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WHEN MYELOPROLIFERATIVE NEOPLASMS MEET COVID-19: INFLAMMATION, ENDOTHELIOPATHY AND COAGULOPATHY
Author(s): ,
Rossella Cacciola
Affiliations:
Experimental and Clinical Medicine,Haemostasis Unit - University of Catania,Catania,Italy
,
Elio Gentilini Cacciola
Affiliations:
Infectious Disaeses,La Sapienza University,Rome,Italy
,
Veronica Vecchio
Affiliations:
Medical School,University of Catania,Catania,Italy
Emma Cacciola
Affiliations:
Med Sur Sci Advance Techno,University of Catania,Catania,Italy
EHA Library. Cacciola R. 06/09/21; 324817; EP1094
Rossella Cacciola
Rossella Cacciola
Contributions
Abstract
Presentation during EHA2021: All e-poster presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: EP1094

Type: E-Poster Presentation

Session title: Myeloproliferative neoplasms - Clinical

Background
Myeloproliferative Neoplasms (MPNs) - polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) - are marked by thrombosis. COVID-19 infection is marked by thrombosis as reported in China and confirmed in autopsies of patients experiencing sudden death. The thrombosis in MPNs is related to inflammation and endotheliopathy. The thrombosis in COVID-19 may be related to devastating enhancement of inflammation (“cytokine storm”) and profound endotheliopathy, known as COVID-19-associated coagulopathy (CAC). It is showed that patients with hematological malignancies and COVID-19 had worse outcomes. It is unclear if COVID-19 exerts additive or synergistic thrombotic effects.

Aims
Therefore, we evaluated Interleukin-6 (IL-6) and Tissue Factor (TF),  as inflammatory and endothelial mediators, D-dimer (DD), thrombin antithrombin complex (TAT) and Fibrinogen (Fib), as coagulation activation mediators, platelet factor 4 (PF4), as platelet activation mediator, and whole blood viscoelastic analysis, as indicator of whole hemostatic activation.

Methods
The cohort study included 120 WHO-defined MPNs patients with COVID-19 ascertained by positive RT-PCR on nasopharyngeal swab (n= 40 PV, n= 40 ET, n= 40 PMF) (60 men, 60 women; mean age 51 years, range 32-60) and 90 WHO-defined MPNs patients without COVID-19 (n= 30 PV, n= 30 ET, n= 30 PMF) (45 men, 45 women, mean age 50 years, range 30-60). All patients gave written informed consent for study enrollment. The mean duration of disease was 12 years. All patients were on ASA 100 mg once daily. Concerning presentation and therapy, our MPNs patients with COVID-19 and without COVID-19 had not comorbidities and drug treatment was consistent with therapeutic standards (hydroxyurea, interferon, anagrelide, ruxolitinib). All patients were on ASA 100 mg once daily. IL-6 was measured by multiplex bead array (Millipore Sigma), TF and  DD, and TAT by ELISA and Fib by Clauss method. PF4 was determined by ELISA. Whole blood viscoelastic analysis including clotting time (CT), and clot formation time (CFT) were measured by thomboelastometry method.

Results
MPNs with COVID-19 had high IL-6 and TF (50±12pg/ml and 1950±500 pg/ml) compared with MPNs without COVID-19 (3±2pg/ml and 19±2 pg/ml), as well as DD, TAT and Fib (549±100 mg/l, 69±10 mg/l and 590±20mg/dl) compared with MPNs without COVID-19 (59±5mg/l, 2±1mg/l and 149±10 mg/l). PF4 was elevated (150.1±62.7 IU/ml) in MPNs with COVID-19 compared with MPNs without COVID-19 (2±1 UI/ml). A positive correlation was found between inflammatory, endothelial and coagulation mediators. A p-value of <.05 was considered statistically significant. Shortened CT  (CT, unit: s. n.v. 100-240 s) (40±20 s) and shortened  CFT (CFT, unit: s, n.v. 30-160 s (14±10 s) there were in MPNs with COVID-19 compared with MPNs without COVID-19 (CT 99±10 s and CFT 39±5 s).

Conclusion

These data suggest that COVID-19 infection in MPNs patients may increase the thrombotic risk and get worse prognosis. In our opinion, this study can serve as a baseline study of COVID-19 thrombotic risk in MPNs and it is worthy of dissemination amongst patients and clinician communities.

Keyword(s): COVID-19, Essential Thrombocytemia, Myelofibrosis, Polycythemia vera

Presentation during EHA2021: All e-poster presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: EP1094

Type: E-Poster Presentation

Session title: Myeloproliferative neoplasms - Clinical

Background
Myeloproliferative Neoplasms (MPNs) - polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) - are marked by thrombosis. COVID-19 infection is marked by thrombosis as reported in China and confirmed in autopsies of patients experiencing sudden death. The thrombosis in MPNs is related to inflammation and endotheliopathy. The thrombosis in COVID-19 may be related to devastating enhancement of inflammation (“cytokine storm”) and profound endotheliopathy, known as COVID-19-associated coagulopathy (CAC). It is showed that patients with hematological malignancies and COVID-19 had worse outcomes. It is unclear if COVID-19 exerts additive or synergistic thrombotic effects.

Aims
Therefore, we evaluated Interleukin-6 (IL-6) and Tissue Factor (TF),  as inflammatory and endothelial mediators, D-dimer (DD), thrombin antithrombin complex (TAT) and Fibrinogen (Fib), as coagulation activation mediators, platelet factor 4 (PF4), as platelet activation mediator, and whole blood viscoelastic analysis, as indicator of whole hemostatic activation.

Methods
The cohort study included 120 WHO-defined MPNs patients with COVID-19 ascertained by positive RT-PCR on nasopharyngeal swab (n= 40 PV, n= 40 ET, n= 40 PMF) (60 men, 60 women; mean age 51 years, range 32-60) and 90 WHO-defined MPNs patients without COVID-19 (n= 30 PV, n= 30 ET, n= 30 PMF) (45 men, 45 women, mean age 50 years, range 30-60). All patients gave written informed consent for study enrollment. The mean duration of disease was 12 years. All patients were on ASA 100 mg once daily. Concerning presentation and therapy, our MPNs patients with COVID-19 and without COVID-19 had not comorbidities and drug treatment was consistent with therapeutic standards (hydroxyurea, interferon, anagrelide, ruxolitinib). All patients were on ASA 100 mg once daily. IL-6 was measured by multiplex bead array (Millipore Sigma), TF and  DD, and TAT by ELISA and Fib by Clauss method. PF4 was determined by ELISA. Whole blood viscoelastic analysis including clotting time (CT), and clot formation time (CFT) were measured by thomboelastometry method.

Results
MPNs with COVID-19 had high IL-6 and TF (50±12pg/ml and 1950±500 pg/ml) compared with MPNs without COVID-19 (3±2pg/ml and 19±2 pg/ml), as well as DD, TAT and Fib (549±100 mg/l, 69±10 mg/l and 590±20mg/dl) compared with MPNs without COVID-19 (59±5mg/l, 2±1mg/l and 149±10 mg/l). PF4 was elevated (150.1±62.7 IU/ml) in MPNs with COVID-19 compared with MPNs without COVID-19 (2±1 UI/ml). A positive correlation was found between inflammatory, endothelial and coagulation mediators. A p-value of <.05 was considered statistically significant. Shortened CT  (CT, unit: s. n.v. 100-240 s) (40±20 s) and shortened  CFT (CFT, unit: s, n.v. 30-160 s (14±10 s) there were in MPNs with COVID-19 compared with MPNs without COVID-19 (CT 99±10 s and CFT 39±5 s).

Conclusion

These data suggest that COVID-19 infection in MPNs patients may increase the thrombotic risk and get worse prognosis. In our opinion, this study can serve as a baseline study of COVID-19 thrombotic risk in MPNs and it is worthy of dissemination amongst patients and clinician communities.

Keyword(s): COVID-19, Essential Thrombocytemia, Myelofibrosis, Polycythemia vera

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