Rituximab-induced B cell depletion has been proven to be a useful therapy for autoimmune hemolytic anemia (AIHA). The aim of this retrospective study was to evaluate the effectiveness of rituximab in the treatment of 36 patients with AIHA refractory to several treatments. These patients had received a median of four (1-8) previous treatments, and 13 patients had undergone splenectomy. Rituximab was administered by intravenous infusion at a dose of 375 mg/m2 once weekly for 4 doses in 29 patients, and 7 patients received 1-6 doses. Overall, 28 of 36 patients (77%) achieved response. Twenty-two patients (61%) reached a complete response (CR), and 6 patients (16%) obtained a partial response (PR). All patients that reached CR (61%) were able to maintain the response during more than 6 months with a median follow-up of 14 months (1-86 months). Sixteen patients maintained response (Maintained Response; MR) for more than 1 year. The predictors of MR were achievement of CR and negative Coombs test result. Splenectomized patients showed a better response rate than those non-splenectomized. Rituximab was well tolerated, and only one patient presented a transitory rash during infusion. Rituximab induced clinical responses in multi-treated severe refractory both warm and cold AIHA patients with little toxicity and consequently, this therapy should be considered as an early therapeutic option in this setting.Response to Reviewers: In order to read the response to reviewers see attachment. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 2 AbstractRituximab-induced B cell depletion has been proven to be a useful therapy for autoimmune hemolytic anemia (AIHA). The aim of this retrospective study was to evaluate the effectiveness of rituximab in the treatment of 36 patients with AIHA refractory to several treatments. These patients had received a median of four (1-8) previous treatments, and 13 patients had undergone splenectomy.Rituximab was administered by intravenous infusion at a dose of 375 mg/m 2 once weekly for 4 doses in 29 patients, and 7 patients received 1-6 doses.Overall, 28 of 36 patients (77%) achieved response. Twenty-two patients (61%) reached a complete response (CR), and 6 patients (16%) obtained a partial response (PR). All patients that reached CR (61%) were able to maintain the response during more than 6 months with a median follow-up of 14 months (1-86 months). Sixteen patients maintained response (Maintained Response; MR) for more than 1 year. The predictors of MR were achievement of CR and negative Coombs test result. Splenectomized patients showed a better response rate than those non-splenectomized. Rituximab was well tolerated, and only one patient presented a transitory rash during infusion. Rituximab induced clinical responses in multi-treated severe refractory both warm and cold AIHA pati...

BackgroundVascular complications, such as HAT, are an important cause of graft loss and recipient mortality. We aimed to characterize post-transplant thrombotic events in a cohort of liver transplant recipients, and identify independent risk factors for these complications.MethodsWe conducted a thrombophilic study of 293 orthotopic liver transplants performed in the Digestive Surgery Department of the 12 de Octubre Hospital (Madrid, Spain) between January 2001 and December 2006.ResultsThe most frequent post-transplant thrombotic events were HAT (9%) and PVT (1.7%). The one variable associated with post-transplant thrombotic event was a high fibrinogen level in the global cohort of liver transplantation. But toxicity as event post-OLT has been associated with post-transplant thrombotic event in the retrospective group and high fibrinogen level and low protein C levels were associated post-transplant thrombotic event in the prospective group. Liver disease relapse (HR 6.609, p < 0.001), high levels of FVIII (HR 1.008, p = 0.019)) and low levels of antithrombin (HR 0.946, p < 0.001) were associated with poor overall survival (OS).In conclusion, high fibrinogen and decreased protein C levels were associated with allograft thrombosis. Further studies are required in order to assess the clinical relevance of these parameters in prospective studies and to study the effect of anticoagulation prophylaxis in this group of risk.

BackgroundPortal vein thrombosis is a frequent complication in end-stage cirrhosis with a considerable peri-operative risk for liver transplant candidates. We aimed to characterize the pre-transplant portal vein thrombosis in a cohort of liver transplant recipients, and to identify independent risk factors for this complication.Methods380 consecutive primary orthotopic liver transplants were performed in the Digestive Surgery Department of “12 de Octubre” Hospital (Madrid, Spain), between January 2001 and December 2006. The main risk factors considered were smoking, obesity, metabolic disorders, previous immobility, surgery or trauma, nephrotic syndrome, associated tumor, inflammatory disease, neoplasm myeloprolipherative. Furthermore we have reported genetic thrombophilia results for 271 recipients.ResultsSixty-two (16.3%) patients developed pre-transplant portal vein thrombosis and its presence had no impact in the overall survival of liver recipients. Obesity was the only independent risk factor for pre-transplant portal vein thrombosis.ConclusionWe recommend close control of cardiovascular factors in patients with liver cirrhosis in order to avoid associated thrombosis.

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Background: The prothrombin G20210A (FII G20210A) and Factor V (FV) Leiden polymorphisms are the most common hereditary risk factors for venous thromboembolism. Little is known about the role of the thombophilic factors on the risk of thromboembolic events (TE) in recipients of orthotopic liver transplantation (OLT). This study aims to evaluate the influence of the recipients’ genetic mutations (FII G20210A, FV Leiden and methilene tetrahydrofolate reductase (MTHFR) C677T homozygosity) on the incidence of TE before OLT; and those acquired with the grafted liver (FII G20210A, FV Leiden-resistance to activated protein C, MTHFR C677T homozygosity and other trombophilic factors) on the risk of TE after the OLT. Patients and Methods: Between January 2001 and July 2006, 378 OLT, including 23 retransplantations, were performed in our institution. Clinical data were available on 341 patients. In 255 recipients, genetic and functional tests were performed after OLT and included FII G20210A, FV Leiden and MTHFR C677T, PT, APTT, fibrinogen, antithrombin, protein C, protein S, resistance to activated protein C, FVIII activity, anticoagulant lupus study, anticardiolipin antibodies and homocystein. Samples for FII G20210A, FV Leiden and MTHFR C677T were obtained for 155 donor grafts (112 deceased and 39 live donors). The genetic mutations were detected by real-time PCR technology. Results: From 341 patients with clinical data available, 42 suffered TE before OLT and 30 patients after OLT. Among the 255 recipients whom genetic studies were performed, 10 carriers of FV Leiden (2.7%), 16 carriers of FII G2010A09 ((3.9%) and 31 homozygous MTHFR C677T (12.2 %) were found. The incidence of TE before transplantation was similar for carriers and noncarriers of the genetic trombophilic alterations (FV Leiden: 1.5% vs 2.1%; FII G20210A: 0% vs 4.9%; MTHFR C677T: 13% vs 11%). Among the donors we found 1 carrier of FV Leiden (0.6%), 4 carriers of FII G20210A (2.2%), and 24 homozygous MTHFR C677T (9.4%). We did not find significant differences in the incidence of TE after OLT in recipients of a grafted liver with or without genetic thrombophilic alterations (FV Leiden: 0% vs 0.8%; FII G20210A: 0% vs 2.5%; MTHFR C677T: 7.7% vs 7.5%). A correlation between high FVIII levels and post OLT thrombosis was found (p: 0.007). Other phenotypic studies after transplantation were similar on patients with and without thrombosis. Conclusion: The incidence of TE before transplantation is similar for carriers and noncarriers of FII G20210A, FV Leiden and homozygous MTHFR C677T. The presence of FII G20210A, FV Leiden and homozygous MTHFR C677T on the donors did not increased the risk of TE after OLT. This study adds information about an unclear aspect of thrombophilia in OLT. Further studies are required to clarify the reasons for the association of high levels of FVIII with vascular thrombosis after OLT. This study was funded by FMM 2004/009.