-
Critical Care (London, England) Nov 2023Trauma-induced coagulopathy (TIC) is common in trauma patients with major hemorrhage. Prothrombin complex concentrate (PCC) is used as a potential treatment for the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Trauma-induced coagulopathy (TIC) is common in trauma patients with major hemorrhage. Prothrombin complex concentrate (PCC) is used as a potential treatment for the correction of TIC, but the efficacy, timing, and evidence to support its use in injured patients with hemorrhage are unclear.
METHODS
A systematic search of published studies was performed on MEDLINE and EMBASE databases using standardized search equations. Ongoing studies were identified using clinicaltrials.gov. Studies investigating the use of PCC to treat TIC (on its own or in combination with other treatments) in adult major trauma patients were included. Studies involving pediatric patients, studies of only traumatic brain injury (TBI), and studies involving only anticoagulated patients were excluded. Primary outcomes were in-hospital mortality and venous thromboembolism (VTE). Pooled effects of PCC use were reported using random-effects model meta-analyses. Risk of bias was assessed for each study, and we used the Grading of Recommendations Assessment, Development, and Evaluation to assess the quality of evidence.
RESULTS
After removing duplicates, 1745 reports were screened and nine observational studies and one randomized controlled trial (RCT) were included, with a total of 1150 patients receiving PCC. Most studies used 4-factor-PCC with a dose of 20-30U/Kg. Among observational studies, co-interventions included whole blood (n = 1), fibrinogen concentrate (n = 2), or fresh frozen plasma (n = 4). Outcomes were inconsistently reported across studies with wide variation in both measurements and time points. The eight observational studies included reported mortality with a pooled odds ratio of 0.97 [95% CI 0.56-1.69], and five reported deep venous thrombosis (DVT) with a pooled OR of 0.83 [95% CI 0.44-1.57]. When pooling the observational studies and the RCT, the OR for mortality and DVT was 0.94 [95% CI 0.60-1.45] and 1.00 [95% CI 0.64-1.55] respectively.
CONCLUSIONS
Among published studies of TIC, PCCs did not significantly reduce mortality, nor did they increase the risk of VTE. However, the potential thrombotic risk remains a concern that should be addressed in future studies. Several RCTs are currently ongoing to further explore the efficacy and safety of PCC.
Topics: Adult; Humans; Child; Venous Thromboembolism; Blood Coagulation Factors; Blood Coagulation Disorders; Hemorrhage; Randomized Controlled Trials as Topic
PubMed: 37919775
DOI: 10.1186/s13054-023-04688-z -
International Journal of Laboratory... May 2016Monitoring warfarin with Fiix-prothrombin time (Fiix-PT), which is only affected by coagulation factors II and X, stabilizes anticoagulation and reduces thromboembolism... (Meta-Analysis)
Meta-Analysis Review
Fiix-prothrombin time monitoring improves warfarin anticoagulation outcome in atrial fibrillation: a systematic review of randomized trials comparing Fiix-warfarin or direct oral anticoagulants to standard PT-warfarin.
BACKGROUND
Monitoring warfarin with Fiix-prothrombin time (Fiix-PT), which is only affected by coagulation factors II and X, stabilizes anticoagulation and reduces thromboembolism compared to PT/INR monitoring. We compared outcome in nonvalvular atrial fibrillation (NVAF) patients treated with Fiix-warfarin, direct oral anticoagulants (DOACs), or PT-warfarin.
METHODS
A systematic efficacy and safety assessment by retrieving data from the Fiix trial and the four major phase III DOAC trials in NVAF. Prespecified outcomes included stroke and systemic embolism (SSE), SSE and myocardial infarction (MI), major bleeding (MB), composite major vascular events (SSEMI and MB; CMVE), and deaths. We calculated relative risk, 95% CI, and 95% confidence limits (CL) for each outcome and performed meta-analysis using fixed- and random-effects modeling.
RESULTS
There were 613 and 628 observation years with Fiix-warfarin and PT-warfarin in the Fiix trial, and 70 628 and 57 962 with DOACs and PT-warfarin in DOAC trials. Populations were comparable although death rates were lower in the Fiix trial. Compared to pooled PT-warfarin, Fiix-warfarin reduced SSE (RR 0.54;95% CI 0.26-1.10/95% CL <1.00), SSEMI (0.51;0.26-0.99/<0.90), MB (RR 0.63;0.37-1.07/<0.99), and CMVE (RR 0.66;0.43-1.00/<0.94). Vascular death was lower (RR 0.13;0.04-0.47/<0.42). Compared to pooled DOACs, Fiix-warfarin consistently had lower point estimates for the RR for efficacy and safety, but only significant for lower death rates (vascular death RR 0.14;0.04-0.49/<0.43). Meta-analysis comparing Fiix-warfarin and DOACs with PT-warfarin consistently found Fiix-warfarin to have the lowest point estimates for efficacy.
CONCLUSION
Monitoring warfarin with Fiix-PT reduces risk of vascular events in NVAF patients as much as DOACs. Warfarin monitored with Fiix-PT is an improved anticoagulant.
Topics: Atrial Fibrillation; Drug Monitoring; Humans; Prothrombin Time; Randomized Controlled Trials as Topic; Treatment Outcome; Vascular Diseases; Warfarin
PubMed: 27426862
DOI: 10.1111/ijlh.12537 -
BMC Pregnancy and Childbirth May 2024Preeclampsia (PE), an obstetric disorder, remains one of the leading causes of maternal and infant mortality worldwide. In individuals with PE, the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Preeclampsia (PE), an obstetric disorder, remains one of the leading causes of maternal and infant mortality worldwide. In individuals with PE, the coagulation-fibrinolytic system is believed to be among the most significantly impacted systems due to maternal inflammatory responses and immune dysfunction. Therefore, this systematic review and meta-analysis aimed to assess the association of prothrombin time (PT), thrombin time (TT) and activated partial thromboplastin time (APTT) levels with preeclampsia.
METHODS
This systematic review and meta-analysis was conducted in accordance with the PRISMA guidelines. Articles relevant to the study, published from July 26, 2013, to July 26, 2023, were systematically searched across various databases including PubMed, Scopus, Embase, and Hinari. The methodological quality of the articles was evaluated using the Joanna Briggs Institute critical appraisal checklist. Utilizing Stata version 14.0, a random-effects model was employed to estimate the pooled standardized mean difference (SMD) along with the respective 95% CIs. The I statistics and Cochrane Q test were utilized to assess heterogeneity, while subgroup analyses were performed to explore its sources. Furthermore, Egger's regression test and funnel plot were employed to assess publication bias among the included studies.
RESULTS
A total of 30 articles, involving 5,964 individuals (2,883 with PE and 3,081 as normotensive pregnant mothers), were included in this study. The overall pooled SMD for PT, APTT, and TT between PE and normotensive pregnant mothers were 0.97 (95% CI: 0.65-1.29, p < 0.001), 1.05 (95% CI: 0.74-1.36, p < 0.001), and 0.30 (95% CI: -0.08-0.69, p = 0.11), respectively. The pooled SMD indicates a significant increase in PT and APTT levels among PE patients compared to normotensive pregnant mothers, while the increase in TT levels among PE patients was not statistically significant.
CONCLUSIONS
The meta-analysis underscores the association between PE and prolonged PT and APTT. This suggests that evaluating coagulation parameters like PT, APTT, and TT in pregnant women could offer easily accessible and cost-effective clinical indicators for assessing PE. However, multicenter longitudinal studies are needed to evaluate their effectiveness across various gestational weeks of pregnancy.
Topics: Humans; Pregnancy; Female; Pre-Eclampsia; Partial Thromboplastin Time; Prothrombin Time; Thrombin Time; Blood Coagulation
PubMed: 38741046
DOI: 10.1186/s12884-024-06543-7 -
Scientific Reports May 2024Malaria infection leads to hematological abnormalities, including deranged prothrombin time (PT). Given the inconsistent findings regarding PT in malaria across... (Meta-Analysis)
Meta-Analysis
Malaria infection leads to hematological abnormalities, including deranged prothrombin time (PT). Given the inconsistent findings regarding PT in malaria across different severities and between Plasmodium falciparum and P. vivax, this study aimed to synthesize available evidence on PT variations in clinical malaria. A systematic literature search was performed in PubMed, Embase, Scopus, Ovid, and Medline from 27 November 2021 to 2 March 2023 to obtain studies documenting PT in malaria. Study quality was evaluated using the Joanna Briggs Institute checklist, with data synthesized through both qualitative and quantitative methods, including meta-regression and subgroup analyses, to explore heterogeneity and publication bias. From 2767 articles, 21 studies were included. Most studies reported prolonged or increased PT in malaria patients compared to controls, a finding substantiated by the meta-analysis (P < 0.01, Mean difference: 8.86 s, 95% CI 5.32-12.40 s, I: 87.88%, 4 studies). Severe malaria cases also showed significantly higher PT than non-severe ones (P = 0.03, Hedges's g: 1.65, 95% CI 0.20-3.10, I: 97.91%, 7 studies). No significant PT difference was observed between P. falciparum and P. vivax infections (P = 0.88, Mean difference: 0.06, 95% CI - 0.691-0.8, I: 65.09%, 2 studies). The relationship between PT and malaria-related mortality remains unclear, underscoring the need for further studies. PT is typically prolonged or increased in malaria, particularly in severe cases, with no notable difference between P. falciparum and P. vivax infections. The inconsistency in PT findings between fatal and non-fatal cases highlights a gap in current understanding, emphasizing the need for future studies to inform therapeutic strategies.
Topics: Humans; Malaria, Vivax; Malaria, Falciparum; Plasmodium vivax; Plasmodium falciparum; Prothrombin Time; Severity of Illness Index
PubMed: 38698102
DOI: 10.1038/s41598-024-60170-y -
Annals of the Academy of Medicine,... Apr 2021Coronavirus disease 2019 (COVID-19)-induced coagulopathy (CIC) has been widely reported in the literature. However, the spectrum of abnormalities associated with CIC has... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Coronavirus disease 2019 (COVID-19)-induced coagulopathy (CIC) has been widely reported in the literature. However, the spectrum of abnormalities associated with CIC has been highly variable.
METHODS
We conducted a systematic review of the literature (until 1 June 2020) to assess CIC and disease severity during the early COVID-19 pandemic. Primary outcomes were pooled mean differences in platelet count, D-dimer level, prothrombin time, activated partial thromboplastin time (aPTT) and fibrinogen level between non-severe and severe patients, stratified by degree of hypoxaemia or those who died. The risk factors for CIC were analysed. Random-effects meta-analyses and meta-regression were performed using R version 3.6.1, and certainty of evidence was rated using the Grading of Recommendation, Assessment, Development, and Evaluation approach.
RESULTS
Of the included 5,243 adult COVID-19 patients, patients with severe COVID-19 had a significantly lower platelet count, and higher D-dimer level, prothrombin time and fibrinogen level than non-severe patients. Pooled mean differences in platelet count (-19.7×109/L, 95% confidence interval [CI] -31.7 to -7.6), D-dimer level (0.8μg/mL, 95% CI 0.5-1.1), prothrombin time (0.4 second, 95% CI 0.2-0.6) and fibrinogen level (0.6g/L, 95% CI 0.3-0.8) were significant between the groups. Platelet count and D-dimer level were significant predictors of disease severity on meta-regression analysis. Older men had higher risks of severe coagulopathic disease.
CONCLUSION
Significant variability in CIC exists between non-severe and severe patients, with platelet count and D-dimer level correlating with disease severity. Routine monitoring of all coagulation parameters may help to assess CIC and decide on the appropriate management.
Topics: Adult; Aged; Blood Coagulation Disorders; COVID-19; Humans; Male; Pandemics; Prothrombin Time; SARS-CoV-2
PubMed: 33990820
DOI: 10.47102/annals-acadmedsg.2020420 -
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 -
Thrombosis and Haemostasis Oct 2016Urgent reversal of warfarin is required for patients who experience major bleeding or require urgent surgery. Treatment options include the combination of vitamin K and... (Meta-Analysis)
Meta-Analysis Review
Urgent reversal of warfarin is required for patients who experience major bleeding or require urgent surgery. Treatment options include the combination of vitamin K and coagulation factor replacement with either prothrombin complex concentrate (PCC) or fresh frozen plasma (FFP). However, the optimal reversal strategy is unclear based on clinically relevant outcomes. We searched in MEDLINE, EMBASE and Cochrane library to December 2015. Thirteen studies (5 randomised studies and 8 observational studies) were included. PCC use was associated with a significant reduction in all-cause mortality compared to FFP (OR= 0.56, 95 % CI; 0.37-0.84, p=0.006). A higher proportion of patients receiving PCC achieved haemostasis compared to those receiving FFP, but this was not statistically significant (OR 2.00, 95 % CI; 0.85-4.68). PCC use was more likely to achieve normalisation of international normalised ratio (INR) (OR 10.80, 95 % CI; 6.12-19.07) and resulted in a shorter time to INR correction (mean difference -6.50 hours, 95 %CI; -9.75 to -3.24). Red blood cell transfusion was not statistically different between the two groups (OR 0.88, 95 % CI: 0.53-1.43). Patients receiving PCC had a lower risk of post-transfusion volume overload compared to FFP (OR 0.27, 95 % CI; 0.13-0.58). There was no statistically significant difference in the risk of thromboembolism following administration of PCC or FFP (OR 0.91, 95 % CI; 0.44-1.89). In conclusion, as compared to FFP, the use of PCC for warfarin reversal was associated with a significant reduction in all-cause mortality, more rapid INR reduction, and less volume overload without an increased risk of thromboembolic events.
Topics: Anticoagulants; Blood Coagulation Factors; Hemorrhage; Humans; International Normalized Ratio; Observational Studies as Topic; Plasma; Randomized Controlled Trials as Topic; Warfarin
PubMed: 27488143
DOI: 10.1160/TH16-04-0266 -
Neurocritical Care Jun 2023Anticoagulant-associated intracranial hemorrhage has a high mortality rate, and many factors can cause intracranial hemorrhage. Until now, systematic reviews and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Anticoagulant-associated intracranial hemorrhage has a high mortality rate, and many factors can cause intracranial hemorrhage. Until now, systematic reviews and assessments of the certainty of the evidence have not been published.
METHODS
We conducted a systematic review to identify risk factors for anticoagulant-associated intracranial hemorrhage. The protocol for this systematic review was prospectively registered with PROSPERO (CRD42022316750). All English studies that met the inclusion criteria published before January 2022 were obtained from PubMed, EMBASE, Web of Science, and Cochrane Library. Two researchers independently screened articles, extracted data, and evaluated the quality and evidence of the included studies. Risk factors for intracranial hemorrhage were used as the outcome index of this review. Random or fixed-effect models were used in statistical methods. I statistics were used to evaluate heterogeneity.
RESULTS
Of 7322 citations, we included 20 studies in our analysis. For intracranial hemorrhage, moderate-certainty evidence showed a probable association with race, Glasgow Coma Scale, stroke, leukoaraiosis, cerebrovascular disease, tumor, atrial fibrillation, previous bleeding, international normalized ratio, serum albumin, prothrombin time, diastolic blood pressure, and anticoagulant. Low-certainty evidence may be associated with age, cerebral microbleeds, smoking, alcohol intake, platelet count, and antiplatelet drug. In addition, we found very low-certainty evidence that there may be little to no association between the risk of intracranial hemorrhage and hypertension and creatinine clearance. Leukoaraiosis, cerebral microbleeds, cerebrovascular disease, and international normalized ratio are not included in most risk assessment models.
CONCLUSIONS
This study informs risk prediction for anticoagulant-associated intracranial hemorrhage and informs guidelines for intracranial hemorrhage prevention and future research.
Topics: Humans; Anticoagulants; Leukoaraiosis; Intracranial Hemorrhages; Risk Factors; Cerebral Hemorrhage
PubMed: 36670269
DOI: 10.1007/s12028-022-01671-4 -
Frontiers in Cardiovascular Medicine 2022Coagulation parameters are important determinants for COVID-19 infection. We conducted meta-analysis to assess the association between early hemostatic parameters and...
INTRODUCTION
Coagulation parameters are important determinants for COVID-19 infection. We conducted meta-analysis to assess the association between early hemostatic parameters and infection severity.
METHODS
Electronic search was made for papers that addressed clinical characteristics of COVID-19 patients and disease severity. Results were filtered using exclusion and inclusion criteria and then pooled into a meta-analysis to estimate the standardized mean difference (SMD) with 95% confidence interval (CI) for D-dimers, fibrinogen, prothrombin time, platelet count (PLT), activated partial thromboplastin time. To explore the heterogeneity and robustness of our fundings, sensitivity and subgroup analyses were conducted. Publication bias was assessed with contour-enhanced funnel plots and Egger's test by linear regression. Coagulation parameters data from retrospective cohort study of 451 patients with COVID-19 at National Research Center for Cardiac Surgery were included in meta-analysis of published studies.
RESULTS
Overall, 41 original studies (17,601 patients) on SARS-CoV-2 were included. For the two groups of patients, stratified by severity, we identified that D-dimers, fibrinogen, activated partial thromboplastin time, and prothrombin time were significantly higher in the severe group [SMD 0.6985 with 95%CI (0.5155; 0.8815); SMD 0.661 with 95%CI (0.3387; 0.9833); SMD 0.2683 with 95%CI (0.1357; 0.4009); SMD 0.284 with 95%CI (0.1472; 0.4208)]. In contrast, PLT was significantly lower in patients with more severe cases of COVID-19 [SMD -0.1684 with 95%CI (-0.2826; -0.0542)]. Neither the analysis by the leave-one-out method nor the influence diagnostic have identified studies that solely cause significant change in the effect size estimates. Subgroup analysis showed no significant difference between articles originated from different countries but revealed that severity assessment criteria might have influence over estimated effect sizes for platelets and D-dimers. Contour-enhanced funnel plots and the Egger's test for D-dimers and fibrinogen revealed significant asymmetry that might be a sign of publication bias.
CONCLUSIONS
The hemostatic laboratory parameters, with exception of platelets, are significantly elevated in patients with severe COVID-19. The two variables with strongest association to disease severity were D-dimers and fibrinogen levels. Future research should aim outside conventional coagulation tests and include analysis of clotting formation and platelet/platelet progenitors characteristics.
PubMed: 35360017
DOI: 10.3389/fcvm.2022.794092 -
Blood Advances Oct 2023Postpartum hemorrhage (PPH) is a leading cause of maternal morbi-mortality. Although obstetric risk factors are well described, the impact of predelivery hematologic and... (Meta-Analysis)
Meta-Analysis
Postpartum hemorrhage (PPH) is a leading cause of maternal morbi-mortality. Although obstetric risk factors are well described, the impact of predelivery hematologic and hemostatic biomarkers remains incompletely understood. In this systematic review, we aimed to summarize the available literature on the association between predelivery hemostatic biomarkers and PPH/severe PPH. Searching MEDLINE, EMBASE, and CENTRAL databases from inception to October 2022, we included observational studies on unselected pregnant women without bleeding disorder reporting on PPH and on predelivery hemostatic biomarkers. Two review authors independently performed title, abstract and full-text screening, upon which quantitative syntheses of studies reporting on the same hemostatic biomarker were conducted, calculating the mean difference (MD) between women with PPH/severe PPH and controls. A search on 18 October 2022 yielded 81 articles fitting our inclusion criteria. The heterogeneity between studies was considerable. With regard to PPH, the estimated average MD in the investigated biomarkers (platelets, fibrinogen, hemoglobin, Ddimer, activated partial thromboplastin time, and prothrombin time) were not statistically significant. Women who developed severe PPH had lower predelivery platelets than controls (MD = -26.0 109/L; 95% confidence interval, -35.8 to -16.1), whereas differences in predelivery fibrinogen concentration (MD = -0.31 g/L; 95% confidence interval, -0.75 to 0.13) and levels of factor XIII or hemoglobin were not statistically significant in women with and without severe PPH. Predelivery platelet counts were, on average, lower in women with severe PPH compared with controls, suggesting the potential usefulness of this biomarker for predicting severe PPH. This trial was registered at the International Prospective Register of Systematic Reviews as CRD42022368075.
Topics: Female; Pregnancy; Humans; Postpartum Hemorrhage; Hemostatics; Hemoglobins; Fibrinogen; Biomarkers
PubMed: 37307172
DOI: 10.1182/bloodadvances.2023010143