Background
Liver biopsy carries a small risk of bleeding complications. No validated clinical or laboratory tool helps predict liver biopsy–related bleeding.
Objectives
To determine whether global ...hemostasis tests and/or a clinical questionnaire could identify patients at risk of liver biopsy–related bleeding.
Patients/Methods
Consecutive patients scheduled for liver biopsy with an overnight hospital stay were prospectively included. Before liver biopsy, routine hemostasis tests, Platelet Function Analyzer 100, thromboelastometry, thrombin generation assay, plasma clot lysis time, and a clinical questionnaire were performed. Bleeding was defined as a liver hematoma or new free fluid on a systematic ultrasound performed 24 h after liver biopsy or a decrease in hemoglobin level of 2 g/dL or more in patients with pre‐existing free fluid in the abdominal cavity.
Results
Three hundred two patients were included: 173 underwent percutaneous and 129 transjugular liver biopsy. There were 21 bleeding episodes (7%); 20 based on ultrasonographic criteria, 1 on laboratory criteria. None of the hemostasis tests and no item of the clinical questionnaire were associated with liver biopsy–related bleeding in the overall study group. Same results were obtained in subgroup analyses focusing on patients who underwent percutaneous liver biopsy, transjugular liver biopsy, or on patients with cirrhosis. Pain 2 h after liver biopsy was more frequent in patients with liver biopsy–related bleeding (55% vs. 23% p = .002).
Conclusions
An extensive hemostasis workup, including global hemostasis assays, does not improve prediction of liver biopsy–related bleeding. Pain 2 h after liver biopsy should alert the clinician to the possibility of procedure‐related bleeding.
Introduction
Dominant‐negative effects have been described for 10 F11 variants in the literature.
Aim
The current study aimed at identifying putative dominant‐negative F11 variants.
Material and ...methods
This research consisted in a retrospective analysis of routine laboratory data.
Results
In a series of 170 patients with moderate/mild factor XI (FXI) deficiencies, we identified heterozygous carriers of previously reported dominant‐negative variants (p.Ser243Phe, p.Cys416Tyr, and p.Gly418Val) with FXI activities inconsistent with a dominant‐negative effect. Our findings also do not support a dominant‐negative effect of p.Gly418Ala. We also identified a set of patients carrying heterozygous variants, among which five out of 11 are novel, with FXI activities suggesting a dominant‐negative effect (p.His53Tyr, p.Cys110Gly, p.Cys140Tyr, p.Glu245Lys, p.Trp246Cys, p.Glu315Lys, p.Ile421Thr, p.Trp425Cys, p.Glu565Lys, p.Thr593Met, and p.Trp617Ter). However, for all but two of these variants, individuals with close to half normal FXI coagulant activity (FXI:C) were identified, indicating an inconstant dominant effect.
Conclusion
Our data show that for some F11 variants recognized has having dominant‐negative effects, such effects actually do not occur in many individuals. The present data suggest that for these patients, the intracellular quality control mechanisms eliminate the variant monomeric polypeptide before homodimer assembly, thereby allowing only the wild‐type homodimer to assemble and resulting in half normal activities. In contrast, in patients with markedly decreased activities, some mutant polypeptides might escape this first quality control. In turn, assembly of heterodimeric molecules as well as mutant homodimers would result in activities closer to 1:4 of FXI:C normal range.
Life expectancy for patients with haemophilia (PWH) has significantly increased in the last decades, due to improvement of clotting factor replacement therapy. However, despite a lower cardiovascular ...mortality rate and contrasting prevalence for non‐fatal ischaemic heart disease (IHD), cardiovascular diseases are increasing in PWH. The prevalence of cardiovascular risk factors in PWH is as prevalent as in the general population, whereas an increased risk of hypertension has been observed in some studies. Furthermore, PWH are not protected against atherosclerosis. Coronary artery disease treatment is extremely challenging in PWH. Two ‘institutional’ guidelines for the management of IHD in PWH have been published. Since these recommendations, the use of new drugs such as prasugrel, ticagrelor, bivalirudin, new oral anticoagulants and new drug‐eluting stents have been recommended in the general population but should be evaluated in PWH. Some questions arise: which trough level during long‐term single or dual antiplatelet treatment (DAT) is really needed? The clinical role of platelet testing remains ill defined but may be considered in selected patients. A multidisciplinary approach is necessary for the management of IHD in PWH in order to treat the patient as any patient according to the cardiological guidelines during the acute phase, and long‐term management should be discussed.
Anticoagulation in the cirrhotic patient Turco, Laura; de Raucourt, Emmanuelle; Valla, Dominique-Charles ...
JHEP reports,
09/2019, Letnik:
1, Številka:
3
Journal Article
Recenzirano
Odprti dostop
In the past, patients with liver cirrhosis were thought to be prone to increased bleeding risk. However, those with compensated liver cirrhosis actually have normal coagulative balance, which can ...become altered when liver function worsens, or infection, bleeding, or acute kidney insufficiency occur. When this happens, it is now recognized that patients with liver cirrhosis are at higher risk of thrombotic rather than haemorrhagic complications. Anticoagulation plays a favourable role both when used therapeutically or prophylactically. Successful anticoagulation is associated with a lower rate of decompensation and with improved survival. To date, treatment has involved the use of low molecular weight heparins and vitamin K antagonists. Preliminary data suggest that novel non-vitamin K antagonist oral anticoagulants can be used safely in patients with liver cirrhosis.
Introduction
Serpin E2 or protease nexin‐1 (PN‐1) is a glycoprotein belonging to the serpin superfamily, whose function is closely linked to its ability to inhibit thrombin and proteases of the ...plasminergic system.
Objectives
In the absence of specific quantitative methods, an ELISA for the quantification of human PN‐1 was characterized and used in biological fluids.
Methods
The ELISA for human PN‐1 was developed using two monoclonal antibodies raised against human recombinant PN‐1. PN‐1 was quantified in plasma, serum, platelet secretion from controls and patients with hemophilia A and in conditioned medium of aortic tissue.
Results
A linear dose–response curve was observed between 2 and 35 ng/mL human PN‐1. Intra‐ and interassay coefficients of variation were 6.2% and 11.1%, respectively. Assay recoveries of PN‐1 added to biological samples were ≈95% in plasma, ≈97% in platelet reaction buffer, and ≈93% in RPMI cell culture medium. Levels of PN‐1 secreted from activated human platelets from controls was similar to that of patients with hemophilia A. PN‐1 could be detected in conditioned media of aneurysmal aorta but not in that of control aorta.
Conclusion
This is the first fully characterized ELISA for human serpin E2 level in biological fluids. It may constitute a relevant novel tool for further investigations on the pathophysiological role of serpin E2 in a variety of clinical studies.
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