PROCOAGULANT MICROPARTICLE IS A NEW SURROGATE BIOMARKER FOR THROMBOTIC EVENTS IN PATIENTS WITH MYELOPROLIFERATIVE NEOPLASMS.
(Abstract release date: 05/19/16)
EHA Library. Taniguchi Y. 06/09/16; 132897; E1348
Mr. Yasuhiro Taniguchi
Contributions
Contributions
Abstract
Abstract: E1348
Type: Eposter Presentation
Background
Previous studies have identified several clinical and genetic markers for thrombosis in myeloproliferative neoplasm (MPN) patients, such as age >60 years, thrombosis history, cardiovascular risk factors, and the presence of JAK2 mutation. Microparticles (MPs) are circulating small vesicles released from the membranes of activated or apoptotic cells, which contribute to thrombosis with their procoagulant activities. However, to date, there have been a very few reports evaluating the relationship between the levels of MPs and procoagulable state in MPN patients.
Aims
In this study, we characterized MPs in MPN patients and assess their relationship with the thrombotic events in MPN patients in comparison with previously reported risk factors in the practical setting.
Methods
We analyzed 52 patients with MPNs: 17 with PV, 31 with ET, 1 with Primary myelofibrosis (PMF), and 3 with secondary MF, according to the revised WHO criteria and 12 healthy controls. The patient group consisted of 35 men and 17 women with a median age of 68 years ranging from 30 to 87 (at analyses). Thrombotic events were observed in 16 cases (30.8%). To assess the levels of MPs, we extracted platelet free plasma (PFP), in which MPs were enriched from sodium citrate-anticoagulated blood by centrifugations. Quantification and phenotypic characterization of MPs were performed by Flow cytometry. This study was approved by the ethics committee at Kindai University, and patients provided written informed consent.
Results
There was no difference in the total amount of MPs between MPN patients and controls (MPNs vs. controls: median 2240 vs. 3110/μL PFP; p=0.058), whereas MPN patients had more AnnexinV+ or tissue factor (TF) + procoagulant MPs (PCMPs) than controls (median±SD 15.1±6.2% vs. 11.5±7.4%, p<0.05; 2.5±1.6% vs. 0.89±0.52%, p<0.05, respectively). The majority of PCMPs derived from platelets and endothelial cells in MPN patients, which was confirmed by positivity for CD41a and CD146, respectively. The levels of AnnexinV+ and TF+ MPs tended to decrease in response to cytoreductive treatment in MPN patients but with no significant difference (n=35: p=0.143, p=0.084, respectively). Also, there was no statistically significant association between PCMP levels and common hematopoietic parameters (e.g. Hb, WBC, and PLT counts), suggesting that PCMPs were elevated independently of excessive hematopoiesis in MPN patients. In addition, none of age, cardiovascular risk factors, and JAK2 mutation showed a statistically significant relationship with thrombosis history in untreated MPN patients (n=17) by univariate analysis. In this setting, only high levels of TF+ MPs showed a strong association with thrombosis history (p<0.01). The ROC analysis revealed that the best cut-off value of TF+ MPs in accordance with thrombosis history was > 52.0/μL PFP with 100% sensitivity and 75.0% specificity (AUC: 0.88, 95% CI: 0.71-1.0; p=0.102). These data indicate that elevated levels of TF+ MPs will be a new surrogate biomarker to predict thrombotic events in MPN patients.
Conclusion
The current study shows the presence of elevated PCMPs in the peripheral circulation of MPN patients, which was supposed to contribute to the thrombotic events in these patients. Moreover, measuring PCMPs, especially TF+ MP levels, seems to be a promising strategy to predict thrombosis in MPN patients. Further studies to analyze their pathologic roles in thrombosis may provide us with a new approach to prevent thrombotic events in MPN patients.
Session topic: E-poster
Keyword(s): Microparticles, Myeloproliferative disorder, Thrombosis
Type: Eposter Presentation
Background
Previous studies have identified several clinical and genetic markers for thrombosis in myeloproliferative neoplasm (MPN) patients, such as age >60 years, thrombosis history, cardiovascular risk factors, and the presence of JAK2 mutation. Microparticles (MPs) are circulating small vesicles released from the membranes of activated or apoptotic cells, which contribute to thrombosis with their procoagulant activities. However, to date, there have been a very few reports evaluating the relationship between the levels of MPs and procoagulable state in MPN patients.
Aims
In this study, we characterized MPs in MPN patients and assess their relationship with the thrombotic events in MPN patients in comparison with previously reported risk factors in the practical setting.
Methods
We analyzed 52 patients with MPNs: 17 with PV, 31 with ET, 1 with Primary myelofibrosis (PMF), and 3 with secondary MF, according to the revised WHO criteria and 12 healthy controls. The patient group consisted of 35 men and 17 women with a median age of 68 years ranging from 30 to 87 (at analyses). Thrombotic events were observed in 16 cases (30.8%). To assess the levels of MPs, we extracted platelet free plasma (PFP), in which MPs were enriched from sodium citrate-anticoagulated blood by centrifugations. Quantification and phenotypic characterization of MPs were performed by Flow cytometry. This study was approved by the ethics committee at Kindai University, and patients provided written informed consent.
Results
There was no difference in the total amount of MPs between MPN patients and controls (MPNs vs. controls: median 2240 vs. 3110/μL PFP; p=0.058), whereas MPN patients had more AnnexinV+ or tissue factor (TF) + procoagulant MPs (PCMPs) than controls (median±SD 15.1±6.2% vs. 11.5±7.4%, p<0.05; 2.5±1.6% vs. 0.89±0.52%, p<0.05, respectively). The majority of PCMPs derived from platelets and endothelial cells in MPN patients, which was confirmed by positivity for CD41a and CD146, respectively. The levels of AnnexinV+ and TF+ MPs tended to decrease in response to cytoreductive treatment in MPN patients but with no significant difference (n=35: p=0.143, p=0.084, respectively). Also, there was no statistically significant association between PCMP levels and common hematopoietic parameters (e.g. Hb, WBC, and PLT counts), suggesting that PCMPs were elevated independently of excessive hematopoiesis in MPN patients. In addition, none of age, cardiovascular risk factors, and JAK2 mutation showed a statistically significant relationship with thrombosis history in untreated MPN patients (n=17) by univariate analysis. In this setting, only high levels of TF+ MPs showed a strong association with thrombosis history (p<0.01). The ROC analysis revealed that the best cut-off value of TF+ MPs in accordance with thrombosis history was > 52.0/μL PFP with 100% sensitivity and 75.0% specificity (AUC: 0.88, 95% CI: 0.71-1.0; p=0.102). These data indicate that elevated levels of TF+ MPs will be a new surrogate biomarker to predict thrombotic events in MPN patients.
Conclusion
The current study shows the presence of elevated PCMPs in the peripheral circulation of MPN patients, which was supposed to contribute to the thrombotic events in these patients. Moreover, measuring PCMPs, especially TF+ MP levels, seems to be a promising strategy to predict thrombosis in MPN patients. Further studies to analyze their pathologic roles in thrombosis may provide us with a new approach to prevent thrombotic events in MPN patients.
Session topic: E-poster
Keyword(s): Microparticles, Myeloproliferative disorder, Thrombosis
Abstract: E1348
Type: Eposter Presentation
Background
Previous studies have identified several clinical and genetic markers for thrombosis in myeloproliferative neoplasm (MPN) patients, such as age >60 years, thrombosis history, cardiovascular risk factors, and the presence of JAK2 mutation. Microparticles (MPs) are circulating small vesicles released from the membranes of activated or apoptotic cells, which contribute to thrombosis with their procoagulant activities. However, to date, there have been a very few reports evaluating the relationship between the levels of MPs and procoagulable state in MPN patients.
Aims
In this study, we characterized MPs in MPN patients and assess their relationship with the thrombotic events in MPN patients in comparison with previously reported risk factors in the practical setting.
Methods
We analyzed 52 patients with MPNs: 17 with PV, 31 with ET, 1 with Primary myelofibrosis (PMF), and 3 with secondary MF, according to the revised WHO criteria and 12 healthy controls. The patient group consisted of 35 men and 17 women with a median age of 68 years ranging from 30 to 87 (at analyses). Thrombotic events were observed in 16 cases (30.8%). To assess the levels of MPs, we extracted platelet free plasma (PFP), in which MPs were enriched from sodium citrate-anticoagulated blood by centrifugations. Quantification and phenotypic characterization of MPs were performed by Flow cytometry. This study was approved by the ethics committee at Kindai University, and patients provided written informed consent.
Results
There was no difference in the total amount of MPs between MPN patients and controls (MPNs vs. controls: median 2240 vs. 3110/μL PFP; p=0.058), whereas MPN patients had more AnnexinV+ or tissue factor (TF) + procoagulant MPs (PCMPs) than controls (median±SD 15.1±6.2% vs. 11.5±7.4%, p<0.05; 2.5±1.6% vs. 0.89±0.52%, p<0.05, respectively). The majority of PCMPs derived from platelets and endothelial cells in MPN patients, which was confirmed by positivity for CD41a and CD146, respectively. The levels of AnnexinV+ and TF+ MPs tended to decrease in response to cytoreductive treatment in MPN patients but with no significant difference (n=35: p=0.143, p=0.084, respectively). Also, there was no statistically significant association between PCMP levels and common hematopoietic parameters (e.g. Hb, WBC, and PLT counts), suggesting that PCMPs were elevated independently of excessive hematopoiesis in MPN patients. In addition, none of age, cardiovascular risk factors, and JAK2 mutation showed a statistically significant relationship with thrombosis history in untreated MPN patients (n=17) by univariate analysis. In this setting, only high levels of TF+ MPs showed a strong association with thrombosis history (p<0.01). The ROC analysis revealed that the best cut-off value of TF+ MPs in accordance with thrombosis history was > 52.0/μL PFP with 100% sensitivity and 75.0% specificity (AUC: 0.88, 95% CI: 0.71-1.0; p=0.102). These data indicate that elevated levels of TF+ MPs will be a new surrogate biomarker to predict thrombotic events in MPN patients.
Conclusion
The current study shows the presence of elevated PCMPs in the peripheral circulation of MPN patients, which was supposed to contribute to the thrombotic events in these patients. Moreover, measuring PCMPs, especially TF+ MP levels, seems to be a promising strategy to predict thrombosis in MPN patients. Further studies to analyze their pathologic roles in thrombosis may provide us with a new approach to prevent thrombotic events in MPN patients.
Session topic: E-poster
Keyword(s): Microparticles, Myeloproliferative disorder, Thrombosis
Type: Eposter Presentation
Background
Previous studies have identified several clinical and genetic markers for thrombosis in myeloproliferative neoplasm (MPN) patients, such as age >60 years, thrombosis history, cardiovascular risk factors, and the presence of JAK2 mutation. Microparticles (MPs) are circulating small vesicles released from the membranes of activated or apoptotic cells, which contribute to thrombosis with their procoagulant activities. However, to date, there have been a very few reports evaluating the relationship between the levels of MPs and procoagulable state in MPN patients.
Aims
In this study, we characterized MPs in MPN patients and assess their relationship with the thrombotic events in MPN patients in comparison with previously reported risk factors in the practical setting.
Methods
We analyzed 52 patients with MPNs: 17 with PV, 31 with ET, 1 with Primary myelofibrosis (PMF), and 3 with secondary MF, according to the revised WHO criteria and 12 healthy controls. The patient group consisted of 35 men and 17 women with a median age of 68 years ranging from 30 to 87 (at analyses). Thrombotic events were observed in 16 cases (30.8%). To assess the levels of MPs, we extracted platelet free plasma (PFP), in which MPs were enriched from sodium citrate-anticoagulated blood by centrifugations. Quantification and phenotypic characterization of MPs were performed by Flow cytometry. This study was approved by the ethics committee at Kindai University, and patients provided written informed consent.
Results
There was no difference in the total amount of MPs between MPN patients and controls (MPNs vs. controls: median 2240 vs. 3110/μL PFP; p=0.058), whereas MPN patients had more AnnexinV+ or tissue factor (TF) + procoagulant MPs (PCMPs) than controls (median±SD 15.1±6.2% vs. 11.5±7.4%, p<0.05; 2.5±1.6% vs. 0.89±0.52%, p<0.05, respectively). The majority of PCMPs derived from platelets and endothelial cells in MPN patients, which was confirmed by positivity for CD41a and CD146, respectively. The levels of AnnexinV+ and TF+ MPs tended to decrease in response to cytoreductive treatment in MPN patients but with no significant difference (n=35: p=0.143, p=0.084, respectively). Also, there was no statistically significant association between PCMP levels and common hematopoietic parameters (e.g. Hb, WBC, and PLT counts), suggesting that PCMPs were elevated independently of excessive hematopoiesis in MPN patients. In addition, none of age, cardiovascular risk factors, and JAK2 mutation showed a statistically significant relationship with thrombosis history in untreated MPN patients (n=17) by univariate analysis. In this setting, only high levels of TF+ MPs showed a strong association with thrombosis history (p<0.01). The ROC analysis revealed that the best cut-off value of TF+ MPs in accordance with thrombosis history was > 52.0/μL PFP with 100% sensitivity and 75.0% specificity (AUC: 0.88, 95% CI: 0.71-1.0; p=0.102). These data indicate that elevated levels of TF+ MPs will be a new surrogate biomarker to predict thrombotic events in MPN patients.
Conclusion
The current study shows the presence of elevated PCMPs in the peripheral circulation of MPN patients, which was supposed to contribute to the thrombotic events in these patients. Moreover, measuring PCMPs, especially TF+ MP levels, seems to be a promising strategy to predict thrombosis in MPN patients. Further studies to analyze their pathologic roles in thrombosis may provide us with a new approach to prevent thrombotic events in MPN patients.
Session topic: E-poster
Keyword(s): Microparticles, Myeloproliferative disorder, Thrombosis
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