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Background It is still unknown whether COVID-19 vaccines induce a prothrombotic state or increase the hypercoagulable condition in subjects with a predisposition to thrombosis. Objectives We evaluated the coagulation profile in a series of healthy subjects who received the first dose of the BNT162b2 or the ChAdOx1 vaccines and assessed whether hypercoagulability developed. Patients/methods Volunteers among the staff of the University of Padua or health care professionals in the Padua University Hospital who had received either the ChAdOx1 or BNT162b2 vaccine in the previous 10 ± 2 days were eligible. A cohort of unvaccinated volunteers among family members of the University staff acted as control group. Global coagulation monitoring was assessed by whole blood rotational thromboelastometry, whole blood impedance aggregometry and thrombin generation. Platelet count was also obtained. Results One hundred and ninety subjects were enrolled: 101 (53.2%) received the ChAdOx1 vaccine and 89 (46.8%) the BNT162b2 vaccine. Twenty-eight non-vaccinated subjects acted as controls. Thromboelastometry parameters were all comparable among groups. Thrombin receptor activating peptide (TRAP)-, ADP- and ASPI-induced platelet aggregation were similar among groups, as well as platelet count. Endogenous thrombin potential (ETP) was comparable among groups. The results were confirmed after controlling for age, gender and hormonal. Considering women taking combined oral contraceptives or thrombophilia carriers, no differences were detected in thromboelastometry or thrombin generation parameters between subjects who received ChAdOx1 vs. BNT162b2 vaccines. Conclusions No significant activation of fibrinogen-driven coagulation, plasma thrombin generation or clinically meaningful platelet aggregation after ChAdOx1 or BNT162b2 vaccination was observed.

Portal vein thrombosis (PVT) is a common complication in cirrhosis, and when complete, it increases morbidity and mortality in liver transplant candidates. The aim of the study was to assess the hemostatic status, as well as clinical characteristics of thrombus and patients, as predictors of therapeutic efficacy of anticoagulation for the treatment of PVT in cirrhotics.Patients with cirrhosis consecutively treated for PVT with enoxaparin were enrolled. All patients underwent evaluation of coagulation status and thrombophilia screening. Thrombus characteristics and extension were evaluated at baseline and during follow-up. Anticoagulation was continued until recanalization or up to 12 months. Variables correlated with the response to anticoagulation were used to create a predictive score that was validated in an external multicenter cohort.A total of 65 patients were included and had partial PVT in most cases (72%). Treatment with enoxaparin resulted in an overall response rate of 66% (43/65) after a median time of 4.4 months and 76% (33/43) within the first 6 months. At multivariate analysis, efficacy of anticoagulation correlated with the severity of liver disease, complete verus partial PVT, age of the thrombus, and time interval from treatment start (6 months). The areas under the curve of the statistical model for predicting the response to anticoagulation were 0.84 and 0.76 for the training (n=65) and validation (n=60) cohorts, respectively.Early diagnosis and early treatment are key factors for the successful management of PVT in cirrhosis, so that screening of PVT and prompt start of anticoagulant treatment should be mandatory.

Thrombotic events in congenital hypo-afibrinogenemia have been rarely reported, either in association or not with replacement therapy or thrombotic risk factors. We describe clinical findings and management of thrombosis of abdominal aorta with peripheral embolism in a patient with congenital afibrinogenemia. A review of arterial thrombosis in inherited hypo-afibrinogenemia was also performed. The patient with a severe bleeding history requiring prophylaxis with fibrinogen concentrates (FC) was admitted for ischaemia of the 4th right toe. An angio-CT of abdominal aorta showed a thrombosis from the origin of renal arteries to the carrefour with a distal floating part. No thrombotic risk factors were found; a previous traumatic lesion of aortic wall might have triggered the thrombus formation, whereas the role of FC prophylaxis remains uncertain. The patient was successfully treated with FC, enoxaparin followed by fondaparinux, and low-dose aspirin without bleeding or thrombosis recurrence. After 2 years, aortic thrombus was almost completely recovered. Sixteen hypo/afibrinogenemia patients with arterial thrombosis were found in Literature, showing that thrombosis often occurs at a young age, involves large vessels, its recurrence is not unusual, and therapeutic strategy is not defined yet. Our therapeutic approach was effective and also safe, but further studies are needed to improve the knowledge of pathogenesis and the anti-thrombotic management in this peculiar setting.

SummaryWe investigated a family with prekallikrein deficiency, using both standard coagulation tests and molecular biology techniques. The propositus was found to be a compound heterozygote for a Trp383 stop codon and a Cys529Tyr point mutation. The former mutation was located in exon 11, the latter in exon 14. The propositus inherited the first defect from his father and the second from his mother. Both parents had slightly low prekallikrein levels, but the combination of the two genetic defects produced a phenotype characterized by an extremely low prekallikrein activity and antigen. The propositus’ plasma showed a progressive reduction in APTT when incubated for a long time. Conversely, plasma deficient in factor XII, factor XI or high molecular weight kininogen (HMWK) failed to show shortening of the APTT. No circulating anticoagulant was found because the patient’s APTT was fully corrected by pooled normal and factor XII-, factor XI- or HMWK deficient plasma. No associated abnormality was apparent in the propositus or his parents. As expected, no tendency for bleeding was noted even after tonsillectomy.

SummaryThe role of circulating microparticles (MP) of different origin and tissue factor (TF)-bearing in overweight and obese patients with and without metabolic syndrome is still a matter of debate. In a case-control study, the presence of hypercoagulability was evaluated in overweight and obese patients by measuring MP, thrombin generation (TG) and FVIIa-AT complexes. Twenty overweight patients (body mass index [BMI] range 25–29.9 kg/m2), 20 with I degree (30–34.9 kg/m2), 20 with II degree (35–39.9 kg/m2) and 20 with III degree obesity (≥ 40 kg/m2) were enrolled and compared to 40 age and gender-matched normal weight individuals. A significant increase in median levels of all MP subtypes was observed in the three degrees of obese patients compared to controls. Overweight patients had higher levels of annexin V-MP (AMP), endothelial-derived, leukocyte-derived and TF-bearing MP than controls. Obese patients had a significantly shorter median lag time (p< 0.05), higher median peak thrombin (p< 0.01) and increased median endogenous thrombin potential [ETP] (p< 0.001) compared to controls. Overweight subjects had significantly increased ETP compared to controls (p< 0.05). Both AMP levels and ETP were found to positively correlate with BMI, waist circumference, and inflammatory parameters. No significant increase in FVIIa-AT complex was seen in cases compared to controls. We conclude that obesity is associated with overproduction of procoagulant MP and increase TG. Interestingly, hypercoagulability is found in overweight patients free of metabolic syndrome and increases with the severity of obesity. Assessment of MP and TG may be helpful in the early characterisation of the prothrombotic state in obese patients.

The prevalence of lupus anticoagulant (LA) and antiphospholipid antibodies (APA) in young patients ( 0.5). An inherited coagulation defect was found in seven (7.5%) patients. Our data suggest that the presence of LA or APA is associated with an increased incidence of thrombotic manifestation in young patients. Moreover LA is more frequent in patients with idiopathic DVT. Because the incidence of recurrent thrombotic manifestations in patients with LA or APA is estimated to be ∼50% within 2 years from the first thrombotic episode, the tests should be performed in all patients with juvenile thrombosis.

The effect of pre-eclampsia on coagulation and fibrinolysis in newborns is still under investigation. We have evaluated several coagulation and fibrinolysis parameters in umbilical cord blood of 20 newborns from pre-eclamptic women and of 40 newborns from normotensive women with similar gestational age. Additionally, the presence of factor V Leiden and prothrombin G20210A mutation in cord blood has been assessed. Neonates from pre-eclamptic women exhibited significantly lower birth weight (2.48 +/- 0.92 versus 2.88 +/- 0.68 kg, P < 0.05) and were more frequently admitted to the neonatal intensive care unit (45 versus 20%, P < 0.01) as compared with neonates from normotensive women. Cord blood protein C antigen and activated protein C resistance mean levels were slightly higher in the group of neonates from pre-eclamptic mothers. Fibrinogen levels were lower in this group as compared with control newborns (132.17 +/- 46.97 versus 156.08 +/- 49.58 mg%, P < 0.02), and unrelated to birth weight. No significant differences between cases and controls were found in plasminogen activator inhibitor-1 or tissue plasminogen activator cord blood levels. Heterozygous prothrombin 20210A was found in three newborns from normotensive mothers, whereas no factor V Leiden mutation was found in either group. In conclusion, pre-eclampsia seems to have only mild effects on coagulation and fibrinolytic factors in the cord blood of newborns. Since no excess of common polymorphisms predisposing to thrombosis was found in newborns from pre-eclamptic mothers, it is unlikely that the carriership status of these genetic defects of newborns influences the adverse pregnancy/neonatal outcomes.

Five monkey recipients of a porcine renal xenograft were studied to determine the relationship between fibrin formation in acute humoral xenograft rejection (AHXR) and procoagulant and anticoagulant factor levels to establish whether changes in coagulation parameters could be used to predict AHXR and determine whether AHXR is associated with overt disseminated intravascular coagulopathy (DIC) in this model. Variable degrees of compensated consumptive coagulopathy were observed in each primate. Elevated thrombin-antithrombin (TAT), F1+2 and D-dimer levels consistent with thrombin generation and fibrin formation were recorded. There was no consumption of the main clotting inhibitors (including antithrombin) or a progressive, severe drop in fibrinogen levels and platelet counts, although grafts were left in situ. After transplantation, D-dimer levels remained persistently high, so they were of limited value in defining this coagulopathy. At post mortem, no cases of multiorgan involvement typical of overt DIC were observed. The lack of a rapid postoperative recovery of clotting inhibitor levels after transplantation was invariably associated with early poor outcome. This study shows that AHXR is associated with various degrees of compensated consumptive coagulopathy in our pig-to-primate model. No clear relationship was found between coagulation parameter levels and graft outcome.

A. Zanetto1 , A. Ferrarese1, K. Rodriguez1, M. Fadin2, S. Gavasso2, C. Radu2, P. Zerbinati2, A. Vitale3, U. Cillo3, F. Farinati4, F.P. Russo1, G. Germani1, P. Simioni2, P. Burra1, M. Senzolo1 1 Multivisceral Transplant Unit, Department of Surgical, Oncological and Gastroenterological Sciences, Padua University Hospital, Padua, Italy 2 Department of Cardiologic, Thoracic, and Vascular Sciences, Padua University Hospital, Padua, Italy 3 Hepatobiliary Surgery and Liver Transplantation Unit, Padua University Hospital, Padua, Italy 4 Gastroenterology, Department of Surgical, Oncological and Gastroenterological Sciences, Padua University Hospital, Padua, Italy

s / Digestive and Liver Disease 46S (2014) e129–e135 e133 management mean costs =16,440$ for patient). HCV etiology had a strong impact on post-LT survival (Hazard Ratio =1.59, 95% CI =1.22–2.09, p=0.0007). Using recent data on SOF efficacy and costs in the base-case scenario, 12-week pre-LT SOF therapy showed a median survival benefit of 3.1 QALYs, an ICER of 35,168$/QALY, and a NHB of 0.9 QALYs, whereas the ICER and NHB of a 24-week therapy were 52,527$/QALY and −0.2 QALY respectively. Conclusions: SOF used as pre-transplant therapy in HCV patients proved to be a cost-effective treatment strategy compared with post-LT SOC therapy. Conflict of interest: None declared. Disclosures: S. Fagiuoli acted as either Advisory Board Member or Speaker’s Bureau for: BMS, MSD, Gilead Sciences, Abvie, Roche, Janssen, Novartis, Grifols, Biotest, Kedrion, Bayer. Liver Transplantation NITp Working Group Luciano De Carlis (Surgery and Transplantation, Ospedale Niguarda Ca’ Granda, Milan, Italy), Michele Colledan (Gastroenterology and Transplantation Hepatology, Ospedali Riuniti, Bergamo, Italy), Giorgio Rossi (Liver Transplantation Unit, Fond, IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy), Enzo Andorno (IRCCS San Martino, Genoa, Italy), Andrea Risaliti (Liver Transplant Unit, University of Udine, Udine, Italy), Vincenzo Mazzaferro (Liver Transplantation, IRCCS INT, Milan, Italy), Marco Vivarelli (Liver Transplantation Unit, Ancona Hospital, Ancona, Italy), Umberto Tedeschi (Liver Transplantation Unit, Verona Hospital, Verona, Italy), Davide Bitetto (Gastroenterology and Transplant Hepatology, Ospedale Papa Giovanni XXIII, Bergamo, Italy), Angelo Sangiovanni (Gastroenterology Unit, Maggiore Hospital Policlinico, Milan, Italy), Lucio Caccamo (Liver Transplantation Unit, Fond. IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy), Daniele Neri (University of Padova, Padua, Italy), Giuseppe Piccolo (Fond, IRCCS Ca’ Granda OMP, Milan, Italy), Francesco Paolo Russo (University of Padova, Padua, Italy), Luciano Biti (Liver Transplantation Unit, Verona Hospital, Italy), Paolo Angeli (University of Padova, Padua, Italy), Vittorio Corno (Gastroenterology and Transplantation Hepatology, Ospedali Riuniti, Bergamo, Italy) http://dx.doi.org/10.1016/j.dld.2014.08.012 OC-09 TUMORIGENIC POTENTIAL OF CANCER STEM CELLS (CSCS) ISOLATED FROM HUMAN CHOLANGIOCARCINOMA (CCA) SUBTYPES IN CIRRHOTIC LIVER A. Torrice1 , G. Carpino2, A. Fraveto1, A. Renzi3, M.C. Bragazzi1, F. Giuliante4, A.M. Derose4, V. Cardinale1, R. Gentile1, P. Onori3, C. Napoletano5, A. Franchitto3, A. Cantafora1, G. D’Argenio6, N. Caporaso6, G. Grazi7, E. Gaudio3, D. Alvaro1 1 Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy 2 Health Science, University of Rome “Foro Italico”, Rome, Italy 3 SAIMLAL, Sapienza, University of Rome, Rome, Italy 4 Surgery, Hepatobiliary Unit, Catholic University of the Sacred Heart School of Medicine, Rome, Italy 5 Experimental Medicine, Sapienza University of Rome, Rome, Italy 6 Gastroenterology Unit, Department of Clinical and Experimental Medicine, Federico II University of Naples, Naples, Italy 7 Hepato-Biliary Surgery, Regina Elena National Cancer Institute, Rome, Italy Introduction: Two different forms of CCA has been considered. A pure mucin-secreting form (Mucin-CCA) located either intra or extra-hepatically and a Mixed-CCA form with a peripheral location. We previously identified different subpopulations of CCA CSCs, including epithelial (CD133+, LGR5+, EpCAM+),mesenchymal (CD90+) and quiescent (CD13+) CSCs. Aim: To evaluate the tumorigenic potential of different subpopulation of CSCs isolated from human Mucinand Mixed-CCAs. Methods: CSC subpopulations were immunoselected from human CCA samples (n=18 surgically resected patients) or from primary cultures. The tumorigenic potential of CSC subpopulations was tested either in vitro (spheroid formation), or in xenografts obtained by subcutaneous or intrahepatic injection in normal or cirrhotic (CCL4-induced) livers in SCID mice. In vitro, epithelial CSCs (CD133+, EpCAM+, LGR5+) formed a higher (p 80% (p