vitamin-k-semiquinone-radical and Myeloproliferative-Disorders

Thromboembolic events in myeloproliferative neoplasms (MPNs) are one of the most important causes of mortality and morbidity, in which vitamin K antagonists (VKAs) have been used mostly. Recently, direct oral anticoagulants (DOACs) are used in venous thromboembolism (VTE) and cancer-associated thrombosis (CAT). With the adoption of data from CAT and VTE, the usage of DOACs in MPNs is increasing.. In this paper, we performed a systematic review to the current literature regarding the usage of DOACs in MPNs. Eleven studies involving 944 patients were included. The reasons for initiating DOACs were secondary prophylaxis for thrombosis (arterial or venous) and atrial fibrillation (AF) in 562 and 382 patients, respectively. A total of 84 (8.9%) recurrent thrombotic (arterial or venous) events recorded. Forty-six (8.1%) events occurred in the thrombosis group (arterial or venous) and 38 (9.9%) events occurred in patients with AF.. Ease of management and patient comfort should be regarded as benefits of DOACs compared to VKAs. However, it would be appropriate to bring an individualized approach until we obtain high-quality data with prospectively designed studies involving more patients and longer follow-up time concerning the use of DOACs in patients with MPNs.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Myeloproliferative Disorders; Neoplasms; Thrombosis; Venous Thromboembolism; Vitamin K

Topics: Anticoagulants; Factor Xa Inhibitors; Humans; Male; Middle Aged; Myeloproliferative Disorders; Venous Thromboembolism; Vitamin K

Splanchnic vein thrombosis (SVT) encompasses Budd-Chiari syndrome (BCS), extrahepatic portal vein obstruction (EHPVO), and mesenteric vein thrombosis. Philadelphia-negative myeloproliferative neoplasms (MPNS) are the leading systemic cause of non-cirrhotic and non-malignant SVT and are diagnosed in 40% of BCS patients and one-third of EHPVO patients. In SVT patients the molecular marker JAK2 V617F is detectable up to 87% of those with overt MPN and up to 26% of those without. In the latter, other MPN molecular markers, such as mutations in JAK2 exon 12, CALR and MPL genes, are extremely rare. Immediate anticoagulation with heparin is used to treat acute patients. Upon clinical deterioration, catheter-directed thrombolysis or a transjugular intrahepatic portosystemic shunt is used in conjunction with anticoagulation. Orthotopic liver transplantation is the only reliable option in BCS patients with a lack of a response to other treatments, without contraindication due to MPN. Long-term oral anticoagulation with vitamin K-antagonists (VKA) is recommended in all SVT patients with the MPN-related permanent prothrombotic state; the benefits of adding aspirin to VKA are uncertain. Cytoreduction is warranted in all SVT patients with an overt MPN, but its appropriateness is doubtful in those with molecular MPN without hypercythaemia.

Topics: Administration, Oral; Anticoagulants; Biopsy; Bone Marrow Cells; Budd-Chiari Syndrome; Calreticulin; Exons; Genetic Markers; Haplotypes; Heparin; Humans; Janus Kinase 2; Liver Transplantation; Molecular Diagnostic Techniques; Mutation; Myeloproliferative Disorders; Portal Vein; Portasystemic Shunt, Surgical; Receptors, Thrombopoietin; Splanchnic Circulation; Thrombolytic Therapy; Treatment Outcome; Veins; Venous Thrombosis; Vitamin K

Atrial arrhythmias (AA) induce a high rate of thromboses and require vitamin K antagonists (VKA) or direct anticoagulants (DOAC) prescriptions. Essential thrombocythemia (ET) and polycythemia vera (PV) are also pro-thrombotic diseases. The prevention of thromboses is based on the association of cytoreductive drug and low-dose aspirin (LDA). We studied the incidence and complications of AA among patients with ET or PV. We identified 96/713 patients (13.5%) carrying AA. These patients were older (median 72.1 vs. 61.3 years old, p < 0.0001). In a case-control analysis, we observed that patients with AA had a higher frequency of cardiovascular risk factors (77/96, 80% vs. 61/96, 61%; p = 0.01). A higher incidence of thromboses before and after myeloproliferative neoplasm (MPN) diagnosis was seen in this group: 26/96, 27.1% vs. 14/96, 14.6% (p = 0.03) and 34/96, 35% vs. 18/96, 18.8% (p = 0.009). Most of the events were arterial (82 vs. 61%, p = 0.09). This translates into a shorter thrombosis-free survival (11.0 vs. 21.6 years, p = 0.01). Continuation of LDA in this situation exposed patients to more thrombotic events (p = 0.04) but VKA did not seem to be good anticoagulant drugs either. The association of AA and MPN is more frequent than expected. AA clearly increased the thrombotic risk of these patients. Anticoagulant drugs should be carefully managed between cardiologists and hematologists. Association of LDA and VKA or the role of DOAC in such population should be rapidly discussed to reduce the thrombotic rate.

Topics: 4-Hydroxycoumarins; Adult; Aged; Aged, 80 and over; Anticoagulants; Arrhythmias, Cardiac; Female; France; Humans; Incidence; Indenes; Male; Middle Aged; Myeloproliferative Disorders; Risk Factors; Thrombosis; Vitamin K

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.

Topics: Adult; Aged; Aged, 80 and over; Bone Marrow Neoplasms; Cohort Studies; Female; Fibrinolytic Agents; Humans; Male; Middle Aged; Myeloproliferative Disorders; Premedication; Pulmonary Embolism; Recurrence; Retrospective Studies; Venous Thromboembolism; Vitamin K

The optimal initial treatment of splanchnic vein thrombosis is uncertain. Anticoagulant therapy has been shown to be associated with vessel recanalization and decreased recurrence. Furthermore, information regarding potential predictors of chronic complications is not well understood.. A retrospective cohort study involving consecutive patients diagnosed with first-episode noncirrhotic splanchnic vein thrombosis referred to the thrombosis clinic of the authors' institution between 2008 and 2011 was conducted. Demographic and clinical information was collected. The response to initial anticoagulant therapy was evaluated by determining radiographic recanalization of vessels and clinical resolution (defined as the absence of ongoing splanchnic vein thrombosis symptoms or complications requiring treatment beyond anticoagulant therapy).. Twenty-two patients were included. Anticoagulant therapy alone resulted in vessel recanalization in 41% of patients and 68% achieved clinical resolution. Two patients experienced bleeding events. Factors associated with a lack of clinical resolution included signs of portal hypertension⁄liver failure on presentation, complete vessel occlusion at diagnosis, presence of a myeloproliferative disorder or JAK2V617F tyrosine kinase mutation and the absence of a local⁄transient predisposing factor.. Anticoagulant therapy appeared to be an effective initial treatment in patients with splanchnic vein thrombosis. Clinical factors may help to identify patients who are at risk for developing complications thus requiring closer monitoring. These findings were limited by the small sample size and need to be explored in larger prospective studies.

Topics: Abdominal Pain; Adult; Aged; Anticoagulants; Female; Heparin, Low-Molecular-Weight; Humans; Hypertension, Portal; Janus Kinase 2; Liver Failure; Male; Middle Aged; Mutation; Myeloproliferative Disorders; Portal Vein; Retrospective Studies; Splanchnic Circulation; Splenic Vein; Treatment Outcome; Venous Thrombosis; Vitamin K

Topics: Anticoagulants; Budd-Chiari Syndrome; Contraception; Contraindications; Female; Heparin; Humans; Hypertension, Portal; Liver; Liver Transplantation; Male; Myeloproliferative Disorders; Portal System; Portal Vein; Portasystemic Shunt, Transjugular Intrahepatic; Pregnancy; Retrospective Studies; Risk Factors; Sclerosis; Stents; Venous Thrombosis; Vitamin K

Topics: Aged; Aminocaproic Acid; Antifibrinolytic Agents; Autoantibodies; Humans; IgA Vasculitis; Male; Myeloproliferative Disorders; Postoperative Complications; Prothrombin; Vitamin K