Evidence summary for the use of VWF propeptide to VWF:Ag ratio and desmopressin trial for the diagnosis of type 1C VWD
| Outcomes . | Impact . | participants (n, studies) . | Certainty of the evidence (GRADE) . |
|---|---|---|---|
| VWFpp/VWF:Ag ratio correlation with VWF:Ag half-life | In Sztukowska,50 a pronounced drop in VWF survival in the type Vicenza VWD patients was reported: mean half-life significantly shorter than in control groups (1.3 ± 0.2 h, vs 15.4 ± 2.5 h; P < .0001). A dramatic increase in VWFpp ratio in the type Vicenza VWD cases was shown: VWFpp ratio from 7.14 to 17.7, mean 13.02 ± 0.49; 10× higher than in the control group (P < .001).In Haberichter,43 a substantially increased VWFpp/VWF:Ag ratio was predictive of a significantly decreased VWF half-life in 7 individuals who had a >twofold desmopressin response and an initial VWF:Ag <30 IU/dL. Three individuals had a decreased VWF half-life that was not predicted by an increased VWFpp/VWF:Ag ratio. Individuals who had a substantially increased VWFpp/VWF:Ag ratio and significantly reduced VWF:Ag level were also found to have an enhanced response to desmopressin (>fourfold increase). The desmopressin response was found to correlate with the VWFpp/VWF:Ag ratio (r = 0.92; P < .001) | (2 Observational studies) | ⨁◯◯◯ VERY LOW |
| Correlation of the VWFpp/VWF:Ag ratio with the presence or absence of a VWF gene mutation | In Haberichter,21 all affected individuals harbored a VWF gene mutation and showed an increased ratio, whereas no mutation was detected in unaffected individuals. In Eikenboom,44 the increased VWFpp/VWF:Ag ratio was particularly raised (median, 4.3) in patients with slightly abnormal multimers and mutations. An increased VWFpp/VWF:Ag ratio was a good predictor of VWD patients with mutations in the VWF gene: a VWFpp/VWF:Ag >3 had a positive predictive value for the presence of a VWF mutation of 98% with a specificity of 99% in the entire cohort of patients and family members.In Stufano,45 the genetic analysis of the mutation at codon 1205 in the group (n = 14) with the markedly increased VWF clearance distinguished between VWD type 1 Vicenza (characterized by the presence of the mutation p.R1205H) and AVWS (absence of this mutation). | (3 Observational studies) | ⨁⨁◯◯ LOW |
| Outcomes . | Impact . | participants (n, studies) . | Certainty of the evidence (GRADE) . |
|---|---|---|---|
| VWFpp/VWF:Ag ratio correlation with VWF:Ag half-life | In Sztukowska,50 a pronounced drop in VWF survival in the type Vicenza VWD patients was reported: mean half-life significantly shorter than in control groups (1.3 ± 0.2 h, vs 15.4 ± 2.5 h; P < .0001). A dramatic increase in VWFpp ratio in the type Vicenza VWD cases was shown: VWFpp ratio from 7.14 to 17.7, mean 13.02 ± 0.49; 10× higher than in the control group (P < .001).In Haberichter,43 a substantially increased VWFpp/VWF:Ag ratio was predictive of a significantly decreased VWF half-life in 7 individuals who had a >twofold desmopressin response and an initial VWF:Ag <30 IU/dL. Three individuals had a decreased VWF half-life that was not predicted by an increased VWFpp/VWF:Ag ratio. Individuals who had a substantially increased VWFpp/VWF:Ag ratio and significantly reduced VWF:Ag level were also found to have an enhanced response to desmopressin (>fourfold increase). The desmopressin response was found to correlate with the VWFpp/VWF:Ag ratio (r = 0.92; P < .001) | (2 Observational studies) | ⨁◯◯◯ VERY LOW |
| Correlation of the VWFpp/VWF:Ag ratio with the presence or absence of a VWF gene mutation | In Haberichter,21 all affected individuals harbored a VWF gene mutation and showed an increased ratio, whereas no mutation was detected in unaffected individuals. In Eikenboom,44 the increased VWFpp/VWF:Ag ratio was particularly raised (median, 4.3) in patients with slightly abnormal multimers and mutations. An increased VWFpp/VWF:Ag ratio was a good predictor of VWD patients with mutations in the VWF gene: a VWFpp/VWF:Ag >3 had a positive predictive value for the presence of a VWF mutation of 98% with a specificity of 99% in the entire cohort of patients and family members.In Stufano,45 the genetic analysis of the mutation at codon 1205 in the group (n = 14) with the markedly increased VWF clearance distinguished between VWD type 1 Vicenza (characterized by the presence of the mutation p.R1205H) and AVWS (absence of this mutation). | (3 Observational studies) | ⨁⨁◯◯ LOW |