High rate of recurrent venous thromboembolism in patients with myeloproliferative neoplasms and effect of prophylaxis with vitamin K antagonists

Abstract

The optimal duration of treatment with vitamin K antagonists (VKA) after venous thromboembolism (VTE) in patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) is uncertain. To tackle this issue, we retrospectively studied 206 patients with MPN-related VTE (deep venous thrombosis of the legs and/or pulmonary embolism). After this index event, we recorded over 695 pt-years 45 recurrences, venous in 36 cases, with an incidence rate (IR) of 6.5 per 100 pt-years (95% confidence interval (CI): 4.9-8.6). One hundred fifty-five patients received VKA; the IR of recurrent thrombosis per 100 pt-years was 4.7 (95% CI: 2.8-7.3) on VKA and 8.9 (95% CI: 5.7-13.2) off VKA (P=0.03). In patients receiving VKA, the IR of recurrent thrombosis per 100 pt-years was 5.3 (95% CI: 3.2-8.4) among 108 patients on long-term VKA and 12.8 (95% CI: 7.3-20.7) after discontinuation among the 47 who ceased treatment (P=0.008), with a doubled risk of recurrence after stopping VKA (hazard ratio: 2.21, 95% CI: 1.19-5.30). The IR of major bleeding per 100 pt-years was 2.4 (95%: CI: 1.1-4.5) on VKA and 0.7 (95% CI: 0.08-2.5) off VKA (P=0.08). In conclusion, in MPN patients with VTE recurrent thrombosis is significantly reduced by VKA and caution should be adopted in discontinuation; however, the incidence of recurrence on treatment remains high, calling for clinical trials aimed to improve prophylaxis in this setting.

Splanchnic vein thrombosis in myeloproliferative neoplasms: risk factors for recurrences in a cohort of 181 patients

“…12 Briefly, for each patient, the following information was recorded: demographic data, WHO diagnosis, location of thrombosis, method of objective diagnosis, the presence of microvascular disturbances (that is, erythromelalgia, transient ocular attacks, pulsatile headache, dizziness and tinnitus) or constitutional symptoms (that is, pruritus, fatigue, night sweats, fever, weight loss and pain in the limbs), mutational profile, results of the laboratory investigation for thrombophilia, full blood count at diagnosis and at thrombosis, and the presence of cardiovascular risk factors (that is, history of previous thrombosis before the index event, smoking habit, hypertension, dyslipidaemia and diabetes). Moreover, the presence of circumstantial risk factors at the time of any episode of VTE such as surgery, pregnancy, puerperium (until 6 weeks from delivery), oral contraceptive intake, hormone replacement therapy, trauma, leg cast, prolonged bed immobilization (>10 days) and long travel (>8 h) was also recorded; in the absence of the previously mentioned risk factors, VTE was considered unprovoked.…”

“…Finally, the data regarding cytoreductive or antithrombotic treatment after VTE, the duration of the treatment and the reasons for discontinuation of the treatment was recorded. A diagnosis of VTE was accepted only if it was confirmed by objective methods according to current clinical practice, as previously reported, 12 and was defined as a positive result using techniques such as angiography, ultrasonography, computerized tomography or nuclear magnetic resonance.…”

Should We Screen for Janus Kinase 2 V617F Mutation in Cerebral Venous Thrombosis?

“…Still, as was the case in one of the 2 JAK2 V617F-positive patients in the present study, in a cohort of 48 MPN patients with CVT, oral anticoagulation failed to prevent recurrence, [28] and further research is needed to improve preventive treatment. This recurrence risk could be higher in the presence of an increased leukocyte count at the time of the first thrombosis in patients under the age of 60 years old, in patients over 60 years old [37,40], in those with inherited thrombophilia [38], and in patients with a previous history of thromboembolism [41]. …”

“…However, the benefit of VKA in decreasing the risk of recurrence subsequent to a venous thrombotic event in MPN patients is well established [37,38,39], while the benefit of cytoreductive treatment has been shown mainly in patients with an arterial thrombosis [37]. Still, as was the case in one of the 2 JAK2 V617F-positive patients in the present study, in a cohort of 48 MPN patients with CVT, oral anticoagulation failed to prevent recurrence, [28] and further research is needed to improve preventive treatment.…”

How I treat essential thrombocythemia

“…Because ET patients with genetic or acquired thrombophilia are at high risk of recurrent thrombosis, 83 we prescribe cytoreductive treatment (generally hydroxyurea) and oral anticoagulation through life. These patients should be regularly monitored for portal hypertension and esophageal varices.…”