Hydroxyurea prevents arterial and late venous thrombotic recurrences in patients with myeloproliferative neoplasms but fails in the splanchnic venous district. Pooled analysis of 1500 cases

Abstract

We collected 1500 patients with myeloproliferative neoplasms (MPN) and arterial or venous thrombosis (935/565), pooling three independent cohorts previously reported. Long-term treatment with antiplatelet drugs or vitamin K-antagonists (VKA) was given to 1391 (92.7%) patients; 975 (65%) patients received hydroxyurea (HU). We recorded 348 recurrences (venous in 142 cases) over 6075 patient-years, with an incidence rate of 5.7 per 100 pt-years (95% CI 5.1–6.4). The site of the first thrombosis predicted the site of recurrence. Independent factors influencing the rate of novel arterial thrombosis were HU (HR 0.67, 95% CI 0.46–0.98), antiplatelet treatment (HR 0.54, 95% CI 0.35–0.82), and VKA (HR 0.58, 95% CI 0.35–0.96). On the contrary, the recurrence of venous thromboses was significantly diminished only by VKA (HR 0.60, 95% CI 0.37–0.95), while HU prevented late but not early recurrences after venous thrombosis at common sites. Of note, we failed to demonstrate a positive effect of HU in the prevention of recurrent splanchnic vein thrombosis. In conclusion, in MPN patients, HU plays a role in the prevention of arterial thrombosis, together with aspirin and VKA, whereas its action in the prevention of recurrent venous thrombosis is uncertain. Such findings call for future studies to optimize and personalize secondary prophylaxis after MPN-related thrombosis.

Splanchnic vein thromboses associated with myeloproliferative neoplasms: An international, retrospective study on 518 cases

“…Opposed to cytoreduction, VKA halves the incidence of recurrent thromboses, being a significant independent protective factor in the multivariable analysis (OR 0.48). These findings are consistent with those obtained in a multicenter cohort of MPN‐related thrombosis (n = 1500), in which recurrences were significantly reduced by VKA after an index venous event, and by hydroxyurea after an index arterial thrombosis . Notably, hydroxyurea was not protective in the subgroup of SVT (n = 218) …”

Clinical, laboratory, and genetic risk factors for thrombosis in sickle cell disease

“…Interestingly, hydroxyurea may have differential effects on the venous and arterial vasculature, as demonstrated in myeloproliferative neoplasms. [40][41][42] In a study of patients with polycythemia vera, hydroxyurea conferred no protective benefit against VTE but led to a threefold reduction in arterial thrombotic events. 40 Hydroxyurea targets multiple processes implicated in arterial thrombosis, such as qualitative changes in white blood cells, reduced expression of endothelial adhesion molecules, and enhanced nitric oxide generation.…”

An agenda for future research projects in polycythemia vera and essential thrombocythemia

“… 12 , 15 – 20 The antithrombotic role of cytoreductive drugs is uncertain. Hydroxyurea (HU) has demonstrated significant efficacy in preventing arterial thromboses, but doubts remain as to its ability to prevent recurrent venous thromboembolism (VTE), 29 – 31 particularly in patients with splanchnic venous thrombosis. 32 , 33 The antithrombotic efficacy of interferon-α has not yet been convincingly demonstrated, and the performance of ruxolitinib in PV patients resistant/intolerant to HU is largely uncertain.…”

“…The prevention of recurrent venous thromboembolism by vitamin K-antagonists (VKA) was estimated in several retrospective studies showing an annual incidence of VTE recurrences as high as 5.6-6.5, 31 , 43 – 46 that rose to as high as 12.8 after discontinuation. 45 In addition, the incidence of major bleeding on VKA of 1.7-1.8 per 100 patients/years 44 , 45 is unsatisfactory when compared with non-MPN patients.…”