Background
Interpretation of thyroid function tests by means of biological variation (BV) data is essential to identify significant changes between serial measurements at an individual level. Data on ...thyroid parameters in adults are limited.
Objectives
We aimed at determining the BV of four thyroid function test (thyroid‐stimulating hormone (TSH), free thyroxin (FT4), free triiodothyronine (FT3) and thyroglobulin (Tg)) by applying recent recommendations to acquire BV data on a latest generation of immunoassay.
Methods
Nineteen healthy volunteers (8 males and 11 females) were drawn every week during 5 consecutive weeks. Samples were analysed in duplicate on the Cobas 602 analyzer (Roche Diagnostics). After normality assessment, outlier exclusion and homogeneity of variance analysis, analytical variation (CVA), within‐subject biological variation (CVI) and between‐subject biological variation (CVG) were determined using nested ANOVA.
Results
CVA, CVI and CVG were 0.9%, 19.7% and 37.6% for TSH; 3.6%, 4.6% and 10.8% for FT4; 2.2%, 6.0% and 8.6% for FT3; and 0.9%, 15.4% and 84.9% for Tg. Index of individuality (II) for all parameters was between 0.2 and 0.7. The percentage above which the change between two measures is truly significant (reference change value) was 54.7% for TSH, 16.2% for FT4, 17.7% for FT3 and 42.8% for Tg.
Conclusion
Based on recent international recommendations, our study provides updated BV data for four thyroid function tests in European healthy volunteers. Reliable BV characteristics, and especially RCV, can facilitate the interpretation of consecutive thyroid function tests in an individual and therefore have the potential to efficiently support clinical decisions regarding thyroid diseases.
Patients with chronic liver disease (CLD) and cirrhosis present a rebalanced hemostatic system in the three phases of haemostasis. This balance is however unstable and can easily tip towards bleeding ...or thrombosis. Management of both spontaneous bleeding and bleeding during invasive procedures remains a challenge in this patient population. Transfusion of blood products can result in circulatory overload and thereby worsen portal hypertension. As an alternative to fresh frozen plasma (FFP), prothrombin complex concentrates (PCC) may have merit in patients with liver disease because of their low volume. The impact of PCC in in‐vitro spiking experiments of cirrhotic plasma is promising, but also warrants cautious use in light of thromboembolic risk. The majority of existing studies carried‐out in CLD patients are retrospective or do not have an adequate control arm. A prospective study (the PROTON trial) was set up in 2013 to investigate the utility of PCC in patients undergoing liver transplantation. However, the study has never recruited the planned number of patients. Robust data on PCC safety in CLD is also required. The limited existing evidence does not seem to indicate an excessive thromboembolic risk. Currently, the utilisation of PCC in CLD cannot be routinely recommended but can provide an option for carefully selected cases in which other measures were not sufficient to control bleeding and after delicately weighing risks and benefits.
Background
Evaluation of an individual’s thrombin‐generating capacity enables a global assessment of the coagulation cascade and is therefore thought to better reflect the clotting function of blood. ...However, the lack of standardization still hampers the use in routine clinical practice.
Methods
Nineteen healthy subjects were sampled once a week for 5 consecutive weeks. Thrombin generation assay (TGA) was performed in duplicate by calibrated automated thrombogram (CAT) on platelet poor plasma with and without thrombomodulin. After exclusion of outliers, a nested analysis of variance (ANOVA) was performed to evaluate the biological variability (BV) results. Analytical variation (CVA), within‐individual variation (CVI), between‐individual variation (CVG), index of individuality (II), and reference change value (RCV) were calculated.
Results
All parameters taken together, the CVA, CVI, and CVG without TM, ranged from 2.8% to 6.5%, from 4.1% to 13.3% and from 10.4% to 28.4%, respectively. For TG with TM, CVI and CVG were higher and ranged from 5.0% to 18.1% and from 14.9% to 35.3%, respectively. For endogenous thrombin potential (ETP), a CVI of 4.1% and CVG of 10.4% were obtained without addition of thrombomodulin (TM). With addition of TM, both CVI and CVG were higher: 14.0% and 34.8%, respectively. The II was low and the RCV ranged from 17.2% to 50.4%.
Conclusion
CAT parameters are highly individualized and population‐based reference values could be called into question. The assessment of BV and RCV for thrombin generation assays could optimize interpretation of serial patient results and guide setting of analytical specification goals.
Changes in primary hemostasis have been described in patients with chronic liver disease (CLD) and cirrhosis and are still subject to ongoing debate. Thrombocytopenia is common and multifactorial. ...Numerous studies also reported platelet dysfunction. In spite of these changes, primary hemostasis seems to be balanced. Patients with CLD and cirrhosis can suffer from both hemorrhagic and thrombotic complications. Variceal bleeding is the major hemorrhagic complication and is mainly determined by high portal pressure. Non portal hypertension-related bleeding due to hemostatic failure is uncommon. Thrombocytopenia can complicate management of invasive procedures in CLD patients. Recently, oral thrombopoietin agonists have been approved to raise platelets before invasive procedures. In this review we aim to bundle literature, published over the past decade, discussing primary hemostasis in CLD and cirrhosis including (1) platelet count and the role of thrombopoietin (TPO) agonists, (2) platelet function tests and markers of platelet activation, (3) von Willebrand factor and (4) global hemostasis tests.
•PIVKA-II is increasingly used for the diagnosis and follow-up of HCC.•Biological variation data were generated from 18 European healthy volunteers.•CVA was 2.82% while sex-independent CVI and CVG ...were 13.35% and 16.05%, respectively.
PIVKA-II (DCP) is increasingly used for the diagnosis and the surveillance of hepatocellular carcinoma (HCC) in at-risk populations. However, to date, few data are available concerning the intra- and inter-individual variability of this marker, which makes the interpretation of serial measurements difficult in the context of monitoring.
19 European healthy volunteers (HVs) were taken each week during five consecutive weeks. Samples were analyzed in duplicate on the Lumipulse® analyzer (Fujirebio, Gent, Belgium). Analytical variation (CVA), within-subject biological variation (CVI) and between-subject biological variation (CVG) were calculated using nested ANOVA following normality assessment, outlier exclusion, and homogeneity of variance analysis.
No significant difference was observed for the mean values (p = 0.23) between men (mean: 30.66 mAU/mL) and women (mean: 33.90 mAU/mL) subgroups. CVA was 2.82% while sex-independent CVI and CVG were 13.35% and 16.05%, respectively. Taking these values, the calculated reference change value (RCV) and index of individuality were 37.70% and 0.85, respectively.
We reported for the first-time biological variation data for PIVKA-II in a cohort of European HVs. We believe that our results can be used to set analytical specification goals as well as to improve the interpretation of serial measurements of PIVKA-II for monitoring purposes.
Heart failure (HF) with preserved ejection fraction (HFpEF) is associated with high burden of comorbidities known to increase the mean platelet volume (MPV). This parameter has been associated with ...morbidity and mortality in HF. However, the role of platelets and the prognostic relevance of MPV in HFpEF remain largely unexplored. We aimed to evaluate the clinical usefulness of MPV as a prognostic marker in HFpEF. We prospectively enrolled 228 patients with HFpEF (79 ± 9 years; 66% females) and 38 controls of similar age and gender (78 ± 5 years; 63% females). All subjects underwent two-dimensional echocardiography and MPV measurements. Patients were followed-up for a primary end point of all-cause mortality or first HF hospitalization. The prognostic impact of MPV was determined using Cox proportional hazard models. Mean MPV was significantly higher in HFpEF patients compared with controls (MPV: 10.7 ± 1.1fL vs. 10.1 ± 1.1fL, p = .005). HFpEF patients (n = 56) with MPV >75th percentile (11.3 fL) displayed more commonly a history of ischemic cardiomyopathy. Over a median follow-up of 26 months, 136 HFpEF patients reached the composite endpoint. MPV >75th percentile was a significant predictor of the primary endpoint (HR: 1.70 1.08; 2.67, p = .023) adjusted for NYHA class, chronic obstructive pulmonary disease, loop diuretics, renal function, and hemoglobin. We demonstrated that MPV was significantly higher in HFpEF patients compared with controls of similar age and gender. Elevated MPV was a strong and independent predictor of poor outcome in HFpEF patients and may be relevant for clinical use.
What is the context?
Heart failure with preserved ejection fraction (HFpEF) is associated with several comorbidities known to increase the mean platelet volume (MPV).
MPV is a measure of platelet size and a potential marker of platelet reactivity. An increased MPV results from an increased platelet turnover.
MPV has been associated with morbidity and mortality from heart failure.
No study has previously compared MPV between HFpEF and controls and investigated the prognostic relevance of MPV in HFpEF disease.
What is new?
In this study, we compared the MPV between HFpEF patients and controls of similar age and gender, prospectively enrolled between 2015 and 2021. We evaluated the prognostic role of elevated MPV in HFpEF patients.
Our main results:
The MPV was higher in HFpEF patients compared to controls of similar age and gender.
HFpEF patients with elevated MPV displayed more commonly a history of ischemic cardiomyopathy.
Elevated MPV was a strong and independent predictor of poor outcome in HFpEF patients.
What is the impact?
MPV may be relevant for clinical use to predict clinical outcome in HFpEF patients.
Elevated MPV reflecting platelet activity supports the potential role of platelets in HFpEF's pathophysiology.
Does haemophilia slow down the development of liver fibrosis? van Dievoet, Marie‐Astrid; Leclercq, Isabelle; Hermans, Cedric ...
Haemophilia : the official journal of the World Federation of Hemophilia,
January 2019, 2019-Jan, 2019-01-00, 20190101, Letnik:
25, Številka:
1
Journal Article
SARS-CoV-2 targets endothelial cells through the angiotensin-converting enzyme 2 receptor. The resulting endothelial injury induces widespread thrombosis and microangiopathy. Nevertheless, early ...specific markers of endothelial dysfunction and vascular redox status in COVID-19 patients are currently missing.
Observational study including ICU and non-ICU adult COVID-19 patients admitted in hospital for acute respiratory failure, compared with control subjects matched for cardiovascular risk factors similar to ICU COVID-19 patients, and ICU septic shock patients unrelated to COVID-19.
Early SARS-CoV-2 infection was associated with an imbalance between an exacerbated oxidative stress (plasma peroxides levels in ICU patients vs. controls: 1456.0 ± 400.2 vs 436 ± 272.1 mmol/L; P < 0.05) and a reduced nitric oxide bioavailability proportional to disease severity (5-α-nitrosyl-hemoglobin, HbNO in ICU patients vs. controls: 116.1 ± 62.1 vs. 163.3 ± 46.7 nmol/L; P < 0.05). HbNO levels correlated with oxygenation parameters (PaO2/FiO2 ratio) in COVID-19 patients (R2 = 0.13; P < 0.05). Plasma levels of angiotensin II, aldosterone, renin or serum level of TREM-1 ruled out any hyper-activation of the renin-angiotensin-aldosterone system or leucocyte respiratory burst in ICU COVID-19 patients, contrary to septic patients.
Endothelial oxidative stress with ensuing decreased NO bioavailability appears as a likely pathogenic factor of endothelial dysfunction in ICU COVID-19 patients. A correlation between NO bioavailability and oxygenation parameters is observed in hospitalized COVID-19 patients. These results highlight an urgent need for oriented research leading to a better understanding of the specific endothelial oxidative stress that occurs during SARS-CoV-2.
Stated in the acknowledgments section.
Objectives As severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) pandemic is increasing its victims on a global scale with recurring outbreaks, it remains of outmost importance to rapidly ...identify people requiring an intensive care unit (ICU) hospitalization. The aim of this study was to identify Coronavirus Disease 2019 (COVID-19) biomarkers, to investigate their correlation with disease severity and to evaluate their usefulness for follow-up. Methods Fifty patients diagnosed with SARS-Cov-2 were included in March 2020. Clinical and biological data were collected at admission, during hospitalization and one month after discharge. Patients were divided into two severity groups: non-ICU (28) and ICU and/or death (22) to stratify the risk. Results Blood parameters in COVID-19 patients at admission showed increased C-reactive protein (CRP) (100%), ferritin (92%), lactate dehydrogenase (LDH) (80%), white blood cell (WBC) count (26%) with lymphopenia (52%) and eosinopenia (98%). There were significant differences in levels of CRP, ferritin, D-dimers, fibrinogen, lymphocyte count, neutrophil count and neutrophil-to-lymphocyte ratio (NLR) among the two severity groups. Mapping of biomarker's kinetics distinguished early and late parameters. CRP, ferritin, LDH, lymphopenia and eosinopenia were present upon admission with a peak at the first week. Late biomarkers such as anemia, neutrophilia and elevated liver biomarkers appeared after one week with a peak at three weeks of hospitalization. Conclusions We confirmed that high-values of CRP, NLR, D-dimers, ferritin as well as lymphopenia and eosinopenia were consistently found and are good markers for risk stratification. Kinetics of these biomarkers correlate well with COVID-19 severity. Close monitoring of early and late biomarkers is crucial in the management of critical patients to avoid preventable deaths.
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