ADAMTS13, von Willebrand Factor, Platelet Microparticles, Factor VIII, and Impact of Somatic Mutations in the Pathogenesis of Splanchnic Vein Thrombosis Associated with BCR-ABL-Negative Myeloproliferative Neoplasms
Academic Article
Publication Date:
2024
Short description:
ADAMTS13, von Willebrand Factor, Platelet Microparticles, Factor VIII, and Impact of Somatic Mutations in the Pathogenesis of Splanchnic Vein Thrombosis Associated with BCR-ABL-Negative Myeloproliferative Neoplasms / Castelli, R., Berzuini, A., Manetti, R., Delitala, A.P., Castro, D., Sanna, G., Sircana, M.C., Profili, N.I., Bartoli, A., La Cava, L., Lambertenghi Deliliers, G., Donadoni, M., Gidaro, A.. - In: LIFE. - ISSN 2075-1729. - 14:486(2024), pp. 1-12. [10.3390/life14040486]
abstract:
Background: Myeloproliferative neoplasms (MPNs) are often associated with splanchnic
vein thrombosis (SVT). Not all the factors involved in the thrombotic tendency are currently known.
Objectives: This study aims to evaluate a possible association between ADAMTS13, von Willebrand factor (VWF), platelet microvesicles (MV), and factor VIII activity (FVIII:C) with thrombotic events in MPN patients.
Materials and methods: In total, 36 consecutive MPN patients with SVT were enrolled.
The MPNs were diagnosed based on clinical characteristics and one or more gene mutations among JAK-2, CALR, and MPL. As controls, 50 randomly selected patients with MPN without thrombosis, 50 patients with deep vein thrombosis without MPNs, and 50 healthy blood donors were evaluated.
Complete blood count, ADAMTS13, VWF, MV, and FVIII:C in plasma were measured in all the
subjects.
Results: The JAK-2 mutation was found in 94% of the patients with SVT, but none were
triple-negative for genetic mutations (JAK2 V617F, CALR, MPL, and exon 12). Compared to the
normal subjects, in all the MPN patients (with or without SVT), the levels of ADAMTS13 were found to be significantly lower (p < 0.001) and the MV concentrations were significantly higher (p < 0.001).
Among the MPN patients, the VWF and FVIII:C levels were significantly higher in the patients with
SVT than those without thrombosis (p = 0.007 and p = 0.04, respectively). Splenomegaly was present in 78% of MPN patients with SVT and in 30% of those without SVT (p < 0.001). The ADAMTS13/VWF
ratio was reduced in all the patients, but not in the healthy blood donors (p < 0.001).
Conclusions: The significant increase in circulating MV, VWF, and FVIII:C in the MPN patients and in the patients with thrombosis supports the role of endothelium damage in promoting thrombotic events. In particular, a significant increase in VWF and FVIII:C levels was found in the MPN patients with SVT.
vein thrombosis (SVT). Not all the factors involved in the thrombotic tendency are currently known.
Objectives: This study aims to evaluate a possible association between ADAMTS13, von Willebrand factor (VWF), platelet microvesicles (MV), and factor VIII activity (FVIII:C) with thrombotic events in MPN patients.
Materials and methods: In total, 36 consecutive MPN patients with SVT were enrolled.
The MPNs were diagnosed based on clinical characteristics and one or more gene mutations among JAK-2, CALR, and MPL. As controls, 50 randomly selected patients with MPN without thrombosis, 50 patients with deep vein thrombosis without MPNs, and 50 healthy blood donors were evaluated.
Complete blood count, ADAMTS13, VWF, MV, and FVIII:C in plasma were measured in all the
subjects.
Results: The JAK-2 mutation was found in 94% of the patients with SVT, but none were
triple-negative for genetic mutations (JAK2 V617F, CALR, MPL, and exon 12). Compared to the
normal subjects, in all the MPN patients (with or without SVT), the levels of ADAMTS13 were found to be significantly lower (p < 0.001) and the MV concentrations were significantly higher (p < 0.001).
Among the MPN patients, the VWF and FVIII:C levels were significantly higher in the patients with
SVT than those without thrombosis (p = 0.007 and p = 0.04, respectively). Splenomegaly was present in 78% of MPN patients with SVT and in 30% of those without SVT (p < 0.001). The ADAMTS13/VWF
ratio was reduced in all the patients, but not in the healthy blood donors (p < 0.001).
Conclusions: The significant increase in circulating MV, VWF, and FVIII:C in the MPN patients and in the patients with thrombosis supports the role of endothelium damage in promoting thrombotic events. In particular, a significant increase in VWF and FVIII:C levels was found in the MPN patients with SVT.
Iris type:
1.1 Articolo in rivista
Keywords:
thrombosis; microparticles; ADAMTS13; von Willebrand factor (VWF); factor VIII C (FVIII:C);
splanchnic vein thrombosis; myeloproliferative neoplasms; somatic mutations; polycythemia vera;
essential thrombocythemia; idiopathic myelofibrosis
List of contributors:
Castelli, Roberto; Berzuini, Alessandra; Manetti, Roberto; Delitala, Alessandro Palmerio; Castro, Dante; Sanna, Giuseppe; Sircana, Marta Chiara; Profili, Nicia Isabella; Bartoli, Arianna; La Cava, Leyla; Lambertenghi Deliliers, Giorgio; Donadoni, Mattia; Gidaro, Antonio
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