title: Never ignore extremely elevated D-dimer levels: they are specific for serious illness.
abstract: BACKGROUND
  D-dimer is routinely measured as part of the clinical diagnosis algorithms for venous thromboembolism (VTE). In these algorithms, low D- dimer cut-off values are used to generate a dichotomous test result that is sensitive, but very non-specific for VTE. A consequence of any test dichotomisation is loss of information that is hidden in the continuous spectrum of results. For D-dimer, the information conveyed by extremely elevated results may be particularly relevant. Our aim was to assess the differential diagnosis of extremely elevated D-dimer levels in a hospital setting.
  
  
  METHODS
  Retrospective cohort study of patients > 18 years with an extremely elevated (> 5000 μg/l; > 10x cut-off to exclude VTE) D-dimer test result. Electronic medical records were reviewed for diagnoses.
  
  
  RESULTS
  A total of 759 extremely elevated D-dimer results were identified. After exclusion of 120 duplicate cases, 53 patients undergoing cardiopulmonary resuscitation, and 5 cases without diagnostic information, 581 cases were analysed. Their D-dimer ranged between 5030 and 239,000 μg/l, with a mean of 17,598 μg/l (SD 22,972 μg/l). Altogether, 89% of these patients had a diagnosis of VTE, sepsis and/or cancer. The prevalence was highest for pulmonary embolism (183 patients; 32%), followed by cancer (168 patients; 29%), sepsis (142 patients; 24%), trauma/surgery (142 patients; 24%), and deep vein thrombosis (73 patients; 13%).
  
  
  CONCLUSIONS
  Although D-dimer testing has a reputation for being very non-specific, an extremely elevated D-dimer is uniquely associated with severe disease, mainly including VTE, sepsis and/or cancer. These results suggest that, even if sharply elevated D-dimers are a seemingly solitary finding, clinical suspicion of severe underlying disease should be maintained.
authors.affiliation: Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Schutte
authors.forename: A
authors.initials: A
authors.lastname: Thijs
authors.forename: Y M
authors.initials: YM
authors.lastname: Smulders
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003937:Diagnosis, Differential; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D011655:Pulmonary Embolism / Q000175:diagnosis / Q000378:metabolism*; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D018805:Sepsis / Q000175:diagnosis / Q000378:metabolism*; D020246:Venous Thrombosis / Q000175:diagnosis / Q000378:metabolism*
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D