Investigation of von Willebrand factor multimer abnormalities before and after aortic valve replacement using the Hydragel-5 assay
Marwan Hamiko MD a), Lena Gerdes a), Miriam Silaschi MD a), Holger Seidel MD b), Philipp Westhofen PhD b), Johannes Kruppenbacher MD b), Hans-Joerg Hertfelder MD, PhD b) c), Johannes Oldenburg MD c), Farhad Bakhtiary MD a), Markus Velten MD d), Mehmet Oezkur MD e), Georg Daniel Duerr MD e)
a-Department of Cardiac Surgery, University Hospital Bonn, Bonn, Germany
b-Center for Bleeding Disorders and Transfusion Medicine, (CBT), Bonn, Germany
c-Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Bonn, Germany
d-Department of Anesthesiology and Pain Management, The University of Texas Southwestern Medical Center, Dallas, TX, USA
e-Department of Cardiovascular Surgery, University Medical Center, Johannes-Gutenberg University, Mainz, Germany
Abstract
Background
Severe aortic stenosis (sAS) is associated with acquired von Willebrand syndrome (AVWS) by loss of high-molecular-weight multimers (HMWM) of von Willebrand factor (VWF), potentially resulting in perioperative bleeding. Analysis of VWF multimers remains challenging. Recently, the new, rapid Hydragel 5 assay has been developed, using electrophoretic protein separation for dividing VWF-multimers into low (LMWM), intermediate (IMWM), and HMWM, the hemostatically active part of VWF. Here, we evaluated its impact on predicting blood loss in presence of AVWS after surgical aortic valve replacement (SAVR).
Methods
We prospectively examined 52 patients (age: 68 ± 7 years; 54 % male) admitted to SAVR. They were divided in two groups (A: normal VWF, n = 28; B: abnormal VWF, n = 24, defined as VWF-activity/antigen (VWF:Ac/Ag)-ratio < 0.7 and/or HMWM loss). Blood samples and echocardiographic data were collected before, seven days and three months after SAVR. Blood loss and transfusions were recorded.
Results
Baseline characteristics and clinical data were similar in both groups. HMWM loss was present in 38.5 % of all patients. HMWM, the VWF:Ac/Ag- and HMWM/(IMWM+LMWM)-ratios were significantly decreased preoperatively in group B but normalized after SAVR. Bleeding, re-thoracotomy and transfusion rates were comparable. HMWM loss was inversely correlated with the peak aortic gradient (Pmax) and positively with the aortic valve area (AVA), while HMWM/(IMWM+LMWM)-ratio negatively correlated with the mean aortic gradient (Pmean).
Conclusion
HMWM and HMWM/(IMWM+LMWM)-ratio inversely correlate with severity of AS and normalize after SAVR. The Hydragel-5 assay’s might be valuable for routine diagnostics to assess bleeding risk and postoperative normalization of AS and VWF abnormalities in SAVR patients.