Figure 2.
Limitations of VWFpp/VWF:Ag ratio in detection of fast VWF clearance in patients with low VWF and the impact of clearance on bleeding phenotype. (A) Only 8% (6 of 75) of patients with low VWF had VWFpp/VWF:Ag ratios >3 (above the dashed blue line). In contrast, 20% (15 of 75) of the patients with low VWF had enhanced clearance based on fall-off rates after desmopressin (to the right of the dashed red line: shaded area with >30% fall-off in VWF:Ag levels at 4 hours, per ASH/ISTH/NHF/WFH guidelines). The blue line illustrates VWFpp/VWF:Ag ratio >3. Patients with low VWF with suspected enhanced clearance, as defined by VWFpp/VWF:Ag >3 only are shown in the blue box. Patients with low VWF with confirmed enhanced clearance after desmopressin trial only are shown in the light red box. Finally, patients with low VWF with both positive VWFpp/VWF:Ag and enhanced clearance after desmopressin are in the purple box. (B) Because the majority of patients with low VWF were of blood group O (64 of 75; 85.3%), the VWFpp/VWF:Ag vs desmopressin fall-off comparison was repeated with a blood group O–specific VWFpp/VWF:Ag cutoff of >2.15 (corresponds to lower 97.5% CI for normal subjects in blood group O). Even with this lower cutoff, only 12% (9 of 75) of patients with low VWF had an elevated VWFpp/VWF:Ag ratio. (C) In patients with low VWF, 24 hour fall-off in plasma VWF:Ag levels (n = 24) strongly correlated with 4-hour fall-off of VWF:Ag levels (Spearman’s r). The 24-hour fall-off is expressed as fold change (T+24/T+1−1). (D) Conversely, there was no correlation between the 24-hour fall-off in VWF:Ag and steady-state plasma VWFpp/VWF:Ag ratios (Spearman’s r). (E-F) Elimination half-lives (t1/2el in hours) in patients with low VWF correlated inversely with the 4-hour fall-off plasma VWF:Ag levels after desmopressin (Pearson’s r) but did not correlate with VWFpp/VWF:Ag ratios (Spearman’s r). (G) Patients with low VWF with a threefold or higher increment in plasma VWF:Ag levels after desmopressin (illustrated as fold change, T+1/T+0) had significantly lower bleeding scores than patients with low VWF with attenuated desmopressin responses (median, 4 vs 6; P < .01). The upper limit of the normal condensed MCMDM-1 VWD score range is illustrated by the black dotted line (<3 for both males and females). (H) Increment in plasma VWF:Ag levels after desmopressin was significantly associated with the condensed MCMDM-1 VWD bleeding score. (C-H) Fast clearance, red dots; normal clearance, blue dots.

Limitations of VWFpp/VWF:Ag ratio in detection of fast VWF clearance in patients with low VWF and the impact of clearance on bleeding phenotype. (A) Only 8% (6 of 75) of patients with low VWF had VWFpp/VWF:Ag ratios >3 (above the dashed blue line). In contrast, 20% (15 of 75) of the patients with low VWF had enhanced clearance based on fall-off rates after desmopressin (to the right of the dashed red line: shaded area with >30% fall-off in VWF:Ag levels at 4 hours, per ASH/ISTH/NHF/WFH guidelines). The blue line illustrates VWFpp/VWF:Ag ratio >3. Patients with low VWF with suspected enhanced clearance, as defined by VWFpp/VWF:Ag >3 only are shown in the blue box. Patients with low VWF with confirmed enhanced clearance after desmopressin trial only are shown in the light red box. Finally, patients with low VWF with both positive VWFpp/VWF:Ag and enhanced clearance after desmopressin are in the purple box. (B) Because the majority of patients with low VWF were of blood group O (64 of 75; 85.3%), the VWFpp/VWF:Ag vs desmopressin fall-off comparison was repeated with a blood group O–specific VWFpp/VWF:Ag cutoff of >2.15 (corresponds to lower 97.5% CI for normal subjects in blood group O). Even with this lower cutoff, only 12% (9 of 75) of patients with low VWF had an elevated VWFpp/VWF:Ag ratio. (C) In patients with low VWF, 24 hour fall-off in plasma VWF:Ag levels (n = 24) strongly correlated with 4-hour fall-off of VWF:Ag levels (Spearman’s r). The 24-hour fall-off is expressed as fold change (T+24/T+1−1). (D) Conversely, there was no correlation between the 24-hour fall-off in VWF:Ag and steady-state plasma VWFpp/VWF:Ag ratios (Spearman’s r). (E-F) Elimination half-lives (t1/2el in hours) in patients with low VWF correlated inversely with the 4-hour fall-off plasma VWF:Ag levels after desmopressin (Pearson’s r) but did not correlate with VWFpp/VWF:Ag ratios (Spearman’s r). (G) Patients with low VWF with a threefold or higher increment in plasma VWF:Ag levels after desmopressin (illustrated as fold change, T+1/T+0) had significantly lower bleeding scores than patients with low VWF with attenuated desmopressin responses (median, 4 vs 6; P < .01). The upper limit of the normal condensed MCMDM-1 VWD score range is illustrated by the black dotted line (<3 for both males and females). (H) Increment in plasma VWF:Ag levels after desmopressin was significantly associated with the condensed MCMDM-1 VWD bleeding score. (C-H) Fast clearance, red dots; normal clearance, blue dots.

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