Etiology and portal vein thrombosis in Budd-Chiari syndrome

AIM： To research the etiology, portal vein thrombosis and other features of Budd-Chiari syndrome （BCS） patients prospectively.
METHODS： A total of 75 patients （40 female, 35 male） who were diagnosed between January 2002 and July 2004 as having BCS were studied prospectively. Findings from on physical examination, ultrasonography, duplex ultrasonography and venography were analyzed. Hemogram and blood chemistry were studied at the time of diagnosis and on each hospital visit. Bone marrow examination and immune phenotyping were performed by a hematologist when necessary. Protein C, S, antithrombin Ⅲ, activated protein C resistance, and anticardiolipin antibodies, antinuclear antibodies, and anti ds-DNA were studied twice. The presence of ascite, esophageal varices, and portal thrombosis were evaluated at admission and on every visit.
RESULTS： At least one etiological factor was determined in 54 （72%） of the patients. The etiology could not be defined in 21 （28%） patients. One etiological factor was found in 39, 2 factors in 14 and 3 factors in 1 patient. The most common cause was the web （16%）, the second was Hydatid disease （11%）, the third was Behcet’s disease （9%）. Portal vein thrombosis was present in 11 patients and at least one etiology was identified in 9 of them （82%）.
CONCLUSION： Behcet’s disease and hydatid disease are more prominent etiological factors in Turkey than in other countries. Patients with web have an excellent response to treatment without signs of portal veinthrombosis while patients having thrombofilic factors more than one are prone to develop portal vein thrombosis with worse clinical outcome.     

Pathogenesis and treatment of Budd-Chiari syndrome combined with portal vein thrombosis

OBJECTIVES: Combined Budd-Chiari syndrome and Portal Vein Thrombosis (BCS-PVT) is a challenging clinical condition with as yet unknown outcome. The aim of the present study was to investigate etiology, treatment options, and prognosis of patients with BCS-PVT. METHODS: Patients diagnosed with nonmalignant BCS between 1984 and 2001 were identified in a large international study and classified into isolated BCS (n = 204), BCS-PVT without spleno-mesenteric vein thrombosis (SMVT; n = 15), and BCS-PVT with SMVT (n = 18). RESULTS: Multifactorial etiology was present in 58% of patients with combined BCS-PVT. Number of etiological factors increased significantly with the extent of thrombosis (p = 0.002). Main treatment options included anticoagulation and portosystemic shunting, of which extended TIPS showed the most beneficial results. Five-year survival was 59% (95% CI 39-80%) in BCS-PVT versus 85% (95% CI 76-88%) in isolated BCS (p = 0.11). Survival tended to be worse in BCS-PVT patients with SMVT as compared to patients without SMVT (RR = 3.47, p = 0.11). CONCLUSIONS: In BCS, extension of thrombosis into the splanchnic venous bed was significantly related to the number of etiological factors, and was associated with poor outcome. These results strongly support a liberal use of anticoagulants, which so far had been widely debated. Alternatively, derivative shunt procedures appear difficult, yet not impossible.     

Budd-Chiari syndrome and portal vein thrombosis due to essential thrombocytosis

Budd-Chiari syndrome secondary to essential thrombocytosis has been described in a few reports in the English literature. Associated portal vein thrombosis occurs very rarely. Herein, we report a case presented with ascites and finally diagnosed with hepatic and portal vein thrombosis, and essential thrombocytosis. We discussed the therapeutic approaches in the light of pertinent literature.     

The JAK2 46/1 haplotype in Budd-Chiari syndrome and portal vein thrombosis

The germline JAK2 46/1 haplotype has been associated with the development of JAK2(V617F)-positive as well as JAK2(V617F)-negative myeloproliferative neoplasms (MPNs). In this study we examined the role of the 46/1 haplotype in the etiology and clinical presentation of patients with splanchnic vein thrombosis (SVT), in which MPNs are the most prominent underlying etiological factor. The single-nucleotide polymorphism rs12343867, which tags 46/1, was genotyped in 199 SVT patients. The 46/1 haplotype was overrepresented in JAK2(V617F)-positive SVT patients compared with controls (P < .01). Prevalence of the 46/1 haplotype in JAK2(V617F)-negative SVT patients did not differ from prevalence in the controls. However, JAK2(V617F)-negative SVT patients with a proven MPN also exhibited an increased frequency of the 46/1 haplotype (P = .06). Interestingly, 46/1 was associated with increased erythropoiesis in JAK2(V617F)-negative SVT patients. We conclude that the 46/1 haplotype is associated with the development of JAK2(V617F)-positive SVT. In addition, our findings in JAK2(V617F)-negative SVT patients indicate an important role for the 46/1 haplotype in the etiology and diagnosis of SVT-related MPNs, independent of JAK2(V617F), that requires further exploration.     

Acute partial Budd-Chiari syndrome and portal vein thrombosis in cytomegalovirus primary infection: a case report

Background  

Splanchnic vein thrombosis may complicate inherited thrombotic disorders. Acute cytomegalovirus infection is a rare cause of acquired venous thrombosis in the portal or mesenteric territory, but has never been described extending into a main hepatic vein.     

Hepatic vein thrombosis (Budd-Chiari syndrome)

Hepatic vein thrombosis is caused by one or several thrombogenic conditions, of which myeloproliferative disorders are the most frequent. Thrombosis and its fibrous sequelae can affect the veins diffusely or locally. Severity is determined by the extent and velocity of the thrombotic process. Development of venous collateral vessels is an important compensatory mechanism. Some patients can be totally free of symptoms. Major complications are intractable ascites, liver insufficiency, and gastrointestinal bleeding. Diagnosis can be made via ultrasonography or magnetic resonance imaging in a majority of cases. The main prognostic factors are age, Child-Pugh score, and response of ascites to diuretics. Medical therapy includes control of causal factors, anticoagulation, and nonspecific treatment of complications. Procedures aiming to restore outflow of hepatic blood are indicated in patients with uncontrolled manifestations. Percutaneous angioplasty, followed by portosystemic shunt (including a transjugular intrahepatic portosystemic stent shunt) and eventually liver transplantation can be proposed in a graded manner. The current 10-year survival rate is about 75%.     

Acute Budd-Chiari syndrome, portal and splenic vein thrombosis in a patient with ulcerative colitis associated with antiphospholipid antibodies and protein C deficiency

We report the case of a female patient who had severe thrombotic complications in peripheral (V. jugularis, subclavia, brachialis, poplitea) and visceral (portal and splenic) veins 4 years after the first diagnosis of severe ulcerative pancolitis. A thrombolysis therapy for subclavian and jugular vein thrombosis was performed without complication, but she soon developed acute thrombosis of the hepatic veins (acute Budd-Chiari syndrome). She quickly recovered after liver transplantation and now - 6 years later - she lives a normal life with continuous anticoagulation and medical therapy of the colitis.3 possible causes for the severe coagulation defect in this patient can be supposed: Thrombocytosis, protein C deficiency and an antiphospholipid antibody syndrome.     

Etiology of portal vein thrombosis in adults. A prospective evaluation of primary myeloproliferative disorders

In a prospective study of 33 adults with portal vein thrombosis unrelated to a liver tumor, we have assessed the prevalence of primary myeloproliferative disorders using conventional criteria and cultures of bone marrow progenitor cells. A primary myeloproliferative disorder was documented in 14 patients investigated at the time of recognition of portal vein thrombosis. Among these 14 patients, the main clue to the presence of the myeloproliferative disorder was (a) the observation of suggestive abnormalities of peripheral blood cell counts in 4 patients; (b) characteristic findings at bone marrow biopsy or determination of total red cell volume in 3 patients; and (c) formation of "spontaneous" erythroid colonies in cultures of bone marrow progenitor cells in erythropoietin-poor medium in 7 patients. In 2 other patients, agnogenic myeloid metaplasia with myelosclerosis of apparently recent onset developed 5 yr after recognition of portal vein thrombosis. In conclusion, primary myeloproliferative disorders--in a full-blown or latent form, or at an early stage--are a major cause of portal vein thrombosis.     

Left branch portal vein thrombosis associated with hyperhomocysteinemia

A 34 year-old man, who was a smoker, was hospitalised because of severe epigastric and right upper quadrant pain. An isolated left branch portal vein thrombosis was diagnosed using ultrasonography and arteriography. Two thrombogenic pathologies were found: i) a latent myeloproliferative syndrome with spontaneous presence of erythroid colony forming unit (CFU-E) in bone marrow culture, normal blood cell count, platelet count and medullogram; ii) a hyperhomocysteinemia associated with low serum folate levels and a methyl tetrahydrofolate reductase mutation. The association of these two factors probably resulted in portal vein thrombosis. This is the first adult case of a portal vein thrombosis associated with hyperhomocysteinemia. Increased homocysteine serum levels could be a previously unrecognized factor for portal vein thrombosis. Homocysteinemia should be systematically investigated in patients with idiopathic portal vein thrombosis since folate supplements could prevent deleterious vascular effects of hyperhomocysteinemia.     

Inherited coagulation disorders in cirrhotic patients with portal vein thrombosis

The prevalence and pathogenesis of portal vein thrombosis (PVT) in patients with cirrhosis without hepatocellular carcinoma are not clearly defined. The role of thrombophilic genetic factors is well established in other venous thrombotic diseases, as well as in noncirrhotic portal thrombosis. Recently, new, inherited thrombophilic disorders (factor V Leiden [FVL], mutation G20210A of prothrombin [PTHR A(20210)], and mutation TT677 of methylenetetrahydrofolate reductase [MTHFR C677-->T]) have been identified and associated with increased risk of venous thrombosis. The aim of our study was to investigate the role of these thrombophilic disorders in the pathogenesis of PVT in cirrhotic patients. Twenty-three cirrhotic patients with PVT and 40 cirrhotics without PVT were included. A group of 184 patients with deep vein thrombosis (DVT) and 431 healthy persons served as controls. The FVL, PTHR A(20210), and MTHFR C(677)-->T genotypes were identified by a polymerase chain reaction and restriction analysis. The frequencies of FVL, PTHR A(20210) mutation, and homozygous MTHFR C(677)-->T were 13%, 34.8%, and 43.5% in cirrhotic patients with PVT and 7.5%, 2.5%, and 5% in cirrhotic patients without PVT, respectively. Five patients in the former group had associated defects. A thrombophilic genotype was detected in 69.5% of the patients with PVT. Identification of this high-risk group may have implications in patients who are candidates for major surgery or liver transplantation, and may influence the duration of oral anticoagulation.     

Primary antiphospholipid syndrome presented with portal vein thrombosis]

Antiphospholipid Antibody Syndrome (APS) is defined by arterial and venous thrombosis, recurrent spontaneous abortions and thrombocytopenia associated with persistence of antiphospholipid antibodies. Thrombosis may involve virtually all arterial or venous sites, but deep vein thrombosis of the lower limbs are the most common; however, unusual thrombi that involve the portal vein have been described. We report females with documented portal vein thrombosis and primary APS. The treatment of these patients is difficult because of the risk of bleeding and the recurrent thrombosis if they don't receive appropriate long-term anticoagulant therapy.     

肝硬化并发门静脉血栓临床表现和诊断进展

正门静脉血栓形成(portal vein thrombosis,PVT)是晚期肝硬化的常见并发症之一~([1])。近年来,文献报道PVT在肝硬化患者的患病率为0.6%～26.0%~([2,3])。PVT的临床表现差异很大,可无症状,也可表现为致命性并发症,如静脉曲张破裂出血、肠梗死等。随着影像学技术的不断提高,越来越多不同程度的PVT被诊断出来~([4～6])。1肝硬化并发PVT的临床特点1.1急性PVT PVT的临床表现取决于血栓形成的     

Portal vein thrombosis associated with antiphospholipid syndrome

Received: April 25, 2000 / Accepted: October 6, 2000     

Increased CD11b neutrophil expression in Budd-Chiari syndrome or portal vein thrombosis secondary to polycythaemia vera

Budd-Chiari syndrome and portal vein thrombosis (BCS/PVT) are frequently associated with polycythaemia vera (PV). In an attempt to elucidate the mechanisms of BCS/PVT secondary to PV (T-PV), CD11b neutrophil expression, neutrophil oxidative burst and platelet-neutrophil complexes (PNC) were assessed in 17 such patients. Three groups served as controls: BCS/PVT not secondary to PV (T-nPV; n = 20), PV without thrombosis (PV-nT; n = 16), and healthy controls (HC; n = 20). Baseline CD11b expression (in mean fluorescence intensity units) was 101 [95% confidence interval (CI): 79-128] in T-PV patients, versus 25 (95% CI: 18-35) in T-nPV, 59 (95% CI: 43-80) in PV-nT, and 34 (95% CI: 25-48) in HC (P < 0.001). After N-formyl-L-methionyl-L-leucyl-L-phenylalanine activation, T-PV patients also showed higher CD11b values: 190 (95% CI: 151-238), versus 55 (95% CI: 41-72) in T-nPV, 111 (95% CI: 81-153) in PV-nT, and 77 (95% CI: 63-95) in HC (P < 0.001). In BCS/PVT, CD11b neutrophil expression had 90% specificity and 100% sensitivity for the association with PV. Finally, PV patients had higher oxidative burst and PNC than T-nPV patients or HC (P < 0.05). These results support a role for neutrophils in BCS/PVT secondary to PV and indicate that neutrophil CD11b expression could be of use for PV screening in BCS/PVT patients.     

Transjugular intrahepatic portosystemic shunt (TIPS) for Budd-Chiari syndrome or portal vein thrombosis: review of indications and problems

OBJECTIVE: The aim of this study was to evaluate the role of transjugular intrahepatic portosystemic shunt (TIPS) in patients who present with portal vein thrombosis (PVT) or Budd-Chiari Syndrome (BCS). METHODS: Nine patients with recent PVT and four patients with BCS underwent TIPS. The diagnosis was confirmed by color Doppler ultrasound and by angiogram in most patients. Patients were followed clinically and had TIPS checked periodically for patency. The end point was mortality, subsequent surgical shunting or orthotopic liver transplantation (OLT). RESULTS: TIPS was placed in 13 of 15 (87%) patients with BCS or PVT. The mean decrease in pressure gradient was 56%. Median and mean follow-up were 14 months and 16.9 months. Procedure related complications occurred in two of 13 (15%), both in the PVT group. Direct procedural mortality was one of 13 (8%). The majority of patients with PVT (five of eight) underwent OLT. Of the remaining three, one patient subsequently developed a cavernous transformation of portal vein but is stable, one patient is stable, without further variceal bleeding, and one patient died because of multiple organ failure. In patients with BCS, three of four (75%) did well with TIPS, but one patient required immediate surgical shunting after occlusion of the TIPS. Two patients underwent OLT and the fourth patient is stable 2 yr later but has cirrhosis on biopsy. CONCLUSIONS: In patients with BCS, TIPS placement is effective and can be used as a bridge to liver transplantation. TIPS in the noncavernous PVT group should only be recommended when cirrhosis and uncontrollable variceal bleeding are present.     

Safety and efficacy of ruxolitinib in splanchnic vein thrombosis associated with myeloproliferative neoplasms

Splanchnic vein thrombosis (SVT) is one of the vascular complications of myeloproliferative neoplasms (MPN). We designed a phase 2 clinical trial to evaluate safety and efficacy of ruxolitinib in reducing splenomegaly and improving disease‐related symptoms in patients with MPN‐associated SVT. Patients diagnosed with myelofibrosis (12 cases), polycythemia vera (5 cases) and essential thrombocythemia (4 cases) received ruxolitinib for 24 weeks in the core study period. Spleen volume was assessed by magnetic resonance imaging (MRI) and splanchnic vein circulation by echo‐Doppler analysis. Nineteen patients carried JAK2V617F, one had MPLW515L, and one CALRL367fs*46 mutation. Eighteen patients had spleno‐portal‐mesenteric thrombosis, two had Budd–Chiari syndrome, and one had both sites involved; 16 patients had esophageal varices. Ruxolitinib was well tolerated with hematological toxicities consistent with those of patients without SVT and no hemorrhagic adverse events were recorded. After 24 weeks of treatment, spleen volume reduction ≥35% by MRI was achieved by 6/21 (29%) patients, and a ≥50% spleen length reduction by palpation at any time up to week 24 was obtained by 13/21 (62%) patients. At week 72, 8 of the 13 (62%) patients maintained the spleen response by palpation. No significant effect of treatment on esophageal varices or in splanchnic circulation was observed. MPN‐related symptoms, evaluated by MPN‐symptom assessment form (SAF) TSS questionnaire, improved significantly during the first 4 weeks and remained stable up to week 24. In conclusion, this trial shows that ruxolitinib is safe in patients with MPN‐associated SVT, and effective in reducing spleen size and disease‐related symptoms.