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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 -
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 -
Journal of Acute Medicine Sep 2021Optimal management for trauma-induced coagulopathy (TIC) is a clinical conundrum. In conjunction with the transfusion of fresh-frozen plasma (FFP), additional...
BACKGROUND
Optimal management for trauma-induced coagulopathy (TIC) is a clinical conundrum. In conjunction with the transfusion of fresh-frozen plasma (FFP), additional administration of prothrombin complex concentrate (PCC) was proposed to bring about further coagulative benefit. However, investigations evaluating the efficacy as well as corresponding side effects were scarce and inconsistent. The aim of this study was to systematically review current literature and to perform a meta-analysis comparing FFP+PCC with FFP alone.
METHODS
Web search followed by manual interrogation was performed to identify relevant literatures fulfilling the following criteria, subjects as TIC patients taking no baseline anticoagulants, without underlying coagulative disorders, and reported clinical consequences. Those comparing FFP alone with PCC alone were excluded. Comprehensive Meta-analysis software was utilized, and statistical results were delineated with odd ratio (OR), mean difference (MD), and 95% confidence interval (CI). I was calculated to determine heterogeneity. The primary endpoint was set as all-cause mortality, while the secondary endpoint consisted of international normalized ratio (INR) correction, transfusion of blood product, and thrombosis rate.
RESULTS
One hundred and sixty-four articles were included for preliminary evaluation, 3 of which were qualified for meta-analysis. A total of 840 subjects were pooled for assessment. Minimal heterogeneity was present in the comparisons (I < 25%). In the PCC + FFP cohort, reduced mortality rate was observed (OR: 0.631; 95% CI: 0.450-0.884, = 0.007) after pooling. Meanwhile, INR correction time was shorter under PCC + FFP (MD: -608.300 mins, < 0.001), whilst the rate showed no difference ( = 0.230). The PCC + FFP group is less likely to mandate transfusion of packed red blood cells ( < 0.001) and plasma ( < 0.001), but not platelet ( = 0.615). The incidence of deep vein thrombosis was comparable in the two groups ( = 0.460).
CONCLUSIONS
Compared with FFP only, PCC + FFP demonstrated better survival rate, favorable clinical recovery and no elevation of thromboembolism events after TIC.
PubMed: 34595091
DOI: 10.6705/j.jacme.202109_11(3).0001 -
The Cochrane Database of Systematic... Sep 2017People with hemophilia A or B with inhibitors are at high risk of bleeding complications. Infusion of bypassing agents, such as recombinant activated FVII (rFVIIa) and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
People with hemophilia A or B with inhibitors are at high risk of bleeding complications. Infusion of bypassing agents, such as recombinant activated FVII (rFVIIa) and plasma-derived activated prothrombin complex concentrate, are suggested as alternative therapies to factor VIII (haemophilia A) or IX (haemophilia B) for individuals who no longer respond to these treatments because they develop inhibitory antibodies. The ultimate goal of treatment is to preserve the individual's joints, otherwise destroyed by recurrent bleeds.
OBJECTIVES
To assess the effects of bypassing agent prophylaxis to prevent bleeding in people with hemophilia A or B and inhibitors.
SEARCH METHODS
We searched for relevant studies from the Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, comprising of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched trial registries (16 February 2017) and bibliographic references of retrieved studies were reviewed for potential articles to be included in the review.Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Coagulopathies Trials Register: 12 December 2016.
SELECTION CRITERIA
We included randomized and quasi-randomized controlled studies (cross-over or parallel design) evaluating the effect of prophylaxis treatment with bypassing agents compared with on-demand treatment, or studies evaluating the effects of high-dose compared with low-dose prophylaxis in males of any age with hemophilia with inhibitors.
DATA COLLECTION AND ANALYSIS
Two authors independently selected studies and extracted data and assessed the risk of bias according to standard Cochrane criteria. They assessed the quality of the evidence using the GRADE criteria.
MAIN RESULTS
We included four randomized studies (duration 7 to 15 months) involving 116 males. Risk of bias was judged to be high in two studies due to the open-label study design and in one study due to attrition bias.Two studies compared on-demand treatment to prophylaxis with bypassing agents. In one study (34 males) prophylaxis significantly reduced mean overall bleeding rates, MD - 7.27 (95% CI -9.92 to -4.62) (low quality evidence), mean number of overall bleeding events per month, MD -1.10 (95% CI -1.54 to -0.66), mean number of hemarthrosis, MD -6.60 (95% CI -9.32 to -3.88) (low quality evidence) and mean number of joints that had hemarthrosis, MD -0.90 (95% CI -1.36 to -0.44). The meta-analysis did not conclusively demonstrate significant benefit of prophylaxis on health-related quality of life as measured by Haem-A-QoL score, EQ-5D total score and utility score, EQ-5D VAS and SF-36 physical summary and mental summary score (low quality evidence for all health-related quality of life analyses).The remaining two studies compared dose regimens. The results from one study (22 males) did not conclusively demonstrate benefit or harm of high-dose versus low-dose recombinant activated factor VIIa (rFVIIa) as a prophylaxis for overall bleeding rate, MD -0.82 (95% CI -2.27 to 0.63) (moderate quality evidence), target joint bleeding rate, MD -3.20 (95% CI -7.23 to 0.83) (moderate quality evidence) and serious adverse events, RR 9.00 (95% CI, 0.54 to 149.50) (moderate quality evidence).The overall quality of evidence was moderate to low due to imprecision from limited information provided by studies with small sample sizes and incomplete outcome data in one study.
AUTHORS' CONCLUSIONS
The evidence suggests that prophylaxis with bypassing agents may be effective in reducing bleeding in males with hemophilia with inhibitors. However, there is a lack of evidence for the superiority of one agent over the other or for the optimum dosage regimen. Further studies are needed to evaluate the benefits and harms of prophylaxis treatment on health-related quality of life, as well as the effects of dose of bypassing agents on the outcomes.
Topics: Coagulants; Factor VIIa; Hemarthrosis; Hemophilia A; Hemophilia B; Humans; Male; Prothrombin; Randomized Controlled Trials as Topic; Recombinant Proteins
PubMed: 28944952
DOI: 10.1002/14651858.CD011441.pub2 -
International Wound Journal Oct 2021Livedoid vasculopathy (LV) is considered a disease of hypercoagulability. Association of LV with genetic variants is poorly characterised and large-scale genetic...
Livedoid vasculopathy (LV) is considered a disease of hypercoagulability. Association of LV with genetic variants is poorly characterised and large-scale genetic association studies have not been performed. The aim of the study was to systematically review variants in LV patients and to analyse the available clinical data. A systematic search of the literature in PubMed and Embase databases was performed to identify articles investigating genetic variation in LV patients. Thirty studies or case reports were identified that reported 265 LV patients tested for at least one out of six genetic variations. Among them, PAI-1 -675 4G/5G was the most common, accounting for 85.26% (81/95). Heterozygous 4G/5G was the major genotype. PAI-1 A844G, MTHFR C677T, and MTHFR A1298C were the second, third, and fourth most common variants in LV patients. Prothrombin G20210A and Factor V G1691A were mainly present in LV patients from Europe, North America, and South America. This review highlights the associations between LV and genetic variants. The distribution of variants may be geographically or ethnicity dependent; however, large sample case-control studies are needed to clarify associations.
Topics: Case-Control Studies; Factor V; Genotype; Homocystinuria; Humans; Methylenetetrahydrofolate Reductase (NADPH2); Prothrombin
PubMed: 33686673
DOI: 10.1111/iwj.13563 -
The Annals of Thoracic Surgery Apr 2019Prothrombin complex concentrate (PCC) has recently emerged as an effective alternative to fresh frozen plasma (FFP) in treating excessive perioperative bleeding. This... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Prothrombin complex concentrate (PCC) has recently emerged as an effective alternative to fresh frozen plasma (FFP) in treating excessive perioperative bleeding. This systematic review and meta-analysis evaluated the safety and efficacy of PCC administration as first-line treatment for coagulopathy after adult cardiac surgery.
METHODS
PubMed/MEDLINE, EMBASE, and the Cochrane Library were searched from inception to the end of March 2018 to identify eligible articles. Adult patients undergoing cardiac surgery and receiving perioperative PCC were compared with patients receiving FFP.
RESULTS
A total of 861 adult patients from four studies were retrieved. No randomized studies were identified. Pooled odds ratios (ORs) showed that the PCC cohort was associated with a significant reduction in the risk of RBC transfusion (OR, 2.22; 95% confidence interval [CI], 1.45 to 3.40) and units of RBC received (OR, 1.34; 95% CI, 0.78 to 1.90). No differences were observed between the groups for reexploration for bleeding (OR, 1.09; 95% CI, 0.66 to 1.82), chest drain output at 24 hours (OR, 66.36; 95% CI, -82.40 to 216.11), hospital mortality (OR, 0.94; 95% CI, 0.59 to 1.49), stroke (OR, 0.80; 95% CI, 0.41 to 1.56), and occurrence of acute kidney injury (OR, 0.80; 95% CI, 0.58 to 1.12). A trend toward increased risk of renal replacement therapy was observed in the PCC group (OR, 0.41; 95% CI, 0.16 to 1.02).
CONCLUSIONS
In patients with significant bleeding after cardiac surgery, PCC administration seems to be more effective than FFP in reducing perioperative blood transfusions. No additional risks of thromboembolic events or other adverse reactions were observed. Randomized controlled trials are needed to establish the safety of PCC in cardiac surgery definitively.
Topics: Blood Coagulation Factors; Cardiac Surgical Procedures; Female; Humans; Male; Plasma; Postoperative Hemorrhage; Prognosis; Risk Assessment; Treatment Outcome
PubMed: 30458156
DOI: 10.1016/j.athoracsur.2018.10.013 -
Seminars in Thrombosis and Hemostasis Feb 2022Patients admitted to the intensive care unit (ICU) with coronavirus disease 2019 (COVID-19), the infectious pathology caused by severe acute respiratory syndrome...
Patients admitted to the intensive care unit (ICU) with coronavirus disease 2019 (COVID-19), the infectious pathology caused by severe acute respiratory syndrome coronavirus 2, have a high risk of thrombosis, though the precise mechanisms behind this remain unclarified. A systematic literature search in PubMed and EMBASE identified 18 prospective studies applying dynamic coagulation assays in ICU COVID-19 patients. Overall, these studies revealed normal or slightly reduced primary hemostasis, prolonged clot initiation, but increased clot firmness. Thrombin generation assay parameters generally were equivalent to the control groups or within reference range. Fibrinolysis assays showed increased clot resistance. Only six studies related their findings to clinical outcome. We also prospectively included 51 COVID-19 patients admitted to the ICU. Blood samples were examined on day 1, 3-4, and 7-8 with platelet function tests, rotational thromboelastometry (ROTEM), in vivo and ex vivo thrombin generation, and clot lysis assay. Data on thrombosis, bleeding, and mortality were recorded during 30 days. Primary hemostasis was comparable to healthy controls, but COVID-19 patients had longer ROTEM-clotting times and higher maximum clot firmness than healthy controls. Ex vivo thrombin generation was similar to that of healthy controls while in vivo thrombin generation markers, thrombin-antithrombin (TAT) complex, and prothrombin fragment 1 + 2 (F1 + 2) were higher in ICU COVID-19 patients than in healthy controls. Impaired fibrinolysis was present at all time points. TAT complex and F1 + 2 levels were significantly higher in patients developing thrombosis ( = 16) than in those without. In conclusion, only few previous studies employed dynamic hemostasis assays in COVID-19 ICU-patients and failed to reveal a clear association with development of thrombosis. In ICU COVID-19 patients, we confirmed normal platelet aggregation, while in vivo thrombin generation was increased and fibrinolysis decreased. Thrombosis may be driven by increased thrombin formation in vivo.
Topics: Blood Coagulation Tests; COVID-19; Cohort Studies; Critical Care; Fibrinolysis; Hemostasis; Humans; Prospective Studies; SARS-CoV-2; Thrombelastography; Thrombin; Thrombosis
PubMed: 34715692
DOI: 10.1055/s-0041-1735454 -
Journal of Medical Virology Oct 2020Recently, Coronavirus Disease 2019 (COVID-19) pandemic is the most significant global health crisis. In this study, we conducted a meta-analysis to find the association... (Meta-Analysis)
Meta-Analysis
Recently, Coronavirus Disease 2019 (COVID-19) pandemic is the most significant global health crisis. In this study, we conducted a meta-analysis to find the association between liver injuries and the severity of COVID-19 disease. Online databases, including PubMed, Web of Science, Scopus, and Science direct, were searched to detect relevant publications up to 16 April 2020. Depending on the heterogeneity between studies, a fixed- or random-effects model was applied to pool data. Publication bias Egger's test was also performed. Meta-analysis of 20 retrospective studies (3428 patients), identified that patients with a severe manifestation of COVID-19 exhibited significantly higher levels of alanine aminotransferase, aspartate aminotransferase, and bilirubin values with prolonged prothrombin time. Furthermore, lower albumin level was associated with a severe presentation of COVID-19. Liver dysfunction was associated with a severe outcome of COVID-19 disease. Close monitoring of the occurrence of liver dysfunction is beneficial in early warning of unfavorable outcomes.
Topics: Alanine Transaminase; Aspartate Aminotransferases; Bilirubin; COVID-19; Humans; Liver; Liver Diseases; Prothrombin Time
PubMed: 32445489
DOI: 10.1002/jmv.26055 -
Clinical and Applied... Jul 2018Anticoagulation therapy is administered to patients to prevent or stop thrombin generation in vivo. Although plasma tests of in vivo thrombin generation have been... (Review)
Review
Anticoagulation therapy is administered to patients to prevent or stop thrombin generation in vivo. Although plasma tests of in vivo thrombin generation have been available for more than 2 decades, they are not routinely used in clinical trials or practice to monitor anticoagulation therapy. We observed a fall in one such marker, the D-dimer antigen, in patients receiving anticoagulation therapy. We therefore conducted a systematic review of the medical literature to document the change in serum biomarkers of thrombin generation following the initiation of anticoagulation therapy. Using a defined search strategy, we screened PubMed and Embase citations and identified full-length articles published in English. Eighteen articles containing serial changes in 1 of 3 markers of thrombin generation (D-dimer antigen, thrombin-antithrombin complexes, and prothrombin fragment 1+2 antigen levels) in the 14 days following the initiation of anticoagulation were identified. Even though the assays used varied considerably, each of the 3 markers of thrombin generation declined in the initial period of anticoagulation therapy, with changes evident as early as 1 day after beginning therapy. These observations provide a rationale for further exploration of these markers as measures of the adequacy of anticoagulation using classic as well as novel anticoagulants. Particular patient groups that would benefit from additional means of monitoring anticoagulation therapy are discussed.
Topics: Anticoagulants; Biomarkers; Drug Monitoring; Humans; Infusions, Parenteral; Thrombin
PubMed: 29439639
DOI: 10.1177/1076029617746506