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THROMBOTIC AND BLEEDING RISK FACTORS IN ESSENTIAL THROMBOCYTHEMIA
Author(s): ,
Anastasiia Zherniakova
Affiliations:
Russian Research Institute of Hematology and Transfusiology,Saint-Petersburg,Russian Federation
,
Irina Martynkevich
Affiliations:
Russian Research Institute of Hematology and Transfusiology,Saint-Petersburg,Russian Federation
,
Vasilii Shuvaev
Affiliations:
Russian Research Institute of Hematology and Transfusiology,Saint-Petersburg,Russian Federation
,
Lubov' Polushkina
Affiliations:
Russian Research Institute of Hematology and Transfusiology,Saint-Petersburg,Russian Federation
,
Mikhail Fominykh
Affiliations:
Russian Research Institute of Hematology and Transfusiology,Saint-Petersburg,Russian Federation
,
Vera Udal'eva
Affiliations:
Russian Research Institute of Hematology and Transfusiology,Saint-Petersburg,Russian Federation
,
Irina Zotova
Affiliations:
Russian Research Institute of Hematology and Transfusiology,Saint-Petersburg,Russian Federation
,
Dzariat Shichbabaeva
Affiliations:
Russian Research Institute of Hematology and Transfusiology,Saint-Petersburg,Russian Federation
,
Sergey Voloshin
Affiliations:
Russian Research Institute of Hematology and Transfusiology,Saint-Petersburg,Russian Federation
,
Stanislav Bessmeltsev
Affiliations:
Russian Research Institute of Hematology and Transfusiology,Saint-Petersburg,Russian Federation
,
Aleksandr Chechetkin
Affiliations:
Russian Research Institute of Hematology and Transfusiology,Saint-Petersburg,Russian Federation
Kudrat Abdulkadyrov
Affiliations:
Russian Research Institute of Hematology and Transfusiology,Saint-Petersburg,Russian Federation
(Abstract release date: 05/18/17) EHA Library. Zherniakova A. 05/18/17; 182748; PB2034
Dr. Anastasiia Zherniakova
Dr. Anastasiia Zherniakova
Contributions
Abstract

Abstract: PB2034

Type: Publication Only

Background
Thrombosis and hemorrhage are the main category of complications, that affects the overall survival (OS), quality of life and therapy option choice in essential thrombocythemia (ET). Molecular marker presence (JAK2V617F, MPL, CALR) or its absence (triple-negative status (TN)) in ET supposed to impact on the clinical course, thrombosis rate and ET prognosis.

Aims

The aim of this study was to investigate interactions between the presence of molecular marker, thrombosis/bleeding rates and the OS in ET.

Methods

Outpatient’s charts of 240 ET patients, who had been diagnosed with ET at our institution according to WHO 2008 criteria. The following data were assessed: complete blood count, bone marrow biopsy results, bone marrow cytogenetic, the restriction fragment length polymorphism (RFLP) results used for JAK2V617F detection, in case of JAK2V617F-negative status the PCR-RFLP (MPL detection) and the direct sequencing (CALR detection) results. Different thrombotic/bleeding complications rates were analyzed. The OS in ET patients was compared according to molecular markers revealed.

Results

According to their mutational status 182/240 (75.9%) patients (pts) were JAK2V617F-positive (JAK2+); 30/240 (12.5%) – CALR-positive (CALR+): type 1 (CALR1+) 13/30 pts (43.3%), type 2 (CALR2+) 17/30 pts (56.7%). Only two pts were MPL-positive (MPL+) (0.8%), TN were 26/240 pts (10.8%). Among 240 pts 183 (76.3%) hadn’t any thrombotic complication or bleeding event (no complications/NC), 57/240 (23.7%) had complications: 49/57 (85.9%) reported arterial or/and venous thrombosis, stroke or heart failure (thrombosis+) and 11/57 (19.3%) had bleeding events (hemorrhage+). Thrombotic complications in JAK2+ had 27.4% (50/182) pts, in TN 30.7% (8/26) pts, in CALR1+ 18.2% (2/11) pts and no cases of thrombosis were detected in CALR2+ and MPL+ subgroups (p<0,001). There were significant statistical differences in median platelet count as follows: 742х109/l (thrombosis+) and 937х109/l (hemorrhage+) (p=0.003). No significant statistical differences in median hemoglobin and leukocyte count (р=0.75 and р=0.47) were detected. There were more than a half pts older than 60 years in groups NC (51%) and thrombosis+ (59%) and in group hemorrhage+ only 36% (p<0,001). Cardiovascular risk factors were reported in 24% pts (NC), 69% pts (thrombosis+) and 36% pts (hemorrhage+) (p<0,001). There were no significant statistical differences in follows risk factors as thrombosis >1000x109/l and leukocytosis >11x109/l (р=0.85 and р=0.72). No significant differences in OS among groups NC, thrombosis+ and hemorrhage+ (р=0.12) were found.

Conclusion
Leukocytosis >11x109/l and thrombocytosis >1000x109/l cannot be assessed as independent thrombosis risk factors in ET. JAK2V617F mutation was associated with increased risk of thrombotic complications in ET. CALR mutations were correlated with lower thrombosis risk and better OS rate, comparing to JAK2+ and TN status despite the fact of CALR+ patients had higher platelets level. Along with common thrombosis risk factors (age >60 and cardiovascular risk factors) mutational status may help to identify ET course and to optimize individual therapy option choice.

Session topic: 16. Myeloproliferative neoplasms - Clinical

Keyword(s): Mutation status, Essential Thrombocytemia

Abstract: PB2034

Type: Publication Only

Background
Thrombosis and hemorrhage are the main category of complications, that affects the overall survival (OS), quality of life and therapy option choice in essential thrombocythemia (ET). Molecular marker presence (JAK2V617F, MPL, CALR) or its absence (triple-negative status (TN)) in ET supposed to impact on the clinical course, thrombosis rate and ET prognosis.

Aims

The aim of this study was to investigate interactions between the presence of molecular marker, thrombosis/bleeding rates and the OS in ET.

Methods

Outpatient’s charts of 240 ET patients, who had been diagnosed with ET at our institution according to WHO 2008 criteria. The following data were assessed: complete blood count, bone marrow biopsy results, bone marrow cytogenetic, the restriction fragment length polymorphism (RFLP) results used for JAK2V617F detection, in case of JAK2V617F-negative status the PCR-RFLP (MPL detection) and the direct sequencing (CALR detection) results. Different thrombotic/bleeding complications rates were analyzed. The OS in ET patients was compared according to molecular markers revealed.

Results

According to their mutational status 182/240 (75.9%) patients (pts) were JAK2V617F-positive (JAK2+); 30/240 (12.5%) – CALR-positive (CALR+): type 1 (CALR1+) 13/30 pts (43.3%), type 2 (CALR2+) 17/30 pts (56.7%). Only two pts were MPL-positive (MPL+) (0.8%), TN were 26/240 pts (10.8%). Among 240 pts 183 (76.3%) hadn’t any thrombotic complication or bleeding event (no complications/NC), 57/240 (23.7%) had complications: 49/57 (85.9%) reported arterial or/and venous thrombosis, stroke or heart failure (thrombosis+) and 11/57 (19.3%) had bleeding events (hemorrhage+). Thrombotic complications in JAK2+ had 27.4% (50/182) pts, in TN 30.7% (8/26) pts, in CALR1+ 18.2% (2/11) pts and no cases of thrombosis were detected in CALR2+ and MPL+ subgroups (p<0,001). There were significant statistical differences in median platelet count as follows: 742х109/l (thrombosis+) and 937х109/l (hemorrhage+) (p=0.003). No significant statistical differences in median hemoglobin and leukocyte count (р=0.75 and р=0.47) were detected. There were more than a half pts older than 60 years in groups NC (51%) and thrombosis+ (59%) and in group hemorrhage+ only 36% (p<0,001). Cardiovascular risk factors were reported in 24% pts (NC), 69% pts (thrombosis+) and 36% pts (hemorrhage+) (p<0,001). There were no significant statistical differences in follows risk factors as thrombosis >1000x109/l and leukocytosis >11x109/l (р=0.85 and р=0.72). No significant differences in OS among groups NC, thrombosis+ and hemorrhage+ (р=0.12) were found.

Conclusion
Leukocytosis >11x109/l and thrombocytosis >1000x109/l cannot be assessed as independent thrombosis risk factors in ET. JAK2V617F mutation was associated with increased risk of thrombotic complications in ET. CALR mutations were correlated with lower thrombosis risk and better OS rate, comparing to JAK2+ and TN status despite the fact of CALR+ patients had higher platelets level. Along with common thrombosis risk factors (age >60 and cardiovascular risk factors) mutational status may help to identify ET course and to optimize individual therapy option choice.

Session topic: 16. Myeloproliferative neoplasms - Clinical

Keyword(s): Mutation status, Essential Thrombocytemia

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