-
PLoS Neglected Tropical Diseases Aug 2021Coagulation mechanisms are reported to be affected in dengue illness and evidenced by prolonged activated partial thromboplastin time (APTT) and prothrombin time (PT).... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Coagulation mechanisms are reported to be affected in dengue illness and evidenced by prolonged activated partial thromboplastin time (APTT) and prothrombin time (PT). The main aim of this systematic review and meta-analysis is to determine the magnitude of coagulation abnormalities among patients with dengue fever infection.
METHOD
This systematic review and meta-analysis were conducted per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The Joana Brigg's Institute (JBI) critical appraisal checklist was used for quality appraisal. STATA version 11 software was used for meta-analysis. The magnitude of coagulation abnormalities among dengue fever patients was determined by using a random-effects model. Subgroup and sensitivity analysis were performed to investigate the possible source of heterogeneity. Egger weighted regression tests were used to check the presence of publication bias among the included articles.
RESULT
Forty-two studies with a total of 12,221 dengue fever patients were eligible for meta-analysis in this study. Of which 22, 15, and 26 studies were used to determine the magnitude of prolonged APTT, PT, and thrombocytopenia, respectively. The magnitude of prolonged APTT and PT among patients with dengue fever infection were 42.91% (95% CI: 30.95, 54.87) I2 = 99.1% and 16.48% (95% CI: 10.95, 22.01) I2 = 97.0%, respectively. Besides, the magnitude of thrombocytopenia among dengue fever patients was 70.29% (95% CI: 62.69, 77.89) I2 = 99.3%. The magnitude of prolonged APTT in children and adults was 51.21% (95% CI: 24.54, 77.89) and 44.89% (95% CI: 28.32, 61.45), respectively. Similarly, the overall magnitude of prolonged PT in children and adults were 13.40% (95% CI: 6.09, 20.71) and 18.73% (95% CI: 7.49, 29.96), respectively.
CONCLUSION
The result of this study showed that there is a high magnitude of prolonged APTT and PT in dengue fever patients. Therefore, screening and early correction of coagulation abnormalities may be helpful to reduce further complications in those patients.
Topics: Adult; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Child; Dengue; Humans; Partial Thromboplastin Time; Prothrombin Time; Thrombocytopenia
PubMed: 34407078
DOI: 10.1371/journal.pntd.0009666 -
Frontiers in Immunology 2021Activation of the complement system has been observed in coronavirus disease 19 (COVID-19). We conducted a systematic review and meta-analysis with meta-regression to... (Meta-Analysis)
Meta-Analysis
Activation of the complement system has been observed in coronavirus disease 19 (COVID-19). We conducted a systematic review and meta-analysis with meta-regression to investigate possible differences in the serum concentrations of two routinely measured complement components, C3 and C4, in COVID-19 patients with different severity and survival status. We searched PubMed, Web of Science and Scopus, between January 2020 and February 2021, for studies reporting serum complement C3 and C4, measures of COVID-19 severity, and survival. Eligibility criteria were a) reporting continuous data on serum C3 and C4 concentrations in COVID-19 patients, -b) investigating COVID-19 patients with different disease severity and/or survival status, c) adult patients, d) English language, e) ≥10 patients, and f) full-text available. Using a random-effects model, standardized mean differences (SMD) with 95% confidence intervals (CIs) were calculated to evaluate differences in serum C3 and C4 concentrations between COVID-19 patients with low vs. high severity or survivor vs. non-survivor status. Risk of bias was assessed using the Newcastle-Ottawa scale whereas publication bias was assessed with the Begg's and Egger's tests. Certainty of evidence was assessed using GRADE. Nineteen studies in 3,764 COVID-19 patients were included in the meta-analysis. Both C3 and C4 concentrations were significantly lower in patients with high disease severity or non-survivor status than patients with low severity or survivor status (C3 SMD=-0.40, 95% CI -0.60 to -0.21, p<0.001; C4 SMD=-0.29, 95% CI -0.49 to -0.09, p=0.005; moderate certainty of evidence). Extreme between-study heterogeneity was observed (C3, I = 82.1%; C4, I = 84.4%). Sensitivity analysis, performed by sequentially removing each study and re-assessing the pooled estimates, showed that the magnitude and direction of the effect size was not modified. There was no publication bias. In meta-regression, the SMD of C3 was significantly associated with white blood cell count, C-reactive protein (CRP), and pro-thrombin time, whereas the SMD of C4 was significantly associated with CRP, pro-thrombin time, D-dimer, and albumin. In conclusion, lower concentrations of C3 and C4, indicating complement activation, were significantly associated with higher COVID-19 severity and mortality. C3 and C4 might be useful to predict adverse clinical consequences in these patients. PROSPERO, Registration number: CRD42021239634.
Topics: Biomarkers; COVID-19; Complement Activation; Complement C3; Complement C4; Humans; SARS-CoV-2; Severity of Illness Index
PubMed: 34163491
DOI: 10.3389/fimmu.2021.696085 -
Aging Nov 2020COVID-19 patients frequently exhibit coagulation abnormalities and thrombotic events. In this meta-analysis, we investigated the association between coagulopathy and the... (Meta-Analysis)
Meta-Analysis
COVID-19 patients frequently exhibit coagulation abnormalities and thrombotic events. In this meta-analysis, we investigated the association between coagulopathy and the severity of COVID-19 illness. Using PubMed, Embase, Cochrane, WanFang Database, CNKI, and medRxiv, a systematic literature search was conducted for studies published between December 1, 2019 and May 1, 2020. We then analyzed coagulation parameters in COVID-19 patients exhibiting less severe and more severe symptoms. All statistical analyses were performed using Stata14.0 software. A total of 3,952 confirmed COVID-19 patients from 25 studies were included in the meta-analysis. Patients with severe symptoms exhibited higher levels of D-dimer, prothrombin time (PT), and fibrinogen (FIB) than patients with less severe symptoms (SMD 0.83, 95% CI: 0.70-0.97, I 56.9%; SMD 0.39, 95% CI: 0.14-0.64, I 79.4%; and SMD 0.35, 95% CI: 0.17-0.53, I 42.4%, respectively). However, platelet and activated partial thromboplastin times did not differ (SMD -0.26, 95% CI: -0.56-0.05, I 82.2%; and SMD -0.14, 95% CI: -0.45-0.18, I 75.7%, respectively). These findings demonstrate that hypercoagulable coagulopathy is associated with the severity of COVID-19 symptoms and that D-dimer, PT, and FIB values are the main parameters that should be considered when evaluating coagulopathy in COVID-19 patients.
Topics: Biomarkers; Blood Coagulation Disorders; Blood Coagulation Tests; COVID-19; Disease Susceptibility; Humans; Publication Bias; Retrospective Studies; SARS-CoV-2; Sensitivity and Specificity; Severity of Illness Index
PubMed: 33229625
DOI: 10.18632/aging.104138 -
Thrombosis Research Dec 2012Prothrombin complex concentrates are used for rapid reversal of vitamin K antagonists in patients with bleeding or those requiring surgery or invasive procedures.... (Review)
Review
INTRODUCTION
Prothrombin complex concentrates are used for rapid reversal of vitamin K antagonists in patients with bleeding or those requiring surgery or invasive procedures. Current guidelines suggest 4-factor products are preferred over 3-factor prothrombin complex concentrates.
MATERIALS AND METHODS
We performed a systematic review comparing the effectiveness of 3-factor to 4-factor prothrombin complex concentrates in normalizing the international normalized ratio to ≤ 1.5 in patients with acquired coagulopathy due to vitamin K antagonist use. Studies reporting administration of prothrombin complex concentrates for emergent reversal of vitamin K antagonists that included results of baseline prothrombin time/international normalized ratio and follow-up testing within 60 minutes of prothrombin complex concentrates administration were included.
RESULTS
A total of 18 studies were included representing 654 patients. The most common indications for prothrombin complex concentrate were intracerebral hemorrhage, urgent surgery or invasive procedure, and gastrointestinal bleeding. Baseline international normalized ratio values ranged from 3.3-5.1 in the 3-factor group and from 2.3 to greater than 20 in the 4-factor group. The international normalized ratio repeated within one hour of prothrombin complex concentrates administration ranged from 1.2-1.9 in the 3-factor group and 1.0-1.9 in the 4-factor group. International normalized ratio decreased to ≤ 1.5 within one hour after prothrombin complex concentrates administration in 6 of 9 studies in the 3-factor group, and 12 of 13 studies in the 4-factor group.
CONCLUSION
More reliable correction of the international normalized ratio was seen with 4-factor compared to 3-factor prothrombin complex concentrates which may have clinical implications since 4-factor products are unavailable in some countries.
Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Factors; Drug Interactions; Humans; International Normalized Ratio; Middle Aged; Vitamin K; Warfarin; Young Adult
PubMed: 23137921
DOI: 10.1016/j.thromres.2012.10.001 -
Hematology/oncology and Stem Cell... Jun 2022Numerous studies have been published regarding outcomes of cancer patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus causing... (Meta-Analysis)
Meta-Analysis
Numerous studies have been published regarding outcomes of cancer patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus causing the coronavirus disease 2019 (COVID-19) infection. However, most of these are single-center studies with a limited number of patients. To better assess the outcomes of this new infection in this subgroup of susceptible patients, we performed a systematic review and meta-analysis to evaluate the impact of COVID-19 infection on cancer patients. We performed a literature search using PubMed, Web of Science, and Scopus for studies that reported the risk of infection and complications of COVID-19 in cancer patients and retrieved 22 studies (1018 cancer patients). The analysis showed that the frequency of cancer among patients with confirmed COVID-19 was 2.1% (95% confidence interval [CI]: 1.3-3) in the overall cohort. These patients had a mortality of 21.1% (95% CI: 14.7-27.6), severe/critical disease rate of 45.4% (95% CI: 37.4-53.3), intensive care unit (ICU) admission rate of 14.5% (95% CI: 8.5-20.4), and mechanical ventilation rate of 11.7% (95% CI: 5.5-18). The double-arm analysis showed that cancer patients had a higher risk of mortality (odds ratio [OR]=3.23, 95% CI: 1.71-6.13), severe/critical disease (OR=3.91, 95% CI: 2.70-5.67), ICU admission (OR=3.10, 95% CI: 1.85-5.17), and mechanical ventilation (OR=4.86, 95% CI: 1.27-18.65) than non-cancer patients. Furthermore, cancer patients had significantly lower platelet levels and higher D-dimer levels, C-reactive protein levels, and prothrombin time. In conclusion, these results indicate that cancer patients are at a higher risk of COVID-19 infection-related complications. Therefore, cancer patients need diligent preventive care measures and aggressive surveillance for earlier detection of COVID-19 infection.
Topics: Humans; COVID-19; SARS-CoV-2; Respiration, Artificial; Intensive Care Units; Prognosis; Neoplasms
PubMed: 32745466
DOI: 10.1016/j.hemonc.2020.07.005 -
Asian Journal of Surgery Feb 2022As the number of fusion levels increases, the complexity of spinal correction surgery also increases. Thus, we conducted this study to determine the safety and efficacy... (Meta-Analysis)
Meta-Analysis Review
As the number of fusion levels increases, the complexity of spinal correction surgery also increases. Thus, we conducted this study to determine the safety and efficacy of tranexamic acid (TXA) involving eight or more spinal fusion levels. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Assessing the Methodological Quality of Systematic Reviews (AMSTAR) guidelines, a search of the PubMed, Embase, CENTRAL, Web of Science, and ClinicalTrials.gov databases was conducted for relevant studies published prior to May 30, 2019. The primary outcomes, including blood loss and transfusion requirement, and the secondary outcomes, including general indices, postoperative hemoglobin, and coagulation function, were analyzed using Rev Man 5.3.5 software and STATA version 12.0. Eight randomized controlled trials (473 participants) were included in the study. Compared to the control treatments, TXA reduced intraoperative blood loss, total blood loss, transfusion volume, and prothrombin time. There were no significant differences between the TXA and non-TXA groups in transfusion rate, operative time, hospital stay, complications, hemoglobin level, and other coagulation function parameters. In the pediatric subgroup analysis, TXA additionally improved hemoglobin levels, platelet count, and prothrombin time international normalized ratio. The present meta-analysis showed that TXA reduced blood loss and transfusion volume in both adults and children. In pediatric patients, TXA led to a greater benefit in postoperative hemoglobin levels and coagulation function. Intravenous TXA is safe and effective in children with eight or more spinal corrective levels.
Topics: Adult; Antifibrinolytic Agents; Blood Loss, Surgical; Blood Transfusion; Child; Humans; Spine; Tranexamic Acid
PubMed: 34930653
DOI: 10.1016/j.asjsur.2021.06.065 -
Journal of Orthopaedic Surgery and... Jul 2023Calcaneal fractures are a common orthopedic disease, account for approximately 2% of all bone fractures, and represent 60% of fractures of tarsal bones. Tranexamic acid... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Calcaneal fractures are a common orthopedic disease, account for approximately 2% of all bone fractures, and represent 60% of fractures of tarsal bones. Tranexamic acid (TXA) is a synthetic antifibrinolytic drug that competitively blocks the lysine-binding sites of plasminogen, plasmin, and tissue plasminogen activator, delaying fibrinolysis and blood clot degradation. However, the effect of TXA on patients with calcaneal surgery remains controversial. Our objective was to evaluate the effectiveness of TXA in calcaneal fractures surgeries.
METHODS
The electronic literature databases of Pubmed, Embase, and Cochrane library were searched in December 2022. The data on blood loss, the stay in the hospital, the duration of surgery, hemoglobin, hematocrit, platelet count, prothrombin time, activated partial thromboplastin time, and wound complication were extracted. The Stata 22.0 software was used for the meta-analysis.
RESULTS
Four randomized controlled studies met our inclusion criteria. This meta-analysis showed that TXA significantly reduced postoperative blood loss during the first 24 h (p < 0.001), improved the level of hemoglobin (p < 0.001) and hematocrit (p = 0.03), and reduced the risk of wound complications (p = 0.04). There was no significant difference between the two groups regarding total and intraoperative blood loss, hospital stay, duration of surgery, platelet count, activated partial thromboplastin time, and prothrombin time.
CONCLUSION
TXA significantly reduced blood loss during the first 24 h postoperatively, improved the level of hemoglobin and hematocrit, and reduced the risk of wound complications. Given the evidence, TXA can be used in patients with calcaneal fractures and had the potential benefit of blood reduction.
PROTOCOL REGISTRATION
The protocol was registered in PROSPERO (registration No. CRD42023391211).
Topics: Humans; Tranexamic Acid; Tissue Plasminogen Activator; Randomized Controlled Trials as Topic; Calcaneus; Tarsal Bones; Ankle Injuries
PubMed: 37438798
DOI: 10.1186/s13018-023-03924-0 -
Clinical Toxicology (Philadelphia, Pa.) Sep 2017Paracetamol (acetaminophen) poisoning is the most common cause of acute liver failure in the developed world. A paracetamol treatment nomogram has been used for over... (Review)
Review
CONTEXT
Paracetamol (acetaminophen) poisoning is the most common cause of acute liver failure in the developed world. A paracetamol treatment nomogram has been used for over four decades to help determine whether patients will develop hepatotoxicity without acetylcysteine treatment, and thus indicates those needing treatment. Despite this, a small proportion of patients still develop hepatotoxicity. More accurate risk predictors would be useful to increase the early detection of patients with the potential to develop hepatotoxicity despite acetylcysteine treatment. Similarly, there would be benefit in early identification of those with a low likelihood of developing hepatotoxicity, as this group may be safely treated with an abbreviated acetylcysteine regimen.
AIM
To review the current literature related to risk prediction tools that can be used to identify patients at increased risk of hepatotoxicity.
METHODS
A systematic literature review was conducted using the search terms: "paracetamol" OR "acetaminophen" AND "overdose" OR "toxicity" OR "risk prediction rules" OR "hepatotoxicity" OR "psi parameter" OR "multiplication product" OR "half-life" OR "prothrombin time" OR "AST/ALT (aspartate transaminase/alanine transaminase)" OR "dose" OR "biomarkers" OR "nomogram". The search was limited to human studies without language restrictions, of Medline (1946 to May 2016), PubMed and EMBASE. Original articles pertaining to the theme were identified from January 1974 to May 2016. Of the 13,975 articles identified, 60 were relevant to the review. Paracetamol treatment nomograms: Paracetamol treatment nomograms have been used for decades to help decide the need for acetylcysteine, but rarely used to determine the risk of hepatotoxicity with treatment. Reported paracetamol dose and concentration: A dose ingestion >12 g or serum paracetamol concentration above the treatment thresholds on the paracetamol nomogram are associated with a greater risk of hepatotoxicity. Paracetamol elimination half-life: Patients with more severe hepatotoxicity are more likely to have a longer paracetamol elimination half-life. While median elimination half-life increases in those developing hepatotoxicity, there is wide variation in half-life, making this an insensitive parameter to use as a negative risk prediction tool. Prothrombin time (PT): An initially normal PT is associated with a lower risk of developing hepatotoxicity, but cannot be used alone to identify patients not requiring acetylcysteine treatment. Hepatic aminotransferase activity: A normal ALT activity on presentation is associated with a high negative predictive value of hepatotoxicity following paracetamol-poisoning. Psi parameter: The psi parameter takes into account the time from ingestion, the serum paracetamol concentration and the time to initiation of acetylcysteine. A hepatotoxicity risk nomogram based on this parameter may be easier to use, but is limited to acute ingestions. Paracetamol-aminotransferase multiplication product: If a hepatotoxicity risk nomogram is not available, an alternate strategy may be to use the paracetamol-aminotransferase product (<1500 low risk, 1500-10,000 low to moderate risk, >10,000 mg/L × IU/L high risk) to define liver injury risk. Serial blood tests can be performed if patients present prior to 8 h post-overdose for ultimate specificity, or a single blood test can be taken if presenting more than 8 h post-overdose. Patients receiving acetylcysteine within 8 h of their overdose, with a product less than 10,000 mg/L × IU/L have a low likelihood of developing hepatotoxicity. Any clinical trials of intensified treatment (e.g., higher dose) to prevent fulminant hepatic failure might potentially use a product of >10,000 mg/L × IU/L as a criterion for inclusion. The paracetamol-aminotransferase product <1500 mg/L × IU/L may also identify those suitable for an abbreviated acetylcysteine regimen. Newer biomarkers: These show promise in the early identification of patients with a higher risk of developing hepatic injury. Point of care devices measuring paracetamol adducts need further trials.
CONCLUSIONS
Risk prediction tools can stratify those that are more likely to develop hepatotoxicity. Currently, the paracetamol-aminotransferase multiplication product may be such a tool. Novel biomarkers show promise but need further validation and greater clinical availability. These tools may help inform clinical trials on modified acetylcysteine regimens.
Topics: Acetaminophen; Acetylcysteine; Alanine Transaminase; Analgesics, Non-Narcotic; Antioxidants; Biomarkers; Blood Coagulation; Chemical and Drug Induced Liver Injury; Decision Support Techniques; Humans; Liver; Liver Function Tests; Nomograms; Predictive Value of Tests; Prognosis; Prothrombin Time; Risk Assessment; Risk Factors; Severity of Illness Index
PubMed: 28447858
DOI: 10.1080/15563650.2017.1317349 -
Advanced Biomedical Research 2020Since the start of coronavirus epidemic in Wuhan, China, in early December 2019, many literatures addressed its epidemiology, virology, and clinical presentation. In...
BACKGROUND
Since the start of coronavirus epidemic in Wuhan, China, in early December 2019, many literatures addressed its epidemiology, virology, and clinical presentation. In this review, we systematically reviewed the published literature in the field of liver function tests profile in COVID-19 patients at the admission time.
MATERIALS AND METHODS
systematic literature search were performed in EMBASE, PubMed, Science Direct, and Scopus using "severe acute respiratory syndrome 2 coronavirus (SARS-CoV-2)", "SARS," "SARS-CoV," "coronavirus," "novel coronavirus," "liver," "hepatitis," "Liver function" keywords. The search was limited to range from 2019 to May 19, 2020.
RESULTS
From a total 7298 articles, 145 were screened and 18 were eligible for further analysis. The highest rate of liver associated comorbidities was reported 11%. The aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were the most frequent assessed enzymes. Increase in AST level was seen in 10%-53% of patients while The ALT increase was seen in 5%-28% of COVID-19 patients at the admission time. The prothrombin time was increase in 7%-12% of patients and the D-dimer was reports increase in 14%-36% of COVID-19 patients at the admission time. Furthermore, albumin decrease was seen in 6%-98% of COVID-19 patients at the admission time.
CONCLUSION
In conclusion, by using the results of study, it could be suggested that the liver function tests assessment is critical assessment in COVID-19 patients at the admission time. This liver function test could be used as potential prognostic factor in COVID-19 severity in future.
PubMed: 33912490
DOI: 10.4103/abr.abr_73_20 -
Journal of Personalized Medicine Sep 2022Vitamin K antagonists (VKAs) are used in the prophylaxis and treatment of thromboembolic disorders. Despite a high efficacy, their narrow therapeutic window and high... (Review)
Review
Vitamin K antagonists (VKAs) are used in the prophylaxis and treatment of thromboembolic disorders. Despite a high efficacy, their narrow therapeutic window and high response variability hamper their management. Several patients experience fluctuations in dose−response and are at increased risk of over- or under-anticoagulation. Therefore, it is essential to monitor the prothrombin time/international normalized ratio to determine the so-called stable dose and to adjust the dosage accordingly. Three polymorphisms, CYP2C9∗2, CYP2C9∗3 and VKORC1-1639G>A, are associated with increased sensitivity to VKAs. Other polymorphisms are associated with a request for a higher dose and VKA resistance. We described the clinical cases of two patients who were referred to the Clinical Pharmacology and Pharmacogenetics Unit of the University Hospital of Salerno for pharmacological counseling. One of them showed hypersensitivity and the other one was resistant to VKAs. A systematic review was performed to identify randomized clinical trials investigating the impact of pharmacogenetic testing on increased sensitivity and resistance to VKAs. Although international guidelines are available and information on the genotype-guided dosing approach has been included in VKA drug labels, VKA pharmacogenetic testing is not commonly required. The clinical cases and the results of the systematically reviewed RCTs demonstrate that the pharmacogenetic-based VKA dosing model represents a valuable resource for reducing VKA-associated adverse events.
PubMed: 36294717
DOI: 10.3390/jpm12101578