Presentation Details
| A Retrospective Study of Acquired Von Willebrand Syndrome in Myeloproliferative Neoplasms Mohammed Al Sharif 1, 2, Brian Harnett 3, Subia Tasneem 1, Brian Leber 4, 5, Christopher Hillis 5, Catherine P.M.Hayward 1, 3, 4. 1Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.2 Department of Pathology and Laboratory Medicine, King Abdullah Bin Abdulaziz University Hospital, Princess Nourah University, Riyadh, Saudi Arabia.3 Department of Medicine, McMaster University, Hamilton, ON, Canada.4 Hamilton Regional Laboratory Medicine Program, Hamilton, ON, Canada.5 Hematology/Oncology, Juravinski Cancer Center, Hamilton, ON, Canada |
Abstract
Background: Myeloproliferative Neoplasms (MPN) cause overproduction of red cells, platelets, and/or white cells and can manifest with bleeding, thrombosis, bone marrow scarring/fibrosis, and transformation to acute leukemia. Bleeding in MPN can reflect acquired von Willebrand syndrome (AVWS), with loss of high molecular weight (HMW) von Willebrand factor (VWF) multimers and extreme platelet elevation, and decisions on aspirin therapy. Nonetheless, there are uncertainties about the prevalence of AVWS in MPN and its association to high platelet counts and bleeding. Objectives: Assess AVWS clinical-laboratory correlations for a cohort of MPN patients who had VWF screens performed. Method: Clinical and laboratory data were evaluated for retrospective cohort of MPN patients, seen at the Juravinski Cancer Clinic in Hamilton from January 2019 until February 2023, with research ethics approval. VWF screens included: activity by VWF:GPIbR or VWF:GPIbM; VWF antigen (Ag) by Liatest; VWF activity/antigen ratio; FVIIIC; multimers for some. Data were assessed for: evidence of AVWS and if AVWS had influenced aspirin therapy (documented in records), associations between VWF and other clinical and laboratory findings, including platelet counts and bleeding. Result: During the four year period, 27 MPN patients (59.3% female, 40.7% male; median age 60 years, IQR: 60-70) had VWF screens (96% with multimer analysis). MPN diagnoses included: Essential Thrombocythemia, n=18 (66.7%); Polycythemia Vera, n=4 (14.8%); Primary Myelofibrosis, n=2 (7.4%); Pre-fibrotic Primary Myelofibrosis, n=2 (7.4%); and Chronic Myeloid Leukemia, n=1 (3.7%). MPN driver mutations were: JAK2 (V617F) n=13 (48.1%), CALR n=6 (22.2%), triple negative n=4 (14.9%), JAK2 negative n=3 (11.1%), and BCR-ABL1 n=1 (3.7%). Most had thrombocytosis (96.3%, platelet counts X109/L: median=839, IQR=839 – 1155, range 166–2,572). Many (24/27, 88.8%) had evidence of AVWS, defined as a VWF activity/VWF:Ag ratio below the local cutoff of 0.63 (ratios: median=0.40, range: 0.02-0.99, IQR=0.4 – 0.56), with low VWF activity (<0.50 U/mL) in 16/24 (66.7% ) of AVWS cases (median activity=0.22 U/mL, range: 0.04-0.44; IQR=0.22-0.26). Three patients developed AVWS during follow-up whereas five had their AVWS resolve with MPN treatment. Among AVWS cases, VWF activity/antigen ratios showed weak association to platelet counts (R2=0.22, p=0.013) and stronger association to VWF activity (R2=0.73, p<0.0001). With a few exceptions (3/24, 12.5%, all with high VWF:Ag), most (21/24, 87%) MPN patients with AVWS had loss, or relative loss, of high molecular weight multimers (HMW), indicating that VWF activity/antigen ratios were sensitive to multimer changes. Only 5 (21%) MPN patients with AVWS had documented bleeding (nasal n=3, vaginal n=1, oral n=1), which was mild (n=1 needing aspirin discontinuation) and without relationships to VWF activity (p=0.26) or platelet counts (p=0.68). Conclusion: Most patients with MPN who had VWF screens at our center had AVWS with low VWF activity/antigen ratios (due to loss of HMW VWF), more commonly with VWF deficiency, with only a few having mild bleeding. A larger prospective study of VWF screens in unselected patients with MPN would help define the overall prevalence of VWF abnormalities in MPN and their significance and relationship to platelet counts.
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