Prevention and Management of Thrombosis in BCR/ABL-Negative Myeloproliferative Neoplasms

Falanga, Anna; Marchetti, Marina; Schieppati, Francesca

doi:10.1055/a-1334-3259

Cited by 16 publications

(21 citation statements)

References 96 publications

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“…As shown in Table IV, patients in the HU arm were significantly older than those in the ANA arm. In addition, HU patients presented more frequently with JAK2 V617F mutation, cardiovascular risk factors, and a history of thrombosis; thus, they were considered high-risk patients and received HU as recommended (41). These risk factors are associated with increased levels of MPs in our study.…”

Section: Discussionmentioning

confidence: 79%

The Clinical Significance of Circulating Microparticles Concerning Thrombosis in BCR/ABL1-negative Myeloproliferative Neoplasms

Aswad

Kissová

Ovesná

et al. 2021

In Vivo

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Background/Aim: This work aimed to prospectively evaluate the clinical significance of circulating microparticles (MPs) in relation to thrombotic risk factors and thrombotic complications in patients with BCR/ABL1-negative myeloproliferative neoplasms (MPN). Patients and Methods: In a cohort of 206 patients with MPN, MPs' procoagulant activity was measured by the Zymuphen functional assay in 429 samples, while plateletand erythrocyte-MPs were enumerated by flow cytometry in 558 samples. Results: MPN patients had higher MP levels than the control group. The levels of MPs were higher in male patients, smokers, and those who were older than 60 years, and in the presence of JAK2 V617F mutation, history of thrombosis, platelets >400×10 9 /l, hematocrit >45%, or leukocytes >10×10 9 /l. Cytoreductive treatment reduced MP levels, with anagrelide being associated with lower MP levels than hydroxyurea. Conclusion: The relationship with thrombotic risk factors indicates a possible role of MPs in the complex thrombotic mechanism, though cytoreductive treatment seems to affect this role through reducing MP levels.Circulating microparticles (MPs) are cell-derived vesicles ranging in size between 0.1 and 1 μm; are non-nucleated, have no synthetic capability, and contain a membrane skeleton with antigens indicating their cellular origin (1). Most commonly, MPs originate from platelets and megakaryocytes but also erythrocytes, leukocytes, endothelial cells, and tumor cells during activation or apoptosis (1, 2). MPs enhance coagulation by exposing the procoagulant anionic phosphatidylserine (PS) on their surface and/or expressing functional tissue factor (TF) (3). A higher level of MPs was detected in many pathological conditions, including autoimmune, hematological, cardiovascular, infectious, nephrological, and oncological disorders (1). BCR-ABL1 negative myeloproliferative neoplasms (MPN) belong to oncological disorders that have been linked to elevated levels of MPs (4-8).MPN are clonal myeloid disorders, including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Patients with MPN show excessive proliferation of hematopoietic precursors in the bone marrow leading to abundant levels of mature blood cells being released into the circulation (9). Thrombosis is a common complication of MPN that significantly impacts patients' mortality, accounting for the death of 33% of PV, 16% of ET, and 2% of PMF patients (10-12). Thrombosis may occur at venous, arterial, or microcirculatory sites and can be the first sign of MPN. Management of MPN is based on predicting the risk of thrombosis and starting treatment to prevent complications in vulnerable patients (13). Thus, identifying prognostic factors is the initial step in MPN patients. Thrombosis in MPN has been linked to higher MPs levels, and utilization of MPs as a surrogate biomarker of thrombosis has been suggested (6,8,14). Patients and Methods Patients. Analyses of MPs were conducted in a cohort of 206 patients diagnosed with BCR/ABL1-negativ...

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Section: Discussionmentioning

confidence: 79%

The Clinical Significance of Circulating Microparticles Concerning Thrombosis in BCR/ABL1-negative Myeloproliferative Neoplasms

Aswad

Kissová

Ovesná

et al. 2021

In Vivo

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“…Among intrinsic platelet characteristics, we can discern membrane abnormalities [ 10 ] and JAK2-signalling hyperactivation. Endothelium can be also JAK2-mutated, releasing increased quantities of P-selectin and the von Willebrand Factor (vWF), and expressing higher levels of adhesion molecules and receptors, enhancing platelet activation [ 11 ]. The role of megakaryocytes in platelets activity has also been investigated, observing alterations in gene expression and the transcriptome [ 12 , 13 ].…”

Section: Platelets In Mpns: Role and Controversiesmentioning

confidence: 99%

Platelets Contribution to Thrombin Generation in Philadelphia-Negative Myeloproliferative Neoplasms: The “Circulating Wound” Model

Lucchesi

Napolitano

Bochicchio

et al. 2021

IJMS

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Current cytoreductive and antithrombotic strategies in MPNs are mostly based on cell counts and on patient’s demographic and clinical history. Despite the numerous studies conducted on platelet function and on the role of plasma factors, an accurate and reliable method to dynamically quantify the hypercoagulability states of these conditions is not yet part of clinical practice. Starting from our experience, and after having sifted through the literature, we propose an in-depth narrative report on the contribution of the clonal platelets of MPNs—rich in tissue factor (TF)—in promoting a perpetual procoagulant mechanism. The whole process results in an unbalanced generation of thrombin and is self-maintained by Protease Activated Receptors (PARs). We chose to define this model as a “circulating wound”, as it indisputably links the coagulation, inflammation, and fibrotic progression of the disease, in analogy with what happens in some solid tumours. The platelet contribution to thrombin generation results in triggering a vicious circle supported by the PARs/TGF-beta axis. PAR antagonists could therefore be a good option for target therapy, both to contain the risk of vascular events and to slow the progression of the disease towards end-stage forms. Both the new and old strategies, however, will require tools capable of measuring procoagulant or prohaemorrhagic states in a more extensive and dynamic way to favour a less empirical management of MPNs and their potential clinical complications.

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“…Small series of patients with MPN treated with DOACs have been published. 1 Of inter est, recently, the results of a large ret rospec tive study of 442 patients with MPN receiv ing DOACs (fac tor Xa inhib i tors) or VKAs either for VTE or atrial fibril la tion con firm a sim i lar risk/ben e fit pro file of both reg i mens for treat ment of VTE in MPN. 55…”

Section: Long-term/extended Dura Tion and Type Of Anticoagulation In Mpn And In Covid-19mentioning

confidence: 99%

“…The dis ease man age ment, par tic u larly in PV and ET, remains highly depen dent on the patient ' s throm botic risk. 1 Recently, the coronavirus dis ease 2019 (COVID - 19) pan demic caused by severe acute respi ra tory syn drome coronavirus 2 (SARS -CoV -2) spread all over the world, caus ing mil li ons of deaths. The severe form of COVID -19 is char ac ter ized by inter sti tial pneu mo nia, multiorgan dys func tion, and a high throm botic inci dence, espe cially venous throm bo em bo lism (VTE).…”

Section: Introductionmentioning

confidence: 99%

MPN and thrombosis was hard enough . . . now there's COVID-19 thrombosis too

Falanga

2021

Hematology

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Both myeloproliferative neoplasms (MPNs) and coronavirus disease 2019 (COVID-19) are characterized by an intrinsic thrombotic risk. Little is known about the incidence and the outcome of thrombotic events in patients with MPN infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but common mechanisms of coagulation activation, typical of both disorders, suggest that these patients can be at particularly high risk. To define the best thromboprophylaxis and treatment regimens in both MPN and COVID-19, individual- and disease-specific thrombotic risk factors, bleeding risk, and concomitant specific treatments need to be considered. In this case-based review, an individualized approach is presented in a case of SARS-CoV-2 infection occurring in a man with polycythemia vera (PV). A primary anticoagulant thromboprophylaxis strategy and adjustment of his PV treatment were implemented. However, during the hospital stay, he experienced pulmonary embolism and therapeutic anticoagulation had to be set. Then his condition improved, and discharge was planned. Postdischarge decisions had to be made about the type and duration of venous thromboembolism treatment as well as the management of PV-specific drugs. The steps of our decisions and recommendations are presented.

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Prevention and Management of Thrombosis in BCR/ABL-Negative Myeloproliferative Neoplasms

Cited by 16 publications

References 96 publications

The Clinical Significance of Circulating Microparticles Concerning Thrombosis in BCR/ABL1-negative Myeloproliferative Neoplasms

The Clinical Significance of Circulating Microparticles Concerning Thrombosis in BCR/ABL1-negative Myeloproliferative Neoplasms

Platelets Contribution to Thrombin Generation in Philadelphia-Negative Myeloproliferative Neoplasms: The “Circulating Wound” Model

MPN and thrombosis was hard enough . . . now there's COVID-19 thrombosis too

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