Summary of findings for the use of VWF multimer analysis and VWF:CB/VWF:Ag ratio for the classification of type 2 VWD
| VWF multimer analysis VWF:CB/VWF:Ag Sensitivity: 0.94 (95% CI, 0.90-0.99)/Sensitivity: 0.84 (95% CI, 0.71-0.92) Specificity: 0.97 (95% CI, 0.94-0.99)/Specificity: 0.95 (95% CI, 0.90-0.98) | Prevalences: 80%* |
| VWF multimer analysis VWF:CB/VWF:Ag Sensitivity: 0.94 (95% CI, 0.90-0.99)/Sensitivity: 0.84 (95% CI, 0.71-0.92) Specificity: 0.97 (95% CI, 0.94-0.99)/Specificity: 0.95 (95% CI, 0.90-0.98) | Prevalences: 80%* |
| . | . | . | Factors that may decrease certainty of evidence . | Effect per 1000 patients tested Pretest probability of 80% . | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Outcome . | Studies (n); patients (n) . | Study design . | Risk of bias . | Indirectness . | Inconsistency . | Imprecision . | Publication bias . | VWF multimer analysis . | VWF:CB/Ag . | Test accuracy CoE . |
| True positives (patients with VWD type 2) | 9;476 | Cohort & case-control type studies | Very serious† | Not serious | Not serious | Serious‡ | None | 720 (720-792) | 720 (624-768) | ⨁◯◯◯ VERY LOW |
| 0 fewer TP in VWF multimer analysis | ||||||||||
| False negatives (patients incorrectly classified as not having VWD type 2) | 80 (8-80) | 80 (32-176) | ||||||||
| 0 fewer FN in VWF multimer analysis | ||||||||||
| True negatives (patients without VWD type 2) | 9;948 | Cohort & case-control type studies | Very serious† | Not serious | Not serious | Serious‡ | None | 194 (188-198) | 190 (178-196) | ⨁◯◯◯ VERY LOW |
| 4 more TN in VWF multimer analysis | ||||||||||
| False positives (patients incorrectly classified as having VWD type 2) | 6 (2-12) | 10 (4-22) | ||||||||
| 4 fewer FP in VWF multimer analysis | ||||||||||
| . | . | . | Factors that may decrease certainty of evidence . | Effect per 1000 patients tested Pretest probability of 80% . | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Outcome . | Studies (n); patients (n) . | Study design . | Risk of bias . | Indirectness . | Inconsistency . | Imprecision . | Publication bias . | VWF multimer analysis . | VWF:CB/Ag . | Test accuracy CoE . |
| True positives (patients with VWD type 2) | 9;476 | Cohort & case-control type studies | Very serious† | Not serious | Not serious | Serious‡ | None | 720 (720-792) | 720 (624-768) | ⨁◯◯◯ VERY LOW |
| 0 fewer TP in VWF multimer analysis | ||||||||||
| False negatives (patients incorrectly classified as not having VWD type 2) | 80 (8-80) | 80 (32-176) | ||||||||
| 0 fewer FN in VWF multimer analysis | ||||||||||
| True negatives (patients without VWD type 2) | 9;948 | Cohort & case-control type studies | Very serious† | Not serious | Not serious | Serious‡ | None | 194 (188-198) | 190 (178-196) | ⨁◯◯◯ VERY LOW |
| 4 more TN in VWF multimer analysis | ||||||||||
| False positives (patients incorrectly classified as having VWD type 2) | 6 (2-12) | 10 (4-22) | ||||||||
| 4 fewer FP in VWF multimer analysis | ||||||||||
Typically seen in patients with VWD type 2 in need for additional testing for subtype classification.
Case-control design makes patient selection bias serious. Different cutoffs were used in the VWF:CB/Ag ratios (0.5 in Popov vs 0.7 in Flood). The majority of included studies were judged to be low risk of bias for test and reference standard interpretation. Although there was unclear reporting regarding flow and timing in some studies, the certainty of evidence was generally not downgraded for risk of bias.
A different clinical decision would be considered if the upper vs lower boundary of the pooled effect estimate was used.