D‐dimer test for excluding the diagnosis of pulmonary embolism
Appendices
Appendix 1. MEDLINE search strategy
Database: Ovid MEDLINE(R)
1. exp Pulmonary Embolism/
2. (pulmonary adj embol$).ti,ab.
3. (pulmonary adj thrombo$).ti,ab.
4. (lung adj embol$).ti,ab.
5. (lung adj thrombo$).ti,ab.
6. (PE or PTE).ti,ab.
7. or/1‐6
8. Fibrin Fibrinogen Degradation Products/an, me [Analysis, Metabolism]
9. Biological Markers/an, bl, me [Analysis, Blood, Metabolism]
10. Enzyme‐Linked Immunosorbent Assay/
11. "Nephelometry and Turbidimetry"/
12. d‐dimer.ti,ab.
13. (fibrin adj2 d).ti,ab.
14. dimeri?ed plasmin.ti,ab.
15. elisa?.ti,ab.
16. elfa?.ti,ab.
17. enzyme linked.ti,ab.
18. latex agglutination.ti,ab.
19. (latex adj3 assay?).ti,ab.
20. blood agglutination.ti,ab.
21. Immunoturbidimetr$.ti,ab.
22. turbidimetr$.ti,ab.
23. SimpliRed.ti,ab.
24. Minutex.ti,ab.
25. NycoCard.ti,ab.
26. "Instant I.A".ti,ab.
27. Vidas.ti,ab.
28. LIATEST.ti,ab.
29. ("IL test" or IL‐DD).ti,ab.
30. Turbiquant.ti,ab.
31. Asserachrom.ti,ab.
32. Enzygnost.ti,ab.
33. Fibrinostika.ti,ab.
34. "BC DD".ti,ab.
35. (Tinaquant or Tina‐quant).ti,ab.
36. TriniLIZE.ti,ab.
37. biopool.ti,ab.
38. TintElize.ti,ab.
39. HemosIL.ti,ab.
40. Innovance‐DD.ti,ab.
41. stratus.ti,ab.
42. FDP.ti,ab.
43. Dimertest.ti,ab.
44. (LPIA or EIA).ti,ab.
45. or/8‐44
46. 7 and 45
Appendix 2. EMBASE search strategy
Database: Ovid Embase
1. lung embolism/
2. (pulmonary adj embol$).ti,ab.
3. (pulmonary adj thrombo$).ti,ab.
4. (lung adj embol$).ti,ab.
5. (lung adj thrombo$).ti,ab.
6. (PE or PTE).ti,ab.
7. or/1‐6
8. fibrin degradation product/cr [Drug Concentration]
9. biological marker/cr [Drug Concentration]
10. D dimer/cr [Drug Concentration]
11. enzyme linked immunosorbent assay/
12. turbidimetry/
13. d‐dimer.ti,ab.
14. (fibrin adj2 d).ti,ab.
15. dimeri?ed plasmin.ti,ab.
16. elisa?.ti,ab.
17. elfa?.ti,ab.
18. enzyme linked.ti,ab.
19. Immunoturbidimetr$.ti,ab.
20. turbidimetr$.ti,ab.
21. latex agglutination.ti,ab.
22. (latex adj3 assay?).ti,ab.
23. blood agglutination.ti,ab.
24. SimpliRed.ti,ab.
25. Minutex.ti,ab.
26. NycoCard.ti,ab.
27. "Instant I.A".ti,ab.
28. Vidas.ti,ab.
29. LIATEST.ti,ab.
30. ("IL test" or IL‐DD).ti,ab.
31. Turbiquant.ti,ab.
32. Asserachrom.ti,ab.
33. Enzygnost.ti,ab.
34. Fibrinostika.ti,ab.
35. "BC DD".ti,ab.
36. (Tinaquant or Tina‐quant).ti,ab.
37. TriniLIZE.ti,ab.
38. biopool.ti,ab.
39. TintElize.ti,ab.
40. (HemosIL‐DD or HemosIL‐DDHS).ti,ab.
41. Innovance‐DD.ti,ab.
42. stratus.ti,ab.
43. FDP.ti,ab.
44. Dimertest.ti,ab.
45. (LPIA or EIA).ti,ab.
46. or/8‐45
47. 7 and 46
Appendix 3. QUADAS‐2
| Domains, Signalling Questions (SQ) and Applicability | Rating criteria |
| Domain 1: Patient selection | |
| A. Risk of bias | Describe the methods of patients' selection given in the paper: |
| SQ1: Was a consecutive or random sample of patients enrolled? | Yes: It is stated that the sample was consecutive or a random sample No: It is stated that the sample was not consecutive or a random sample Unclear: The method of sampling is ambiguous |
| SQ2: Did the study avoid inappropriate exclusions? | Yes: The study excluded patients without CPR scores No: The study excluded patients who had received a PTP score using CPRs. Unclear: The test history of the patients in the study is not revealed in the report |
| SQ3: Did the study avoid inappropriate inclusions? | Yes: The study included only outpatients who had received a PTP score for PE using a CPR No: The study included some inappropriate patients, for example, those without a PTP score from a CPR, or included inpatients Unclear: The study's inclusion criteria allow for inappropriate inclusions |
| Applicability Question 1: Are there concerns that the included patients and setting do not match the review question? | High: The study population meets the eligibility criteria Low: The patient population is skewed in some way, for example the study includes mainly younger patients Unclear: Not enough information is given about the study population |
| B. Concerns regarding applicability | Give the paper's description of the inclusion/exclusion criteria, including setting, prior tests, symptoms here |
| Domain 2: Index test | |
| A. Risk of bias | Give the paper's description of the D‐dimer assay, how it was conducted and interpreted including the training of the individual of those carrying out the test |
| SQ1: If a threshold was used was it prespecified? | Yes: Plasma D‐dimer levels are prespecified in the study methods section as a positive test result No: The threshold for a positive test result is not prespecified Unclear: It is unclear if a threshold was used |
| B. Concerns regarding applicability | |
| AQ2: Are there concerns that the index test, its conduct or its interpretation differ from the review question? | Yes: The plasma D‐Dimer test did not use standard methods and is unvalidated No: The presence of plasma D‐dimer was detected using standard D‐dimer test methods previously validated Unclear: The basis of the outcome is unclear |
| Domain 3: Reference standard | |
| A. Risk of bias | Give the paper's description of the pulmonary angiography, scintigraphy, computed tomography PA and follow‐up and how they were conducted and interpreted including the training of the individual of those carrying out the test |
| SQ1: Is the reference standard likely to correctly classify the target condition? | Yes: The reference standard(s) was either pulmonary angiography, CTPA, MRPA, or V/Q scanning No: The reference standard(s) was not any of the above Unclear: Information regarding the conduct of the reference standard is insufficient |
| SQ2: Were the reference standard test results interpreted without knowledge of the index test results? | Yes: The person classifying the RS test results was unaware of the D‐dimer test results No: The person classifying the RS test results was aware of the D‐dimer test results Unclear: No information is available regarding the blinding of test results |
| SQ3: Did the person conducting the pulmonary angiography, V/Q scanning, CTPA, or MRPA have expertise comparable to a radiologist? | Yes: It is stated that a radiologist or similar (e.g. vascular specialist with an interest in VTE) read the test results No: The person conducting the pulmonary angiography, V/Q scanning, CTPA, or MRPA was not a radiologist or similar Unclear: The expertise and background discipline of the reader is not made clear |
| Applicability: Could the reference standard, its conduct, or its interpretation have introduced bias? | High: The RS tests were performed by a person with expertise and were interpreted blind Low: The RS tests were not performed by a person with expertise or were not interpreted blind. Unclear: No information about the persons conducting the tests, or interpreting the results is given |
| Domain 4: Flow and timing | |
| A. Risk of bias | Describe the reasons why any patient recruited into the study did not contribute to the 2 x 2 table (i.e. patients who did not undergo the RS tests) referring to the flow diagram |
| SQ1: was there an appropriate interval between the index test and the reference standard? | Yes: The index and reference standard tests were all conducted within 7 days of each other No: Some of the reference standard test results were obtained after more than 7 days Unclear: No information about the relative timing of the tests is provided |
| SQ2: Did all the patients receive the same reference standard? | Yes: A complete set of RS test results are available for all study patients No: The RS results are not available for all patients, or some patients had follow‐up only Unclear: It is not clear whether all patients received an acceptable reference standard |
| SQ3: Were all patients included in the final analysis? | Yes: Data for all study patients are reported No: Data for all study patients are not reported Unclear: It is not clear whether there were patients recruited but not included in the 2 x 2 table |
| CPR | Predictive elements and scoring system |
| Three‐level Wells score | The predictive elements of this CPR are: clinical signs and symptoms of DVT (3 points), alternative diagnosis less likely than PE (3 points), heart rate > 100 beats per minute (1.5 points), immobilisation for more than 3 days or recent (< 4 weeks) surgery (1.5 points), previous VTE (1.5 points), haemoptysis (1 point), cancer treatment in the previous 6 months or palliative care (1 point). Low probability ‐ less than 2; intermediate probability ‐ 2 to 6; high probability ‐ more than 6. |
| Two‐level Wells score | The predictive elements of the two‐level Wells score are the same as the three‐level Wells score but patients are categorised into two as opposed to three categories, PE likely or PE unlikely based on a score of more than 4 or 4 or less points respectively. |
| The simplified Wells score | The same predictive elements as the three‐level Wells score are used but the points scoring has been simplified ‐ each item now scores 1 point. Patients are regarded as low risk if they have 1 point or less, and high risk if they score more than 1. |
| The Geneva score | The predictive elements of the Geneva score are: recent surgery (3 points), previous history of PE or DVT (2 points), heart rate > 100 beats per minute (1 point), 60‐79 years old (1 point), 80 or more years old (2 points), chest radiograph showing atelectasis (1 point), chest radiograph showing elevated hemidiaphragm (1 point), partial pressure of oxygen (PaO2) < 49 mm Hg (4 points), PaO2 49‐59 mm Hg (3 points), PaO2 60‐71 mm Hg (2 points), PaO2 72‐82 mm Hg (1 point), and partial pressure of carbon dioxide (PaCO2) < 36 mm Hg (2 points), PaCO2 36‐38.9 mm Hg (1 point). Risk of PE is scored low (0 ‐ 4 points), intermediate (5 ‐ 8 points), or high (9 or more points). |
| The revised Geneva score | The predictive elements of the revised Geneva score are: age > 65 years old (1 point), previous history of PE or DVT (3 points), surgery with general anaesthesia or fracture within one month of the symptoms arising (2 points), active malignancy (2 points), heart rate 75‐94 beats per minute (3 points), heart rate > 94 beats per minute (5 points), pain on leg venous palpation and unilateral oedema (4 points), haemoptysis (2 points), and unilateral leg pain (3 points). This CPR is scored low risk (0 ‐ 3 points), intermediate (4 ‐ 10 points), or high risk (11 or more points). |
| The simplified revised Geneva score | The same predictive elements are used as in the revised score Geneva score but the points scoring has been simplified. Each item now scores 1 point. The risk of PE is scored low (0 ‐ 1 point), intermediate (2 ‐ 4 points), or high (5 or more points). |
| The Charlotte rule | The elements of the Charlotte rule are: > 50 years old, heart rate higher than the systolic blood pressure, unexplained hypoxaemia (O2 < 95%), recent surgery (previous four weeks), haemoptysis, and unilateral leg swelling. The risk score from the Charlotte rule is classified as either safe (all of the predictive elements absent), or unsafe (any of the predictive elements present). |
