Prospective Study of the Diagnostic Accuracy of the Simplify D-dimer Assay for Pulmonary Embolism in Emergency Department Patients: Materials and Methods
Typical indications for the PE rule-out protocol included symptoms of dyspnea, chest pain, or syncope, or physical signs such as a rapid pulse or low pulse oximetry reading that could not be explained by another disease process. Exclusions were hemodynamic instability (clinical signs of shock as described by Jones et al), inability to obtain a blood sample for the d-dimer assay, or patient unwillingness to participate. Prior to diagnostic testing, physicians completed a Web-based electronic data collection form that contained > 70 data fields. The contents and methodology of this Web-based form have been published. The form first asks the clinician to provide his or her own three-tiered, unstructured pretest probability (low, < 15%; moderate, 15 to 40%; high, > 40%), and later parts of the data form contained elements required to compute the Canadian score and the Charlotte rule. The Charlotte rule, when negative, predicts a low-enough pretest probability to allow PE to be ruled out safely using either a quantitative d-dimer or a qualitative d-dimer in conjunction with a normal alveolar dead space measurement. comments
The Charlotte rule has not yet been tested or validated to allow PE to be ruled out with a qualitative d-dimer alone. D-dimer results were obtained prior to any pulmonary vascular imaging, and all patients with positive d-dimer assay results underwent imaging. Imaging was performed in a minority of patients with negative d-dimer results at the discretion of the attending emergency physician. Our institutionally approved PE rule-out protocol required that clinicians order pulmonary vascular imaging in patients with either a positive Charlotte rule or a high unstructured pretest probabili-ty. However, in these higher-risk patients, physicians were free to simultaneously order the Simplify D-dimer assay in addition to performing pulmonary vascular imaging.
Arterial blood was used with the Simplify D-dimer assay. Blood was drawn by qualified respiratory therapists, usually from the radial artery; >1 mL was collected in an arterial blood gas syringe containing lithium-heparin. The d-dimer assay was then performed in the ED by the respiratory therapist using a written protocol in accordance with manufacturer recommendations. All therapists underwent a structured training process overseen by the principle investigator, which included a semiannual quality assurance evaluation as required by government agencies.