SimpliRed and diagnosis of deep venous thrombosis
Date First Published:
March 1, 2000
Last Updated:
May 6, 2003
Report by:
Steve Jones, Clinical Research Fellow (Manchester Royal Infirmary)
Search checked by:
Magnus Harrison, Manchester Royal Infirmary
Three-Part Question:
In a [patient with a suspected DVT] does the [SimpliRed test] reliably [rule out the diagnosis]?
Clinical Scenario:
A patient attends the Emergency Department with signs and symptoms consistent with a Deep Venous Thrombosis. Somebody suggests that there is a new bedside blood test, called SimpliRed, that may help to rule out the diagnosis in your patient. You know that ruling out a diagnosis is possible by having a test with a high sensitivity or negative predictive value. You wonder what evidence there is to suggest that SimpliRed fulfils these criteria?
Search Strategy:
Medline 1966-11/00 using the OVID interface.
Search Details:
{[(exp thrombosis OR exp venous thrombosis OR thrombosis.mp OR venous thrombosis.mp OR deep venous thrombosis.mp) AND (exp fibrin fibrinogen degradation products OR simplired.mp OR d-dimer$.mp)] LIMIT to human and English} OR Medline 1966-11/00 using OVID interface. simplired.mp.
Outcome:
741 and 37 papers found of which 13 were relevant and of sufficient quality. These 13 remaining papers are shown in the table.
Relevant Paper(s):
| Study Title | Patient Group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
|---|---|---|---|---|---|
| A novel and rapid whole-blood assay for D-dimer in patients with clinically suspected deep vein thrombosis. Wells PS, Brill-Edwards P, Stevens P, et al. 1995, Canada | 214 consecutive patients referred for investigation of ?DVT | Prospective cohort | Prevalence | 25% | No sample size calculation Excluded patients with inconclusive venograms or plethysmogram |
| Sensitivity | 88% (CI 77-96) | ||||
| Specificity | 77% (CI 63-80) | ||||
| Negative predictive value (NPV) | 95% (CI 89-98) | ||||
| Likelihood ratio for negative result (NLR) | 0.16 | ||||
| Application of a bedside whole blood D-dimer assay in the diagnosis of deep vein thrombosis. Brenner B, Pery M, Lanir N, et al. 1995, Israel | 86 consecutive patients referred for investigation of ?DVT | Prospective cohort | Prevalence | 58% | Small patient numbers No sample size calculation No confidence intervals |
| Sensitivity | 94% | ||||
| Specificity | 61% | ||||
| NPV | 88% | ||||
| NLR | 0.1 | ||||
| Reliable rapid blood test for the exclusion of venous thromboembolism in symptomatic outpatients. Turkstra F, van Beek EJ, ten Cate JW, Buller HR. 1996, Netherlands | 234 consecutive patients referred for ?DVT or ?PE | Prospective cohort | Prevalence | 27% | No sample size calculation (but good numbers) |
| Sensitivity | 100% (CI 95-100) | ||||
| Specificity | 58% (CI 50-65) | ||||
| NPV | 100% (CI 96-100) | ||||
| Reliability of five rapid D-dimer assays compared to ELISA in the exclusion of deep venous thrombosis. Janssen MC, Heebels AE, de Metz M, et al. 1997, Netherlands | 132 patients referred to ED or OPD for investigation of ?DVT | Prospective cohort | Prevalence | 67% | No sample size calculation Technique of assay may have affected results Reference standard not applied to all patients |
| Sensitivity | 61% (CI 51-71) | ||||
| Specificity | 90% (CI 81-99) | ||||
| NPV | 52% (CI 29-75) | ||||
| NLR | 0.43 | ||||
| The use of D-dimer testing and impedance plethysmographic examination in patients with clinical indications of deep vein thrombosis. Ginsberg JS, Kearon C, Douketis J, et al. 1997, Canada | 398 consecutive patients referred to thromboembolic OPD as first episode of ?DVT | Prospective management study | NPV D-dimer alone | 97.1% (CI 94.5 –98.8) | No sample size calculation Reference standard not applied to all patients |
| NPV D-dimer and plethysmography together | 98.5% (CI 96.3 – 99.6) | ||||
| Whole-blood immunoassay (SimpliRED) versus plasma immunoassay (NycoCard) for the diagnosis of clinically suspected deep vein thrombosis. Mayer W, Hirschwehr R, Hippmann G, et al. 1997, Austria | 108 consecutive patients referred to vascular laboratory as ?DVT | Prospective cohort | Prevalence | 31% | Small patient numbers No sample size calculation Used single ultrasound as reference standard |
| Sensitivity | 100% (CI 89-100) | ||||
| Specificity | 75% (CI 63-84) | ||||
| NPV | 100% (CI 94-100) | ||||
| Bedside testing (SimpliRED) in the diagnosis of deep vein thrombosis. Evaluation of 250 patients. Wildberger JE, Vorwerk D, Kilbinger M, et al. 1998, Germany | 250 consecutive patients referred for venography | Prospective cohort | Sensitivity | 96% | No sample size calculation Patient selection bias No confidence intervals |
| Specificity | 59% | ||||
| NPV | 97% | ||||
| NLR | 0.06 | ||||
| SimpliRED D-dimer can reduce the diagnostic tests in suspected deep vein thrombosis [letter]. Wells PS, Anderson DR, Bormanis J, et al 1998, Canada | 496 consecutive outpatients referred with ?DVT | Prospective cohort | Overall sensitivity | 94% | No sample size calculation Patient selection bias No confidence intervals |
| Overall specificity | 71% | ||||
| NPV | 98% (CI 96-99) | ||||
| NLR | 0.08 | ||||
| Low pretest probability: | 87% | ||||
| Sensitivity | 76% | ||||
| Specificity | 99% (CI 97-100) | ||||
| NPV | 0.17 | ||||
| NLR | 89% | ||||
| Medium pretest probability: | 64% | ||||
| Sensitivity | 97% (CI 90-99) | ||||
| Specificity | 0.17 | ||||
| NPV | 98% | ||||
| NLR | 54% | ||||
| High pretest probability: | 86% (CI 42-97) | ||||
| Sensitivity | 0.04 | ||||
| Specificity | |||||
| NPV | |||||
| NLR | |||||
| SimpliRED D-dimer assay: comparability of capillary and citrated venous whole blood, between-assay variability, and performance of the test for exclusion of deep vein thrombosis in symptomatic outpati Mauron T, Baumgartner I, Z'Brun A, et al. 1998, Switzerland | 45 consecutive outpatients referred with ?DVT | Prospective cohort | Prevalence | 33% | Small patient numbers No sample size calculation Wide confidence intervals |
| Sensitivity | 53% (CI 28-78) | ||||
| Specificity | 70% (CI 54-86) | ||||
| NPV | 75% (CI 59-91) | ||||
| NLR | 0.67 | ||||
| Rapid fibrin D-dimer tests for deep venous thrombosis: factors affecting diagnostic utility. Carter CJ, Serrano K, Breen DJ, et al. 1999, Canada | 200 consecutive patients referred to diagnostic radiology department with ?DVT Inpatients and outpatients |
Prospective cohort | Prevalence | 28% | No sample size calculation Used single ultrasound as reference standard Wide confidence intervals |
| Sensitivity | 87% (CI 80-96) | ||||
| Specificity | 79% | ||||
| NPV | 94% | ||||
| NLR | 0.16 | ||||
| Combination of a clinical risk assessment score and rapid whole blood D-dimer testing in the diagnosis of deep vein thrombosis in symptomatic patients. Lennox AF, Delis KT, Serunkuma S, et al. 1999, UK | 200 consecutive patients referred to diagnostic radiology department with ?DVT Inpatients and outpatients |
Prospective cohort | Prevalence | 23% | No sample size calculation Incorrect test procedure likely to give falsely high sensitivities No confidence intervals |
| Sensitivity | 91% | ||||
| Specificity | 82% | ||||
| NPV | 97% | ||||
| NLR | 0.11 | ||||
| A negative SimpliRed D-dimer assay result does exclude the diagnosis of deep venous thrombosis or pulmonary embolus in emergency department patients. Farrell S, Hayes T, Shaw M. 2000, USA | 173 consecutive patients referred to ED with ?DVT (48) or ?PE (125) | Prospective clinical trial | Prevalence | 33% | Did not recruit all patients required Used single ultrasound as reference standard Wide confidence intervals |
| Sensitivity | 56% (CI 32-81) | ||||
| NPV | 77% (CI 62-92) | ||||
| NLR | 0.61 (CI 0.34 -1.11) | ||||
| Exclusion of deep venous thrombosis with D-dimer testing – comparison of 13 D-dimer methods in 99 outpatients suspected of deep venous thrombosis using venography as reference standard. van der Graaf F, van den Borne H, van der Kolk M, et al. 2000, Netherlands | 112 outpatients referred to department | Prospective cohort | Prevalence | 50% | Small patient numbers No sample size calculation Wide confidence intervals |
| Sensitivity | 80% (CI 66-90) | ||||
| Specificity | 94% (CI 83-99) | ||||
| NPV | 82% (CI 70-91) | ||||
| NLR | 0.21 |
Author Commentary:
The "gold standard" investigation for DVT is contrast venography. This has now been replaced in many centres with a strategy of single or serial compression ultrasound, hence the use of different reference standard tests.
If an investigation is to be used in order to rule out a diagnosis, then it must have a sensitivity of 95% or above. In some of the studies mentioned this is the case, however such is the variability of the results obtained in the other studies the safety of SimpliRed as a lone exclusionary test must be in question. The reasons for this variability may include the operators of the assay or the various techniques used. Many of the results however are still inadequate.
If an investigation is to be used in order to rule out a diagnosis, then it must have a sensitivity of 95% or above. In some of the studies mentioned this is the case, however such is the variability of the results obtained in the other studies the safety of SimpliRed as a lone exclusionary test must be in question. The reasons for this variability may include the operators of the assay or the various techniques used. Many of the results however are still inadequate.
Bottom Line:
It is not safe to use SimpliRed as a lone exclusionary test for a patient presenting to the Emergency Department with a possible DVT.
References:
- Wells PS, Brill-Edwards P, Stevens P, et al.. A novel and rapid whole-blood assay for D-dimer in patients with clinically suspected deep vein thrombosis.
- Brenner B, Pery M, Lanir N, et al.. Application of a bedside whole blood D-dimer assay in the diagnosis of deep vein thrombosis.
- Turkstra F, van Beek EJ, ten Cate JW, Buller HR.. Reliable rapid blood test for the exclusion of venous thromboembolism in symptomatic outpatients.
- Janssen MC, Heebels AE, de Metz M, et al.. Reliability of five rapid D-dimer assays compared to ELISA in the exclusion of deep venous thrombosis.
- Ginsberg JS, Kearon C, Douketis J, et al.. The use of D-dimer testing and impedance plethysmographic examination in patients with clinical indications of deep vein thrombosis.
- Mayer W, Hirschwehr R, Hippmann G, et al.. Whole-blood immunoassay (SimpliRED) versus plasma immunoassay (NycoCard) for the diagnosis of clinically suspected deep vein thrombosis.
- Wildberger JE, Vorwerk D, Kilbinger M, et al.. Bedside testing (SimpliRED) in the diagnosis of deep vein thrombosis. Evaluation of 250 patients.
- Wells PS, Anderson DR, Bormanis J, et al. SimpliRED D-dimer can reduce the diagnostic tests in suspected deep vein thrombosis [letter].
- Mauron T, Baumgartner I, Z'Brun A, et al.. SimpliRED D-dimer assay: comparability of capillary and citrated venous whole blood, between-assay variability, and performance of the test for exclusion of deep vein thrombosis in symptomatic outpati
- Carter CJ, Serrano K, Breen DJ, et al.. Rapid fibrin D-dimer tests for deep venous thrombosis: factors affecting diagnostic utility.
- Lennox AF, Delis KT, Serunkuma S, et al.. Combination of a clinical risk assessment score and rapid whole blood D-dimer testing in the diagnosis of deep vein thrombosis in symptomatic patients.
- Farrell S, Hayes T, Shaw M.. A negative SimpliRed D-dimer assay result does exclude the diagnosis of deep venous thrombosis or pulmonary embolus in emergency department patients.
- van der Graaf F, van den Borne H, van der Kolk M, et al.. Exclusion of deep venous thrombosis with D-dimer testing – comparison of 13 D-dimer methods in 99 outpatients suspected of deep venous thrombosis using venography as reference standard.