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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 -
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 -
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 -
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 -
Journal of Clinical Laboratory Analysis Jul 2022Hypercoagulability in lung cancer patients is associated with a high incidence of mortality and morbidity in the world. Therefore, this meta-analysis aimed to explore... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hypercoagulability in lung cancer patients is associated with a high incidence of mortality and morbidity in the world. Therefore, this meta-analysis aimed to explore the correlation of the basic coagulation abnormalities in lung cancer patients compared with the control.
METHOD
PubMed, Scopus, and other sources were employed to identify eligible studies. The outcome variable was expressed using mean ± standard deviation (SD). Heterogeneity among studies and publication bias were evaluated. The quality of included studies was also assessed based on Newcastle-Ottawa Scale checklist.
RESULT
Finally, through a total of eight studies, prolonged prothrombin time (PT; standard mean difference [SMD]: 1.29; 95% CI: 0.47-2.11), plasma D-dimer value (SMD 3.10; 95% CI 2.08-4.12), fibrinogen (SMD 2.18; 95% CI:1.30-3.06), and platelet (PLT) count (SMD 1.00; 95% CI 0.84-1.16) were significantly higher in lung cancer patients when compared with the control group. The single-arm meta-analysis also showed that compared with control, lung cancer patients had high pooled PT 13.7 (95% CI:12.2-15.58) versus 11.79 (95% CI = 10.56-13.02), high D-dimer 275.99 (95% CI:172.9-11735.9) versus 0.2 (95% CI:0.20-0.37), high plasma fibrinogen 5.50 (95% CI:4.21-6.79) versus 2.5 (95% CI:2.04-2.91), and high PLT count 342.3 (95% CI:236.1-448.5) versus 206.6 (95% CI:176.4-236.7).
CONCLUSION
In conclusion, almost all the coagulation abnormalities were closely associated with lung cancer, and hence coagulation indexes provide an urgent clue for early diagnosis and timely management.
Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; Lung Neoplasms
PubMed: 35719003
DOI: 10.1002/jcla.24550 -
AIDS Research and Treatment 2022Coagulation abnormalities are common complications of human immunodeficiency virus (HIV) infection. Highly active antiretroviral treatment (HAART) decreased the... (Review)
Review
BACKGROUND
Coagulation abnormalities are common complications of human immunodeficiency virus (HIV) infection. Highly active antiretroviral treatment (HAART) decreased the mortality of HIV but increased coagulopathies. HIV-related thrombocytopenia, prolonged prothrombin time (PT), activated partial thromboplastin time (APTT), and high D-dimer level commonly manifested in patients with HIV. Thus, this study is aimed to compare coagulation parameters of HAART-treated and HAART-naïve HIV-infected patients with HIV-seronegative controls.
METHODS
A systematic literature search was conducted using the databases PubMed/MEDLINE, Embase, Web of Science, and Google Scholar of studies published until July 2021. The primary outcome of interest was determining the pooled mean difference of coagulation parameters between HIV-infected patients and seronegative controls. The Joana Briggs Institute (JBI) critical appraisal tool was used for quality appraisal. Statistical analyses were performed using Stata11.0 software. The statistical results were expressed as the effect measured by standardized mean difference (SMD) with their related 95% confidence interval (CI).
RESULTS
A total of 7,498 participants (1,144 HAART-naïve patients and 2,270 HAART-treated HIV-infected patients and 3,584 HIV-seronegative controls) from 18 studies were included. HIV-infected patients (both on HAART and HAART-naive) exhibited significantly higher levels of PT than HIV-seronegative controls (SMD = 0.66; 95% CI: 0.53-0.80 and SMD = 1.13; 95% CI: 0.60-2.0, respectively). The value of APTT was significantly higher in patients with HIV on HAART than in seronegative controls. However, the values of PLT count, APTT, and fibrinogen level were significantly higher in seronegative controls. Besides, the level of fibrinogen was significantly higher in HAART-treated than treatment-naïve patients (SMD = 0.32; 95%CI: 0.08, 0.57). Moreover, the level of APTT and PT had no statistical difference between HAART and HAART-naïve HIV-infected patients.
CONCLUSIONS
This study identified that HIV-infected patients are more likely to develop coagulation abnormalities than HIV-seronegative controls. Therefore, coagulation parameters should be assessed regularly to prevent and monitor coagulation disorders in HIV-infected patients.
PubMed: 35492260
DOI: 10.1155/2022/6782595 -
Journal of Clinical Anesthesia Apr 2020The aim of this study is to evaluate the safety and efficacy of Viscoelastic Haemostatic Assays (VHA) to guide transfusions in patients undergoing surgical procedures. (Review)
Review
OBJECTIVE
The aim of this study is to evaluate the safety and efficacy of Viscoelastic Haemostatic Assays (VHA) to guide transfusions in patients undergoing surgical procedures.
DESIGN
Systematic review with meta-analysis of randomized controlled trials up until June 5, 2019.
SETTING
Hospitalized patients.
INTERVENTIONS
VHAs compared to the Standard-Of-Care (SOC), which are represented by standard laboratory tests and/or clinical decisions.
MEASUREMENTS
Primary - Risk of death, acute kidney injury, thrombotic events and reoperation for bleeding; Secondary - Risk of use of red blood cells (RBC), platelets, fresh frozen plasma (FFP), fibrinogen, factor VIIa, prothrombin complex, volume of RBC, platelets and FFP, length of hospital stay, and length of ICU stay.
RESULTS
VHAs were associated to a statistically significant reduction in mortality (7.3% vs. 12.1%; RR = 0.64, p-value = 0.03), risk of acute kidney injury (10.5% vs. 17.6%; RR = 0.53, p-value = 0.005), volume of red blood cells (RBCs) transfused (MD = -1.63 U, p-value = 0.02), risk of platelet transfusion (23.9% vs. 27.3%; RR = 0.74, p-value = 0.006), risk of fresh frozen plasma (FFP) transfusion (RR = 0.57, p-value = 0.001), and volume of FFP transfused (MD = -0.90, p-value = 0.0003). No significant differences were observed in terms of thrombotic events, reexploration for bleeding, RBC transfusion, volume of platelets transfused, use of fibrinogen, prothrombin complex, or factor VIIa, length of hospitalization and length of ICU stay.
CONCLUSION
Viscoelastic haemostatic assays are safe and efficacious for coagulation control in patients undergoing surgical procedures, therefore it should be considered for use in practice.
PubMed: 32299044
DOI: 10.1016/j.jclinane.2020.109809 -
Thrombosis and Haemostasis Apr 2020The aim of the study is to perform a systematic review on the recent available evidence on antiphosphatidylserine/prothrombin (aPS/PT) antibodies and their...
OBJECTIVE
The aim of the study is to perform a systematic review on the recent available evidence on antiphosphatidylserine/prothrombin (aPS/PT) antibodies and their association with clinical manifestations of the antiphospholipid syndrome (APS).
METHODS
A detailed literature search was applied to Ovid MEDLINE, In-Process and Other Non-Indexed Citation 2012 to present and to abstract from EULAR and ACR/ARHP Annual Meetings (2012-2019).
RESULTS
Data from 2,901 patients, 587 diseases controls and 559 healthy controls included in 15 retrieved studies was analyzed. The patient population included 1,219 patients classified as APS according to the Sidney criteria, 285 patients with isolated persistently positive antiphospholipid antibodies (aPL) and 1,397 patients with a clinical suspicion of APS. Twelve studies, including 1,888 patients, analyzed the association between aPS/PT antibodies and thrombosis. We observed a statistically significant association between aPS/PT IgG/IgM positivity and thrombotic events (mean odds ratio [OR]: 6.8 [95% CI: 3.18-16.4], < 0.05), confirmed when analyzing aPS/PT IgG (mean OR: 6.7 [95% CI: 3.04-21.6], < 0.05) and aPS/PT IgM (mean OR: 4.35 [95% CI: 1.54-17.77], 0.05) separately. Seven studies, including 1,388 patients, evaluated the association between aPS/PT antibodies and PM. When pooled together, we found a statistically significant association between any PM and aPS/PT IgG/IgM positivity (mean OR: 10.6 [95% CI: 3.54-35.38], 0.05), particularly aPS/PT IgG positivity (mean OR: 6.7 [95% CI: 3.04-21.6], 0.05).
CONCLUSION
Our results highlight the strong association between aPS/PT and the clinical manifestations of APS. With the available level of evidence, aPS/PT testing can be considered as a robust test applicable in the investigation of patients suspected for APS, also beyond the research settings.
Topics: Animals; Antiphospholipid Syndrome; Autoantibodies; Humans; Phosphatidylserines; Prothrombin; Seroepidemiologic Studies; Thrombosis
PubMed: 32185783
DOI: 10.1055/s-0040-1705115 -
Cureus Feb 2024The conventional method of heparin and protamine management during cardiopulmonary bypass (CPB) is based on total body weight which fails to account for the... (Review)
Review
BACKGROUND
The conventional method of heparin and protamine management during cardiopulmonary bypass (CPB) is based on total body weight which fails to account for the heterogeneous response to heparin in each patient. On the other hand, the literature is inconclusive on whether individualized anticoagulation management based on real-time blood heparin concentration improves post-CBP outcomes.
METHODS
We searched databases of Medline, Excerpta Medica dataBASE (EMBASE), PubMed, Cumulative Index to Nursing and Allied Health Literature (CINHL), and Google Scholar, recruiting randomized controlled trials (RCTs) and prospective studies comparing the outcomes of dosing heparin and/or protamine based on measured heparin concentration versus patient's total body weight for CPB. Random effects meta-analyses and meta-regression were conducted to compare the outcome profiles. Primary endpoints include postoperative blood loss and the correlation with heparin and protamine doses, the reversal protamine and loading heparin dose ratio; secondary endpoints included postoperative platelet counts, antithrombin III, fibrinogen levels, activated prothrombin time (aPTT), incidences of heparin rebound, and re-exploration of chest wound for bleeding.
RESULTS
Twenty-six studies, including 22 RCTs and four prospective cohort studies involving 3,810 patients, were included. Compared to body weight-based dosing, patients of individualized, heparin concentration-based group had significantly lower postoperative blood loss (mean difference (MD)=49.51 mL, 95% confidence interval (CI): 5.33-93.71), lower protamine-to-heparin dosing ratio (MD=-0.20, 95% CI: -0.32 ~ -0.12), and higher early postoperative platelet counts (MD=8.83, 95% CI: 2.07-15.59). The total heparin doses and protamine reversal were identified as predictors of postoperative blood loss by meta-regression.
CONCLUSIONS
There was a significant correlation between the doses of heparin and protamine with postoperative blood loss; therefore, précised dosing of both could be critical for reducing bleeding and transfusion requirements. Data from the enrolled studies indicated that compared to conventional weight-based dosing, individualized, blood concentration-based heparin and protamine dosing may have outcome benefits reducing postoperative blood loss. The dosing calculation of heparin based on the assumption of a one-compartment pharmacokinetic/pharmacodynamic (PK/PD) model and linear relationship between the calculated dose and blood heparin concentration may be inaccurate. With the recent advancement of the technologies of machine learning, individualized, precision management of anticoagulation for CPB may be possible in the near future.
PubMed: 38357407
DOI: 10.7759/cureus.54144 -
Cureus Dec 2021Direct oral anticoagulants (DOAC) including factor Xa inhibitors are associated with bleeding events which can lead to severe morbidity and mortality. Reversal agents... (Review)
Review
Direct oral anticoagulants (DOAC) including factor Xa inhibitors are associated with bleeding events which can lead to severe morbidity and mortality. Reversal agents like andexanet alfa (AA) and 4F-PCC (Four-factor prothrombin concentrate complex) are available for treating bleeding that occurs with DOAC therapy but a comparison on their efficacy is lacking. In this study, we analyzed the efficacy and safety of patients treated with andexanet alfa for bleeding events from DOAC. Databases were searched for relevant studies where AA was used to determine efficacy and safety in bleeding patients who were on factor Xa inhibitors. Published papers were screened independently by two authors. RevMan 5.4 (The Cochrane Collaboration, 2020) was used for data synthesis. Odds ratio (OR) and mean difference (MD) was used to estimate the outcome with a 95% confidence interval (CI). Among 1245 studies were identified after a thorough database search and three studies were included for analysis. AA resulted in lower odds of mortality compared to 4F- PCC (OR, 0.37; 95% CI, 0.20-0.71) among patients with intracerebral hemorrhage. There was no difference in thrombotic events between patients receiving AA and 4F-PCC (OR, 2.40; 95% CI, 0.36-15.84). No differences in length of hospital stay and intensive care unit (ICU) stay were seen between patients receiving AA and 4F-PCC. In conclusion, andexanet alfa reduced in-hospital mortality in patients who had bleeding due to factor Xa inhibitors compared to 4F-PCC. However, there were no differences in thrombotic events, length of ICU, and hospital stay between patients treated with AA and 4F-PCC.
PubMed: 35103198
DOI: 10.7759/cureus.20632