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Journal of Thrombosis and Haemostasis :... Sep 2016Essentials It is unclear if thrombophilia increases the risk of catheter-associated thrombosis in children. We conducted a meta-analysis on thrombophilia and pediatric... (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
Essentials It is unclear if thrombophilia increases the risk of catheter-associated thrombosis in children. We conducted a meta-analysis on thrombophilia and pediatric catheter-associated thrombosis. Presence of ≥1 trait confers additional risk of venous thrombosis in children with catheters. Limitations of included studies preclude us from recommending routine thrombophilia testing.
SUMMARY
Background The association between thrombophilia and deep vein thrombosis (DVT) associated with central venous catheter (CVC) use, the most important pediatric risk factor for thrombosis, is unclear in children. Pediatric studies with small sample sizes have reported conflicting results. We sought to evaluate whether, among children with CVCs, thrombophilia increases the risk of CVC-associated DVT (CADVT). Materials and methods We systematically searched MEDLINE, EMBASE, the Web of Science, the Cochrane Central Register for Controlled Trials, PubMed and reference lists for controlled studies published from the inception of the database until September 2015. Included were studies of children aged <21 years with CVCs who were systematically tested for thrombophilic traits that are commonly screened for in clinical practice. Pooled prevalence rates and pooled odds ratios (pORs) of CADVT with thrombophilia were estimated by use of a random effects model. Results We analyzed 16 cohort studies with 1279 children, 277 of whom had CADVT, and with 12 traits tested. There was significant heterogeneity in the included studies. The presence of one or more traits was associated with CADVT (pOR 3.20; 95% confidence interval [CI] 1.56-6.54). Although the prevalence of most traits was < 0.10, children with protein C deficiency, elevated factor VIII levels and the FV Leiden mutation had an increased prevalence of CADVT. The association with thrombophilia seemed to be stronger for symptomatic CADVT (pOR 6.71; 95% CI 1.93-23.37) than for asymptomatic CADVT (pOR 2.14; 95% CI 1.10-4.18). Conclusions On the basis of the low prevalence of specific traits, the relatively weak association with CADVT, and the limitations of the included studies, we cannot recommend routine testing of thrombophilias in children with CADVT.
Topics: Adolescent; Catheterization, Central Venous; Central Venous Catheters; Child; Child, Preschool; Cohort Studies; Female; Humans; Infant; Infant, Newborn; Male; Odds Ratio; Retrospective Studies; Thrombophilia; Venous Thrombosis; Young Adult
PubMed: 27306795
DOI: 10.1111/jth.13388 -
Journal of Thoracic Disease Jan 2024Women with peripartum cardiomyopathy (PPCM) are at an increased risk of arterial and venous thromboembolic events. The review summarizes the evidence on the incidence of... (Review)
Review
BACKGROUND
Women with peripartum cardiomyopathy (PPCM) are at an increased risk of arterial and venous thromboembolic events. The review summarizes the evidence on the incidence of thromboembolic complications in women with PPCM, diagnostic approaches, related outcomes, and effects of therapies that have been used.
METHODS
English articles were retrieved from Web of Science and PubMed using search terms to capture studies related to PPCM (or postpartum cardiomyopathy) and all combinations of thrombosis- and embolism-related keywords. A total of 347 articles from PubMed and 85 from Web of Science were obtained, and after removing duplicates, 327 articles were screened for original data and classified into four domains: epidemiology, risk factors, diagnosis, and therapy of thromboembolism in PPCM. Ultimately, 30 articles were included. Data were synthesized in summary tables for each domain.
RESULTS
Studies in the United States and Europe reported varying incidence for thromboembolism in PPCM, up to 14% in 6 months. Risk factors include elevated levels of coagulation factors, decreased protein C and S activity, decreased fibrinolysis, and a low left ventricular ejection fraction (LVEF). Cesarean delivery and post-operative status were correlated with a higher incidence of thromboembolic complications. Diagnosis relied mostly on ultrasonography and magnetic resonance and depended on the suspected location of thrombus. Anticoagulation has been used mostly for PPCM patients with a reduced LVEF, with the duration varying across guidelines and healthcare systems. Unfractionated heparin and low molecular weight heparin (LMWH) were considered safe choices during pregnancy, while warfarin and novel oral anticoagulants (NOACs) were used postpartum. The association of bromocriptine with risk of thromboembolic complications remains debated.
CONCLUSIONS
There are important gaps in our understanding of the epidemiology, risk stratification, and optimal secondary prevention of thromboembolism in PPCM. Larger prospective studies with detailed phenotyping are required.
PubMed: 38410599
DOI: 10.21037/jtd-23-945 -
Thrombosis Journal 2018The pathophysiological mechanisms of acute coagulopathy of trauma-shock (ACOTS) are reported to include activated protein C-mediated suppression of thrombin generation... (Review)
Review
BACKGROUND
The pathophysiological mechanisms of acute coagulopathy of trauma-shock (ACOTS) are reported to include activated protein C-mediated suppression of thrombin generation via the proteolytic inactivation of activated Factor V (FVa) and FVIIIa; an increased fibrinolysis via neutralization of plasminogen activator inhibitor-1 (PAI-1) by activated protein C. The aims of this study are to review the evidences for the role of activated protein C in thrombin generation and fibrinolysis and to validate the diagnosis of ACOTS based on the activated protein C dynamics.
METHODS
We conducted systematic literature search (2007-2017) using PubMed, the Cochrane Database of Systematic Reviews (CDSR), and the Cochrane Central Register of Controlled Trials (CENTRAL). Clinical studies on trauma that measured activated protein C or the circulating levels of activated protein C-related coagulation and fibrinolysis markers were included in our study.
RESULTS
Out of 7613 studies, 17 clinical studies met the inclusion criteria. The levels of activated protein C in ACOTS were inconsistently decreased, showed no change, or were increased in comparison to the control groups. Irrespective of the activated protein C levels, thrombin generation was always preserved or highly elevated. There was no report on the activated protein C-mediated neutralization of PAI-1 with increased fibrinolysis. No included studies used unified diagnostic criteria to diagnose ACOTS and those studies also used different terms to refer to the condition known as ACOTS.
CONCLUSIONS
None of the studies showed direct cause and effect relationships between activated protein C and the suppression of coagulation and increased fibrinolysis. No definitive diagnostic criteria or unified terminology have been established for ACOTS based on the activated protein C dynamics.
PubMed: 29946227
DOI: 10.1186/s12959-018-0167-3 -
Critical Care (London, England) Jan 2022Sepsis, the dysregulated host response to infection, triggers abnormal pro-coagulant and pro-inflammatory host responses. Limitations in early disease intervention... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sepsis, the dysregulated host response to infection, triggers abnormal pro-coagulant and pro-inflammatory host responses. Limitations in early disease intervention highlight the need for effective diagnostic and prognostic biomarkers. Protein C's role as an anticoagulant and anti-inflammatory molecule makes it an appealing target for sepsis biomarker studies. This meta-analysis aims to assess the diagnostic and prognostic value of protein C (PC) as a biomarker for adult sepsis.
METHODS
We searched MEDLINE, PubMed, EMBASE, CINAHL and Cochrane Library from database inception to September 12, 2021. We included prospective observational studies of (1) adult patients (> 17) with sepsis or suspicion of sepsis that; (2) measured PC levels with 24 h of study admission with; and (3) the goal of examining PC as a diagnostic or prognostic biomarker. Two authors screened articles and conducted risk of bias (RoB) assessment, using the Quality in Prognosis Studies (QUIPS) and the Quality Assessment in Diagnostic Studies-2 (QUADAS-2) tools. If sufficient data were available, meta-analysis was conducted to estimate the standardized mean difference (SMD) between patient populations.
RESULTS
Twelve studies were included, and 8 were synthesized for meta-analysis. Pooled analysis demonstrated moderate certainty of evidence that PC levels were less reduced in sepsis survivors compared to non-survivors (6 studies, 741 patients, SMD = 0.52, 95% CI 0.24-0.81, p = 0.0003, I = 55%), and low certainty of evidence that PC levels were less reduced in septic patients without disseminated intravascular coagulation (DIC) compared to those with DIC (3 studies, 644 patients, SMD = 0.97, 95% CI 0.62-1.32, p < 0.00001, I = 67%). PC could not be evaluated as a diagnostic tool due to heterogeneous control populations between studies.
CONCLUSION AND RELEVANCE
Our review demonstrates that PC levels were significantly higher in sepsis survivors compared to non-survivors and patients with sepsis but not disseminated intravascular coagulation (DIC). Our evaluation is limited by high RoB in included studies and poor reporting of the sensitivity and specificity of PC as a sepsis biomarker. Future studies are needed to determine the sensitivity and specificity of PC to identify its clinical significance as a biomarker for early sepsis recognition. Trial Registration PROSPERO registration number: CRD42021229786. The study protocol was published in BMJ Open.
Topics: Adult; Biomarkers; Disseminated Intravascular Coagulation; Humans; Observational Studies as Topic; Prognosis; Protein C; Sepsis
PubMed: 35031071
DOI: 10.1186/s13054-022-03889-2 -
Journal of Thrombosis and Haemostasis :... Dec 2020Retinal vascular occlusion is a leading cause of sight loss. Both retinal artery occlusion (RAO) and retinal vein occlusion (RVO) have been associated with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Retinal vascular occlusion is a leading cause of sight loss. Both retinal artery occlusion (RAO) and retinal vein occlusion (RVO) have been associated with hypercoagulable states; however, the burden of thrombophilia in these patients is unclear.
OBJECTIVES
This study aims at estimating the prevalence of inherited and acquired thrombophilias in adults with RAO or RVO through a systematic review and meta-analysis of the literature.
PATIENTS/METHODS
PubMed and EMBASE were systematically searched from inception to 29 February 2020. All studies reporting prevalences of factor V Leiden (FVL) and prothrombin (F-II) G20210A mutations, methylenetetrahydrofolate reductase (MTHFR) C677T and plasminogen activator inhibitor (PAI) 4G polymorphisms, antithrombin III (AT-III), protein C (PC) and protein S (PS) activity deficiencies, hyperhomocysteinemia, and antiphospholipid (APL) antibodies in adults with RAO or RVO were included. Pooled prevalences and 95% confidence intervals (CI) were calculated.
RESULTS
Ninety-five studies were included; FVL and F-II mutations were found in 6% (95% CI: 5-8) and 3% (95% CI: 2-4) of individuals with RVO, respectively, whereas AT-III, PC, and PS activity deficiencies were found in <2%. The MTHFR C677T and PAI 4G homozygous polymorphism were observed in 13% (95% CI: 10-17) and 23% (95% CI: 16-31) of RVO, respectively; 8% presented APL antibodies. Similar findings were observed in individuals with RAO.
CONCLUSIONS
Compared with healthy subjects, patients with retinal vascular occlusion showed similar prevalences of inherited and acquired thrombophilias. These findings do not support routine thrombophilia screening in individuals with RAO or RVO.
Topics: Adult; Factor V; Humans; Methylenetetrahydrofolate Reductase (NADPH2); Prothrombin; Retinal Vein Occlusion; Risk Factors; Thrombophilia
PubMed: 32805772
DOI: 10.1111/jth.15068 -
Thrombosis Research Mar 2018Despite high rates of venous thromboembolism (VTE) among patients with hematologic malignancies, few tools exist to assist providers in identifying those patients at... (Review)
Review
INTRODUCTION
Despite high rates of venous thromboembolism (VTE) among patients with hematologic malignancies, few tools exist to assist providers in identifying those patients at highest risk for this potentially fatal complication. Laboratory biomarkers, such as d-dimer, have demonstrated utility in some clinical settings to distinguish patients at increased risk.
MATERIALS AND METHODS
We performed a systematic review of the literature utilizing search terms including "biomarker", "venous thromboembolism", "hematologic malignancy", "lymphoma", "myeloma" and "leukemia" in the Medline database. A total of 25 studies investigating laboratory biomarkers of increased thrombotic risk in the setting of hematologic malignancy were identified and included in this review.
RESULTS AND CONCLUSIONS
The most studied biomarkers, d-dimer and fibrinogen, demonstrated some degree of efficacy in identifying high-risk patients at levels >4.0 mg/L or <1.0 g/L respectively. Additional markers which demonstrated promise included thrombin generation, mean platelet volume, soluble VEGF, soluble P-selectin and extracellular vesicles. Other biomarkers reviewed, which did not consistently demonstrate significant associations with VTE included prothrombin fragments F1 + 2, factor VIII, protein C, protein S, von Willebrand antigen and activity, antithrombin, thrombin antithrombin complex, antiphospholopid antibody, plasminogen activator inhibitor, tissue factor pathway inhibitor and several variants associated with known hypercoagulable states (factor V Leiden, prothrombin gene variant, methylenetetrahydrofolate reductase variant). Data to support any of the biomarkers discussed here in routine clinical decision-making are currently lacking, but additional investigation in clinical studies, ideally in combination with clinical factors known to be associated with increased thrombotic risk, is warranted.
Topics: Biomarkers; Female; Hematologic Neoplasms; Humans; Male; Risk Factors; Venous Thromboembolism
PubMed: 29407626
DOI: 10.1016/j.thromres.2018.01.037 -
International Journal of Clinical and... 2015Outcome prediction following traumatic brain injury (TBI) is a widely investigated field of research. Several outcome prediction models have been developed for prognosis... (Review)
Review
Outcome prediction following traumatic brain injury (TBI) is a widely investigated field of research. Several outcome prediction models have been developed for prognosis after TBI. There are two main prognostic models: International Mission for Prognosis and Clinical Trials in Traumatic Brain Injury (IMPACT) prognosis calculator and the Corticosteroid Randomization after Significant Head Injury (CRASH) prognosis calculator. The prognosis model has three or four levels: (1) model A included age, motor GCS, and pupil reactivity; (2) model B included predictors from model A with CT characteristics; and (3) model C included predictors from model B with laboratory parameters. In consideration of the fact that interventions after admission, such as ICP management also have prognostic value for outcome predictions and may improve the models' performance, Yuan F et al developed another prediction model (model D) which includes ICP. With the development of molecular biology, a handful of brain injury biomarkers were reported that may improve the predictive power of prognostic models, including neuron-specific enolase (NSE), glial fibrillary acid protein (GFAP), S-100β protein, tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), myelin basic protein (MBP), cleaved tau protein (C-tau), spectrin breakdown products (SBDPs), and ubiquitin C-terminal hydrolase-L1 (UCH-L1), and sex hormones. A total of 40 manuscripts reporting 11 biomarkers were identified in the literature. Many substances have been implicated as potential biomarkers for TBI; however, no single biomarker has shown the necessary sensitivity and specificity for predicting outcome. The limited number of publications in this field underscores the need for further investigation. Through fluid biomarker analysis, the advent of multi-analyte profiling technology has enabled substantial advances in the diagnosis and treatment of a variety of conditions. Application of this technology to create a bio-signature for TBI using multiple biomarkers in combination will hopefully facilitate much-needed advances. We believe that further investigations about brain injury biomarkers may improve the predictive power of the contemporary outcome calculators and prognostic models, and eventually improve the care of patients with TBI.
PubMed: 26884899
DOI: No ID Found -
Frontiers in Cardiovascular Medicine 2022The discovery that cardiac sarcomere proteins are substrates for S-glutathionylation and that this post-translational modification correlates strongly with diastolic...
The discovery that cardiac sarcomere proteins are substrates for S-glutathionylation and that this post-translational modification correlates strongly with diastolic dysfunction led to new concepts regarding how levels of oxidative stress affect the heartbeat. Major sarcomere proteins for which there is evidence of S-glutathionylation include cardiac myosin binding protein C (cMyBP-C), actin, cardiac troponin I (cTnI) and titin. Our hypothesis is that these S-glutathionylated proteins are significant factors in acquired and familial disorders of the heart; and, when released into the serum, provide novel biomarkers. We consider the molecular mechanisms for these effects in the context of recent revelations of how these proteins control cardiac dynamics in close collaboration with Ca fluxes. These revelations were made using powerful approaches and technologies that were focused on thin filaments, thick filaments, and titin filaments. Here we integrate their regulatory processes in the sarcomere as modulated mainly by neuro-humoral control of phosphorylation inasmuch evidence indicates that S-glutathionylation and protein phosphorylation, promoting increased dynamics and modifying the Frank-Starling relation, may be mutually exclusive. Earlier studies demonstrated that in addition to cTnI as a well-established biomarker for cardiac disorders, serum levels of cMyBP-C are also a biomarker for cardiac disorders. We describe recent studies approaching the question of whether serum levels of S-glutathionylated-cMyBP-C could be employed as an important clinical tool in patient stratification, early diagnosis in at risk patients before HFpEF, determination of progression, effectiveness of therapeutic approaches, and as a guide in developing future therapies.
PubMed: 36762302
DOI: 10.3389/fcvm.2022.1060716 -
European Respiratory Review : An... Sep 2018Fibrotic interstitial pneumonias are a group of rare diseases characterised by distortion of lung interstitium. Patients with mutations in surfactant-processing genes,...
Fibrotic interstitial pneumonias are a group of rare diseases characterised by distortion of lung interstitium. Patients with mutations in surfactant-processing genes, such as surfactant protein C (), surfactant protein A1 and A2 ( and ), ATP binding cassette A3 () and Hermansky-Pudlak syndrome (, and ), develop progressive pulmonary fibrosis, often culminating in fatal respiratory insufficiency. Although many mutations have been described, little is known about the optimal treatment strategy for fibrotic interstitial pneumonia patients with surfactant-processing mutations.We performed a systematic literature review of studies that described a drug effect in patients, cell or mouse models with a surfactant-processing mutation. In total, 73 articles were selected, consisting of 55 interstitial lung disease case reports/series, two clinical trials and 16 cell or mouse studies. Clinical effect parameters included lung function, radiological characteristics and clinical symptoms, while experimental outcome parameters included chemokine/cytokine expression, surfactant trafficking, necrosis and apoptosis. SP600125, a c-jun N-terminal kinase (JNK) inhibitor, hydroxychloroquine and 4-phenylbutyric acid were most frequently studied in disease models and lead to variable outcomes, suggesting that outcome is mutation dependent.This systematic review summarises effect parameters for future studies on surfactant-processing disorders in disease models and provides directions for future trials in affected patients.
Topics: Animals; Disease Models, Animal; Genetic Predisposition to Disease; Humans; Idiopathic Interstitial Pneumonias; Lung; Mice; Mutation; Phenotype; Pulmonary Surfactant-Associated Proteins; Respiratory System Agents; Treatment Outcome
PubMed: 29997245
DOI: 10.1183/16000617.0135-2017 -
Cureus Aug 2022Rheumatoid arthritis (RA) is associated with both local and systemic inflammatory processes via the aberrant regulation of inflammatory pathways and imbalances in... (Review)
Review
A Systematic Review of Nutritional Interventions on Key Cytokine Pathways in Rheumatoid Arthritis and Its Implications for Comorbid Depression: Is a More Comprehensive Approach Required?
Rheumatoid arthritis (RA) is associated with both local and systemic inflammatory processes via the aberrant regulation of inflammatory pathways and imbalances in several mediators of inflammation. Cytokines, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1B, IL-6, IL-17, IL-18, rheumatoid factor, anti-cyclic citrullinated protein, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) have been used in diagnosing and tracking the progression of RA. The primary objective of this review is to identify and summarize which specific dietary patterns and nutritional interventions go beyond symptom management to improve the response to known inflammatory cytokines and possibly decrease markers of inflammation in the RA disease process. Analysis of the 41 identified publications demonstrated that certain dietary patterns, the consumption of specific macronutrients, and supplementation with herbals or other compounds have shown some effect on improving cytokine profiles in patients with RA. This review illustrates the importance of proper patient education on the anti-inflammatory and potential protective impacts substantial dietary change may have on the disease progression and symptoms of RA. Identifying nutritional interventions and dietary patterns that improve the inflammatory cytokine profile, and therefore disease progression and inflammatory comorbidities of RA will help further focus research on treatments that may provide a better overall improvement in quality of life for RA patients by focusing on the root cause inflammatory processes that affect not only joint destruction but also depression-rated disability. This review further notes that while depression is commonly found in patients who suffer from chronic illnesses, it is especially prevalent in the RA population. The pathology of depression is associated with systemic inflammation, which is a known outcome of RA and may explain this strong association. Cytokines IL-6, IL-1, and TNF-α, known mediators involved in the progression of RA, are strongly associated with stress-related disorders including depression and anxiety. The presence of these cytokines is also correlated with the severity and duration of depression. This may signal a potential use of cytokines in diagnosing and following the progression of depression not only in patients with RA but also others. Given the statistics presented on depression and suicide in patients with RA, and the shared inflammatory pathway between the two diseases, depression and suicide screening scales should be included along with analysis of inflammatory markers and disease activity scores (DAS) in any future RA study.
PubMed: 35990558
DOI: 10.7759/cureus.28031