OC 77.2 - Discrepant low ACL TOP VWF:GP1bR result is frequent in unselected MPN patients and does not predict bleeding risk

Background: Bleeding complications are common in patients with myeloproliferative neoplasms (MPNs), with a subset developing acquired von Willebrand syndrome. Despite this association, there remains a lack of specific diagnostic criteria, a wide spectrum of von Willebrand Factor (VWF) abnormalities described, and the performance of modern assays remain unclear.

Aims: To comprehensively describe the pattern of VWF laboratory abnormalities seen in the MPN population.

Methods: We collected samples from 74 unselected clinic patients with known MPNs to evaluate VWF quantitatively and qualitatively via multiple methods, correlating laboratory findings with a retrospective analysis of clinical bleeding data. VWF assays were performed on both ACL TOP (latex particle enhanced immunoturbidometric method) and Acustar (automated chemiluminescent immunoassay method) analysers using HemosIL® reagents, along with multimer analysis by gel electrophoresis. Informed consent was obtained, and the study was approved by local ethics committee.

Results: Functional VWF measurements were not concordant between assays, with median ACL TOP VWF:GP1bR/ VWF:Ag ratio of 0.57 (IQR 0.43-0.71) compared to median Acustar VWF:GP1bR/VWF:Ag ratio of 0.90 (IQR 0.82-1.03, p< 0.001). The ACL TOP showed disproportionately lower results (Figure 1), with 73% of patients having a ratio < 0.7, and 35% a ratio < 0.5. Despite these abnormalities, no patients had reduced high molecular weight multimers. There was an inverse relationship observed between platelet count and functional ratios on both ACL TOP (R2=0.20, p< 0.001) and Acustar analysers (R2=0.27, p< 0.001). While clinically significant bleeding events were overall relatively common (11% patients), there was no association with VWF assay abnormalities and generally alternate cause(s) responsible for bleeding.

Conclusion(s): Discrepancies of functional VWF assays appear to be common in MPN patients, particularly by ACL TOP VWF:GP1bR. Based on our limited series, a functional/antigenic ratio of < 0.7 (“type 2 pattern”) alone is poorly predictive of bleeding risk, and routine screening of MPN patients cannot be recommended.