GRADE test accuracy evidence summary for using different VWF levels to diagnose type 1 VWD
| Certainty assessment . | Impact . | Certainty . | ||||||
|---|---|---|---|---|---|---|---|---|
| Studies, n . | Study design . | Risk of bias . | Inconsistency . | Indirectness . | Imprecision . | Other considerations . | ||
| Mutation detection | ||||||||
| 327,31,a | Observational | Not serious* | Not serious | Not serious | Not serious | None | For VWF:Ag < 0.3, mutations were detected in 75-82% of patients in 2 studies. For VWF:Ag = 0.3 to 0.5, mutations were detected in 44-60% of patients in 3 studies. | ⨁⨁◯◯ Low |
| LR of VWD | ||||||||
| 213 ,b | Observational | Not serious* | Not serious | Not serious | Not serious | None | In patients who were investigated for bleeding episodes, for VWF:Ag levels 30-40 dL, LR of having VWD = ∞ (in all of them, VWD was confirmed by second-level tests). For levels 41-50 dL, LR = 0.73 (0.41-1.30), and for levels 51-60 dL, LR = 0.33 (0.18-0.62).13 Using MCMDM-1VWD, in patients with VWD and family history of VWD, for VWF:Ag level < 20, LR = 374 (52.2-2677); for level 20-40, LR = 95.1 (39.1-232); for level 40-60, LR = 1.82 (1.28-2.58); and for level > 60, LR = 0.10 (0.06-0.16).b | ⨁⨁◯◯ Low |
| VWF level and BS correlation | ||||||||
| 227 ,a | Observational | Not serious* | Serious† | Not serious | Not serious | None | The majority of patients with low VWF had significant bleeding histories, as determined using the ISTH BAT or the Condensed MCMDM-1 VWD score.27 There was no difference between BS and VWF levels because the BS used was after patients were recruited in the study and were receiving treatment. Data from unpublished work showed a continuum, with a higher BS in those with lower VWF at the time of enrollment/diagnosis.a | ⨁◯◯◯ Very low |
| Bleeding tendency | ||||||||
| 113 | Observational | Not serious* | Not serious | Not serious | Not serious | None | 70 of 93 (75%) patients with borderline VWF (0.3-0.5) were investigated after a bleeding episode: mucocutaneous bleeding was present in 35, 25 bled after surgery, and 10 bled after dental procedures. Ten patients experienced >1 symptom. | ⨁⨁◯◯ Low |
| Certainty assessment . | Impact . | Certainty . | ||||||
|---|---|---|---|---|---|---|---|---|
| Studies, n . | Study design . | Risk of bias . | Inconsistency . | Indirectness . | Imprecision . | Other considerations . | ||
| Mutation detection | ||||||||
| 327,31,a | Observational | Not serious* | Not serious | Not serious | Not serious | None | For VWF:Ag < 0.3, mutations were detected in 75-82% of patients in 2 studies. For VWF:Ag = 0.3 to 0.5, mutations were detected in 44-60% of patients in 3 studies. | ⨁⨁◯◯ Low |
| LR of VWD | ||||||||
| 213 ,b | Observational | Not serious* | Not serious | Not serious | Not serious | None | In patients who were investigated for bleeding episodes, for VWF:Ag levels 30-40 dL, LR of having VWD = ∞ (in all of them, VWD was confirmed by second-level tests). For levels 41-50 dL, LR = 0.73 (0.41-1.30), and for levels 51-60 dL, LR = 0.33 (0.18-0.62).13 Using MCMDM-1VWD, in patients with VWD and family history of VWD, for VWF:Ag level < 20, LR = 374 (52.2-2677); for level 20-40, LR = 95.1 (39.1-232); for level 40-60, LR = 1.82 (1.28-2.58); and for level > 60, LR = 0.10 (0.06-0.16).b | ⨁⨁◯◯ Low |
| VWF level and BS correlation | ||||||||
| 227 ,a | Observational | Not serious* | Serious† | Not serious | Not serious | None | The majority of patients with low VWF had significant bleeding histories, as determined using the ISTH BAT or the Condensed MCMDM-1 VWD score.27 There was no difference between BS and VWF levels because the BS used was after patients were recruited in the study and were receiving treatment. Data from unpublished work showed a continuum, with a higher BS in those with lower VWF at the time of enrollment/diagnosis.a | ⨁◯◯◯ Very low |
| Bleeding tendency | ||||||||
| 113 | Observational | Not serious* | Not serious | Not serious | Not serious | None | 70 of 93 (75%) patients with borderline VWF (0.3-0.5) were investigated after a bleeding episode: mucocutaneous bleeding was present in 35, 25 bled after surgery, and 10 bled after dental procedures. Ten patients experienced >1 symptom. | ⨁⨁◯◯ Low |
BAT, bleeding assessment tool; BS, bleeding score; LR, likelihood ratio; MCMDM-1 VWD, Molecular and Clinical Marker for the Diagnosis and Management of Type 1 (MCMDM-1) VWD Bleeding Questionnaire.
The majority of included studies were judged to be at a low risk for bias for patient selection and reference standard interpretation. Although there was unclear reporting about when the index test was conducted, the certainty of evidence was not downgraded for risk of bias. The index test risk of bias was moderate in 7 cohort studies.
Results from the 2 studies are not consistent with one another.
Flood,36 . . 2016.
Tosetto,37 . . 2007.