Endothelial dysfunction is a major determinant of the increased hepatic vascular tone of cirrhotic livers. Von Willebrand factor (vWF), P-selectin and 8-iso-PGF2α (isoprostanes), surrogate markers of ...endothelial dysfunction, are increased in patients with cirrhosis. This study was aimed at exploring in patients with cirrhosis and portal hypertension the relation of these endothelial factors with systemic and hepatic haemodynamics and their possible clinical prognostic value.
42 consecutive patients with cirrhosis and portal hypertension had measurement of the hepatic venous pressure gradient (HVPG), cardiopulmonary pressures and vWF, P-selectin and isoprostane levels in blood samples from hepatic and peripheral veins. Patients were followed up to 2 years, death or liver transplantation and any clinical event were recorded.
vWF, P-selectin and isoprostanes were increased in patients with cirrhosis compared with controls (p<0.001). vWF levels significantly correlated with HVPG, Child-Pugh score and MELD. Cox model analysis disclosed an independent indirect association of peripheral vWF with survival free of portal hypertension-related events and of transplantation. The vWF cut-off value of 216 U/dl (Youden index) disclosed two different populations of patients with cirrhosis with a highly different probability of survival free of portal hypertension-related events and transplantation (87% vs 22%, p=0.001). The prognostic role of vWF persisted after adjusting for parameters of liver dysfunction and for HVPG.
In patients with cirrhosis and portal hypertension vWF levels correlate with liver function and HVPG and independently predict clinical outcome.
Backgroud
COVID-19 coagulopathy linked to increased D-dimer levels has been associated with high mortality (Fei Z et al. in Clinical course and risk factors for mortality of adult inpatients with ...COVID-19 in Wuhan, China: a retrospective cohort study. Lancet (London, England) 395(10229):1054–62, 2020). While D-dimer is accepted as a disseminated intravascular coagulation marker, rotational thromboelastometry (ROTEM) also detects fibrinolysis (Wright FL et al. in Fibrinolysis shutdown correlates to thromboembolic events in severe COVID-19 infection. J Am Coll Surg (2020). Available from
https://pubmed.ncbi.nlm.nih.gov/32422349/
cited 14 Jun 2020; Schmitt FCF et al. in Acute fibrinolysis shutdown occurs early in septic shock and is associated with increased morbidity and mortality: results of an observational pilot study. Ann Intensive Care 9(1):19, 2019). We describe the ROTEM profile in severely ill COVID-19 patients and compare it with the standard laboratory coagulation test.
Methods
Adult patients diagnosed with COVID-19 admitted to the ICU were prospectively enrolled after Ethics Committee approval (HCB/2020/0371). All patients received venous thromboembolism prophylaxis; those on therapeutic anticoagulation were excluded. The standard laboratory coagulation test and ROTEM were performed simultaneously at 24–48 h after ICU admission. Sequential organ failure assessment (SOFA), disseminated intravascular coagulation (DIC) and sepsis-induced coagulopathy (SIC) scores were calculated at sample collection.
Results
Nineteen patients were included with median SOFA-score of 4 (2–6), DIC-score of 1 (0–3) and SIC-score of 1.8 (0.9). Median fibrinogen, D-dimer levels and platelet count were 6.2 (4.8–7.6 g/L), 1000 (600–4200 ng/ml) and 236 (136–364 10
9
/L), respectively. Clot firmness was above the normal range in the EXTEM and FIBTEM tests while clot lysis was decreased. There was no significant correlation between ROTEM or D-dimer parameters and the SOFA score.
Conclusion
In COVID-19 patients, the ROTEM pattern was characterized by a hypercoagulable state with decreased fibrinolytic capacity despite a paradoxical increase in D-dimer levels. We suggest that, in COVID-19 patients, the lungs could be the main source of D-dimer, while a systemic hypofibrinolytic state coexists. This hypothesis should be confirmed by future studies.
Several studies have reported a high prevalence of autoimmune diseases such as systemic lupus erythematosus (SLE) in endometriosis patients. The aim of this study was to evaluate the SLE autoimmune ...antibody profile in patients with deep (DE) and non-deep endometriosis (Non-DE).
Four groups of premenopausal patients were evaluated: patients with DE (n = 50); patients with ovarian endometriomas (Non-DE; n = 50); healthy patients without endometriosis (C group; n = 45); and SLE patients without endometriosis (SLE group; N = 46). Blood samples were obtained and the standard SLE autoimmune profile was evaluated in all patients. Pain symptoms related to endometriosis and clinical SLE manifestations were also recorded.
The DE group presented a statistically significant higher proportion of patients with antinuclear antibodies (ANA) (20%) compared to the Non-DE group (4%) and C group (2.2%). Levels of complement were more frequently lower among DE and Non-DE patients although differences did not reach statistical significance. Similarly, anti-dsDNA antibodies and anticoagulant lupus were positive in more patients of the DE group but did not reach statistical significance. The DE group complained of more arthralgia and asthenia compared to the Non-DE and C groups.
The results of this study showed higher positivity of ANA and greater arthralgia and asthenia in patients with DE compared with Non-DE patients and healthy controls, suggesting that they may have a higher susceptibility to autoimmune diseases and present more generalized pain.
•There is an increased risk of comorbidity of autoimmune diseases in endometriosis.•Deep endometriosis patients had more positive antinuclear antibody results.•There were more systemic symptoms in the deep endometriosis group.
The clinical significance of incidental venous thrombosis (IVT) is uncertain. The objective of this study was to compare the clinical characteristics and the outcome of cancer patients with IVT with ...those of patients with symptomatic venous thrombosis (SVT).
Prospective observational study enrolling consecutive cancer patients newly diagnosed with venous thromboembolism (May 2006–April 2009). Diagnosis of IVT was based on vascular filling defects in scheduled computed tomography scans in the absence of clinical symptoms. Anticoagulant therapy was routinely prescribed regardless of SVT or IVT.
IVT was diagnosed in 94 out of 340 (28%) patients. Patients with IVT were older (63.7±10.5 versus 60.8±10.5 years, P = 0.035), more frequently had metastatic cancer (82% versus 65%, P = 0.01) and were less likely to be receiving chemotherapy at the time of the thrombotic event (53% versus 67%, P = 0.018). Mean follow-up was 477 days. A lower risk of venous rethromboses was observed in patients with IVT (log-rank P = 0.043), with no differences in major bleeding and overall survival compared with SVT patients.
A high proportion of venous thrombotic events in cancer patients are diagnosed incidentally during scheduled imaging. Prospective controlled trials evaluating the optimal therapy in this setting are required.
The main causative process in idiopathic sudden sensorineural hearing loss (iSSNHL) has yet to be explained or demonstrated. The clinical picture supports vascular involvement, but obvious ...limitations of inner ear study make this difficult to corroborate.
To determine the role of thrombophilic genetic variants that may affect platelet function and to assess the cardiovascular risk profile in a cohort of patients with iSSNHL.
118 Caucasian patients with iSSNHL were recruited from the same geographical area and enrolled prospectively in this study. Clinical data were obtained for each patient. Polymorphisms of the platelet glycoprotein subunit IIIa gene, ITGB3 (PLA1/A2, rs5918), and of the platelet glycoprotein subunit Ia gene, ITGA2 (C807T, rs1126643) were analyzed. A control group of 161 age- and gender-matched healthy individuals from the same geographical area was recruited for genetic comparisons. In order to determine the cardiovascular risk profile of each patient and of our cohort, a cross-sectional assessment was performed by means of a calibrated Framingham coronary heart disease risk scale. Risk factor proportions were compared to those recommended in European guidelines for coronary prevention, which are also based on the Framingham function.
A significantly high prevalence of the 807T allele of platelet glycoprotein subunit Ia was found in patients compared to controls. There was a significant correlation between the 807TT homozygous genotype and a low probability of recovery. The PLA1/A2 polymorphism of platelet glycoprotein subunit IIIa was not associated with recovery, with a similar genotype prevalence being found in patients and controls. In terms of cardiovascular risk profile, patients did not present an excess of baseline coronary risk factors compared to the general population in the same geographical area.
Patients with iSSNHL had a higher prevalence of the 807T thrombophilic polymorphism of platelet glycoprotein Ia/IIa. Patients homozygous for this polymorphism are less likely to recover from iSSNHL. Classical cardiovascular risk factors were not related to iSSNHL.
Abstract
STUDY QUESTION
Are the levels of total circulating cell-derived microparticles (cMPs) and circulating tissue factor-containing microparticles (cMP-TF) increased in patients with ...endometriosis?
SUMMARY ANSWER
The levels of total cMP, but not cMP-TF, were higher in patients with endometriosis, and these were attributed to higher levels in patients with deep infiltrating endometriosis (DIE).
WHAT IS KNOWN ALREADY
Previous studies have reported elevated levels of total cMP in inflammatory conditions as well as higher levels of other inflammatory biomarkers in endometriosis. Increased expression of tissue factor (a transmembrane receptor for Factor VII/VIIa) in eutopic and ectopic endometrium from patients with endometriosis has been described. There is no previous data regarding total cMP and cMP-TF levels in patients with endometriosis.
STUDY DESIGN, SIZE, DURATION
A prospective case–control study including two groups of patients was carried out. The E group included 65 patients with surgically confirmed endometriosis (37 with DIE lesions) and the C group comprises 33 women without surgical findings of any form of endometriosis. Patients and controls were recruited during the same 10-month period. Controls were the next patient without endometriosis undergoing surgery, after including two patients with endometriosis.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Venous blood samples for total cMP and cMP-TF determinations were obtained at the time of surgery, before anesthesia at a tertiary care center. To assess total cMP, an ELISA functional assay was used and cMP-TF activity in plasma was measured using an ELISA kit.
MAIN RESULTS AND THE ROLE OF CHANCE
Total cMP levels in plasma were higher in the E group compared with the C group (P < 0.0001). The subanalysis of endometriosis patients with DIE or with ovarian endometriomas without DIE showed that total cMP levels were higher in the DIE group (P = 0.001). There were no statistically significant differences in cMP-TF levels among the groups analyzed.
LIMITATIONS, REASONS FOR CAUTION
This is a preliminary study in which the sample size was arbitrarily decided, albeit in keeping with previous studies analyzing cMP in other inflammatory diseases and other biomarkers in endometriosis. The control group included patients with other pathologies as well as healthy controls, and blood samples were taken at different phases of the cycle.
WIDER IMPLICATIONS OF THE FINDINGS
Elevated total cMP levels in DIE patients may reflect an inflammatory and/or procoagulant systemic status in these patients. Further studies are warranted to confirm our findings and to assess the role of cMP levels in the pathophysiology of DIE.
STUDY FUNDING/COMPETING INTEREST(S)
This study was supported in part by a grant from FIS-PI11/01560 and FIS-PI11/00977 within the ‘Plan Nacional de I + D + I’ and co-funded by the ‘ISCIII-Subdirección General de Evaluación’ and ‘Fondo Europeo de Desarrollo Regional (FEDER)’ and by the grant ‘Premi Fi de Residència Emili Letang 2015’ from the Hospital Clínic of Barcelona. The authors have no competing interests to disclose.
Objective: To analyse the clinical and laboratory features of patients with thrombotic microangiopathic haemolytic anaemia (TMHA) associated with antiphospholipid antibodies (aPL). Methods: A ...computer assisted (PubMed) search of the literature was performed to identify all cases of TMHA associated with aPL from 1983 to December 2002. Results: 46 patients (36 female) with a mean (SD) age at presentation of TMHA of 34 (15) years were reviewed. Twenty eight (61%) patients had primary antiphospholipid syndrome (APS). TMHA was the first clinical manifestation of APS in 26 (57%) patients. The clinical presentations were haemolytic-uraemic syndrome (26%), catastrophic APS (23%), acute renal failure (15%), malignant hypertension (13%), thrombotic thrombocytopenic purpura (13%), and HELLP (haemolysis, elevated liver enzymes, and low platelet count in association with eclampsia) syndrome (4%). Lupus anticoagulant was detected in 86% of the episodes of TMHA, and positive anticardiolipin antibodies titres in 89%. Steroids were the most common treatment (69% of episodes), followed by plasma exchange (PE) (62%), anticoagulant or antithrombotic agents (48%), immunosuppressive agents (29%), and immunoglobulins (12%). Recovery occurred in only 10/29 (34%) episodes treated with steroids, and in 19/27 (70%) episodes treated with PE. Death occurred in 10/46 (22%) patients. Conclusions: The results emphasise the need for systematic screening for aPL in all patients with clinical and laboratory features of TMHA. The existence of TMHA in association with an APS forces one to rule out the presence of the catastrophic variant of this syndrome. PE is indicated as a first line of treatment for all patients with TMHA associated with aPL.
Summary
Background
Noninvasive identification of significant portal hypertension in patients with cirrhosis is needed in hepatology practice.
Aim
To investigate whether the combination of sCD163 as a ...hepatic inflammation marker and the fibrosis markers of the Enhanced Liver Fibrosis score (ELF) can predict portal hypertension in patients with cirrhosis.
Methods
We measured sCD163 and the ELF components (hyaluronic acid, tissue inhibitor of metalloproteinase‐1 and procollagen‐III aminopeptide) in two separate cohorts of cirrhosis patients that underwent hepatic vein catheterisation. To test the predictive accuracy we developed a CD163‐fibrosis portal hypertension score in an estimation cohort (n = 80) and validated the score in an independent cohort (n = 80). A HVPG ≥10 mmHg was considered clinically significant.
Results
Both sCD163 and the ELF components increased in a stepwise manner with the patients' Child–Pugh score (P < 0.001, all), and also with increasing HVPG (P < 0.001). receiver operator characteristics (ROC) analyses showed that each one of the individual components predicted a HVPG >10 mmHg with AUROC′s of approximately 0.80. The combined score optimised by logistic regression analyses improved the AUROC to 0.91 in the estimation cohort and 0.90 in the validation cohort. Furthermore, a high value of the combined score was associated with a high short‐term mortality.
Conclusions
The combination of the macrophage activation marker sCD163 and the fibrosis markers predicted significant portal hypertension in patients with cirrhosis. This score may prove useful for screening purposes and highlights the importance of both the inflammatory and the fibrotic components of cirrhotic portal hypertension.
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