title: Factors related to the development of acquired von Willebrand syndrome in patients with essential thrombocythemia and polycythemia vera.
abstract: OBJECTIVE
  We characterized acquired von Willebrand syndrome (AVWS) among essential thrombocythemia (ET) and polycythemia vera (PV) patients.
  
  
  METHODS
  A review of patients with ET or PV evaluated for AVWS.
  
  
  RESULTS
  Of 116 patients with ET, 64 (55%) developed AVWS; of 57 with PV, 28 (49%) developed AVWS. Median platelet counts of ET and PV patients who developed AVWS were 920×109/L and 679×109/L, respectively (P=0.01). Of patients who developed AVWS, 69.5% had platelet counts below 1000×109/L. Bleeding was more common in patients with AVWS, among both ET and PV patients (P<0.001). VWF:RCo levels and VWF:RCo/VWF:Ag ratio were lower among JAK2 V617F positive- vs. JAK2 V617F negative- ET patients (P=0.02 and P=0.002, respectively); whereas VWF:Ag levels were comparable (P=0.96). ET patients harboring the JAK2 V617F mutation were more likely to develop AVWS than were calreticulin-positive patients (70.3% vs. 45.7%, P=0.02), despite lower platelet counts (median 773 vs. 920×109/L, P=0.05). In multivariable analysis, younger age (P=0.002), platelet count (P<0.001), hemoglobin level (P=0.01) and JAK2 V617F mutation (P=0.01) independently predicted the development of AVWS among ET patients; whereas only platelet count predicted its development among PV patients (P<0.001).
  
  
  CONCLUSIONS
  Among ET and PV patients, AVWS was common and associated with higher bleeding rates and higher platelet count; nonetheless, most AVWS patients had platelet counts under 1000×109/L. Thus, AVWS screening should be included in routine assessment of ET and PV patients. Among ET patients, JAK2 V617F was a main driver for the development of AVWS.
authors.affiliation: Hematology Department, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Rottenstreich
authors.affiliation: Braun School of Public Health and Community Medicine, Faculty of Medicine of the Hebrew University and Hadassah, Jerusalem, Israel; Health Sciences Research, Mayo Clinic, Rochester, MN.
authors.forename: G
authors.initials: G
authors.lastname: Kleinstern
authors.affiliation: Hematology Department, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Krichevsky
authors.affiliation: Hematology Department, Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: D
authors.initials: D
authors.lastname: Varon
authors.affiliation: Hematology Department, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: D
authors.initials: D
authors.lastname: Lavie
authors.affiliation: Hematology Department, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. Electronic address: ykalish@gmail.com.
authors.forename: Y
authors.initials: Y
authors.lastname: Kalish
mesh_terms: D000328:Adult; D000368:Aged; D037282:Calreticulin / Q000097:blood; D005260:Female; D006470:Hemorrhage / Q000453:epidemiology*; D006801:Humans; D007557:Israel; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D010976:Platelet Count; D011087:Polycythemia Vera / Q000150:complications*; D012044:Regression Analysis; D012189:Retrospective Studies; D013920:Thrombocythemia, Essential / Q000150:complications* / Q000235:genetics; D014842:von Willebrand Diseases / Q000150:complications / Q000453:epidemiology*; D014841:von Willebrand Factor
chemical_list: D037282:Calreticulin; D014841:von Willebrand Factor; C507924:JAK2 protein, human; D053614:Janus Kinase 2
keywords: Acquired von Willebrand syndrome; Essential thrombocythemia; JAK2 V617F; Myeloproliferative neoplasms; Polycythemia vera