SitemapContact Us
닫기
Search
Advanced Search +
닫기
Quick links
Most Cited Most Read Ahead of Print Archives Go to E-submission

Original Article

Split Viewer

Blood Res 2023; 58(1):

Published online March 31, 2023

https://doi.org/10.5045/br.2023.2022218

© The Korean Society of Hematology

Acquired von willebrand syndrome in patients with philadelphia-negative myeloproliferative neoplasm

Ik-Chan Song, Sora Kang, Myung-Won Lee, Hyewon Ryu, Hyo-Jin Lee, Hwan-Jung Yun, Deog-Yeon Jo

Author Info. +

Division of Hematology/Oncology, Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon, Korea

Correspondence to : Deog-Yeon Jo, M.D., Ph.D.
Division of Hematology/Oncology, Department of Internal Medicine, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon 35015, Korea
E-mail: deogyeon@cnu.ac.kr

Received: November 7, 2022; Revised: December 27, 2022; Accepted: January 25, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Erratum: Blood Res 2023; 58(2): 124-124

Abstract

Go to

Background
Acquired von Willebrand syndrome (AVWS) has not been investigated in Korean patients with Philadelphia chromosome-negative myeloproliferative neoplasm.
Methods
This study analyzed the prevalence at diagnosis and clinical features of AVWS in patients with essential thrombocythemia (ET), polycythemia vera (PV), prefibrotic/early primary myelofibrosis (pre-PMF), or overt PMF (PMF) diagnosed between January 2019 and December 2021 at Chungam National University Hospital, Daejeon, Korea. AVWS was defined as below the lower reference limit (56%) of ristocetin cofactor activity (VWF:RCo).
Results
Sixty-four consecutive patients (36 with ET, 17 with PV, 6 with pre-PMF, and 5 with PMF; 30 men and 34 women) with a median age of 67 years (range, 18‒87 yr) were followed for a median of 25.1 months (range, 2.6‒46.4 mo). AVWS was detected in 20 (31.3%) patients at diagnosis and was most frequent in ET patients (41.4%), followed by patients with pre-PMF (33.3%) and PV (17.6%) patients. VWF:RCo was negatively correlated with the platelet count (r=0.937; P=0.002). Only one episode of minor bleeding occurred in a patient with ET and AVWS. Younger age (<50 yr) [odds ratio (OR), 7.08; 95% confidence interval (CI), 1.27‒39.48; P=0.026] and thrombocytosis (>600×109/L) (OR, 13.70; 95% CI, 1.35‒138.17; P=0.026) were independent risk factors for developing AVWS.
Conclusion
AVWS based on VWF:RCo was common in patients with ET and pre-PMF, but less common in patients with PV in the Korean population. Clinically significant bleeding is rare in these patients.

Graphical Abstract

Go to


Keywords: Myeloproliferative neoplasm, Essential thrombocythemia, Polycythemia vera, Primary myelofibrosis, Acquired von Willebrand syndrome

Article

Original Article

Blood Res 2023; 58(1): 42-50

Published online March 31, 2023 https://doi.org/10.5045/br.2023.2022218

Copyright © The Korean Society of Hematology.

Acquired von willebrand syndrome in patients with philadelphia-negative myeloproliferative neoplasm

Ik-Chan Song, Sora Kang, Myung-Won Lee, Hyewon Ryu, Hyo-Jin Lee, Hwan-Jung Yun, Deog-Yeon Jo

Division of Hematology/Oncology, Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon, Korea

Correspondence to:Deog-Yeon Jo, M.D., Ph.D.
Division of Hematology/Oncology, Department of Internal Medicine, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon 35015, Korea
E-mail: deogyeon@cnu.ac.kr

Received: November 7, 2022; Revised: December 27, 2022; Accepted: January 25, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Erratum: Blood Res 2023; 58(2): 124-124

Abstract

Background
Acquired von Willebrand syndrome (AVWS) has not been investigated in Korean patients with Philadelphia chromosome-negative myeloproliferative neoplasm.
Methods
This study analyzed the prevalence at diagnosis and clinical features of AVWS in patients with essential thrombocythemia (ET), polycythemia vera (PV), prefibrotic/early primary myelofibrosis (pre-PMF), or overt PMF (PMF) diagnosed between January 2019 and December 2021 at Chungam National University Hospital, Daejeon, Korea. AVWS was defined as below the lower reference limit (56%) of ristocetin cofactor activity (VWF:RCo).
Results
Sixty-four consecutive patients (36 with ET, 17 with PV, 6 with pre-PMF, and 5 with PMF; 30 men and 34 women) with a median age of 67 years (range, 18‒87 yr) were followed for a median of 25.1 months (range, 2.6‒46.4 mo). AVWS was detected in 20 (31.3%) patients at diagnosis and was most frequent in ET patients (41.4%), followed by patients with pre-PMF (33.3%) and PV (17.6%) patients. VWF:RCo was negatively correlated with the platelet count (r=0.937; P=0.002). Only one episode of minor bleeding occurred in a patient with ET and AVWS. Younger age (<50 yr) [odds ratio (OR), 7.08; 95% confidence interval (CI), 1.27‒39.48; P=0.026] and thrombocytosis (>600×109/L) (OR, 13.70; 95% CI, 1.35‒138.17; P=0.026) were independent risk factors for developing AVWS.
Conclusion
AVWS based on VWF:RCo was common in patients with ET and pre-PMF, but less common in patients with PV in the Korean population. Clinically significant bleeding is rare in these patients.

Keywords: Myeloproliferative neoplasm, Essential thrombocythemia, Polycythemia vera, Primary myelofibrosis, Acquired von Willebrand syndrome

Fig 1.

Download
Figure 1.Correlation between von Willebrand factor ristocetin cofactor activity (VWF:RCo) and platelet count.
Blood Research 2023; 58: 42-50https://doi.org/10.5045/br.2023.2022218

Fig 2.

Download
Figure 2.Representative changes with time in platelet count and von Willebrand factor ristocetin cofactor activity (VWF:RCo) following hydroxyurea treatment in a patient with essential thrombocythemia.
Blood Research 2023; 58: 42-50https://doi.org/10.5045/br.2023.2022218

Fig 3.

Download
Figure 3.Changes in platelet count after normalization of von Willebrand factor ristocetin cofactor activity following cytoreductive treatment in patients with acquired von Willebrand syndrome.
Blood Research 2023; 58: 42-50https://doi.org/10.5045/br.2023.2022218

Table 1 . Patient characteristics (N=64)..

ET (N=36)PV (N=17)pre-PMF (N=6)PMF (N=5)
Age (yr), median (range)65 (18–84)72 (17–86)60.5 (34–87)77 (42–86)
Female, N (%)20 (55.6)10 (58.8)3 (50.0)1 (20.0)
Palpable splenomegaly, N (%)0 (0.0)0 (0.0)0 (0.0)0 (0.0)
Volumetric splenomegaly, N (%)24 (66.7)15 (88.2)6 (100)5 (100)
Laboratory findings
WBC, ×109/L10.9±4.714.6±4.6a)15.9±3.3a)12.9±9.0
Monocyte, ×109/L0.7±0.60.6±0.30.6±0.31.4±1.2a)
Hemoglobin, g/dL14.0±1.417.9±2.5a)12.7±2.510.7±1.7a)
Platelet, ×109/L870.3±314.0614.2±381.3a)909.5±369.4868.4±420.8
Platelet, ×109/L, N (%)
450–5994 (11.1)2 (11.8)1 (16.7)4 (80.0)
600–99926 (72.2)6 (35.3)4 (66.7)0 (0.0)
1,000–1,4494 (11.1)0 (0.0)0 (0.0)0 (0.0)
≥1,5002 (5.6)2 (11.8)1 (16.7)1 (20.0)
LDH, ×UNL1.3±0.41.5±0.42.0±0.9a)1.9±0.3a)
Driver gene mutation, N (%)
JAK2V617F30 (83.3)17 (100)4 (66.7)3 (60.0)
CALR3 (8.3)-1 (16.7)1 (20.0)
MPL1 (2.8)-0 (0.0)0 (0.0)
JAK2V617F VAF (%)26.3±11.163.6±19.9a)47.6±19.4a)50.5±37.0a)
IPSET, N (%)
Low9 (25.0)---
Intermediate12 (33.3)---
High15 (41.7)---
IPSS, N (%)
Low--2 (33.3)1 (20.0)
Intermediate-1--2 (33.3)1 (20.0)
Intemediate-2--1 (16.7)3 (60.0)
High--1 (16.7)0 (0.0)
Comorbidity, N (%)
Hypertension15 (41.7)13 (76.5)1 (16.7)3 (60.0)
Diabetes mellitus4 (11.1)6 (35.3)1 (16.7)1 (20.0)
Chronic kidney disease6 (16.7)7 (41.2)2 (33.3)2 (40.0)
Smoking7 (19.4)3 (17.6)2 (33.3)1 (20.0)
Dyslipidemia5 (13.9)3 (17.6)1 (16.7)1 (20.0)
Treatments, N (%)
Cytoreductive treatment
Hydroxyurea23 (63.9)17 (88.2)6 (66.7)4 (80.0)
Anagrelide0 (0.0)0 (0.0)1 (16.7)1 (20.0)
Aspirin33 (91.7)17 (100)6 (100)6 (100)
Thrombosis, N (%)b)6 (16.7)3 (17.6)3 (33.3)3 (60.0)
FU (yr), median (range)1.8 (0.1–3.9)2.5 (1.1–3.8)1.3 (0.2–2.9)2.5 (1.3–3.1)

a)P<0.05 compared with ET. b)Thrombosis occurred before and at the time of diagnosis..

Abbreviations: ET, essential thrombocythemia; FU, follow-up; IPSET, International Prognostic Score for Essential Thrombocythemia; IPSS, International Prognostic Scoring System; LDH, lactate dehydrogenase; pre-PMF, prefibrotic/early myelofibrosis; PV, polycythemia vera; UNL, upper normal limit; VAF, variant allele frequency..

Table 2 . Prevalence of acquired von Willebrand syndrome in patients with myeloproliferative neoplasm (N=64)..

ET (N=36)PV (N=17)pre-PMF (N=6)PMF (N=5)
VWF:RCo <56%, N (%)15 (41.7)3 (17.6)2 (33.3)0 (0.0)
VWF:Rco <30%, N (%)3 (8.3)3 (17.6)1 (16.7)0 (0.0)

Abbreviations: ET, essential thrombocythemia; pre-PMF, prefibrotic/early primary myelofibrosis; PV, polycythemia vera; VWF:Rco, von Willebrand factor ristocetin cofactor activity..

Table 3 . Clinical features of patients with essential thrombocythemia, according to von Willebrand factor ristocetin cofactor activity (N=36)..

≥56%
(N=21)		<56%
(N=15)		Pa)≥30%
(N=33)		<30%
(N=3)		Pa)
Age (yr), median (range)65 (40–84)56 (18–83)0.03565 (18–84)69 (56–72)0.560
Volumetric splenomegaly, N (%)13 (61.9)11 (73.3)0.47323 (69.7)1 (33.3)0.201
Laboratory findings
WBC, ×109/L10.5±3.211.5±6.40.52711.0±4.810.0±2.50.718
Monocyte, ×109/L0.7±0.40.7±0.30.9710.7±0.60.5±0.10.562
Hemoglobin, g/dL14.0±1.513.9±1.50.82114.0±1.213.2±0.80.406
Platelet, ×109/L813.7±170.7949.7±440.00.205837.8±228.81,228.3±824.80.037
Platelet ≥600×109/L, N (%)18 (85.7)14 (93.3)0.47329 (87.9)3 (100)0.522
Platelet ≥1,000×109/L, N (%)3 (14.3)3 (20.0)0.6505 (15.2)1 (33.3)0.418
Platelet ≥1,500×109/L, N (%)0 (0.0)2 (13.2)0.0851 (3.0)1 (33.3)0.028
LDH, ×UNL1.4±0.41.2±0.30.1411.3±0.41.5±0.40.488
PT, sec12.1±1.011.5±0.90.05711.9±0.911.0±1.60.139
aPTT, sec35.6±3.835.8±3.60.82935.9±3.632.9±3.70.168
Driver gene mutation, N (%)
JAK2V617F19 (90.5)12 (80.0)0.37029 (87.9)2 (66.7)0.309
JAK2V617F VAF >30%7 (33.3%)3 (20.0%)0.3799 (27.3)1 (33.3)0.825
CALR1 (4.8)2 (13.3)0.6252 (6.1)1 (33.3)0.249
Thrombosis, N (%)b)4 (19.0)2 (13.3)0.6506 (18.2)0 (0.0)0.418
Bleeding, N (%)
Major bleeding0 (0.0)0 (0.0)-0 (0.0)0 (0.0)-
Minor bleeding0 (0.0)1 (6.7)0.2301 (3.0)0 (0.0)0.760
Overall0 (0.0)1 (6.7)0.2301 (3.0)0 (0.0)0.760
Normalization of VWF:RCo after cytoreduction, N (%)c)-11/11 (100)----
Time to normalization of VWF:RCo (wk), median (range)-8 (2–18)----

a)Data presented as mean±SD were analyzed using Student t-test for pared samples; data presented as percentages were analyzed using the Chi-square test. b)Thrombosis occurred before, at the time of, and after diagnosis. c)Platelet counts were 556.5±171.8×109/L at the time of initial normalization of VWF:RCo..

Abbreviations: aPTT, activated partial thromboplastin time; LDH, lactate dehydrogenase; PT, prothrombin time; UNL, upper normal limit; VAF, variant allele frequency; VWF:RCo, von Willabrand factor ristocetin cofactor activity..

Table 4 . Clinical features of patients with polycythemia vera according to von Willebrand factor ristocetin cofactor activity (N=17)..

≥30% (N=14)<30% (N=3)Pa)
Age (yr), median (range)73.5 (44–86)61 (55–72)0.377
Volumetric splenomegaly, N (%)13 (92.9)2 (66.7)0.201
Laboratory findings
WBC, ×109/L15.2±5.016.6±2.70.656
Monocyte, ×109/L00.6±0.2 0.8±0.20.075
Hemoglobin, g/dL17.9±2.617.7±2.60.879
Platelet, ×109/L510.0±206.71,120.7±671.70.009
Platelet >600×109/L, N (%)5 (35.7)3 (100)0.043
Platelet >1,000×109/L, N (%)1 (7.1)1 (33.3)0.201
Platelet >1,500×109/L, N (%)1 (7.1)1 (33.3)0.201
LDH, ×UNL1.5±0.5 1.6±0.10.728
JAK2V617F, N (%)14 (100)3 (100)-
JAK2V617F VAF >50%, N (%)2 (14.3)0 (0.0)0.661
Thrombosis, N (%)b)3 (21.4)0 (0.0)0.377
Bleeding, N (%)0 (0.0)0 (0.0)-
Normalization of VWF:RCo after cytoreduction, N (%)c)-3 (100)-

a)Data presented as mean±SD were analyzed using Student t-test for pared samples; data presented as percentages were analyzed using the Chi-square test. b)Thrombosis occurred before, at the time of, and after diagnosis. c)Platelet counts were 444.0±194.6×109/L at the time of initial normalization of VWF:RCo..

Abbreviations: LDH, lactate dehydrogenase; UNL, upper normal limit; VAF, variant allele frequency; VWF:RCo; von Willabrand factor, ristocetin cofactor activity..

Table 5 . Logistic regression analysis of the risk factors for developing acquired von Willebrand syndrome at diagnosis in patients with myeloproliferative neoplasm (N=64)..

Univariate analysisMultivariate analysis
OR95% CIPOR95% CIP
Age <50 yr4.291.05–17.450.0427.081.27–39.480.026
Male0.730.73–2.810.651---
ET3.291.02–10.620.0472.940.76–11.360.117
IPSET higha)0.280.05–1.620.155---
R-IPSET-T higha)0.470.03–8.600.603---
WBC >11.0×109/L0.890.23–3.420.864---
Monocyte >1.0×109/L0.300.03–3.040.310---
Platelet >600×109/L8.871.07–73.030.04313.701.35–138.170.026
Platelet >800×109/L1.230.45–3.790.631---
Platelet >1,000×109/L1.580.39–6.380.518---
LDH >1.5×UNL1.250.30–5.230.760---
Serum ferritin0.990.98–1.000.201---
Positive JAK2V617F0.900.20–4.010.884---
JAK2V617F VAF >50%0.670.19–2.400.535---
JAK2V617F VAF >70%0.430.08–2.220.314---
Positive CALR mutation1.520.23–9.880.662---
Chronic kidney disease1.830.68–5.830.306---
Diabetes mellitus1.230.30–4.280.863---
Hypertension0.560.19–1.630.283---
Smoking0.600.15–2.470.479---
Dyslipidemia0.930.22–4.050.926---
Volumetric splenomegaly0.770.22–2.700.684---
Thrombosis before or at diagnosis0.650.10–4.140.652---

a)Among ET patients..

Abbreviations: CI, confidence interval; ET, essential thrombocythemia; IPSET, International Prognostic Score for Essential Thrombocythemia; LDH, lactate dehydrogenase; OR, odds ratio; R-IPSET-T, revised IPSET-thrombosis; UNL, upper normal limit; VAF, variant allele frequency..
Blood Res
Volume 59 2024
Current Issue Archives

Stats or Metrics

Share this article on

  • line

Related articles in BR

Blood Research

pISSN 2287-979X
eISSN 2288-0011
qr-code Download