PLATELET ADHESION UNDER FLOW CONDITION IS SIGNIFICANTLY AFFECTED BY HEMATOCRIT LEVELS IN POLYCYTHEMIA VERA PATIENTS
Author(s): ,
Sara Gamba
Affiliations:
Division of Immunohematology and Transfusion Medicine,ASST Papa Giovanni XXIII,Bergamo,Italy
,
Alfonso Vignoli
Affiliations:
Division of Immunohematology and Transfusion Medicine,ASST Papa Giovanni XXIII,Bergamo,Italy
,
Marina Marchetti
Affiliations:
Division of Immunohematology and Transfusion Medicine,ASST Papa Giovanni XXIII,Bergamo,Italy
,
Paola E. van der Meijden
Affiliations:
Department of Biochemistry,CARIM, Maastricht University,Maastricht ,Netherlands
,
Cinzia Giaccherini
Affiliations:
Division of Immunohematology and Transfusion Medicine,ASST Papa Giovanni XXIII,Bergamo,Italy
,
Serena Tessarolo
Affiliations:
Division of Immunohematology and Transfusion Medicine,ASST Papa Giovanni XXIII,Bergamo,Italy
,
Frauke Swieringa
Affiliations:
Department of Biochemistry,CARIM, Maastricht University,Maastricht ,Netherlands
,
Hugo ten Cate
Affiliations:
Department of Internal Medicine,CARIM, Maastricht University,Maastricht ,Netherlands
,
Guido Finazzi
Affiliations:
Division of Hematology,ASST Papa Giovanni XXIII,Bergamo,Italy
,
Alessandro Rambaldi
Affiliations:
Division of Hematology,ASST Papa Giovanni XXIII,Bergamo,Italy
,
Johan W. Heemskerk
Affiliations:
Department of Biochemistry,CARIM, Maastricht University,Maastricht ,Netherlands
Anna Falanga
Affiliations:
Division of Immunohematology and Transfusion Medicine,ASST Papa Giovanni XXIII,Bergamo,Italy
(Abstract release date: 05/17/18) EHA Library. Gamba S. 06/16/18; 214607; S837
Dr. Sara Gamba
Dr. Sara Gamba
Contributions
Abstract

Abstract: S837

Type: Oral Presentation

Presentation during EHA23: On Saturday, June 16, 2018 from 11:30 - 11:45

Location: Room A9

Background

Polycythemia Vera (PV) is complicated by a high rate of thromboembolic events. Aspirin therapy (81–100 mg once-daily) + phlebotomy with a target hematocrit (HCT) of 45% is currently recommended in all PV patients regardless of risk status. Recently, a novel mechanism by which elevated HCT can lead to an increased risk of thrombosis has been described. The red blood cells push the platelets closer to the vessel wall, increasing the probability of their adhesion and activation via von Willebrand factor and collagen (Blood 19: 2537, 2017). This may occur in PV, where multiple cellular events may be needed to trigger thrombosis.

Aims

In a cohort of PV patients, we aim to characterize the in vitro platelet thrombus formation capacity under flow conditions at arterial shear rate in relation to HCT levels.

Methods

Fifty-two PV patients (26 M/26F; median age 65 years, range: 38-87) were enrolled after giving informed consent. Measurement of whole blood thrombus formation was performed in a parallel plate flow-chamber for 4’ at 1,000 s-1 shear-rate over a collagen-coated surface. Thrombi were then stained with an anti-P-selectin-FITC antibody to evaluate the platelet activation status, and annexinV-AlexaFluor647 to detect procoagulant phosphatidylserine (PS) exposure. Results are expressed as mean±SEM of the % of area covered by thrombi or the % of adherent platelets positive for either P-selectin or AnnexinV.

Results

Platelet adhesion was significantly increased in PV (48.9±1.6%) compared to healthy controls (37.5±1.7%, p<0.01). In both PV and controls, almost all platelets forming the inner thrombus core expressed P-selectin, while PS was expressed by some platelets at the external thrombus border. Patients’ thrombi were usually larger and more often interconnected forming a network while thrombi from controls are smaller and well isolated from each other. Considering the total population analyzed, a significant positive correlation (p<0.005) was found between HCT levels and either platelet adhesion and P-selectin positive platelets. Differently, no significant correlation was found between platelet adhesion and platelet count in either PV or controls. On the basis of the median value of HCT of our patient population (43.7%), subjects with an HCT value above the median had a significantly higher adhesion than the subjects with an HCT below the median (42±1.9 vs 51±2.3%, P<0.05). After a multivariate analysis adjusted for sex, age, therapy and JAK2-V617F allele burden, the HCT value was still significantly associated with platelet coverage and p-selectin expression.

Conclusion

Our study demonstrates that an elevated HCT increases platelet adhesion to the vessel wall. This is likely favored by local rheological factors coming from the increased red blood cell count typical of this disease. These findings support the concept that an elevated HCT is a very relevant thrombotic mechanism in PV.

Session topic: 35. Thrombosis and vascular biology & translational Research

Keyword(s): Hematocrit, Platelet adhesion, Polycythemia vera

Abstract: S837

Type: Oral Presentation

Presentation during EHA23: On Saturday, June 16, 2018 from 11:30 - 11:45

Location: Room A9

Background

Polycythemia Vera (PV) is complicated by a high rate of thromboembolic events. Aspirin therapy (81–100 mg once-daily) + phlebotomy with a target hematocrit (HCT) of 45% is currently recommended in all PV patients regardless of risk status. Recently, a novel mechanism by which elevated HCT can lead to an increased risk of thrombosis has been described. The red blood cells push the platelets closer to the vessel wall, increasing the probability of their adhesion and activation via von Willebrand factor and collagen (Blood 19: 2537, 2017). This may occur in PV, where multiple cellular events may be needed to trigger thrombosis.

Aims

In a cohort of PV patients, we aim to characterize the in vitro platelet thrombus formation capacity under flow conditions at arterial shear rate in relation to HCT levels.

Methods

Fifty-two PV patients (26 M/26F; median age 65 years, range: 38-87) were enrolled after giving informed consent. Measurement of whole blood thrombus formation was performed in a parallel plate flow-chamber for 4’ at 1,000 s-1 shear-rate over a collagen-coated surface. Thrombi were then stained with an anti-P-selectin-FITC antibody to evaluate the platelet activation status, and annexinV-AlexaFluor647 to detect procoagulant phosphatidylserine (PS) exposure. Results are expressed as mean±SEM of the % of area covered by thrombi or the % of adherent platelets positive for either P-selectin or AnnexinV.

Results

Platelet adhesion was significantly increased in PV (48.9±1.6%) compared to healthy controls (37.5±1.7%, p<0.01). In both PV and controls, almost all platelets forming the inner thrombus core expressed P-selectin, while PS was expressed by some platelets at the external thrombus border. Patients’ thrombi were usually larger and more often interconnected forming a network while thrombi from controls are smaller and well isolated from each other. Considering the total population analyzed, a significant positive correlation (p<0.005) was found between HCT levels and either platelet adhesion and P-selectin positive platelets. Differently, no significant correlation was found between platelet adhesion and platelet count in either PV or controls. On the basis of the median value of HCT of our patient population (43.7%), subjects with an HCT value above the median had a significantly higher adhesion than the subjects with an HCT below the median (42±1.9 vs 51±2.3%, P<0.05). After a multivariate analysis adjusted for sex, age, therapy and JAK2-V617F allele burden, the HCT value was still significantly associated with platelet coverage and p-selectin expression.

Conclusion

Our study demonstrates that an elevated HCT increases platelet adhesion to the vessel wall. This is likely favored by local rheological factors coming from the increased red blood cell count typical of this disease. These findings support the concept that an elevated HCT is a very relevant thrombotic mechanism in PV.

Session topic: 35. Thrombosis and vascular biology & translational Research

Keyword(s): Hematocrit, Platelet adhesion, Polycythemia vera

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