Von Willebrand Factor Multimer Densitometric Analysis: Validation of the Clinical Accuracy and Clinical Implications in Von Willebrand Disease
Von Willebrand factor (VWF) multimer analysis is important in the classification of von Willebrand disease (VWD). Current visual VWF multimer analysis is time consuming and inaccurate in detecting subtle changes in multimer patterns. Although VWF multimer densitometric analysis may be useful, the ac...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2021-03-01
|
| Series: | HemaSphere |
| Online Access: | http://journals.lww.com/10.1097/HS9.0000000000000542 |
| _version_ | 1797288849996513280 |
|---|---|
| author | Johan Boender Ferdows Atiq Marjon H. Cnossen Johanna G. van der Bom Karin Fijnvandraat Joke de Meris Moniek P. M. de Maat Karin P. M. van Galen Britta A. P. Laros-van Gorkom Karina Meijer Jeroen Eikenboom Frank W. G. Leebeek for the WiN study group* |
| author_facet | Johan Boender Ferdows Atiq Marjon H. Cnossen Johanna G. van der Bom Karin Fijnvandraat Joke de Meris Moniek P. M. de Maat Karin P. M. van Galen Britta A. P. Laros-van Gorkom Karina Meijer Jeroen Eikenboom Frank W. G. Leebeek for the WiN study group* |
| author_sort | Johan Boender |
| collection | DOAJ |
| description | Von Willebrand factor (VWF) multimer analysis is important in the classification of von Willebrand disease (VWD). Current visual VWF multimer analysis is time consuming and inaccurate in detecting subtle changes in multimer patterns. Although VWF multimer densitometric analysis may be useful, the accuracy needs further investigation before it can be widely applied. In this study we aimed to validate VWF multimer densitometric analysis in a large cohort of VWD patients and to identify patient characteristics associated with densitometric outcomes. Patients were included from the Willebrand in the Netherlands (WiN) study, in which a bleeding score (BS) was obtained, and blood was drawn. For multimer analysis, citrated blood was separated on an agarose gel and visualized by Western blotting. IMAGEJ was used to generate densitometric images and medium-large VWF multimer index was calculated. We included 560 VWD patients: 328 type 1, 211 type 2, and 21 type 3 patients. Medium-large VWF multimer index performed excellent in distinguishing visually classified normal VWF multimers from reduced high-molecular-weight (HMW) multimers (area under the curve [AUC]: 0.96 [0.94-0.98], P < 0.001), normal multimers from absence of HMW multimers (AUC 1.00 [1.00-1.00], P < 0.001), and type 2A and 2B from type 2M and 2N (AUC: 0.96 [0.94-0.99], P < 0.001). Additionally, higher medium-large VWF multimer index was associated with lower BS in type 1 VWD: β = -7.6 (-13.0 to -2.1), P = 0.007, adjusted for confounders. Densitometric analysis of VWF multimers had an excellent accuracy compared with visual multimer analysis and may contribute to a better understanding of the clinical features such as the bleeding phenotype of VWD patients. |
| first_indexed | 2024-03-07T18:55:33Z |
| format | Article |
| id | doaj.art-9417f6e0e8384b96a65c589f3b60f36d |
| institution | Directory Open Access Journal |
| issn | 2572-9241 |
| language | English |
| last_indexed | 2024-03-07T18:55:33Z |
| publishDate | 2021-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | HemaSphere |
| spelling | doaj.art-9417f6e0e8384b96a65c589f3b60f36d2024-03-02T00:24:26ZengWileyHemaSphere2572-92412021-03-0153e54210.1097/HS9.0000000000000542202103000-00013Von Willebrand Factor Multimer Densitometric Analysis: Validation of the Clinical Accuracy and Clinical Implications in Von Willebrand DiseaseJohan Boender0Ferdows Atiq1Marjon H. Cnossen2Johanna G. van der Bom3Karin Fijnvandraat4Joke de Meris5Moniek P. M. de Maat6Karin P. M. van Galen7Britta A. P. Laros-van Gorkom8Karina Meijer9Jeroen Eikenboom10Frank W. G. Leebeek11for the WiN study group*1 Department of Hematology, Erasmus MC, University Medical Center Rotterdam, The Netherlands1 Department of Hematology, Erasmus MC, University Medical Center Rotterdam, The Netherlands2 Department of Pediatric Hematology, Erasmus MC-Sophia Children’s Hospital, University Medical Center Rotterdam, The Netherlands3 Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands5 Pediatric Hematology, Amsterdam UMC, Emma Children’s Hospital, University of Amsterdam, The Netherlands7 Netherlands Hemophilia Society, Leiden, The Netherlands1 Department of Hematology, Erasmus MC, University Medical Center Rotterdam, The Netherlands8 Van Creveldkliniek, University Medical Center, University Utrecht, The Netherlands9 Department of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands10 Department of Hematology, University of Groningen, University Medical Center Groningen, The Netherlands11 Department of Internal Medicine, Division of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands1 Department of Hematology, Erasmus MC, University Medical Center Rotterdam, The NetherlandsVon Willebrand factor (VWF) multimer analysis is important in the classification of von Willebrand disease (VWD). Current visual VWF multimer analysis is time consuming and inaccurate in detecting subtle changes in multimer patterns. Although VWF multimer densitometric analysis may be useful, the accuracy needs further investigation before it can be widely applied. In this study we aimed to validate VWF multimer densitometric analysis in a large cohort of VWD patients and to identify patient characteristics associated with densitometric outcomes. Patients were included from the Willebrand in the Netherlands (WiN) study, in which a bleeding score (BS) was obtained, and blood was drawn. For multimer analysis, citrated blood was separated on an agarose gel and visualized by Western blotting. IMAGEJ was used to generate densitometric images and medium-large VWF multimer index was calculated. We included 560 VWD patients: 328 type 1, 211 type 2, and 21 type 3 patients. Medium-large VWF multimer index performed excellent in distinguishing visually classified normal VWF multimers from reduced high-molecular-weight (HMW) multimers (area under the curve [AUC]: 0.96 [0.94-0.98], P < 0.001), normal multimers from absence of HMW multimers (AUC 1.00 [1.00-1.00], P < 0.001), and type 2A and 2B from type 2M and 2N (AUC: 0.96 [0.94-0.99], P < 0.001). Additionally, higher medium-large VWF multimer index was associated with lower BS in type 1 VWD: β = -7.6 (-13.0 to -2.1), P = 0.007, adjusted for confounders. Densitometric analysis of VWF multimers had an excellent accuracy compared with visual multimer analysis and may contribute to a better understanding of the clinical features such as the bleeding phenotype of VWD patients.http://journals.lww.com/10.1097/HS9.0000000000000542 |
| spellingShingle | Johan Boender Ferdows Atiq Marjon H. Cnossen Johanna G. van der Bom Karin Fijnvandraat Joke de Meris Moniek P. M. de Maat Karin P. M. van Galen Britta A. P. Laros-van Gorkom Karina Meijer Jeroen Eikenboom Frank W. G. Leebeek for the WiN study group* Von Willebrand Factor Multimer Densitometric Analysis: Validation of the Clinical Accuracy and Clinical Implications in Von Willebrand Disease HemaSphere |
| title | Von Willebrand Factor Multimer Densitometric Analysis: Validation of the Clinical Accuracy and Clinical Implications in Von Willebrand Disease |
| title_full | Von Willebrand Factor Multimer Densitometric Analysis: Validation of the Clinical Accuracy and Clinical Implications in Von Willebrand Disease |
| title_fullStr | Von Willebrand Factor Multimer Densitometric Analysis: Validation of the Clinical Accuracy and Clinical Implications in Von Willebrand Disease |
| title_full_unstemmed | Von Willebrand Factor Multimer Densitometric Analysis: Validation of the Clinical Accuracy and Clinical Implications in Von Willebrand Disease |
| title_short | Von Willebrand Factor Multimer Densitometric Analysis: Validation of the Clinical Accuracy and Clinical Implications in Von Willebrand Disease |
| title_sort | von willebrand factor multimer densitometric analysis validation of the clinical accuracy and clinical implications in von willebrand disease |
| url | http://journals.lww.com/10.1097/HS9.0000000000000542 |
| work_keys_str_mv | AT johanboender vonwillebrandfactormultimerdensitometricanalysisvalidationoftheclinicalaccuracyandclinicalimplicationsinvonwillebranddisease AT ferdowsatiq vonwillebrandfactormultimerdensitometricanalysisvalidationoftheclinicalaccuracyandclinicalimplicationsinvonwillebranddisease AT marjonhcnossen vonwillebrandfactormultimerdensitometricanalysisvalidationoftheclinicalaccuracyandclinicalimplicationsinvonwillebranddisease AT johannagvanderbom vonwillebrandfactormultimerdensitometricanalysisvalidationoftheclinicalaccuracyandclinicalimplicationsinvonwillebranddisease AT karinfijnvandraat vonwillebrandfactormultimerdensitometricanalysisvalidationoftheclinicalaccuracyandclinicalimplicationsinvonwillebranddisease AT jokedemeris vonwillebrandfactormultimerdensitometricanalysisvalidationoftheclinicalaccuracyandclinicalimplicationsinvonwillebranddisease AT moniekpmdemaat vonwillebrandfactormultimerdensitometricanalysisvalidationoftheclinicalaccuracyandclinicalimplicationsinvonwillebranddisease AT karinpmvangalen vonwillebrandfactormultimerdensitometricanalysisvalidationoftheclinicalaccuracyandclinicalimplicationsinvonwillebranddisease AT brittaaplarosvangorkom vonwillebrandfactormultimerdensitometricanalysisvalidationoftheclinicalaccuracyandclinicalimplicationsinvonwillebranddisease AT karinameijer vonwillebrandfactormultimerdensitometricanalysisvalidationoftheclinicalaccuracyandclinicalimplicationsinvonwillebranddisease AT jeroeneikenboom vonwillebrandfactormultimerdensitometricanalysisvalidationoftheclinicalaccuracyandclinicalimplicationsinvonwillebranddisease AT frankwgleebeek vonwillebrandfactormultimerdensitometricanalysisvalidationoftheclinicalaccuracyandclinicalimplicationsinvonwillebranddisease AT forthewinstudygroup vonwillebrandfactormultimerdensitometricanalysisvalidationoftheclinicalaccuracyandclinicalimplicationsinvonwillebranddisease |