Impact of Continuous Estroprogestin Treatment on Circulating Microparticle Levels in Deep Endometriosis Patients.

There has been increasing interest in the study of new pathogenic mechanisms in endometriosis (END), including the coagulation/fibrinolysis system and its link with inflammation and tissue remodeling. It has been suggested that END patients, especially with deep-infiltrating (DE) forms, could present a hypercoagulable state revealing higher levels of proinflammatory and procoagulant markers, such as total circulating microparticles (cMPs) and cMP-TF (tissue factor), released by cells in response to damage, activation, or apoptosis. However, no previous study has assessed the effect of END hormonal treatments on cMP and cMP-TF levels. Therefore, the aim of this study was to evaluate the impact of these treatments on cMP and cMP-TF levels in DE patients. Three groups were compared: DE patients receiving a continuous combined oral contraceptive regimen (CCOCR) (n = 41), DE patients without CCOCR (n = 45), and a control group (n = 43). cMP and cMP-TF levels were evaluated in platelet-free plasma. A significant decrease in the total cMP levels was found in the DE group with CCOCR versus the group without CCOCR, reflecting a higher chronic inflammatory status in DE patients that decreased with the treatment. cMP-TF levels were higher in DE patients receiving CCOCR versus those not receiving CCOCR, suggesting that treatments containing estrogens play a predominant role in suppressing the inhibitory pathway of TF.

The Spanish Scientific Societies before the ESC 2021 guidelines on vascular disease prevention: Generalizing the measurement of albuminuria to identify vascular risk and prevent vascular disease.

The 2021 guidelines on the prevention of vascular disease (VD) in clinical practice published by the European Society of Cardiology (ESC) and supported by 13 other European scientific societies recognize the key role of screening for chronic kidney disease (CKD) in the prevention of VD. Vascular risk in CKD is categorized based on measurements of estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (ACR). Thus, moderate CKD is associated with a high vascular risk and severe CKD with a very high vascular risk requiring therapeutic action, and there is no need to apply other vascular risk scores when vascular risk is already very high due to CKD. Moreover, the ESC indicates that vascular risk assessment and the subsequent decision algorithm should start with measurement of eGFR and ACR. To optimize the implementation of the ESC 2021 guidelines on the prevention of CVD in Spain, we consider that: 1) Urine testing for albuminuria using ACR should be part of the clinical routine at the same level as blood glucose, cholesterolemia, and GFR estimation when these are used to make decisions on CVD risk. 2) Spanish public and private health services should have the necessary means and resources to optimally implement the ESC 2021 guidelines for the prevention of CVD in Spain, including ACR testing.

Predictive value of the adjusted Global Anti-Phospholipid Syndrome Score on clinical recurrence in APS patients: a longitudinal study.

OBJECTIVE: To assess the effect of the average adjusted global APS score (aGAPSS) over time on recurrence of clinical manifestations in APS patients through a retrospective longitudinal study. MATERIAL AND METHODS: The study included 200 patients with APS. The aGAPSS was calculated for each patient at baseline and on a yearly basis for either up to 6 years (minimum 3 years) or just before the clinical event in patients who experienced clinical recurrence. The mean score per patient was computed. In patients under vitamin K antagonists (VKA) the percentage of time spent within the therapeutic range (TTR) was calculated. Cox regression analysis was performed to determine the cut-off value of the aGAPSS with the strongest association with clinical recurrence. RESULTS: Higher average aGAPSS values were found in patients who experienced clinical recurrence in comparison to patients who did not [8.81 (95% CI 7.53, 10.08) vs 6.38 (95% CI 5.64, 7.12), P = 0.001], patients with thrombotic recurrence compared with patients with obstetric recurrence [9.48 (95% CI 8.14, 10.82) vs 4.25 (95% CI 0.85, 7.65), P = 0.006] and patients with arterial thrombosis compared with patients with venous thrombosis [10.66 (S.D. 5.48) vs 6.63 (S.D. 4.42), P = 0.01]. aGAPSS values >13 points were associated with the highest risk of recurrence in multivariate analysis [HR = 3.25 (95% CI 1.93, 5.45), P < 0.0001]. TTR was not statistically different between patients who had thrombosis recurrence and patients who had not. CONCLUSIONS: Our data support the role of periodic (annual) monitoring of the aGAPSS score in predicting clinical recurrence in patients with APS.

Persistence of antiphospholipid antibodies over time and its association with recurrence of clinical manifestations: A longitudinal study from a single centre.

PURPOSE: To analyze the antiphospholipid antibody (aPL) persistence over time in patients with antiphospholipid syndrome (APS) and its association with clinical recurrence and to identify predictors of aPL persistence over time. PATIENTS AND METHODS: 200 patients with a diagnosis of APS and at least three follow-up aPL determinations were included. Persistent aPL profile was defined as the presence of lupus anticoagulant (LAC) and/or IgG/IgM anticardiolipin (aCL) and/or IgG/IgM anti-ß2 glycoprotein-I (aß2GPI) (> 99th percentile) antibodies in at least 66% of follow-up measurements. Multilevel mixed-effect generalized linear models with logit link were used. RESULTS: 112 (56%) patients maintained persistent aPL profiles over time, while 88 (44%) were transient. Median follow-up time was 172.5 months. Follow-up time did not affect the odds of aPL persistence in multivariate analysis (p = 1.00). Baseline triple aPL positivity [OR 78 (95%CI 16.9-359.7, p < 0.001)] and double aPL positivity [OR = 7.6 (95%CI 3.7-15.7, p < 0.001)] correlated with persistent aPLs over time, while isolated LAC [OR = 0.26 (95% CI 0.08-0.49, p = 0.002)] or isolated IgG/IgM aCL [OR = 0.20 (95% CI 0.11-0.59, p = 0.004)] positivity, were predictors of transient aPL profile. Patients with persistent aPLs had higher rate of clinical recurrence in comparison to patients with transient aPLs [OR = 2.48 (95%CI 1.34-4.58, p = 0.003)]. CONCLUSIONS: More than half of patients with baseline medium-high titer aPL positivity had persistent positive aPLs over time. Patients with persistent aPLs were more prone to present recurrence of clinical manifestations. Multiple aPL positivity increased the odds of a persistent aPL profile over time, while isolated LAC and aCL positivity decreased it.

Is antivitamin K reversal required in patients with cirrhosis undergoing liver transplantation?

BACKGROUND: Antivitamin K agent (AVK) reversal in patients with cirrhosis awaiting liver transplantation (LT) is not defined in guidelines. We investigated the effect of reversion with prothrombin complex concentrate (PCC) on intraoperative transfusion, bleeding, and safety in LT patients on AVK. STUDY DESIGN AND METHODS: In 511 patients undergoing LT, we identified 25 patients treated with AVK (AVK group) and 13 patients with incidental portal vein thrombosis (PVT) without AVK (incidental PVT group). Fifty patients who underwent LT without PVT or AVK matched by age, model for end stage of liver disease (MELD), body mass index (BMI), and cirrhosis etiology were selected as the control group. RESULTS: There were no significant differences between the three groups in intraoperative blood loss, transfusion, and postoperative bleeding. In the AVK group, there were no differences between patients who received PCC and those who did not in intraoperative blood loss, red blood cells, fibrinogen, and platelet transfusion, or postoperative bleeding. PCC use had no effect on RBC transfusion in patients who had international normalized ratio or clotting time above versus below median values of the two parameters at baseline (2.3 and 103 s, respectively). No thrombotic events were detected in patients who received PCC. DISCUSSION: These data suggest that systematic administration of PCC to revert AVK prior to LT should be reconsidered.

Procoagulant microparticles are associated with arterial disease in patients with systemic lupus erythematosus.

Microparticles (MPs) have been associated with inflammatory and thrombotic disease. High levels of MPs have been identified in patients with systemic lupus erythematosus (SLE) and associated with cardiovascular disease. We analyzed the procoagulant activity of MPs and its correlation with arteriosclerosis and arterial thrombosis in SLE patients. Eighty-seven patients with SLE were included: 22 (25.3%) with associated antiphospholipid syndrome (APS), 32 (36.8%) without antiphospholipid antibodies (aPL) and 33 (37.9%) with aPL but without APS. Subclinical arteriosclerosis, defined as the presence and number of plaques, was evaluated by ultrasonography of carotid arteries. Thrombotic events were confirmed by objective methods. The procoagulant activity of MPs was determined by a functional assay with annexin V. Subclinical arteriosclerosis was found in 19 (21.8%) patients. Thirteen episodes of arterial thrombosis and eight of venous thrombosis were recorded. The procoagulant activity of MPs was greater in patients with arterial thrombosis (17.28 ± 8.29 nM vs 12.96 ± 7.90 nM, p < 0.05). In patients without arterial thrombosis, greater procoagulant activity of MPs was identified in patients with multiple (≥ 2) carotid plaques (17.26 ± 10.63 nM vs 12.78 ± 7.15 nM, p = 0.04). In the multivariate analysis, the procoagulant activity of MPs was independently associated with multiple (≥ 2) carotid plaques and arterial thrombosis [OR = 1.094 (95%CI 1.010-1.185), p = 0.027 and OR = 1.101 (95%CI 1.025-1.182), p = 0.008; respectively]. In conclusion, the procoagulant activity of MPs is associated with arteriosclerosis burden and arterial thrombosis in patients with SLE.

Long-term follow-up of antiphospholipid syndrome: real-life experience from a single center.

OBJECTIVE: The objective of this paper is to assess the prevalence of the main clinical manifestations and laboratory features at disease onset and during the ensuing 10 years of a large cohort of patients with antiphospholipid syndrome (APS) from a single center. METHODS: The study included all consecutive APS patients followed longitudinally in our center from 2003 to 2013. Descriptive statistics for demographics, clinical and laboratory features and mortality were performed. RESULTS: A total of 160 patients were included. Most of them, 128 (78.8%), were women and the mean (SD) age at diagnosis was 39.1 (14.0) years. The majority of them, 104 (65.0%), had primary APS, 36 (22.5%) had APS associated with systemic lupus erythematous, and 20 (12.5%) had APS associated with other autoimmune disease. During the study period, thrombotic events occurred in 27 (16.9%) patients, the most common being strokes, nonbacterial thrombotic endocarditis and deep venous thrombosis. Regarding obstetric morbidity, 18 women (14.3%) became pregnant and 90% of pregnancies succeeded in having live births. The most common obstetric complication was early pregnancy loss (15% of pregnancies). Prematurity (11.1% of live births) and intrauterine growth restriction (5.6% of live births) were the most frequent fetal morbidities. Ten (6.3%) patients died and the most frequent causes of death were severe thrombosis, hemorrhage, and cancer. Three (0.9%) cases of catastrophic APS occurred. The survival probability at 10 years was 93.8%. CONCLUSIONS: Patients with APS develop significant morbidity and mortality despite current treatment. It is imperative to identify prognostic factors and therapeutic measures to prevent these complications.

Study of the analytical performance at different concentrations of hematological parameters using Spanish EQAS data.

Background External quality assessment programs are one of the currently available tools to evaluate the analytical performance of clinical laboratories, where the measurement error (ME) obtained can be compared with quality specifications to evaluate possible deviations. The objective of this work was to analyze the ME behavior over the analytical range to assess the need to establish concentration-dependent specifications. Methods A total of 389,000 results from 585 laboratories and 2628 analyzers were collected from the Spanish external quality assessment schemes (EQAS) in hematology during the years 2015-2016. The parameters evaluated included white blood cells, red blood cells, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelets, prothrombin time, activated partial thromboplastin time, neutrophils, lymphocytes, monocytes, eosinophils, basophils, reticulocytes, hemoglobin A2, antithrombin, factor VIII, protein C and von Willebrand factor. The 90th percentile of ME was calculated for every concentration evaluated of each parameter. Results We found a significant variation in the analytical performance of leukocytes, platelets, neutrophils, lymphocytes, monocytes, eosinophils, basophils, prothrombin time, reticulocytes, hemoglobin A2, antithrombin and protein C. Furthermore, this ME variation may not allow complying with the same biological variability requirements within the whole analytical range studied. Conclusions Our work shows the importance of implementing concentration-dependent specifications which can help laboratories to use proper criteria for quality specifications selection and for a better external quality control results evaluation.

Host-Derived Molecules as Novel Chagas Disease Biomarkers: Hypercoagulability Markers in Plasma.

The most severe clinical symptomatology of Chagas disease affects ~30% of those chronically infected with the Trypanosoma cruzi parasite. The pathogenic mechanisms that lead to life-threatening heart and gut tissue disruptions occur "silently" for a longtime in a majority of cases. As a result, despite there are several serological and molecular methods available to diagnose the infection in its acute and chronic stages, diagnosis is often achieved only after the onset of clinical symptoms in the chronic phase of the disease. Furthermore, although there are two drugs to treat it, the assessment of their performance is impractical with current parasite-derived diagnostics, and therapeutic efficacy cannot be acknowledged in a timely manner.In this chapter we present two procedures to measure host-derived molecules as surrogates of therapeutic response against chronic T. cruzi infection. Their outputs relate to the generation and activity of thrombin, a major component of the blood coagulation cascade. This is due to the fact that a hypercoagulability state has been described to occur in chronic Chagas disease patients and revert after treatment with benznidazole.

Circulating Neutrophil Extracellular Traps Are Elevated in Patients With Deep Infiltrating Endometriosis.

Neutrophil extracellular traps (NETs) have been described to be related to the pathogenesis of inflammatory and autoimmune conditions. Endometriosis is currently considered a chronic inflammatory condition. Therefore, we performed a preliminary case-control study to compare the circulating plasma NET levels in patients with surgically confirmed endometriosis (E group, n = 82) and those of patients without surgical findings of endometriosis (C group, n = 35). Venous blood samples were obtained at the time of surgery. Circulating plasma NET levels were assessed as histone-DNA complexes (ie, nucleosomes) by a quantitative sandwich enzyme-linked immunosorbent assay. The results were expressed in arbitrary units. Circulating plasma NET levels were significantly higher in the E group compared with the C group (median [25th; 75th percentiles]): E group: 0.734 [0.484; 1.363]; C group: 0.541 [0.411; 0.653]; P = .005). The subanalysis of E group patients with deep infiltrating endometriosis (DIE group) or without DIE (non-DIE group) showed that plasma NET levels were higher in the DIE group ( P = .02). No differences were observed in NET levels among patients with and without severe pelvic pain or in patients with and without infertility, regardless of the presence of endometriotic lesions. Therefore, our study shows significantly higher NET levels in patients with endometriosis, which seem to be attributed to increased levels in the subgroup of patients with DIE, suggesting that the presence of elevated circulating plasma NET levels may reflect an inflammatory status in this gynecological condition. Further research is warranted to confirm our findings and to assess the exact role of NETs in the pathophysiological mechanisms of endometriosis.

Recomendaciones del Grupo Catalán de Trombosis (Tromboc@t Working Group) para el tratamiento de los pacientes que reciben anticoagulantes orales directos / Tromboc@t Working Group recommendations for management in patients receiving direct oral anticoagulants

Antecedentes y objetivos: En los últimos años los anticoagulantes orales directos (ACOD) se han convertido en una alternativa a los antagonistas de la vitamina K (AVK) para la prevención del ictus y embolia sistémica en pacientes con fibrilación auricular no valvular (FANV), así como para la prevención y tratamiento de la trombosis venosa profunda. Los ensayos clínicos han demostrado la no inferioridad y la potencial superioridad en comparación con la warfarina, lo cual permite ampliar las opciones de anticoagulación. En nuestro medio, las Unidades de Tratamiento Anticoagulante (UTA) y los Centros de Atención Primaria (CAP) son los encargados de la educación, seguimiento, control de adherencia y del manejo en situaciones especiales de los pacientes anticoagulados. Estas consideraciones han motivado la preparación del presente documento de consenso, que tiene como objetivo establecer recomendaciones que incorporen los hallazgos de la investigación científica a la práctica clínica para mejorar la calidad asistencial en el ámbito de la anticoagulación. Material y métodos: Un grupo de expertos del Grupo Catalán de Trombosis (TROMBOC@T) ha revisado la bibliografía publicada entre 2007 y 2016 para poder establecer recomendaciones basadas en la evidencia clínica. Resultados: Como resultado del proyecto se han establecido un conjunto de recomendaciones de carácter práctico que facilitarán el tratamiento, educación, seguimiento y manejo en situaciones especiales de los pacientes anticoagulados con ACOD. Conclusiones: El aumento progresivo del uso de los ACOD requiere establecer y homogeneizar las directrices de actuación clínica en el paciente anticoagulado con estos antitrombóticos tanto en las UTA como en los CAP

Background and objectives: In recent years, direct oral anticoagulants (DOACs) have become an alternative to vitamin K antagonists (VKA) for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) as well as for prevention and treatment of deep venous thrombosis. Pivotal trials have demonstrated non-inferiority and potential superiority compared to warfarin, which increases the options of anticoagulant treatment. In our setting, the Anticoagulant Treatment Units (ATUs) and Primary Care Centres (PCCs) play an important role in the education, follow-up, adherence control and management in special situations of anticoagulated patients. These considerations have motivated us to elaborate the present consensus document that aims to establish clear recommendations that incorporate the findings of scientific research into clinical practice to improve the quality of care in the field of anticoagulation. Material and methods: A group of experts from the Catalan Thrombosis Group (TROMBOC@T) reviewed all published literature from 2009 to 2016, in order to provide recommendations based on clinical evidence. Results: As a result of the project, a set of practical recommendations have been established that will facilitate treatment, education, follow-up and management in special situations of anticoagulated patients with ACODs. Conclusions: Progressive increase in the use of DOACs calls for measures to establish and homogenise clinical management guidelines for patients anticoagulated with DOACs in ATUs and PCCs

The H1 haplotype of the endothelial protein C receptor protects against arterial thrombosis in patients with antiphospholipid syndrome.

INTRODUCTION: Genetic variants in the endothelial protein C receptor gene (PROCR) may contribute to the thrombosis risk by regulating levels of the soluble form of this protein (sEPCR). We evaluated whether PROCR polymorphisms and sEPCR levels play a role in the thrombotic manifestations of antiphospholipid syndrome. MATERIALS AND METHODS: One hundred and seventy-five patients (62 with primary antiphospholipid syndrome, 30 with antiphospholipid syndrome associated with systemic lupus erythematosus, 40 with systemic lupus erythematosus without antiphospholipid antibodies and 43 with systemic lupus erythematosus and antiphospholipid antibodies) and 66 healthy controls were included. PROCR H1 and H3 haplotypes were determined by genotyping 7014G/C and 1651C/G tag-polymorphisms, respectively. sEPCR levels were determined by enzyme-linked immunosorbent assay. RESULTS: PROCR haplotype distribution was similar among groups of patients and controls. PROCR H1 and H3 haplotypes were less prevalent in antiphospholipid syndrome patients with arterial thrombosis than those without arterial thrombosis, but statistical significance was only reached for the H1 haplotype (58.0% vs. 85.7%, p = 0.003; odds ratio: 0.23 [95% CI 0.08-0.65]). No relationship between the PROCR H1 and H3 haplotypes and venous thrombosis was found. sEPCR levels were higher in H3 than in H1 carriers (175.5 [95% CI 60.9-290.1] ng/ml vs. 69.1 [95% CI 61.5-76.9] ng/ml, p < 0.01). No relationship of sEPCR with arterial or venous thrombosis was found. CONCLUSION: The PROCR H1 haplotype was less frequently found in APS patients with arterial thrombosis, suggesting a protective effect of PROCR H1 against arterial thrombosis in these patients. No relationship between sEPCR and thrombosis was found.

Enzyme-linked immunosorbent assays for therapeutic drug monitoring coumarin oral anticoagulants in plasma.

The development of high-throughput immunochemical assays to assist on precision medicine for patients treated with coumarin oral anticoagulants (OA) is reported. The assays are able to quantitate Warfarin (W) and/or Acenocoumarol (ACL) directly in plasma samples without any previous sample pretreatment. The detectabilities (W, 3.52 ±â€¯2.25 nM and ACL, 1.56 ±â€¯0.64 nM) and the working ranges achieved (W, 1.19 ±â€¯0.73 to 12.05 ±â€¯2.99 nM and ACL 0.63 ±â€¯0.20 to 10.19 ±â€¯6.69 nM) are within the therapeutic levels usually found in patients treated with these drugs. The assays are specific with only cross-recognition of 4'-NH2-ACL on the ACL ELISA, which is one of the main metabolites of this drug. Moreover, accuracy studies performed with blind spiked samples show very good correlation between the spiked and the measured concentrations. Finally, a small clinical pilot study has been performed analyzing 96 plasma samples from treated and untreated patients, showing that the assay is able to quantitate ACL. The results obtained allow envisaging the possibility to use these assays for pharmacokinetic studies, dosage assessment or therapeutic drug monitoring.

Tromboc@t Working Group recommendations for management in patients receiving direct oral anticoagulants. / Recomendaciones del Grupo Catalán de Trombosis (Tromboc@t Working Group) para el tratamiento de los pacientes que reciben anticoagulantes orales directos.

BACKGROUND AND OBJECTIVES: In recent years, direct oral anticoagulants (DOACs) have become an alternative to vitamin K antagonists (VKA) for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) as well as for prevention and treatment of deep venous thrombosis. Pivotal trials have demonstrated non-inferiority and potential superiority compared to warfarin, which increases the options of anticoagulant treatment. In our setting, the Anticoagulant Treatment Units (ATUs) and Primary Care Centres (PCCs) play an important role in the education, follow-up, adherence control and management in special situations of anticoagulated patients. These considerations have motivated us to elaborate the present consensus document that aims to establish clear recommendations that incorporate the findings of scientific research into clinical practice to improve the quality of care in the field of anticoagulation. MATERIAL AND METHODS: A group of experts from the Catalan Thrombosis Group (TROMBOC@T) reviewed all published literature from 2009 to 2016, in order to provide recommendations based on clinical evidence. RESULTS: As a result of the project, a set of practical recommendations have been established that will facilitate treatment, education, follow-up and management in special situations of anticoagulated patients with ACODs. CONCLUSIONS: Progressive increase in the use of DOACs calls for measures to establish and homogenise clinical management guidelines for patients anticoagulated with DOACs in ATUs and PCCs.

Lack of grading agreement among international hemostasis external quality assessment programs.

: Laboratory quality programs rely on internal quality control and external quality assessment (EQA). EQA programs provide unknown specimens for the laboratory to test. The laboratory's result is compared with other (peer) laboratories performing the same test. EQA programs assign target values using a variety of methods statistical tools and performance assessment of 'pass' or 'fail' is made. EQA provider members of the international organization, external quality assurance in thrombosis and hemostasis, took part in a study to compare outcome of performance analysis using the same data set of laboratory results. Eleven EQA organizations using eight different analytical approaches participated. Data for a normal and prolonged activated partial thromboplastin time (aPTT) and a normal and reduced factor VIII (FVIII) from 218 laboratories were sent to the EQA providers who analyzed the data set using their method of evaluation for aPTT and FVIII, determining the performance for each laboratory record in the data set. Providers also summarized their statistical approach to assignment of target values and laboratory performance. Each laboratory record in the data set was graded pass/fail by all EQA providers for each of the four analytes. There was a lack of agreement of pass/fail grading among EQA programs. Discordance in the grading was 17.9 and 11% of normal and prolonged aPTT results, respectively, and 20.2 and 17.4% of normal and reduced FVIII results, respectively. All EQA programs in this study employed statistical methods compliant with the International Standardization Organization (ISO), ISO 13528, yet the evaluation of laboratory results for all four analytes showed remarkable grading discordance.

Time to change the classical vision of coagulation in liver disease: from the balance disequilibrium to systems biology network modeling.

The longstanding dogma that patients with liver disease have a hemostasis related bleeding tendency is neglected from the last 10 years however, despite this tremendous change of paradigm no longer progress had been made in this field. A mathematical model is a description of a system using mathematical concepts and language. Mathematical models are able to analyze large amount of data and they can make predictions about behavior. Mathematical models are used in the social sciences, engineering as well as in medicine. Blood coagulation in patients with liver disease is difficult to predict due to its network complexity and moreover, due to all factors that potentially can impact hemostasis in this patient population outside of the coagulation itself, as portal hypertension, endothelial dysfunction and renal injury, between others. Although ambitious and extremely complex, the aforementioned approach requires a substantial investment of multidisciplinary human and technologic resources, this holistic overview is the closest to the real situation. The ability of the mathematical modeling to predict bleeding and thrombotic complications in patients with liver disease deserves to be investigated.

Venous Thrombotic Events After Liver Transplantation.

Thromboprophylaxis is not well defined after liver transplantation (LT). The aim of this study was to evaluate the incidence of splanchnic vein thrombosis (SVT) and nonsplanchnic vein thrombosis (NSVT) after LT. Liver transplantations performed between 2009 and 2013 in our institution were reviewed. Demographic, intraoperative, and postoperative data were recorded. Low-molecular-weight heparin was only administered postoperatively if intraoperative thrombectomy was performed or in patients preoperatively anticoagulated. Of a total of 328 patients, 72% were male with a median age of 56 years, score of model for end-stage liver disease 18 (11-23), and 88% had liver cirrhosis. The incidence of postoperative venous thrombotic events was 4.6%: 8 (2.4%) patients had SVT and 7 (2.1%) patients had NSVT. After logistic regression analysis, intraoperative thrombectomy and Child A classification emerged as risk factors for SVT (odds ratio [OR]: 77, 95% confidence interval [95% CI]: 14-421) and NSVT (OR: 20, 95% CI: 3-170), respectively. The incidence of SVT in patients who undergo intraoperative thrombectomy was 33%, whereas the incidence of NSVT in patients grouped as Child A was 7.5%. Our results suggest that thromboprophylaxis should be considered after LT in patients with cirrhosis grouped as Child A and in patients who undergo intraoperative thrombectomy.

The anticoagulant rivaroxaban lowers portal hypertension in cirrhotic rats mainly by deactivating hepatic stellate cells.

In cirrhosis, increased intrahepatic vascular resistance (IHVR) is the primary factor for portal hypertension (PH) development. Hepatic stellate cells (HSCs) play a major role increasing IHVR because, when activated, they are contractile and promote fibrogenesis. Protease-activated receptors (PARs) can activate HSCs through thrombin and factor Xa, which are known PAR agonists, and cause microthrombosis in liver microcirculation. This study investigates the effects of the oral anticoagulant, rivaroxaban (RVXB), a direct antifactor Xa, on HSC phenotype, liver fibrosis (LF), liver microthrombosis, and PH in cirrhotic rats. Hepatic and systemic hemodynamic, nitric oxide (NO) bioavailability, LF, HSC activation, and microthrombosis were evaluated in CCl4 and thioacetamide-cirrhotic rats treated with RVXB (20 mg/kg/day) or its vehicle for 2 weeks. RVXB significantly decreased portal pressure (PP) in both models of cirrhosis without changes in portal blood flow, suggesting a reduction in IHVR. RVXB reduced oxidative stress, improved NO bioavailability, and ameliorated endothelial dysfunction. Rivaroxaban deactivated HSC, with decreased alpha-smooth muscle actin and mRNA expression of other HSC activation markers. Despite this marked improvement in HSC phenotype, no significant changes in LF were identified. RVXB markedly reduced fibrin deposition, suggesting reduced intrahepatic microthrombosis. CONCLUSION: RVXB decreases PP in two rat models of cirrhosis. This effect is mostly associated with decreased IHVR, enhanced NO bioavailability, HSC deactivation, and reduced intrahepatic microthrombosis. Our findings suggest that RVXB deserves further evaluation as a potential treatment for cirrhotic PH. (Hepatology 2017;65:2031-2044).