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Background Splanchnic vein thrombosis (SVT) is an uncommon manifestation of venous thromboembolism. Historical epidemiological data on SVT-related mortality rate is not available to date. Methods We investigated time trends in SVT-related mortality, 2008–2019, in Veneto, an Italian high-income region of approximatively 5,000,000 inhabitants. SVT-related deaths were identified by the following ICD-10 codes: I81 (portal vein thrombosis), K75.1 (phlebitis of portal vein), K76.3 (liver infarction), K76.5 (hepatic veno-occlusive disease) or I82.0 (Budd-Chiari syndrome). Results During the study period, a total of 557,932 deaths were recorded. SVT was reported in 823 cases; 776 (94%) consisted of portal vein thrombosis. The age-standardized SVT-related mortality rate varied from 1.47 (year 2008) to 1.52 (year 2019) per 100,000 person-years. An increase in the cause-specific annual mortality rate was observed in women (0.56 in 2008 to 1.04 per 100,000 person-years in 2019; average annual percent change +5.7%, 95%CI +3.1; +8.3%). In men, the cause-specific mortality rate moved from 2.53 in 2008 to 2.03 per 100,000 person-years in 2019 (average annual percent change −1.2%, 95%CI -4.0; +1.6%). After conditioning for age and sex, the odds of having a concomitant liver disease were higher for SVT-related deaths (OR 31.6; 95%CI 17.1–37.0) compared with non-SVT-related deaths. This also applies to gastrointestinal cancers (OR 1.28; 95%CI 1.07–1.55), although to a lesser extent. Conclusions We report first epidemiological estimates of SVT-related mortality in a Western country. These values will serve as a reference to weight novel potential factors associated with SVT-related death, putting them into an epidemiological perspective. Summary box What is already known about this subject? Splanchnic vein thrombosis is a rare manifestation of venous thromboembolism, often related to liver diseases. Currently, there is no available data on its impact on the general population in terms of mortality rates. What are the new findings? Splanchnic vein thrombosis-related mortality rate was higher in men than in women and was strongly associated with the presence of liver diseases. In women, the age-standardized splanchnic vein thrombosis-related mortality rate has been increasing since 2008. How might it impact on clinical practice in the foreseeable future? We report first epidemiological estimates of splanchnic vein thrombosis-related mortality rates in a Western country. These values will serve as a reference to weight novel factors or pathologies potentially associated with splanchnic vein thrombosis and interpret them in an epidemiological perspective.

Background Clinical manifestations and optimal management strategies in patients with splanchnic vein thrombosis (SVT) are not well characterized. Methods We conducted a retrospective cohort study including all newly diagnosed SVT evaluated between January 2007 and December 2018. Efficacy outcome was thrombosis resolution, and safety outcomes included death and occurrence of bleeding. Results We included 155 patients with a mean age of 56.2 (18–87). Local risk factors were present in 118 (76.1%) patients and 30 (19.4%) had only systemic/thrombophilia. Local risk factors included abdominal cancers (31%), surgery (20.6%) and liver cirrhosis (19.4%). Thrombophilia screening was conducted in approximately 50% of patients. Factor V Leiden or Prothrombin G20210A mutations were observed in 7.1% of patients whereas 14.4% were JAK2V617F mutation positive. Most common manifestations at onset were abdominal pain (56.1%), whereas 44.6% were incidentally found. Portal vein thrombosis was observed more in primary cases (91.9% vs. 69.5%, p = 0.012). Anticoagulation was used in 93.5% cases. Indefinite anticoagulation was used more frequently in primary SVT (62.2% vs. 41.5%, p = 0.045). Thrombosis resolution and bleeding complications among primary (without local risk factors) and secondary (with local risk factors) SVT were observed in 48.5%, 65%, 8.1%, and 11.9%, respectively with no difference when comparing patients treated with direct oral anticoagulants or warfarin and/or low molecular weight heparin (58% vs. 62%, p = 0.326, 9% vs. 12%, p = 0.518). Conclusions In this cohort anticoagulation resulted in partial or complete thrombosis resolution in a significant proportion of patients with an acceptable bleeding risk regardless local risk factors or type of anticoagulant.

We present a case of acute pulmonary embolism in a patient with myelofibrosis and thrombocytopenia. The patient had a history of portal vein thrombosis and had taken warfarin for the past six years. At the time of his pulmonary embolism diagnosis, his INR was 1.5 and platelet count 58 × 109/L. This article discusses how to balance the risk of thrombosis against the risk of bleeding, and reviews the options for pulmonary embolism treatment including transition to low-molecular-weight heparin, direct oral anticoagulants and/or inferior vena cava filters.

Acute non-cirrhotic and non-malignant portal vein thrombosis (aPVT) is a rare and heterogenous condition. Current guidelines recommend early initiation of therapeutic anticoagulation to prevent extension of thrombosis, and favor recanalization. Although not formally defined, a poor outcome in the acute setting would include thrombosis extension with progression to intestinal infarction. Patients are also at risk of negative long-term outcomes related to complications of portal hypertension, such as variceal bleeding, ascites, and portal cholangiopathy. Identifying patients at risk of these events despite early initiation of anticoagulation remains challenging. Trials comparing treatment strategies in those failing standard therapy with meaningful radiological and clinical endpoints, whether in the short or long term, are desperately needed. The objective of this review will be to discuss a real-life clinical case and propose a treatment approach for aPVT based on the available evidence. We will mainly focus on management strategies including anticoagulation, prognostic factors, and options beyond anticoagulation, such as thrombolysis, thrombectomy, and transjugular intrahepatic portosystemic shunts. This review will not cover tumor portal vein thrombosis or thrombosis associated with cirrhosis.

Background The prevalence of calreticulin (CALR) mutations in splanchnic vein thrombosis (SVT) varies among studies. The role of routine screening for CALR mutations in SVT patients remains a debate. Aim To synthesize the prevalence of CALR mutations according to the different types (i.e., Budd-Chiari syndrome [BCS] and portal vein thrombosis [PVT]) and characteristics (i.e., with and without myeloproliferative neoplasms [MPNs] and JAK2V617F mutation) of SVT patients. Methods Eligible studies were searched by the PubMed and Embase databases. The study quality was assessed according to the STROBE checklist. The proportion of CALR mutations was pooled by using a random-effects model. The heterogeneity and publication bias were calculated. Results Eleven papers were included. The study quality was moderate to high. The pooled proportion of CALR mutations was 1.21%, 1.41%, and 1.59% in SVT, BCS, and PVT patients, respectively; 1.52%, 1.03%, and 1.82% in these patients without JAK2V617F mutation, respectively; 3.71%, 2.79%, and 7.87% in these patients with MPN, respectively; and 15.16%, 17.22%, and 31.44% in these patients with MPN but without JAK2V617F mutation, respectively. Only the meta-analysis examining the prevalence of CLAR mutations in BCS patients with MPN but without the JAK2V617F mutation showed statistically significant heterogeneity. Statistically significant publication bias was seen only in the meta-analysis examining the prevalence of CALR mutations in SVT patients without the JAK2V617F mutation. Conclusion Screening for CALR mutations may have a role in SVT patients with a high probability of MPN in whom the JAK2V617F mutation has been excluded.

Splanchnic vein thrombosis (SVT) and cerebral vein thrombosis (CVT) are uncommon manifestation of venous thromboembolism (VTE), occurring less frequently than deep vein thrombosis of the lower extremities and pulmonary embolism. SVT encompasses portal vein thrombosis, mesenteric vein thrombosis, splenic vein thrombosis and the Budd-Chiari syndrome. It is therefore a heterogeneous disease, with differences in clinical manifestations according to the site of thrombosis. CVT includes thrombosis of the cortical or deep cerebral veins and thrombosis of the major dural venous sinuses. Clinical presentation is variable, with a wide spectrum of signs and symptoms that can mimic other cerebral diseases. There are no clinical algorithms or specific laboratory tests that can guide in the identification of SVT and CVT; therefore, the diagnosis relies exclusively on imaging tests. Conventional angiography once was the gold standard for the diagnosis of SVT and CVT, but it is rarely used nowadays. Abdominal ultrasound (US), computed tomography (CT) and magnetic resonance (MR) with angiography are currently used for the diagnosis of SVT; while cerebral CT and MR with angiography are currently used for the diagnosis of CVT. These imaging tests have different sensitivities/specificities and different advantages/disadvantages that should be kept into consideration when choosing the appropriate imaging test based on the suspected site of thrombosis. This narrative review summarizes the clinical and diagnostic approach to SVT and CVT.

Background The value of D-dimer testing for the diagnosis of thrombosis in unusual sites is not properly established and evidence is scarce. We performed a systematic review of the literature. Methods The search was conducted in MEDLINE and Cochrane Library for papers published in the last 10 years including different presentations of thrombosis in unusual sites. Twenty-three articles were included, from January 1, 2008, to December 31, 2018, comprising 3378 patients with thrombosis in unusual sites (upper extremity deep vein thrombosis, cerebral vein thrombosis and splanchnic vein thrombosis). The Newcastle-Ottawa scale was used to assess the quality of the studies. Results Two articles were related to upper extremity thrombosis, showing a high sensitivity and negative predictive value for D-dimer testing. Twelve articles concerned cerebral vein thrombosis, concluding that the timing of D-dimer testing was important, and that patients with a shorter duration of symptoms showed higher D-dimer levels. Sensitivity and specificity in these patients ranged from 58% to 97% and from 77% to 97.5%, respectively. Nine articles were related to splanchnic vein thrombosis. One described a population of patients with mesenteric venous thrombosis, and the rest included patients with portal vein thrombosis. The D-dimer testing methods and the proposed cut-off levels were remarkably different among the included studies. Conclusion D-dimer testing should not be currently recommended for the diagnosis of thrombosis in unusual sites as a first line diagnostic tool. The development of algorithms combining biomarkers such as D-dimer and clinical decision tools could improve the diagnosis.

Unusual site deep vein thrombosis (USDVT) is an uncommon form of venous thromboembolism (VTE) with heterogeneity in pathophysiology and clinical features. While the need for anticoagulation treatment is generally accepted, there is little data on optimal USDVT treatment. The TRUST study aimed to characterize the epidemiology, treatment and outcomes of USDVT. From 2008 to 2012, 152 patients were prospectively enrolled at 4 Canadian centers. After baseline, patients were followed at 6, 12 and 24months. There were 97 (64%) cases of splanchnic, 33 (22%) cerebral, 14 (9%) jugular, 6 (4%) ovarian and 2 (1%) renal vein thrombosis. Mean age was 52.9years and 113 (74%) cases were symptomatic. Of 72 (47%) patients tested as part of clinical care, 22 (31%) were diagnosed with new thrombophilia. Of 138 patients evaluated in follow-up, 66 (48%) completed at least 6months of anticoagulation. Estrogen exposure or inflammatory conditions preceding USDVT were commonly associated with treatment discontinuation before 6months, while previous VTE was associated with continuing anticoagulation beyond 6months. During follow-up, there were 22 (16%) deaths (20 from cancer), 4 (3%) cases of recurrent VTE and no fatal bleeding events. Despite half of USDVT patients receiving6months of anticoagulation, the rate of VTE recurrence was low and anticoagulant treatment appears safe. Thrombophilia testing was common and thrombophilia prevalence was high. Further research is needed to determine the optimal investigation and management of USDVT.

Background Portal vein thrombosis (PVT) is serious complication of liver cirrhosis (LC), especially in the presence of hepatocellular carcinoma (HCC). The liver plays a key role in homocysteine (Hcy) metabolism: mild hyperhomocysteinemia (HHcy) has been described in LC. HHcy is a risk factor for deep vein thrombosis. Methylen-tetrahydrofolate-reductase (MTHFR) C677T polymorphism is the commonest determinant of mild HHcy and has been involved also in cancer development. Aim To investigate a possible relation between HHcy, MTHFR status, HCC and PVT in patients affected by LC. Materials and methods 100 patients affected by LC, 38 with (PVT group, 24 with HCC) and 62 without PVT (LC group, 14 with HCC) sex-, age-, liver disease stage and etiology-matched were assessed for thrombophilia, smoking status, plasma Hcy, MTHFRC677T polymorphism and homocysteine-related vitamin status. Results A higher prevalence of HCC, HHcy and MTHFR TT status was observed in PVT group. No significant difference in vitamin status was observed between groups. Patients with HCC showed significantly higher plasma Hcy and higher prevalence of HHcy than patients without HCC. They had also higher prevalence of MTHFR TT status. In patients with TT status ( n = 11) and HCC, 10 had HHcy e 9 had PVT. Conclusions Mild HHcy is associated to LC may have a role in PVT development and assessment of plasma Hcy may be suggested in patients with LC (especially if complicated by HCC). Association between HCC and MTHFR TT status is intriguing, due the postulated role for this polymorphism in cancer: it may represent a possible link between HCC and PVT.

Background Portal vein thrombosis (PVT) is an unusual-site thrombosis commonly encountered in patients with malignancies, cirrhosis, and acute abdominal inflammatory conditions (AIC). Current recommendations suggest that anticoagulation may improve recanalization rates but there is limited information on venous thromboembolism (VTE) recurrence rates and whether the etiologies of PVT respond similarly with anticoagulation. Objective To characterize the natural clinical course and outcomes of patients diagnosed with PVT based on etiology. Patients/methods Patients with a diagnosis of PVT between 2005 and 2015 who were followed for at least one year and had revised imaging at 12 months ± 3 months were identified. Comorbidities, demographics, anticoagulation choice and clinical outcomes including VTE recurrence, cavernous transformation, PVT recanalization, progression and mortality were obtained. Results Of 698 patients diagnosed with PVT, 85 patients were evaluable according to criteria: 54 had cirrhosis (63.5%), 15 malignancy (17.6%) and 16 AIC (18.8%). Mean age was 55.6 ± 13.1 years. At presentation, 40% patients were symptomatic and 29.4% received anticoagulation. Patients with AIC were anticoagulated more frequently compared to those with malignancy or cirrhosis (87.5% vs. 33.3% vs. 11.1%). Overall, patients with cirrhosis had lower rates of PVT progression (0% vs. 13.3%, p = 0.02) and patients with AIC had higher rates of cavernous transformation compared to cirrhosis or malignancy-associated PVT (31.3% vs. 7.4% vs. 0%, p = 002). Among untreated patients, those with malignancy had significantly higher rates of VTE recurrence and PVT progression than patients with cirrhosis (20% vs. 4.2% and 20% vs. 0%). Conclusions The natural course of PVT differs among etiologies. In the absence of anticoagulation, patients with malignancy are more prone to VTE recurrence and PVT progression compared to patients with cirrhosis. Given the high rate of VTE recurrence at 12 months in patients with malignancy-associated PVT, anticoagulation should be considered for this group.

Introduction Portal vein thrombosis (PVT) is a well-known complication in patients with liver cirrhosis (LC). The aim of this study is to investigate the outcomes of cirrhotic patients with PVT treated with low-molecular-weight heparin (LMWH). Method Ninety-one LC patients with PVT were treated with dalteparin or enoxaparin for six months. Patients with major bleeding during the last three months, severe thrombocytopenia, or impaired renal function were excluded. Results The median age was 62.9 years, and 59 patients had hepatocellular carcinoma. The overall recanalization rate was 61.5%. Patients with a favorable Child-Pugh class and those recently diagnosed as having a thrombus showed significantly better responses. In those who responded to the anticoagulation therapy, the post-treatment bilirubin and platelet levels were improved compared to those in the pre-treatment state. The relapse rate for PVT was 56.6%, and the median time to relapse was 4.0 months. Bleeding was reported in 13 patients (14.4%), and two patients died due to fatal bleeding. A history of variceal bleeding and low serum albumin were risk factors for bleeding. Conclusion LMWH therapy for PVT in LC is effective. Advanced LC and a delayed start of anticoagulation treatment decrease the effect of LMWH. Despite its effectiveness, there is a risk of hemorrhage, hence anticoagulation should be carefully considered, especially in patients with advanced LC and a history of variceal bleeding.

The development of portal vein thrombosis (PVT) in cirrhotic patients has not been fully elucidated. The disseminated intravascular coagulation (DIC) score, which is based on readily available and relatively inexpensive coagulation parameters, including platelet count, fibrin-related markers, prothrombin time and fibrinogen, has not been reported regarding PVT development in cirrhotic patients to date. We aimed to evaluate the prognostic value of the DIC score in predicting PVT development in cirrhotic patients with hepatitis B.A total of 109 cirrhotic patients with hepatitis B were included. Clinical data, laboratory tests and imaging were collected from the patients at baseline and every three months after enrollment. All patients were followed until the study endpoint (either occurrence of PVT or 12months after baseline). We measured routine laboratory parameters and conducted imaging examinations in cirrhotic patients and evaluated the prognostic value of the DIC score as a novel predictor for PVT in patients with cirrhosis. We also compared the effectiveness of the DIC score with other common coagulation and hemodynamic parameters.Among the 109 patients, 14 (12.8%) developed PVT. At the study endpoint, significant increases in D-dimer, Child-Pugh score and DIC score (all P0.001) and significantly reduced portal flow velocity (P0.001) were noted in the PVT group. Among the selected factors, the DIC score had the largest area under the curve (AUC) (0.845), followed by the Child-Pugh score (0.778), D-dimer (0.732), and portal vein velocity (0.709).Among the selected factors, the DIC score showed non-significantly higher diagnostic performance in predicting the PVT development in cirrhotic patients compared with other factors. A validation cohort of the study is needed in the near future.

The BCR-ABL1 negative myeloproliferative neoplasms (MPNs) are associated with an increased risk of both venous and arterial thromboembolic events. Thromboses may be the presenting clinical feature of an MPN or may occur during the course of the disease. Treatment comprises anticoagulant and antiaggregant agents as in non- MPN thromboses, and treatment of the particular MPN. The duration of anticoagulant treatment that is required for MPN thrombosis is unknown. This study was performed to survey the opinion of hematologists who treat patients with MPN regarding the duration of anticoagulation or antiaggregant therapy in patients in whom thrombosis is the presenting feature of MPN. Five clinical scenarios in which thromboembolism (cerebral vein thrombosis, pulmonary embolism, cerebrovascular accident, splanchnic vein thrombosis, portal vein thrombosis) was a presenting feature of MPN were created using a web-based tool and were sent by email to hematologists in Israel, Italy and England and to hematologists identified as key opinion leaders in the field of MPN. Physicians were asked to recommend duration of anticoagulation and/or aspirin use choosing from 4 alternatives provided. Seventy-three physicians responded to the survey. 42 physicians considered MPNs to be their main area of clinical interest, and 31 did not. 21 physicians saw more than 20 MPN patients per week, and 50 physicians had been in hematology practice for more than 10 years. Responses regarding the duration of anticoagulation and/or the use of aspirin varied for all of the clinical vignettes. Neither physician area-of-interest, volume of MPN patients treated nor years in practice were related to the responses obtained. This study demonstrates that hematologists, including those specializing in MPNs, lack consensus in their approach to the long-term treatment of thromboses as the presenting feature of an MPN. Controlled clinical studies are needed to inform appropriate decision making in this area.

To investigate the predictive value of combined use of D-dimer and P-selectin for splenic or portal vein thrombosis (SPVT) after splenectomy. A prospective study was carried out in 82 patients who had undergone splenectomy for portal hypertension secondary to hepatic cirrhosis. Plasma levels D-dimer and P-selectin were measured before and after the surgery.27 (30.1%) patients developed SPVT following the portal hypertension surgery. The post-operative D-dimer and P-selectin levels in patients with SPVT were significantly higher than in those without PVT (n=55, P0.01). The receiver-operated characteristics curves (ROC) of D-dimer and P-selectin showed a significant predictive value in SPVT (D-dimer, Az=0.880, P0.01; P-slectin, Az=0.933, P0.01). The sensitivity and specificity of D-dimer (500 microg/mL) in diagnosing SPVT were 88.9% and 78.2% respectively. P-selectin90ng/mL had an 85.2% sensitivity and 85.5% specificity for SPVT. The combination of the D-dimer and P-selectin criteria yielded an 82.0% sensitivity and 97.6% specificity for SPVT. In Conclusion, there was a significant elevation in plasma D-dimer and P-selectin in patients with post-operative SPVT. A combination of plasma D-dimer and P-selectin may be used as biomarkers to screen or diagnose SPVT following splenectomy.

INTRODUCTION: Splanchnic vein thrombosis (SVT) is a rare condition with a poorly understood prognosis.MATERIALS AND METHODS: We conducted a population-based cohort study (1994-2013), using data from Danish nationwide medical registries, to examine the short- and long-term prognosis of SVT. We identified 1915 incident cases of SVT and a matched comparison cohort of 18,267 persons without SVT (matched by cancer, cirrhosis, pancreatitis, alcohol-related disease, atrial fibrillation/flutter, venous thromboembolism, heart failure, and inflammatory bowel disease). We used the Kaplan-Meier method to calculate absolute risk of death. Using stratified Cox regression, we computed mortality rate ratios (MRRs) with 95% confidence intervals (CIs), comparing SVT patients with the comparison cohort.RESULTS: We identified 1,500 (78%) patients with portal vein thrombosis, 204 (11%) with hepatic vein thrombosis, and 211 (11%) with mesenteric vein thrombosis. The mortality risks were markedly higher for SVT patients than for the comparison cohort during the first 5years of follow-up (30-day risk: 20.6% vs. 0.7%; 31-364-day risk: 21.7% vs. 4.7%; and 1-5-year risk: 25.4% vs. 17.7%). The corresponding MRRs were 40.7 (95% CI: 32.4-51.1), 7.4 (95% CI: 6.4-8.6), and 2.4 (95% CI: 2.1-2.8), respectively. The 30-day mortality was higher after mesenteric vein thrombosis than portal and hepatic vein thrombosis, whereas portal vein thrombosis had a stronger impact on mortality after 30days than hepatic and mesenteric vein thrombosis.CONCLUSIONS: Splanchnic vein thrombosis has a poor short- and long-term prognosis that varies according to subtype of thrombosis. Reasons for the increased mortality in patients with SVT need further clarification.

Enoxaparin, low-molecular-weight heparin, has become a routine thromboprophylaxis in general surgery.A retrospective cohort study was performed in 281 patients who underwent hepatic resections for liver cancers from 2011 to 2013. These patients were divided into two groups; an enoxaparin (-) group (n=228) and an enoxaparin (+) group (n=53). Short-term surgical results including venous thromboembolism (VTE) and portal vein thrombosis (PVT) were compared.In the enoxaparin (+) group, the patients' age (65 vs. 69 years; p=0.01) and BMI (22.9 vs. 24.4; p0.01) were significantly higher. According to the symptomatic VTE, symptomatic pulmonary embolism occurred in one patient (0.4%) in the enoxaparin (-) group, but the complication rate was not significantly different (p=0.63). The complication rate of PVT was significantly lower in the enoxaparin (+) group (10 vs. 2%; p=0.04). The independent risk factors for PVT were an operation time ≥ 300 minutes (Odds ratio 6.66) and non-treatment with enoxaparin (Odds ratio 2.49).Postoperative anticoagulant therapy with enoxaparin could prevent PVT in patients who underwent hepatic resection for liver cancers.

The coagulation pattern and the determinants of portal vein thrombosis (PVT), both in patients with and without cirrhosis, are still largely unknown. The aim of this study was to evaluate whole blood thromboelastometry profile, performed by ROTEM®, of both cirrhotic and non-cirrhotic subjects with PVT. Two different groups were considered: i) 14 non-cirrhotic PVT patients, ii) 35 cirrhotic patients with PVT. Controls were sex- and age-matched healthy volunteers and cirrhotic subjects without PVT, respectively. ROTEM® assays (i.e. INTEM, EXTEM, NATEM, and FIBTEM) and traditional coagulative parameters (i.e. platelet count, PT/INR, aPTT, and fibrinogen) were performed on blood samples from each subject. There were no significant differences in ROTEM® profile, as for INTEM, EXTEM, and NATEM assays, and in traditional coagulative parameters, between PVT patients, both with and without cirrhosis, and control groups. Interestingly, Maximum Clot Firmness (MCF) in FIBTEM was significantly higher in non-cirrhotic PVT patients (19 mm) than in healthy volunteers (11 mm, p

Introduction Compared to bleeding, major thromboses are a less commonly encountered problem in acute promyelocytic leukemia (APL), and our knowledge about the epidemiology of major thromboses in APL stems mainly from individual case reports. The purpose of this study was to provide a better understanding of the epidemiology of APL-related thrombosis as a first step towards developing preventive strategies. Materials and methods We report a rare case of catastrophic acute myocardial infarction in a patient with APL while she developed the all-trans retinoic acid (ATRA) syndrome. We describe the pathogenesis of APL-related thrombosis and review all previously reported cases of major thromboses in APL. Results We found 94 cases of major thromboses in patients with APL. Both genders were almost equally affected. More than 80% of events occurred before or during induction therapy with deep vein thrombosis/pulmonary embolism (DVT/PE), cardiac events, and cerebrovascular accidents (CVA) constituting more than 75% of all cases. Arterial events were slightly more common than venous events. Only 2 arterial events occurred after completion of induction therapy. Thrombosis was associated with life-threatening hemorrhage in about 15%, significant coagulative defects in about 50%, and ATRA syndrome in about 13% of cases. Cardiac thrombotic events, DVT/PE, and CVA were associated with ATRA syndrome in 24%, 4.5%, and 5% of cases, respectively (p = 0.09). None of the observed trends and associations reached statistical significance. Conclusions This review advances our understanding of the epidemiology of major thromboses in APL. With accumulation of more cases in the literature, some of our results may become statistically significant.

Introduction The relationship between the imbalance in pro- and anti-coagulant factors and portal vein thrombosis (PVT) in individuals with cirrhosis is unclear. The aim of this study was to determine whether the imbalance in pro- and anti-coagulant factors contributes to the development of PVT in cirrhotic patients. Materials and methods Blood samples were collected from 30 consecutive cirrhotic patients with PVT and 30 age-, sex-, and Child-Pugh score-matched cirrhotic patients without PVT (controls), and the plasma levels of coagulation factors II, V, VII, VIII, IX, X, XI and XII and of protein C (PC), protein S (PS) and antithrombin (AT) were analyzed. The ratios of pro- vs. anti-coagulant factors were further investigated. Results The levels of pro- and anti-coagulant factors were not statistically different between the PVT and control groups. Similar results were obtained when the patients were divided according to Child-Pugh classification. No difference was observed for the ratios of pro- vs. anti-coagulant factors between the two groups but the ratios of factor II-to-PC and factor VII-to-PC which were significantly decreased in the PVT group. Most of the ratios did not reach statistical significance in each Child-Pugh category except the followings: factor VIII-to-PS, factor XII–to-PC and factor XII-to-PS in class A patients; factor II-to-PS, factor VII-to-PC and factor VII-to-PS in class B patients. But the difference might not be so convincing. Conclusions PVT in cirrhotic patients may not result from coagulation imbalance.

Budd chiari syndrome (BCS) is characterized by venous outflow obstruction either at hepatic veins or inferior vena cava, while portal vein thrombosis (PVT) is the consequence of thrombotic occlusion in the extrahepatic venous system. The aetiology of both these disorders is complicated wherein genetic, acquired and local factors interact in the pathogenesis. Among the inherited thrombophilia, factor V Leiden mutation has shown stronger association with BCS than PVT while the converse is true for prothrombin G20210A mutation. Very few studies are available on the role of fibrinolytic potential or the single nucleotide polymorphisms (SNPs) of fibrinolysis proteins, in both BCS and PVT. Among the acquired thrombophilia, myeloproliferative disorders (MPD) are the most frequent cause, while antiphospholipid antibodies (APA) and hyperhomocysteinemia have not shown very strong association with BCS and PVT. Oral contraceptives, infection, chronic inflammatory diseases like Behcets syndrome, inflammatory bowel disease, tumors, paroxysmal nocturnal hemoglobinuria (PNH), pregnancy, puerperium, poor nutrition are some of the other acquired and local risk factors associated with both these disorders. There exists a clear geographical variation both in the clinical manifestation and the underlying aetiology. Almost all the studies have proved that a multifactorial aetiology is the requisite for the manifestation. Evaluation of an extensive thrombophilia profile is essential for optimal management of patients which is further justified with the availability of specific treatment options for at least some thrombophilia markers.

Hemostatic activation may be important for tumor biology. Hepatocellular carcinoma (HCC) is commonly associated with portal vein thrombosis (PVT). Little is known about factors predictive for PVT in patients with HCC or its correlation with systemic venous thromboembolism (VTE).We conducted a retrospective chart review of 194 consecutive patients diagnosed with HCC at the University of Rochester between 1998 and 2004 to identify the frequency and risk factors for PVT and its correlation with VTE and survival.Sixty patients (31%) had PVT with a higher rate in the non-transplant group compared to transplanted patients (34% vs. 24%; p=0.15). In multivariate analysis, Child Turcotte Pugh (CTP) class, stage, major vessel involvement, serum albumin, and serum AFP were independently associated with PVT (p0.05 for each). The presence of PVT was associated with reduced survival (median survival 2.3 months for those with PVT versus 17.6 months for those without PVT, HR 2.05, p=0.004). The incidence of systemic VTE in the total population was 6.7%, and patients with PVT had a higher rate of systemic VTE compared to patients without PVT (11.5% vs. 4.4%; p=0.04).PVT is common in patients with HCC, indicates advanced disease, is associated with worse survival and correlates with systemic VTE, suggesting a common mechanism of hemostatic activation. Advanced stage, higher CTP class, major vessel involvement, low serum albumin, and high AFP levels are predictive of PVT in patients with HCC.

An 11-year-old girl was admitted to hospital with a five-week history of worsening epigastric pain, anorexia, episodic vomiting and intermittent fever. There was no history of precipitant trauma, injury or illness, nor did the patient have any history of central venous cannulation. Abdominal examination revealed generalized tenderness but no rebound tenderness or guarding. The liver edge was palpable just below the costal margin and was non-tender. The spleen was not palpable and there was no evidence of ascites. Investigation demonstrated a markedly elevated C reactive protein (242 mg/l), mild leucocytosis (17 109/l) and neutrophilia (14.1 109/l). There were mild abnormalities of liver function but lipase was within normal limits. A plain abdominal X-ray

Introduction The aim of this study was to investigate the clinical and biochemical effects of recombinant activated factor VII (rFVIIa) in the treatment of bleeding in children with liver disease. Patients and Methods 12 patients (0.3–15.9 years) with chronic liver disease were included. The indication for treatment was life threatening bleeding and failing conventional therapy (group A, 7 patients) or as prophylaxis before invasive procedures (group B, 6 patients). One patient received treatment on both indications. rFVIIa was administered as intravenous bolus doses of 34–163 μg/kg (median 66 μg/kg) alone or in combination with packed red cells and/or octreotide and/or fresh frozen plasma. The follow-up included repeated INR and haemoglobin measurements as well as clinical evaluation. Results In group A rFVIIa was given on 22 occasions and bleeding decreased, was unchanged, increased or could not be evaluated on 10, 7, 2 and 3 occasions respectively. On 14 occasions rFVIIa and octreotide were administered simultaneously, in 8 of those bleeding decreased. In group B no bleeding complication was seen, interpreted as a positive effect. One thrombotic event was suspected but could not be verified by computerized tomography. Conclusions rFVIIa may be beneficial in the short-term management of life threatening bleeding in some children with liver disease. This effect may be further enhanced with the additional use of octreotide. Furthermore, rFVIIa is useful for prophylaxis at invasive procedures, even without additional treatment with fresh frozen plasma. The possible risk of portal vein thrombosis needs to be considered.