Table 1.
Characteristics of included study cohorts. Data were sorted according to primary suspicion of pulmonary embolism (PE) or deep vein thrombosis (DVT) and setting. All studies used D-dimer cut-off value of 500 ug/L and age×10 μg/L
| Reference* | PE or DVT | No of patients (% male) | Mean age (SD) | Prevalence of VTE (%) | Setting | Reference test to rule out VTE | D-dimer assay† | CDR used (cut-off) |
|---|---|---|---|---|---|---|---|---|
| Douma 2010, derivation set6 34 | PE | 1721 (41) | 61 (19) | 24 | Hospital; outpatients presenting in emergency department or outpatient clinics | ((a) D-dimer <500 μg/L; or (b) negative results from CUS and from HCT in patients with non-high CDR; or (c) normal VQ scan or normal pulmonary angiogram) and (3 month event free follow-up) | ELFA | Wells54 (≤4) |
| Douma 2010, validation set 26 36 | PE | 1819 (49) | 59 (19) | 21 | Hospital; outpatients presenting in emergency department or outpatient clinics | ((a) Non-high CDR and D-dimer <500 μg/L; or (b) negative HCT) and (3 month event free follow-up) | ELFA | Revised Geneva score40 (≤10) |
| Penaloza 2012, French cohort16 38 | PE | 1529 (39) | Not given | 28 | Hospital; outpatients presenting in emergency department or outpatient clinics | ((a) D-dimer <500 μg/L; or (b) normal pulmonary angiogram; or (c) negative VQ scan; or (d) negative HCT; or (e) low CDR and non-diagnostic VQ or HCT and negative CUS) and (3 month event free follow-up) | ELFA or quantitative latex agglutination assay | Revised Geneva score40 (≤10) |
| Penaloza 2012, European cohort16 37 | PE | 1645 (42) | 59 | 18 | Hospital; outpatients presenting in emergency department or outpatient clinics | (a) Non-high CDR and D-dimer ELISA <500 μg/L; or (b) non-high CDR and negative moderate sensitivity D-dimer test; or (c) low CDR and low probability VQ scan or negative computed tomography angiography; or (d) negative multidetector HCT | ELFA or quantitative latex agglutination assay | Revised Geneva score40 (≤10) |
| Penaloza 2012, US cohort16 42 | PE | 7940 (33) | 49 | 5.1 | Hospital; outpatients presenting in emergency department or outpatient clinics | ((a) D-dimer <500 μg/L; or (b) normal VQ scan; or (c) non-diagnostic VQ scan and negative CUS and/or negative D-dimer (d) negative multidetector CT angiography) and (45 days follow-up) | ELFA or quantitative latex agglutination assay | Revised Geneva score40 (≤10) |
| Douma 2010, validation set 16 35 | PE | 3306 (43) | 53 (18) | 20 | Hospital: inpatients and outpatients | ((a) Unlikely clinical probability and D-dimer ≤500 μg/L; or (b) negative HCT) and (3 month event free follow-up) | ELFA or quantitative latex agglutination assay | Wells54 (≤4) |
| Van Es 201217 55 | PE | 456 (46) | 65 | 27 | Hospital: inpatients and outpatients | ((a) Unlikely clinical probability and D-dimer ≤500 μg/L; or (b) negative HCT) and (3 month event free follow-up) | ELFA or quantitative latex agglutination assays | Wells54 (≤4) |
| Schouten 2012‡18 56 | DVT | 1374 (27) | 59 (17) | 20 | Primary care patients | Normal first and repeated CUS | ELFA or quantitative latex agglutination assay | Wells9 (≤1) |
| Douma 2012, cohort 17 19 | DVT | 812 (36) | 59 (17) | 39 | Hospital; outpatients presenting in emergency department or outpatient clinics | ((a) Non-high CDR and D-dimer <500 μg/L; or (b) negative results from first CUS and D-dimer <500 μg/L; or (c) normal results from repeated CUS) and (3 month event free follow-up) | Quantitative latex agglutination assay | Wells9 (≤2) |
| Douma 2012, cohort 219 31 | DVT | 474 (38) | 61 (19) | 23 | Hospital; outpatients presenting in emergency department or outpatient clinics | ((a) D-dimer <500 μg/L; or (b) normal CUS in combination with a non-high clinical probability; or (c) normal phlebography) and (3 month event free follow-up) | ELFA | Clinical probability estimated by treating doctor31 (<80%) |
| Douma 2012, cohort 319 32 | DVT | 359 (41) | 66 (17) | 23 | Hospital; outpatients presenting in emergency department or outpatient clinics | ((a) Low CDR and D-dimer <500 μg/L and 3 month event free follow-up; or (b) normal CUS or impedance plethysmography. Patients with intermediate CDR and D-dimer <500 μg/L imaged at treating doctor’s discretion) and (3 month event free follow-up) | Quantitative latex agglutination assay | Wells9 (≤2) |
| Douma 2012, cohort 419 33 | DVT | 556 (38) | 65 (16) | 10 | Hospital; outpatients presenting in emergency department or outpatient clinics | ((a) Non-high CDR and normal D-dimer test and 3 month event free follow-up; or (b) normal repeated CUS) and (3 month event free follow-up) | Quantitative latex agglutination assay | Wells9 (≤2) |
| Douma 2012, cohort 5 19 (Tan et al, unpublished) | DVT | 617 (52) | 58 (18) | 37 | Hospital; outpatients presenting in emergency department or outpatient clinics | (a) Unlikely CDR and D-dimer <500 μg/L; or (b) negative results from (first) leg venous CUS in combination with normal D-dimer <500 μg/L; or (c) normal repeated CUS | Quantitative latex agglutination assay | Wells9 (≤1) |
PE=pulmonary embolism; DVT=deep vein thrombosis; VTE=venous thromboembolism; CDR=clinical decision rule; ELISA=enzyme linked immunosorbent assay; ELFA=enzyme linked fluorescent assay; CUS=compression ultrasonography of leg (if repeated; 6-8 days after initial presentation); HRCT=helical computed tomography of chest; VQ=ventilation perfusion.
*Second reference refers to primary studies describing cohort.
†Classified according to Heim et al and Di Nisio et al.2 48
‡Study also presented data for cut-off value of 750 ug/L in patients aged >60 years.18 These data were not included in this meta-analysis.