title: The risk of a first and a recurrent venous thrombosis associated with an elevated D-dimer level and an elevated thrombin potential: results of the THE-VTE study.
abstract: BACKGROUND
  D-dimer and thrombin generation have been associated with the risk of recurrent venous thrombosis. However, for both measurements, different assays are available, and in vitro thrombin generation may be affected by the problem of contact activation during blood sampling.
  
  
  OBJECTIVE
  To determine the association between hypercoagulability and first and recurrent thrombosis by the use of different D-dimer and thrombin generation assays, to assess whether the addition of corn trypsin inhibitor (CTI) prior to blood sampling to inhibit contact activation improved the association between thrombin generation and thrombosis risk, and to calculate the DASH score with two different D-dimer assays.
  
  
  METHODS
  A case-control study (626 patients and 361 controls) with subsequent follow-up of the cases was performed (2987 patient-years after stopping of anticoagulant therapy). Blood was drawn 2-3 months after discontinuation of anticoagulation for the first event in citrate tubes with and without CTI.
  
  
  CONCLUSIONS
  An elevated D-dimer level and elevated thrombin generation were associated with an increased risk of a first event regardless of the assay used (odds ratios: 1.8-3.4). An elevated D-dimer level but not elevated thrombin generation was associated with the risk of recurrence. Patients with elevated D-dimer levels had a more than two-fold increased recurrence rate (Vidas - hazard ratio [HR] 2.3, 95% confidence interval [CI] 1.4-3.8; HemosIL - HR 2.4, 95% CI 1.5-3.9; Thrombinoscope and Technoclone assay - HR 1.3). Elimination of contact factor activation did not improve the predictive value of thrombin generation. In patients with unprovoked first events, the DASH score had a similar predictive value for deep vein thrombosis and pulmonary embolism, both when calculated with Vidas D-dimer and when calculated with HemosIL D-dimer.
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: van Hylckama Vlieg
authors.affiliation: Department of Heamatology, Addenbrookes Hospital, Cambridge, UK.
authors.forename: C A
authors.initials: CA
authors.lastname: Baglin
authors.affiliation: Department of Heamatology, Addenbrookes Hospital, Cambridge, UK.
authors.forename: R
authors.initials: R
authors.lastname: Luddington
authors.affiliation: Department of Heamatology, Addenbrookes Hospital, Cambridge, UK.
authors.forename: S
authors.initials: S
authors.lastname: MacDonald
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.|Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: F R
authors.initials: FR
authors.lastname: Rosendaal
authors.affiliation: Department of Heamatology, Addenbrookes Hospital, Cambridge, UK.
authors.forename: T P
authors.initials: TP
authors.lastname: Baglin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects; D001800:Blood Specimen Collection / Q000379:methods; D016022:Case-Control Studies; D004739:England / Q000453:epidemiology; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis*; D005500:Follow-Up Studies; D006403:Hematologic Tests / Q000295:instrumentation / Q000379:methods; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D010940:Plant Proteins / Q000494:pharmacology; D011655:Pulmonary Embolism / Q000097:blood / Q000453:epidemiology; D012008:Recurrence; D012306:Risk; D012720:Severity of Illness Index; D013917:Thrombin / Q000096:biosynthesis*; D019851:Thrombophilia / Q000097:blood / Q000453:epidemiology; D020246:Venous Thrombosis / Q000097:blood / Q000453:epidemiology*; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D005338:Fibrin Fibrinogen Degradation Products; D010940:Plant Proteins; C036309:fibrin fragment D; C052160:trypsin inhibitor, Zea mays; D013917:Thrombin
keywords: D-dimer; corn trypsin inhibitor; hypercoagulability; recurrence; risk; venous thrombosis