards identifying tools to risk
Challenges and Controversies in VTE Prediction: Therapeutic Management of VTE- PE Risk Stratification for Selection of PE Treatment Setting
Patients experiencing PE face their highest mortality risks from PE in the minutes and days that follow the event. Treatment setting for the initial management of PE is an area of wide international practice variation. In some centers in Canada PE is treated in an outpatient setting in up to 55% of patients [31], [32]. In these centers patients are selected for outpatient therapy based on the absence of 1) need for oxygen, 2) hemodynamic instability, 3) history of pre-syncope or syncope as
Conclusion
In many areas of diagnostic and therapeutic management of the PE and DVT clinical decision rules and D-dimer are promising tools to improve cost-effective clinical care. However, knowledge translation barriers and wide international practice variation points to the need for future research. This future research will need to simplify these rules so they are ultimately adopted in routine clinical practice after adequate validation so that practice variation becomes limited. Technology may improve
Conflict of Interest Statement
Marc Rodger has received grant funding from Biomerieux for the conduct of studies exploring the role of D-Dimer in predicting the risk of recurrent VTE in unprovoked VTE patients.
Funding
No funding was obtained to write this review
Acknowledgements
Marc Rodger was supported through the Heart and Stroke Foundation with a Career Investigator Award and is the recipient of a University of Ottawa Faculty of Medicine Research Chair Awards and a University of Ottawa Department of Medicine Research Salary Award. Dr. Phil Wells held a Canada Research Chair in Thromboembolic Diseases.
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