Splanchnic Venous Thrombosis Research Articles

Prevalence of JAK2V617F mutation in deep venous thrombosis patients and its clinical significance as a thrombophilic risk factor: Indian perspective.

Venous thromboembolism is known to be a complex interaction of genetic and acquired factors leading to thrombosis. JAK2V617F mutation is believed to contribute to a thrombophilic phenotype, possibly through enhanced leukocyte-platelet interactions in myeloproliferative neoplasms (MPNs). Several studies have focused on the importance of screening for JAK2V617F mutation in patients with splanchnic venous thrombosis (VT) for the detection of nonovert MPNs. The role of JAK2V617F mutation in VT outside the splanchnic region is still widely unsettled. The primary aim of this study was to find out the prevalence of JAK2V617F mutation in patients with deep venous thrombosis (DVT), its clinical significance as a prothrombotic risk factor, and its possible interactions with other genetic thrombophilic risk factors. A total of 148 patients with idiopathic, symptomatic DVT were evaluated. Median age of presentation was 32 years (range 15-71 years) with a sex ratio of 1.3:1. Overall, the most common genetic prothrombotic factor was factor V Leiden mutation, found in 10.8% (16 of 148) of patients who also showed strong association with increased risk of thrombosis (odds ratio 5.94, confidence interval 1.33-26.4, P = .019). Deficiencies in protein C, protein S, and antithrombin were seen in 8 (5.4%), 10 (6.7%), and 8 (5.4%) patients, respectively. It was observed that the frequency of JAK2V617F mutation was lower in Indian patients, and it also showed weaker association with risk of thrombosis, at least in cases of venous thrombosis outside the splanchnic region.

JAK2V617F: Is It Sufficient as a Single Player in Splanchnic Venous Thrombosis?

Splanchnic venous thrombosis (SVT) includes thrombosis of the hepatic, portal, and mesenteric venous system. Myeloproliferative neoplasms (MPNs) are important factors of SVT in adults. Addition of JAK2V617F mutation in WHO criteria for diagnosis of MPNs has made this test a useful tool for diagnosis. JAK2 is an intracytoplasmic tyrosine kinase that plays a critical role in signal transduction from multiple hematopoietic factor receptors. The mutation is found frequently in patients with SVT; many such patients have no other manifestations of an MPN. Although the correlation of JAK2V617F mutation with thrombotic risk in MPNs has been shown in many studies, the impact of presence of additional thrombophilic factors in these cases is yet not known. As the management of MPNs remains highly dependent on the patient's thrombotic risk, it is important to assess the thrombotic risk factors in detail. Here, we report two cases of JAK2V617F positive MPN who also had other thrombophilic conditions and presented with recurrent thrombosis.

Systemic Venous Inflow to the Liver Allograft to Overcome Diffuse Splanchnic Venous Thrombosis.

Diffuse splanchnic venous thrombosis (DSVT), formerly defined as contraindication for liver transplantation (LT), is a serious challenge to the liver transplant surgeon. Portal vein arterialisation, cavoportal hemitransposition and renoportal anastomosis, and finally combined liver and small bowel transplantation are all possible alternatives to deal with this condition. Five patients with preoperatively confirmed extensive splanchnic venous thrombosis were transplanted using cavoportal hemitransposition (4x) and renoportal anastomosis (1x). Median follow-up was 58 months (range: 0,5 to 130 months). Two patients with previous radiation-induced peritoneal injury died, respectively, 18 days and 2 months after transplantation. The three other patients had excellent long-term survival, despite the fact that two of them needed a surgical reintervention for severe gastrointestinal bleeding. Extensive splanchnic venous thrombosis is no longer an absolute contraindication to liver transplantation. Although cavoportal hemitransposition and renoportal anastomosis undoubtedly are life-saving procedures allowing for ensuring adequate allograft portal flow, careful follow-up of these patients remains necessary as both methods are unable to completely eliminate the complications of (segmental) portal hypertension.

Imaging Diagnosis of Splanchnic Venous Thrombosis.

Splanchnic vein thrombosis (SVT) is a broad term that includes Budd-Chiari syndrome and occlusion of veins that constitute the portal venous system. Due to the common risk factors involved in the pathogenesis of these clinically distinct disorders, concurrent involvement of two different regions is quite common. In acute and subacute SVT, the symptoms may overlap with a variety of other abdominal emergencies while in chronic SVT, the extent of portal hypertension and its attendant complications determine the clinical course. As a result, clinical diagnosis is often difficult and is frequently reliant on imaging. Tremendous improvements in vascular imaging in recent years have ensured that this once rare entity is being increasingly detected. Treatment of acute SVT requires immediate anticoagulation. Transcatheter thrombolysis or transjugular intrahepatic portosystemic shunt is used in the event of clinical deterioration. In cases with peritonitis, immediate laparotomy and bowel resection may be required for irreversible bowel ischemia. In chronic SVT, the underlying cause should be identified and treated. The imaging manifestations of the clinical syndromes resulting from SVT are comprehensively discussed here along with a brief review of the relevant clinical features and therapeutic approach.

Clinical Outcome of a Portosplenomesenteric Venous Thrombosis in Necrotizing Acute Pancreatitis with Protein C and S Deficiency Treated by Anticoagulation Therapy Alone.

Cases of splanchnic venous thrombosis have not been described in Cameroon. Their prevalence in acute pancreatitis is variable. With the emergence of acute intra-abdominal infections including typhoid fever and peritoneal tuberculosis in situations of acquired immunodeficiency syndrome, these cases will become frequent. We report the case of a portosplenomesenteric venous thrombosis related to necrotizing acute pancreatitis associated with proteins C and S deficiency, in a 46-year-old Cameroonian man, without particular past medical history. He was admitted for abdominal pain which had been evolving for 3 weeks and accompanied by vomiting. In the absence of hemorrhagic risk factor, the patient received low molecular weight heparin followed by oral warfarin. The abdominal ultrasound check on the 12th day showed a partial recanalization of venous thrombosis. The abdominal contrast-enhanced CT scanner at day 30 on oral anticoagulation therapy showed collateral vessels and small bowel edema. At the same time the upper gastrointestinal endoscopy showed grade II esophageal varices. We have maintained oral anticoagulation therapy. This case highlights that an early effective anticoagulation heparin therapy is needed for a clear benefit in case of suspected PSMVT. It is certain that the sooner the treatment is given, the better outcome will be.

On the Absence of Calreticulin (CALR) Mutations in Chronic Myeloprolierative Neoplasms (MPNs) with Splanchnic Venous Thrombosis (SVT): Experience from a Single Institution

Background: According to recent findings, the management of myeloproliferative neoplasms (MPNs) is highly dependent on presence or absence of thrombotic events. The JAK2 mutation has been identified as a marker of MPNs. It is also an occult marker in several patients with splanchnic venous thrombosis (SVT), but its contribution as an additional thrombotic risk factor in MPNs is still under discussion. Moreover, a pro-thrombotic risk factor, either inherited or acquired (Factor V Leiden mutation, deficiencies in protein C, protein S and Prothrombin mutation 20210) can be identified in these patients. Recently, another milestone in the molecular diagnosis of MPNs, somatic mutations in the CALR gene, has been reported. A total of 36 types of frame-shifting insertions and deletions were detected in the exon 9 of CALR gene, which encodes a Ca2+ binding protein in endoplasmic reticulum called calreticulin. Type-1, 52-bp deletion (p.L367fs*46), and type-2, 5-bp TTGTC insertion (p.K385fs*47) variants constitute more than 80% of these mutations These mutations were reported to have a incidence of over 60% to 80% in JAK2 and MPLmutation-negative Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF) patients. Compared to those with JAK2 mutation, CALR-mutated ET patients are younger and have a lower leukocyte count and higher platelet count. CARL mutations have been also reported as a favorable prognostic factor on thrombosis-free survival (TFS) for ET patients.Aims: In this study, we evaluated the incidence of SVT, JAK2 and CALR mutations, and prothrombotic risk factors in patients with MPNs observed in our center from January 2000 to January 2014.Methods: We performed a retrospective review of clinical charts of 466 Ph1 negative MPN patients followed in our center, classified according to the WHO 2008 classification. Patient and disease characteristics, including JAK2V617F, MPL and CALR mutations and thrombotic risk factors were recorded.Results: The median age of patients with diagnosis of MPN was 43 years. Fourteen patients (13 females, 1 male; 3%) of median age 46 years presented a SVT. Three had a Budd Chiari syndrome and 11 a portal venous thrombosis. According to a histological review, these patients were classified as follows: ET, 2 cases, PMF, 3 cases, Polycythemia Vera (PV) 1 case, Myelofibrosis in a prefibrotic phase (MF0) 8 cases. Classification of 11 cases with Myelofibrosis according to the IPSS identified 7 as INT1, 1 as INT2 and 3 as low risk. Among all 14 patients diagnosed with SVT, 12 were JAK2V617F positive with a median allelic burden of 30%, 1 patient was MPL positive, and 1 patient was triple-negative. CALR mutation was not observed in any of the patients. Two cases were diagnosed with MPN 30 months after SVT, 3 patients experienced SVT after a median follow-up of 108 months from MPN diagnosis while in 9 patients the diagnosis of MPN was concomitant to SVT. In the latter patients, median Hb levels were 12.4 g/dL , WBC 8260 /µL, HCT 36.3%, PLT 337.000/ µL and a modest hepatomegaly and splenomegaly were documented. Prothrombotic risk factors were found in 9 of 13 patients. Two patients experienced a thrombotic episode prior to the diagnosis of SVT and two subsequently during the follow-up. Interestingly, 9 (70%) of MPN patients with SVT exhibited at least one prothromobtic risk factor, such as factor V Leiden, Protein C deficiency, hyperhomocystinemia and 50% had two or more associated defects. Thirteen of the 14 patients are currently being treated as follows hydroxyurea (9), interferon (1), and ruxolitinib (3). All patients received oral anticoagulant treatment except for three who are on antiplatelet therapy. MPN patients without SVT had a lower prevalence of prothrombotic risk factors and developed venous thrombosis in different anatomical sites: in these cases WBC count, platelet values and the presence of JAK2V617F mutation correlated with the development of the thrombotic event.Conclusions: Although SVT has a low incidence in MPN patients, a potential benefit of testing for mutations in CALR gene and for additional prothrombotic risk factors is suggested in the whole MPN population for the prevention and treatment of this complication. DisclosuresNo relevant conflicts of interest to declare.

Risk Factors and Outcome of Splanchnic venous thrombosis in Patients with necrotizing acute pancreatitis

BackgroundSplanchnic venous thrombosis (SVT) is considered a rare but important complication in patients with acute pancreatitis (AP) and literatures regarding this topic were sparse. The aim of the present study was to investigate the risk factors of SVT in necrotizing acute pancreatitis (NAP) and assess the prognosis of these patients. MethodsBoth univariate and multivariate logistic regression analyses were applied using 15 indices including age, gender, Acute Physiology and Chronic Health Evaluation II scores (APACHE II), CRP (C - reactive protein) levels, etc to explore potential risk factors for the development of SVT in NAP patients. Moreover, clinical outcome measures such as mortality, organ failure and length of hospital and ICU stay were also compared between NAP patients with or without SVT. ResultsAccording to the statistical results, only intra-abdominal pressure (IAP) was proved to be an independent risk factor for SVT (OR, 1.283; 95% CI, 1.091–1.509,P=0.003). In addition, Balthazar’s CT score and occurrence of IPN (infected pancreatic necrosis) also reached statistical significance (P=0.040 and 0.047, respectively), but the 95% confidence interval shown in the multivariate logistic regression suggested that the observed ORs are not significant (1.326;95% CI 0.984-1.787 and 2.61;95 CI 0.972-7.352, respectively), which indicates weaker association between the two parameters and SVT. Regarding the clinical outcomes, patients with SVT showed higher mortality, longer hospital and intensive care unit duration, higher rates of a variety of complications and more utilization of invasive interventions. ConclusionsIAP is an independent risk factor for the development of SVT in patients with NAP, while Balthazar’s CT score and occurrence of IPN are also associated with SVT, although not as strong as IAP. Moreover, occurrence of SVT relates with extremely poor prognosis in NAP patients, evidenced by increased mortality, morbidity and need for invasive interventions.

Thinking Outside the Bowels: Splanchnic Venous Thrombosis Presenting as Subacute Abdominal Pain

Thinking Outside the Bowels: Splanchnic Venous Thrombosis Presenting as Subacute Abdominal Pain

PTH-095 Portal Hypertension Due To Splanchnic Venous Thrombosis Following Open Or Skunk Wire Necrosectomy Of Acute Severe Pancreatitis

IntroductionIsolated splenic vein thrombosis (ISVT) is a well recognised complication of acute pancreatitis with incidences ranging widely but more recently in a large meta analysis reported as approximately 14% with...

From portal to splanchnic venous thrombosis: What surgeons should bear in mind.

The present study aims to review the evolution of surgical management of portal (PVT) and splanchnic venous thrombosis (SVT) in the context of liver transplantation over the last 5 decades. PVT is more commonly managed by endovenous thrombectomy, while SVT requires more complex technical expedients. Several surgical techniques have been proposed, such as extensive eversion thrombectomy, anastomosis to collateral veins, reno-portal anastomosis, cavo-portal hemi-transposition, portal arterialization and combined liver-intestinal transplantation. In order to achieve satisfactory outcomes, careful planning of the surgical strategy is mandatory. The excellent results that are obtained nowadays confirm that, even extended, splanchnic thrombosis is no longer an absolute contraindication for liver transplantation. Patients with advanced portal thrombosis may preferentially be referred to specialized centres, in which complex vascular approaches and even multivisceral transplantation are performed.

Clinical and Molecular Profile Of Hereditary Antithrombin (AT) Deficiency: A Single Institution Cohort

IntroductionHereditary antithrombin (AT) deficiency is an autosomal dominant thrombophilia. It is classified into type 1 (quantitative) or type 2 (qualitative) deficiency based on the AT antigen and activity levels (Haemophilia 2008:14; 1229). The goal of this study was to correlate clinical phenotype with AT molecular defects. MethodsAfter IRB approval, patients with a diagnosis of hereditary AT deficiency established at the Mayo Clinic, Rochester, were identified from the clinical database (1997-2012). AT activity was assayed by a chromogenic Factor Xa assay and AT antigen level was assayed by latex immunoassay. Peripheral blood leukocyte genomic DNA was extracted using standard methods.PCR-amplification and ABI BigDye Terminator cycle sequencing kit was performed for all SERPINC1 exons, intronic splicing regions and the 3'UTR. SERPINC1 sequence was analyzed using Mutation Surveyor software (SoftGenetics). Clinical data were obtained from patient interview and medical record review. An event was defined as an episode of venous thromboembolism (VTE), including deep vein thrombosis and/or pulmonary embolism; arterial thrombosis, including cerebrovascular event and/or myocardial infarction, and an obstetric event, including miscarriages and/or spontaneous abortions. Statistical analysis was performed with SAS 9.1.3 (SAS Institute Inc. Cary, NC). ResultsOf 30 patients with hereditary AT deficiency; sequence data was available on 22. Twenty-nine (97%) patients were white, and 19 (63%) were females. Six patients (20%) were smokers and 9 (30%) had a body mass index of >30. Based on the AT activity and antigen levels, 18 (81%) had type 1 AT deficiency, while the remainder had type 2. Eleven patients were heterozygous for six novel (all type 1) mutations. One patient was also a homozygous carrier for the Factor V Leiden mutation.The median age at first thrombotic event was 24.4 years (range, 16.2-70.7), and the median age at diagnosis of AT deficiency was 40.7 years (range, 17.8-76). Both, the median ages at first thrombotic event and at diagnosis were comparable in type 1 versus type 2 AT deficiency patients (P=0.52 and 0.97 respectively). Thirteen patients (43%) had unprovoked thrombotic events. Majority had VTE (n=21, 70%), which included one patient each with splanchnic venous thrombosis, and cerebral venous sinus thrombosis. At last follow up, twenty-one patients (70%) were on chronic anticoagulation [17 (81%) were on warfarin, 2 (9.5%) on enoxaparin and 2 (9.5%) were on rivaroxaban]. Median number of events was 1 (range 0-7). Four patients (19%) had bleeding complications from anticoagulation. Only one death was noted in the cohort and cause of death could not be determined. ConclusionsType 1 hereditary AT deficiency is the most clinically prevalent subtype in practice. Of the patients who developed thrombosis; clinical characteristics did not differ between type 1 and type 2 AT deficiency. We report 6 novel mutations in patients with hereditary AT deficiency. Disclosures:No relevant conflicts of interest to declare.

Outcome of patients with splanchnic venous thrombosis presenting without overt MPN: A role for the JAK2 V617F mutation re-evaluation

Although investigation for JAK2 V617F mutation is recommended in patients presenting with splanchnic venous thrombosis (SVT), no specific clinical advice is given to SVT patients presenting without myeloproliferative neoplasms (MPN) and JAK2 V617F mutation. In MPN-free SVT patients, to investigate the clinical outcome, the clinical impact of re-evaluation for the JAK2 V617F mutation, and relationships with the occurrence and time to diagnosis of MPN. A cohort of non-cirrhotic SVT patients, enrolled at a single centre and prospectively analyzed. In 121 SVT patients prospectively followed from 1994 to 2012, a MPN was present in 28 (23.1%). Additional 13 patients (10.7%) showed only the JAK2 V617F mutation. During the follow-up, the JAK2 V617F mutation and/or MPN were identified in 8 patients (median time of development: 21 months, range 6-120), whereas 72 remained (MPN and JAK2 V617F)-free until the end of the observation. The mortality rate was higher among patients presenting with MPN and/or the JAK2 V617F mutation than in patients who developed later or remained disease-free (p=0.032). The thrombosis-free survival was lower in patients with (p=0.04) or developing later MPN and the JAK2 V617F mutation (p=0.005) than in patients (MPN and JAK2 V617F)-free. The incidence of bleeding was similar among groups. MPN with or without circulating positive clones for JAK2 V617F mutation can occur long after a SVT, identifying at risk patients for new thrombotic events. If confirmed in other studies, re-evaluation for JAK2 V617F mutation may be of help in early MPN detection and clinical management of SVT patients.

Splanchnic Venous Thrombosis and Pancreatitis

Pancreatitis is an inflammatory process with local and systemic manifestations. One such local manifestation is thrombosis in splanchnic venous circulation, predominantly of the splenic vein. The literature on this important complication is very sparse. This review offers an overview of mechanism of thrombosis, its pathophysiology, diagnosis, and management in the setting of acute as well as chronic pancreatitis.

The association of the JAK2 46/1 haplotype with non-splanchnic venous thrombosis

The inherited JAK2 46/1 haplotype is strongly associated with the development of myeloproliferative neoplasms (MPNs), and its increased frequency has also been reported in splanchnic venous thrombosis (SVT). In the present study, the role of the JAK2 46/1 haplotype in non-splanchnic venous thrombosis (non-SVT) was investigated. We genotyped 438 patients with non-SVT, 226 patients with MPNs and 459 healthy controls for three single nucleotide polymorphisms (SNPs) which tag the JAK2 46/1 haplotype (rs12342421 G>C, rs12343867 T>C and rs10974944 C>G). We found statistically significant association of the rs12342421 GC+CC genotypes (OR=1.40; p=0.023) and the rs12343867 TC+CC genotypes (OR=1.83; p=7.02 x 10(-5)) with non-SVT. We also found that the CC haplotype of these two SNPs was associated with an increased risk of the disease (OR=1.68; p=0.009). Stratification analysis indicated that the observed association of the JAK2 46/1 haplotype with non-SVT was probably largely free of confounding effect of thrombophilic risk factors. In addition, we established a strong association of SNPs rs12342421 and rs10974944 and their CG haplotype with MPNs and with JAK2 V617F-positive MPNs. This study provides statistical evidence that SNPs rs12342421 and rs12343867 are associated with an increased risk of non-SVT. Consistently, haplotypes of the SNPs were also associated with non-SVT risk, suggesting that inherited genetic variation in the JAK2 gene may play a role in the pathogenesis of non-SVT. Furthermore, the reported associations of the JAK2 46/1 haplotype with MPNs as well as with the occurrence of the JAK2 V617F mutation in MPNs were confirmed.

Pediatric Portal Vein Thrombosis

To the Editor: We read with much interest the article by Ferri et al (1) published in the June 2012 issue of JPGN. They had reported interesting original personal and international (Brazil, Egypt, Germany, Israel, United Kingdom, and Turkey) literature data on the presence of thrombophilia in children with the diagnosis of portal vein thrombosis (PVT) without liver disease. As correctly pointed out by them, studies on old and novel thrombophilic risk factors in pediatric PVT are still fragmentary, and sometimes controversial or unexpected. In this regard, the authors had particularly underlined the possible role played by ethnic/geographical variations, and the surprisingly apparent lack of involvement of Janus kinase 2 (JAK2-VS17). This is a novel mutated protein kinase protagonist in adult series of splanchnic venous thrombosis and/or myeloproliferative disorders (2), which has still been seldom investigated in pediatric population. The authors had concluded that even after investigation of hereditary and acquired thrombophilia, PVT remains without a defined cause in the majority of the evaluated patients. We believe that this conclusion may be useful to the journal readership, urging them to also focus on a recent study of our group on genetic risk factors in 19 similar cases of Italian origin with PVT (3). We also did not find the JACK2-VS17 mutation in any of the studied patients. In our own series, among 12 of 19 patients (63%) with neonatal history of umbilical vein catheterization, a genetic variant (factor V Leyden, n = 1; prothrombin G20210A mutation, n = 2) tended to be more frequent (ie, 25%) than in the remaining 7 of 19 of the idiopathic group (factor V Leyden, n = 1; 14.3%). We believe that the data from the study by Ferri et al (1), along with those quoted in their references, and our personal results as well (3), call for a meta-analytical study of literature evidences and prospective larger studies, assessing these and also other thrombophilic markers, to gain a better insight into the mechanisms underlying pediatric PVT. This information will possibly be useful for better establishment of the real need for timely prophylactic anticoagulation strategies when indicated.

Primary mixed-type autoimmune hemolytic anemia concomitant with acute splanchnic venous thrombosis of idiopathic origin in a young woman: an unexplained association

TO THE EDITOR: Mixed autoimmune hemolytic anemia (AIHA) is defined by the presence of both warm and cold types of autoantibodies [1, 2]. The diagnosis is based on the detection of these autoantibodies by using a monospecific direct antiglobulin test; a positive test result shows a pattern of IgG and complement C3d along with the presence of cold agglutinins. Mixed AIHA may be of idiopathic origin or associated with an underlying disease [1]. Venous thromboembolism is a common complication of AIHA, although it is not often identified [3, 4]. In some instances, its occurrence may be related to coexistent antiphospholipid antibodies. However, the association of primary mixed AIHA with idiopathic acute splanchnic venous thrombosis (SVT), as we recently observed, represents an exceptional occurrence; thus far, it has been reported for AIHA only in conjunction with splenectomy [5], but has never been reported as a concomitant manifestation. In the present report, we describe the case of a 19-year-old woman who presented with diffuse abdominal pain and severe anemia. At admission, she presented with life-threatening medical conditions due to severe anemia and critical abdominal features. Her medical history was unremarkable. Findings on clinical images and laboratory parameters were consistent with an acute and severe hemolytic disorder; her Hb level had decreased to 3.9 g/dL, whereas the reticulocyte count, indirect bilirubin level, and lactate dehydrogenase concentration were elevated. On admission, the patient was transfused with packed red blood cells (12 units). A strongly positive result on direct antiglobulin test (IgG3 and C3d) was detected; the indirect antiglobulin test indicated a positive result at 4℃ and a negative result at 22℃ and 39℃ in the presence of a cold panagglutinin antibody (IgM). The concomitant acute abdominal condition was investigated by a comprehensive radiological work-up, including an abdominal echography and a body computed tomography scan, and revealed complete thrombosis of the portal and splenic veins as well as partial occlusion of the superior mesenteric vein. A diagnosis of mixed AIHA associated with SVT was made, and treatment with prednisone (1 mg/kg body weight/day) was promptly initiated; in addition, therapeutic subcutaneous Fraxiparine injections with warfarin were also administered. Additional laboratory investigations revealed no other causes of anemia and ruled out the presence of autoimmune disorders, infections, and liver diseases. Investigations into the possible causes for the development of the thrombosis, including all genetic and acquired abnormalities associated with hypercoagulability states, as well as those aimed to identify a possible underlying neoplastic etiology, did not provide any useful findings. Similarly, the presence of a paroxysmal nocturnal hemoglobinuria clone or abnormal Hb chains was ruled out. The patient was discharged with continued warfarin treatment with a fraxiparine bridge. However, based on the patient's decision, the warfarin treatment was subsequently discontinued, whereas the fraxiparine was maintained for only 6 months, after which a careful reevaluation showed complete SVT resolution and full vein recanalization in the splanchnic area. Moreover, based on the clinical response, the prednisone dose was adjusted and tapered until the minimal effective maintenance dose was reached; immunohematological evaluations were regularly repeated and indicated completely negative results. However, an AIHA recurrence was observed 6 months after the reduction of prednisone to the lowest dosage. At this time, a second line treatment of rituximab (375 mg/m2, 4 weekly courses) was given. A complete response by rituximab was achieved. At approximately 1 year after the primary diagnosis was made, the patient is doing well. As AIHA and acute SVT may have been the initial manifestations of underlying occult disorders, the patient is carefully and regularly evaluated to promptly diagnose any recurrence of her hematological complaints. Thus, we report a rare and unexplained association of primary mixed AIHA with acute SVT, both of idiopathic origin that simultaneously occurred in a young patient.

Cavoportal Hemitransposition in Liver Transplant Recipients with Complete and Diffuse Splanchnic Venous Thrombosis

Aim: In 1998, Tzakis first described cavoportal hemitransposition (CPHT) as a treatment option in liver transplant (LT) recipients with diffuse/complete splanchnic thrombosis. Aim of this study was to review the outcome of CPHT in LT. Material and methods: Between 1-1-2001 and 30-11-2011, 8 CPHT were performed in 2 Belgian centers. Indications for LT were Budd-Chiari syndrome (n=4; 1 with associated hepatocellular carcinoma), cryptogenic cirrhosis (n=1), re-LT because of chronic rejection (n=1), HCV-cirrhosis (n=1) and secondary biliary cirrhosis (n=1). No patient underwent splenectomy before LT. Median recipient age was 46 years (range, 41 -71). Median follow-up was 38 months (range, 2 - 139). Results: Decision to perform a CPHT was taken before LT in 6 patients and intraoperatively in 2. Piggyback reconstruction was performed in 3 recipients, while in 5 recipients a classical caval reconstruction was performed with the use of veno-venous bypass. CPHT was achieved via an end-to-side cavoportal anastomosis in 6 cases and via an end-to-end anastomosis in 2 cases. An interposition donor venous iliac graft was necessary in 6. CPHT was total with complete derivation of infrahepatic caval blood flow into the liver graft. One and 5-year patient survival was 75% and 38%, respectively. One patient underwent splenectomy and gastric devascularisation 1 year after LT because of repetitive gastrointestinal bleedings. This patient also underwent a radiological intervention for resolving a stenosis at the level of the cavoportal anastomosis. Morbidity after LT consisted of prolonged ascites (n=7), renal dysfunction (n=6; 2 needed temporarily hemodialysis), recurrent gastrointestinal bleeding (n=3), thrombosis of the graft portal vein (n=3) and thrombosis of the inferior vena cava (n=1). The main cause of early mortality was bacterial infection, respectively 2 (peritonitis) and 4 months (pneumonia) after LT. The causes of late mortality were late hepatic artery thrombosis, cerebral vascular accident and recurrence of hepatocellular carcinoma, respectively 15, 26 and 50 months after LT. Conclusions: Diffuse/complete splanchnic thrombosis is no longer an absolute contraindication for isolated LT. In these patients, CPHT is a surgically feasible option and an alternative to a more radical multivisceral transplantation. Morbidity and mortality rates which remain however important, can probably be lowered by refining the allograft implantation technique and patient selection.

Non conventional mutations associated with myeloproliferative disorders are absent in splanchnic venous thrombosis cases

Non conventional mutations associated with myeloproliferative disorders are absent in splanchnic venous thrombosis cases

The JAK2 V617F mutation in patients with cerebral venous thrombosis

It is currently unclear whether or not cerebral venous thrombosis, such as splanchnic venous thrombosis, can be the first manifestation of an underlying myeloproliferative neoplasm. To determine the prevalence of the JAK2 V617F mutation in patients with a first episode of cerebral venous thrombosis. In this retrospective cohort study, patients with cerebral venous thrombosis were tested for the JAK2 V617F mutation and were followed until the development of a myeloproliferative neoplasm or censored at the end of follow-up. Ten of 152 patients (6.6%) carried the JAK2 V617F mutation. Three of them had known acquired risk factors for thrombosis, and five had thrombophilia. Six patients met the diagnostic criteria for myeloproliferative neoplasm at the time of cerebral venous thrombosis, and three additional patients developed the disease during the follow-up (median duration 7.8 years, range 6 months to 21.3 years), giving an annual incidence of 0.26% patient-years (95% confidence interval 0.05-0.64). The last patient has no evidence of disease after 3 years of follow-up. Patients without the JAK2 V617F mutation at the time of cerebral venous thrombosis were retested at the end of the follow-up and remained negative, with normal blood counts (log-rank test χ(2) : 159 [P<0.0001]). Cerebral venous thrombosis can be the first symptom of a myeloproliferative neoplasm. Patients with cerebral venous thrombosis can carry the JAK2 V617F mutation, irrespective of blood count.

Splanchnic vein thrombosis in severe acute pancreatitis: a 2-year, single-institution experience

ObjectivesThis study aimed to determine current practice in the management and outcome of splanchnic vein thrombosis complicating acute pancreatitis (AP). MethodsAn audit of prospectively collected data for all patients presenting with AP was conducted. Patients with splanchnic vein thrombosis were grouped according to vessel involvement and whether or not systemic anticoagulation was administered. ResultsOf 127 consecutive patients admitted with AP, 20 had splanchnic venous thrombosis; in all cases the thrombosis was associated with a severe attack of AP. Involvement of the splenic vein (SV), portal vein (PV) and superior mesenteric vein (SMV) was observed in 14, 10 and three patients, respectively. Involvement of more than one vessel was observed in six patients (SV and PV in four patients; SMV and SV in one patient; all three veins in one patient). Thromboses were colocalized with collections in 19 patients. Only four patients received systemic anticoagulation. Resolution of thrombosis was observed in six patients over a median of 77 days. No significant differences were observed in recanalization rates following anticoagulation (P= 0.076). No complications associated with systemic anticoagulation occurred. One patient developed liver failure associated with progressive PV thrombosis and one patient died. ConclusionsSplanchnic vein thrombosis is a relatively common observation in severe AP and is associated with pancreatic necrosis and peripancreatic collections. Recanalization is observed in almost a third of patients, irrespective of whether or not they receive systemic anticoagulation.