vitamin-k-semiquinone-radical and Budd-Chiari-Syndrome

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

Thromboses of abdominal veins outside the iliac-caval axis are rare but clinically relevant. Early deaths after splanchnic vein thrombosis occur in 5-30% of cases. Sequelae can be liver failure or bowel infarction after splanchnic vein thrombosis, renal insufficiency after renal vein thrombosis, ovarian infarction after ovarian vein thrombosis. Local cancer or infections are rare in Budd-Chiari syndrome, and common for other sites. Inherited thrombophilia is detected in 30-50% of patients. Myeloproliferative neoplasms are the main cause of splanchnic vein thrombosis: 20-50% of patients have an overt myeloproliferative neoplasm and/or carry the molecular marker JAK2 V617F. Renal vein thrombosis is closely related to nephrotic syndrome; finally, ovarian vein thrombosis can complicate puerperium. Heparin is used for acute treatment, sometimes in conjunction with systemic or local thrombolysis. Vitamin K-antagonists are recommended for 3-6 months, and long-term in patients with Budd-Chiari syndrome, unprovoked splanchnic vein thrombosis, or renal vein thrombosis with a permanent prothrombotic state such as nephrotic syndrome.

Topics: Anticoagulants; Biomarkers, Tumor; Budd-Chiari Syndrome; Female; Heparin; Humans; Janus Kinase 2; Leukemia; Nephrotic Syndrome; Ovary; Portal Vein; Splanchnic Circulation; Vena Cava, Inferior; Venous Thrombosis; Vitamin K

Direct oral anticoagulants (DOACs) may simplify management of Budd-Chiari syndrome (BCS). Here, we report our experience with off-label use of DOACs for anticoagulation in BCS.. The safety of DOAC vs vitamin K antagonist treatment as well as associated clinical outcomes were retrospectively assessed in 47 BCS patients treated at 6 Austrian centers.. Mean age at study inclusion was 37.9 ± 14.0 years and mean Model for End-Stage Liver Disease was 13.1 ± 5.1. Overall, 63.8% (n = 30) of patients had decompensated liver disease, and 87.2% (n = 41) showed clinical signs of portal hypertension. During a median follow-up of 82.5 (interquartile range, 43.1-121.8) months, 43 (91.5%) patients received anticoagulation alone or following interventional treatment, including 22 (46.8%) patients treated with DOACs (edoxaban: 10, apixaban: 4, rivaroxaban: 3, dabigatran: 3, more than one DOAC sequentially: 2) for a median of 24.4 (interquartile range, 5.7-35.1) months. While 72.7% (n = 16 of 22) of patients were switched from low-molecular-weight heparin (n = 12) or vitamin K antagonist (n = 4) to DOAC after disease stabilization or improvement, 27.3% (n = 6 of 22) of BCS patients were initially treated with DOAC. Complete response (European Association for the Study of the Liver criteria) was achieved or maintained in 14 (63.6%) of 22 patients, with ongoing response in 2 patients, while disease progressed in 6 patients (including 2 patients with hepatocellular carcinoma). Four major spontaneous bleedings (18.2%; incidence rate 8.8 per 100 patient-years; n = 2 upper gastrointestinal bleeding, n = 1 lower gastrointestinal bleeding, n = 1 hepatocellular carcinoma rupture), 7 minor bleedings, and 1 major procedure-related bleeding (4.5%; 2.2 per 100 patient-years) occurred during DOAC therapy. Overall transplant-free survival was 91.6% at 5 years.. DOACs seem to be effective and safe for long-term anticoagulation in patients with BCS, but confirmation by larger prospective studies is needed.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Austria; Budd-Chiari Syndrome; Carcinoma, Hepatocellular; Dabigatran; End Stage Liver Disease; Gastrointestinal Hemorrhage; Humans; Liver Neoplasms; Retrospective Studies; Severity of Illness Index; Vitamin K

Anticoagulants play an important role in the management of Budd-Chiari syndrome. There is a paucity of data on the efficacy and safety of direct-acting oral anticoagulants-dabigatran, among patients with Budd-Chiari syndrome.. In a retrospective analysis of prospectively maintained data, the stent patency rates, major bleeding episode, and a composite endpoint of major bleed and/or mortality rates were compared between Budd-Chiari syndrome patients treated with dabigatran (n = 36) or vitamin K antagonists (n = 62) following endovascular intervention.. The baseline characteristics, including sites of block and types of interventions, were similar between the two groups. The mean duration of follow-up in the dabigatran and vitamin K antagonist groups was 10.5 ± 6.7 and 14.1 ± 6.9 months (P = 0.006), respectively. The endovascular stent patency rates were comparable between the dabigatran and vitamin K antagonist groups at 6 months (91% vs 96.5%) and 12 months (91% vs 93%), P = 0.296 (log-rank test), respectively. Major bleeding events were comparable between the dabigatran and vitamin K antagonist groups at 6 months (3.5% vs 2%) and 12 months (3.5% vs 6.5%), P = 0.895 (log-rank test), respectively. The composite endpoint of mortality and major bleed was comparable between dabigatran and vitamin K antagonists at 6 months (4% vs 5%) and 12 months (4% vs 8%), P = 0.875 (log-rank test), respectively.. Dabigatran, as compared with vitamin K antagonists, is associated with similar stent patency rates and complications among patients with Budd-Chiari syndrome post-endovascular intervention.

Topics: Adult; Anticoagulants; Budd-Chiari Syndrome; Dabigatran; Endovascular Procedures; Female; Follow-Up Studies; Humans; Male; Retrospective Studies; Stents; Vitamin K; Young Adult

Budd-Chiari syndrome (BCS) is recognized as a clinical manifestation of various prothrombotic conditions which may be lethal within 3 years of the onset of symptoms if untreated. This study is a retrospective analysis of patients with BCS managed between 2004 and 2011.. The diagnosis was confirmed with contrast CT-angiography and/or Doppler ultrasound.. BCS was diagnosed in 20 patients (11 females and 9 males), median age 38 years (ranging from 18 to 56). Twelve patients were referred as acute BCS for the liver transplant (LTx) assessment. Thrombosis of the hepatic veins was caused by myeloproliferative disorders (n=8), end-stage liver disease (n=4), protein C deficiency (n=3), paroxysmal nocturnal hemoglobinuria (PNH) (n=1), antiphospholipid syndrome (n=1) and secondary poliglobulia (n=1). In two patients the origin of BCS could not be established despite appropriate screening. Median follow-up was 29 months. Low molecular heparin with subsequent conversion to vitamin K antagonists was routinely applied in all patients. Two patients underwent TIPS procedure with good long term outcome and 10 subjects received LTx; 1 patient was lost to follow-up and 1 died of chest infection 9 years since the diagnosis of BCS was made; 14 patients, including those who received LTx, were alive and well at least one year after BCS diagnosis. All survivors remain stable and are followed-up on a regular basis.. Strict adherence to the diagnostic and therapeutic guidelines plays a crucial role in the management of BCS patients. Our results confirm the efficacy of anticoagulation as well as TIPS and/or OLT in treatment of this rare condition.

Topics: Adolescent; Adult; Anticoagulants; Budd-Chiari Syndrome; Drug Substitution; Female; Guideline Adherence; Heparin, Low-Molecular-Weight; Humans; Liver Transplantation; Male; Middle Aged; Poland; Portasystemic Shunt, Transjugular Intrahepatic; Practice Guidelines as Topic; Predictive Value of Tests; Retrospective Studies; Risk Factors; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Ultrasonography, Doppler; Vitamin K; Young Adult

Topics: Adult; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Budd-Chiari Syndrome; Cohort Studies; Cytochrome P-450 CYP2C9; Female; Humans; Male; Middle Aged; Mixed Function Oxygenases; Polymorphism, Genetic; Vitamin K; Vitamin K Epoxide Reductases

Topics: Adult; Anticoagulants; Budd-Chiari Syndrome; Female; Heparin, Low-Molecular-Weight; Humans; 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

Budd-Chiari syndrome with or without portal thrombosis occurring during paroxysmal noctural hemoglobinuria is a complication with poor prognosis. We report the case of a 17-year-old woman with a double portal and hepatic venous thrombosis revealing a paroxysmal noctural hemoglobinuria and regressive with heparin. Our case suggests that the early diagnosis of the thrombosis with ultrasonography and Doppler, and rapidly initiated anticoagulant treatment may improve the prognosis of this disease.

Topics: 4-Hydroxycoumarins; Adolescent; Anticoagulants; Budd-Chiari Syndrome; Female; Hemoglobinuria, Paroxysmal; Heparin; Humans; Indenes; Portal Vein; Thrombosis; Vitamin K