12/9/2023 0 Comments 2.3 ag ratio![]() 001), and the FVIII:C/VWF:Ag ratio was lower in type 2 VWD compared with type 1 VWD ( P <. The VWFpp/VWF:Ag ratio was higher in type 2 VWD than in type 1 VWD ( P <. Median VWFpp/VWF:Ag ratio was 4.5 (IQR, 3.2 to 6.0), and median FVIII:C/VWF:Ag ratio was 1.6 (IQR, 1.2 to 2.0) in the type 2 patients. 12 In type 2 patients, median VWFpp was 104 U/dL ( IQR, 81 to 136 U/dL), which was higher than that in type 1 patients ( P <. This is in accordance with previously published data by Eikenboom et al. In type 1 patients, median VWFpp was 91 U/dL (IQR, 68 to 116 U/dL), median VWFpp/VWF:Ag ratio was 2.2 (IQR, 1.7 to 3.1), and median FVIII:C/VWF:Ag ratio was 1.8 (IQR, 1.4 to 2.3) ( Table 2 and Figure 1A). Details on the blood-sampling procedure and laboratory measurements at inclusion in the WiN study have been described in more detail by de Wee et al. At the time of the study, no international standard was yet available for VWFpp, and therefore the plasma pool was arbitrarily set at 100 U/dL. Pooled normal plasma was used to create a standard curve. VWFpp was detected with peroxidase-conjugated antibody CLB-Pro 14.3. Next, the diluted samples were incubated for 2 hours at 37☌. 7, 12 First, microtiter plates were coated with antibody CLB-Pro 35 overnight at 4☌ and then blocked with 1% bovine serum albumin at room temperature for 2 hours. ![]() VWFpp antigen was determined with an enzyme-linked immunoassay by using antibodies from Sanquin (Amsterdam, The Netherlands) as described. This assay was also used in the previous report by Eikenboom et al 12 and was measured at the same center. VWFpp was measured centrally at the Leiden University Medical Center (Leiden, The Netherlands). 6 After release into the circulation, the VWFpp and the mature VWF completely dissociate. 5 Part of VWF is thought to be secreted constitutively into the plasma, and the remaining part is stored in Weibel-Palade bodies in the endothelium or α-granules in megakaryocytes. 4 The VWF propeptide (VWFpp) is subsequently removed from the mature VWF however, it stays noncovalently bound. 3 After translocation to the endoplasmic reticulum, the signal peptide is cleaved, and the pro-VWF undergoes extensive posttranslational modifications, including dimerization in the endoplasmic reticulum and multimerization in the Golgi system. 1 Synthesis of VWF is restricted to endothelial cells and megakaryocytes, 2 where it is formed as a precursor protein, pre-proVWF, with a signal peptide, a propeptide, and a mature subunit. Von Willebrand factor (VWF) is a large multimeric glycoprotein that mediates platelet adhesion and aggregation at sites of vascular injury and serves as the carrier of factor VIII (FVIII) to prevent its premature clearance. This study underlines the clinical significance of the VWFpp assay in the diagnosis and classification of VWD. In conclusion, VWFpp identified severe type 1 VWD with very low VWF levels in patients who had previously been classified as type 3 VWD. The majority of these patients had missense mutations with rapid VWF clearance, whereas type 3 patients with no VWFpp were homozygous for null alleles. These patients had a lower bleeding score than type 3 patients who had a complete absence of VWF:Ag and VWFpp (14.0 vs 19.5 P =. A significant proportion of type 3 patients had detectable VWFpp (41%). ![]() On the basis of the ratios, reduced VWF synthesis was observed in 18% of type 1 and only 2% of type 2 patients. We evaluated the use of VWFpp in the classification and diagnosis of VWD. We aimed to define the pathophysiology of 658 patients with type 1, 2, or 3 von Willebrand disease (VWD) with VWF levels ≤30 U/dL from the Willebrand in The Netherlands (WiN) study using the VWFpp/VWF:Ag and FVIII:C/VWF:Ag ratios. The ratios between von Willebrand factor propeptide (VWFpp) or factor VIII activity (FVIII:C) and VWF antigen (VWF:Ag) reflect synthesis, secretion, and clearance of VWF.
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