Addressing and proposing solutions for unmet clinical needs in the management of myeloproliferative neoplasm-associated thrombosis: A consensus-based position paper

Abstract

This article presents the results of a group discussion among an ad hoc constituted Panel of experts aimed at highlighting unmet clinical needs (UCNs) in the management of thrombotic risk and thrombotic events associated with Philadelphia-negative myeloproliferative neoplasms (Ph-neg MPNs). With the Delphi technique, the challenges in Ph-neg MPN-associated thrombosis were selected. The most clinically relevant UCNs resulted in: (1) providing evidence of the benefits and risks of direct oral anticoagulants, (2) providing evidence of the benefits and risks of cytoreduction in patients with splanchnic vein thrombosis without hypercythemia, (3) improving knowledge of the role of the mutated endothelium in the pathogenesis of thrombosis, (4) improving aspirin dosing regimens in essential thrombocythemia, (5) improving antithrombotic management of Ph-neg MPN-associated pregnancy, (6) providing evidence for the optimal duration of anticoagulation for prophylaxis of recurrent VTE, (7) improving knowledge of the association between somatic gene mutations and risk factors for thrombosis, and (8) improving the grading system of thrombosis risk in polycythemia vera. For each of these issues, proposals for advancement in research and clinical practice were addressed. Hopefully, this comprehensive overview will serve to inform the design and implementation of new studies in the field.

Cardiovascular Risk in Polycythemia Vera: Thrombotic Risk and Survival: Can Cytoreductive Therapy Be Useful in Patients with Low-Risk Polycythemia Vera with Cardiovascular Risk Factors?

“…This implies that general risk factors for thrombosis, including smoking habits, diabetes mellitus, arterial hypertension, and hypercholesterolemia, should also be considered, even in the absence of specific therapeutic indications [10]. Recently, a panel of experts is questioning the traditional classification of thrombotic risk in PV; a matter of discussion is whether these definitions predicting thrombotic risk are still valid and whether the newly proposed disease-related risk factors, such as cardiovascular risk factors, leukocytosis, JAK2V617F allele burden, may improve the grading system of the thrombotic risk [11]. According to our experience, it should be useful to design perspective studies to determine the real influence of CVR on the thrombotic risk in patients with PV and on survival in order to evaluate the opportunity to develop new specific therapeutic recommendations, such as early cytoreduction, for patients with PV aged < 60 years and having cardiovascular risk factors.…”

Essential Thrombocythemia and Acquired von Willebrand Syndrome: The Shadowlands between Thrombosis and Bleeding

“…Of note, the highest recurrence rate has been reported in ET patients experiencing unusual site thrombosis (splanchnic or cerebral venous sinus, 8 and 8.8 per 100 patients-year, respectively) [ 83 , 84 ]. The occurrence of major bleeding in ET (1.8–2.4 per 100 patients-year) is comparable to non-ET patients under VKA treatment [ 79 , 85 ]. However, the VKA combination with antiplatelet agents (mainly used during the first 6 months after a first VTE episode in particular cases) increases bleeding risk when compared to VKA alone (2.8% vs. 0.9%, respectively) [ 80 ].…”

“…Apart from the primary prophylaxis of thrombosis, patients with ET also pose a challenge related to the acute treatment of venous thromboembolism (VTE) and whether the secondary prophylaxis after a first VTE episode should be finite or indefinite [ 79 ]. Similar to non-ET patients, low molecular weight heparin followed by VKA is the standard treatment as it has shown to be effective in the prevention of VTE recurrence in a cohort of 494 patients with PV or ET [hazard ratio (HR) 0.32, 95% CI: 0.15–0.64)].…”

Essential thrombocythemia: Biology, clinical features, thrombotic risk, therapeutic options and outcome

“…Recently, a panel of Italian experts analyzed a series of unmet clinical needs in the management of the thrombotic risk and thrombotic events associated with Philadelphia-negative myeloproliferative neoplasms. The Panel agreed that optimization of LDA for primary prophylaxis of thrombosis in ET requires randomized trials investigating once daily versus more frequent LDA administrations to evaluate clinical outcomes in terms of thrombosis and bleeding [53]. For p atients at high risk, the panel of European LeukemiaNet consortium, recommend the cytoreductive therapy and indicates hydroxyurea and rINFalfa as irst line drugs.…”