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Journal of Thrombosis and Thrombolysis Jul 2017Prothrombin complex concentrate (PCC) is used for reversal of vitamin K antagonists (VKA) in patients with bleeding complications. This study aims to assess benefits and... (Comparative Study)
Comparative Study Meta-Analysis Review
Prothrombin complex concentrate (PCC) is used for reversal of vitamin K antagonists (VKA) in patients with bleeding complications. This study aims to assess benefits and harms of 4-factor PCC compared to fresh frozen plasma (FFP) or no treatment in VKA associated bleeding. PubMed, EMBASE and CENTRAL were searched from 1945 to August 2015. Studies reporting 4-factor PCC use for VKA associated bleeding and providing data on INR normalization, mortality or thromboembolic (TE) complications were eligible. Two authors screened titles and full articles for inclusion, extracted data, and assessed risk of bias. Mortality data were pooled using Mantel-Haenszel random effects meta-analysis. Nineteen studies were included (N = 2878); 18 cohort studies and one RCT. Six studies had good methodological quality, 9 moderate and 4 poor. Baseline INR values ranged from 2.2 to >20. The INR within 1 h after PCC administration ranged from 1.4 to 1.9, and after FFP administration from 2.2 to 12. PCC reduced the time to reach INR correction in comparison with FFP or no treatment. The observed mortality rate ranged from 0 to 43% (mean 17%) in the PCC, 4.8-54% (mean 16%) in the FFP and 23-69% (mean 51%) in the no treatment group. Meta-analysis of mortality data resulted in an OR of 0.64 (95% confidence interval [CI] 0.27-1.5) for PCC versus FFP and an OR 0.41 (95% CI 0.13-1.3) for PCC versus no treatment. TE complications were observed in 0-18% (mean 2.5%) of PCC and in 6.4% of FFP recipients. Four-factor PCC is an effective and safe option in reversal of VKA bleeding events.
Topics: Anticoagulants; Blood Coagulation Factors; Hemorrhage; Humans; International Normalized Ratio; Plasma; Vitamin K
PubMed: 28540468
DOI: 10.1007/s11239-017-1506-0 -
BMJ Open Jul 2022There are numerous studies reporting a disproportionally high prevalence of thrombophilia in women with a history of recurrent miscarriage (RM), which has led to...
OBJECTIVE
There are numerous studies reporting a disproportionally high prevalence of thrombophilia in women with a history of recurrent miscarriage (RM), which has led to overdiagnosis and treatment without an improvement in clinical outcomes. The objective of our study was to assess the prevalence of inherited and acquired thrombophilia in a large cohort of women with a history of early RM using internationally agreed diagnostic criteria and inclusion parameters and compare it to the meta-analysis results of existing literature.
METHODS
DESIGN: Retrospective cohort study and systematic review of literature.
SETTING
This is a retrospective cohort study set-up in two dedicated tertiary centres for women with RM in Southwest London and Surrey. We reviewed all the available literature related to causes of RMs. We ascertained the prevalence of thrombophilia in the study population and compared it with historical and published prevalence in the general population.
PARTICIPANTS
1155 women between 2012 and 2017. All patients had three or more first trimester miscarriages and a full thrombophilia screen.
RESULTS
The overall prevalence of thrombophilia in our study population is 9.2% (106/1155) with 8.1% (94/1155) of cases positive for inherited thrombophilia, which is similar to the general population; Factor V Leiden (4.9%; 57/1155) and prothrombin gene mutation (2.9%; 34/1155) were the most common inherited thrombophilias, while only 1% (12/1155) tested positive for acquired thrombophilia. Persistent positive lupus anticoagulant (LA) was found in 0.5% (6/1155) and persistent positive anticardiolipin (ACL) antibodies with a value ≥40 U/mL was found in 0.5% (6/1155) of patients. Tests for LA/ACL were performed a minimum of 12 weeks apart thus meeting the revised Sapporo criteria for a diagnosis of antiphospholipid syndrome.
CONCLUSION
The findings of our study demonstrate that the prevalence of inherited thrombophilia is similar in women with RM to that in the general population. Similarly, the prevalence of acquired thrombophilia, using the revised Sapporo criteria, in the cohort of RMs is similar to that in the general population. Therefore, we do not recommend investigation or treatment of inherited or acquired thrombophilia in women with RM.
PROSPERO REGISTRATION NUMBER
CRD42020223554.
Topics: Abortion, Habitual; Antiphospholipid Syndrome; Cohort Studies; Female; Humans; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy Trimester, First; Retrospective Studies; Thrombophilia
PubMed: 35831047
DOI: 10.1136/bmjopen-2021-059519 -
The British Journal of Nutrition Jul 2022Hyperemesis gravidarum (HG), severe nausea and vomiting in pregnancy, can lead to vitamin deficiencies. Little is known about HG-related vitamin K deficiency. We aimed...
Hyperemesis gravidarum (HG), severe nausea and vomiting in pregnancy, can lead to vitamin deficiencies. Little is known about HG-related vitamin K deficiency. We aimed to summarise available evidence on the occurrence of HG-related vitamin K deficiency and corresponding maternal and neonatal complications. A systematic review was conducted, searching Medline and EMBASE from inception to 12 November 2020. We identified 1564 articles, of which we included fifteen in this study: fourteen case reports ( 21 women) and one retrospective cohort study ( 109 women). Nine out of twenty-one women reported in case reports had a prolonged prothrombin time (PT). The cohort study measured PT in 39/109 women with HG, of whom 10/39 women (26 %) had prolonged PT. In total, 30-50 % women received vitamin K supplementation after vitamin K deficiency had been diagnosed. Four case reports ( 4 women) reported corresponding maternal complications, all consisting of coagulopathy-related haemorrhage. Nine case reports ( 16 neonates) reported corresponding neonatal complications including intracranial haemorrhage ( 2 neonates) and embryopathy ( 14 neonates), which consisted of Binder phenotype ( 14 neonates), chondrodysplasia punctata ( 9 neonates) and grey matter heterotopia ( 3 neonates). In conclusion, vitamin K deficiency and related complications occur among women with HG. In our systematic review, we were unable to assess the incidence rate.
Topics: Pregnancy; Humans; Female; Male; Hyperemesis Gravidarum; Cohort Studies; Retrospective Studies; Vitamin K Deficiency; Vitamin K
PubMed: 34325760
DOI: 10.1017/S0007114521002865 -
International Journal of Environmental... Oct 2019Cephalosporins that contain the N-methylthiotetrazole side chain (NMTT-cephalosporin) have been reported to be associated with coagulation-related adverse events;... (Meta-Analysis)
Meta-Analysis
Cephalosporins that contain the N-methylthiotetrazole side chain (NMTT-cephalosporin) have been reported to be associated with coagulation-related adverse events; however, a comprehensive evaluation regarding the association is lacking. A systematic review and meta-analysis were conducted to assess the safety profile of NMTT-cephalosporins with respect to hypoprothrombinemia and bleeding. The MEDLINE, Embase, Cochrane, and RISS databases were systematically searched for clinical studies up to October 2018. The association between NMTT-cephalosporins and hypoprothrombinemia was estimated using an odds ratio (OR) with a 95% confidence interval (CI). A total of 15 studies on cefamandole, cefoperazone, cefotetan, cefmetazole, and moxalactam were identified and included in the meta-analysis. Hypoprothrombinemia (OR 1.676, 95% CI 1.275-2.203) and prothrombin time (PT) prolongation (OR 2.050, 95% CI 1.398-3.005) were significantly associated with NMTT-cephalosporins, whereas bleeding was not (OR 1.359, 95% CI 0.920-2.009). Subgroup analyses revealed that cefoperazone (OR 2.506, 95% CI 1.293-4.860), cefamandole (OR 3.247, 95% CI 1.083-9.733), and moxalactam (OR 3.367, 95% CI 1.725-6.572) were significantly associated with hypoprothrombinemia. An Antimicrobial Stewardship Program led by a multidisciplinary team could play a critical role in monitoring cephalosporin-related hypoprothrombinemia or PT prolongation in patients with underlying clinical conditions at risk for bleeding. The multidisciplinary team could also assist in communicating the potential safety concerns regarding NMTT-cephalosporin use with healthcare professionals to decrease the risk of adverse events.
Topics: Anti-Bacterial Agents; Cephalosporins; Humans; Hypoprothrombinemias; Male
PubMed: 31623191
DOI: 10.3390/ijerph16203937 -
Journal of Medical Virology Feb 2021The outbreak of 2019 novel coronavirus disease (COVID-19) has posed a grave threat to the global public health. The COVID-19-induced infection is closely related to... (Meta-Analysis)
Meta-Analysis
The outbreak of 2019 novel coronavirus disease (COVID-19) has posed a grave threat to the global public health. The COVID-19-induced infection is closely related to coagulation dysfunction in the affected patients. This paper attempts to conduct a meta-analysis and systematically review the blood coagulation indicators in patients with severe COVID-19. A meta-analysis of eligible studies was performed to compare the blood coagulation indicators in patients with severe and nonsevere COVID-19. PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies published between 1 December 2019 and 7 May 2020. A total of 13 studies with 1341 adult patients were enrolled in this analysis. Platelet (weighted mean difference [WMD] = -24.83, 95% confidence interval [CI]: -34.12 to -15.54; P < .001), d-dimer (WMD = 0.19, 95% CI: 0.09-0.29; P < .001), and fibrinogen (WMD = 1.02, 95% CI: 0.50-1.54; P < .001) were significantly associated with the severity in patients with COVID-19. The meta-analysis revealed that no correlation was evident between an increased severity risk of COVID-19 and activated partial thromboplastin time (WMD = -1.56, 95% CI: -5.77 to 2.64; P = .468) or prothrombin time (WMD = 0.19, 95% CI: -0.13 to 0.51; P = .243). The single arm meta-analysis showed that compared with the nonsevere group, the severe group had a lower pooled platelet (165.12 [95% CI: 157.38-172.85] vs 190.09 [95% CI: 179.45-200.74]), higher d-dimer (0.49 [95% CI: 0.33-0.64] vs 0.27 [95% CI: 0.20-0.34]), and higher fibrinogen (4.34 [95% CI: 1.98-6.70] vs 3.19 [95% CI: 1.13-5.24]). Coagulation dysfunction is closely related to the severity of patients with COVID-19, in which low platelet, high d-dimer, and fibrinogen upon admission may serve as risk indicators for increased aggression of the disease. These findings are of great clinical value for timely and effective treatment of the COVID-19 cases.
Topics: Blood Coagulation Disorders; Blood Platelets; COVID-19; Fibrin Fibrinogen Degradation Products; Fibrinogen; Hospitalization; Humans; Partial Thromboplastin Time; Prognosis; Risk Factors; Severity of Illness Index
PubMed: 32706426
DOI: 10.1002/jmv.26346 -
Journal of Clinical Medicine May 2020The novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection has been predominantly linked to respiratory distress syndrome, but... (Review)
Review
The novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection has been predominantly linked to respiratory distress syndrome, but gastrointestinal symptoms and hepatic injury have also been reported. The mechanism of liver injury is poorly understood and may result as a consequence of viral hepatitis, systemic inflammatory response, gut barrier and microbiome alterations, intensive care treatment or drug toxicity. The incidence of hepatopathy among patients with coronavirus disease 2019 (COVID-19) is unclear, but studies have reported liver injury in patients with SARS and Middle East respiratory syndrome (MERS). We aimed to systematically review data on the prevalence of hepatic impairments and their clinical course in SARS and MERS infections. A systematic literature search (PubMed/Embase/Cinahl/Web of Science) according to preferred reporting items for systematic review and meta-analysis protocols (PRISMA) was conducted from database inception until 17/03/2020 for studies that evaluated the incidence of hepatic abnormalities in SARS CoV-1, SARS CoV-2 and MERS infected patients with reported liver-related parameters. A total of forty-three studies were included. Liver anomalies were predominantly mild to moderately elevated transaminases, hypoalbuminemia and prolongation of prothrombin time. Histopathology varied between non-specific inflammation, mild steatosis, congestion and massive necrosis. More studies to elucidate the mechanism and importance of liver injury on the clinical course and prognosis in patients with novel SARS-CoV-2 infection are warranted.
PubMed: 32403255
DOI: 10.3390/jcm9051420 -
Journal of Thrombosis and Thrombolysis Nov 2021Four-factor prothrombin complex concentrate (PCC) is frequently used as a reversal agent for major bleeding in patients on factor Xa inhibitors. Piran et al. reviewed... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Four-factor prothrombin complex concentrate (PCC) is frequently used as a reversal agent for major bleeding in patients on factor Xa inhibitors. Piran et al. reviewed its safety and efficacy for the first time in 2018. However, more studies have been published on the matter since then. The aim of this study is to investigate the efficacy and safety of this use and update this review.
METHODS
We systematically searched in Medline, Scopus, and the Cochrane Library from 1/1/2018 to 6/19/2020. A random effects model meta-analysis of proportions was used to study the efficacy of PCC on major bleeding control, mortality and thrombosis incidence.
RESULTS
33 studies (n = 2568 patients), with the majority of studies being uncontrolled retrospective cohort studies, were included; atrial fibrillation was the main factor Xa inhibitors indication and approximately 62% of patients presented with intracranial hemorrhage. We estimated the pooled proportion outcomes for hemostasis (80%, CI 0.75-0.84), mortality (15%, CI 0.11-0.19) and thromboembolic adverse events (3%, CI 0.02-0.05). High versus low dose PCC did not affect hemostasis or thrombosis. Patients with ICH had higher mortality rates (22%, CI 0.13-0.32). Heterogeneity was significant (Ι > 50% with p < 0.05) for all pooled proportional outcomes. The quality of evidence was low given that included studies were not randomized or controlled.
CONCLUSION
Our study demonstrates the efficacy and safety of the off label use of 4F PCC in major bleeding associated with factor Xa inhibitors. Our data require further validation with future randomized clinical trials.
Topics: Anticoagulants; Blood Coagulation Factors; Factor IX; Factor Xa Inhibitors; Hemorrhage; Humans; Retrospective Studies; Thromboembolism
PubMed: 34024021
DOI: 10.1007/s11239-021-02480-w -
Transfusion Jul 2017Direct oral anticoagulants (DOACs) are effective and safe for prophylaxis and treatment of thromboembolic phenomena. However, managing DOACs during bleeding emergencies... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Direct oral anticoagulants (DOACs) are effective and safe for prophylaxis and treatment of thromboembolic phenomena. However, managing DOACs during bleeding emergencies is challenging. A systematic review and meta-analysis was conducted on studies addressing efficacy and safety of the drugs used for reversal of DOACs.
STUDY DESIGN AND METHODS
Medline, Embase, Cochrane Library, and ClinicalTrials.gov were searched up to September 2016. Studies that examined clinical and laboratory effects of drugs used to reverse DOACs were included. Risk of bias was assessed using Newcastle-Ottawa scale and Cochrane Collaboration tool. Primary and secondary outcomes assessed were reversal of clinical bleeding, clotting assays, and safety, respectively. Overall effect estimates were pooled, and clinical and statistical heterogeneity were assessed. Meta-analysis was conducted using random-effects model.
RESULTS
Four cohort studies in bleeding patients (n = 230) and eight randomized controlled trials in healthy volunteers (n = 381) were included, both with moderate risk of bias. Reversal of clotting assays in healthy volunteers was frequently reported, demonstrating that prothrombin complex concentrate (PCC) reversed prothrombin time (PT) and endogenous thrombin potential (ETP) substantially. For PT, pooled mean difference was 1.68 seconds (95% confidence interval [CI], -0.33 to 3.70 sec; p < 0.01; I = 97%). For ETP, pooled mean difference was 2.16 seconds (95% CI, 0.57 to 3.75 sec; p < 0.01; I = 98%). Andexanet alfa and idarucizumab both reverse clotting assays. No important safety concerns were identified.
CONCLUSIONS
Clotting assays are partially reversed by PCC in healthy volunteers. Idarucizumab and andexanet alfa have solid laboratory reversal effect and potential to be clinically efficacious and safe. However, clinical evidence is still lacking for all agents.
Topics: Administration, Oral; Aged; Anticoagulants; Blood Coagulation Factors; Female; Humans; Male; Prothrombin Time; Thrombin
PubMed: 28337750
DOI: 10.1111/trf.14096 -
Journal of Clinical Medicine Jul 2023The measurement and identification of plasma biomarkers can support the estimation of risk and diagnosis of deep vein thrombosis (DVT) associated with the use of a... (Review)
Review
BACKGROUND
The measurement and identification of plasma biomarkers can support the estimation of risk and diagnosis of deep vein thrombosis (DVT) associated with the use of a peripherally inserted central catheter (PICC).
OBJECTIVES
This systematic review and meta-analysis aimed to identify the association between the levels of potential biomarkers that reflect the activation of the blood system, long-term vascular complications, inflammatory system, and the occurrence of PICC-related DVT.
METHODS
Seven electronic databases (Embase, Web of Science, Medline, Scopus, Cinahl, Cochrane Central Register of Controlled Trials, and ERIC) were searched to identify literature published until December 2022. Studies were required to report: (I) adult and pediatric patients, outpatient or admitted to clinical, surgical, or ICU with PICC; (II) patients with PICC-related DVT and patients without PICC-related DVT as a comparator; and (III) at least one biomarker available. The Newcastle-Ottawa Scale was used to evaluate the quality of the studies. Study precision was evaluated by using a funnel plot for platelets level. We provided a narrative synthesis and meta-analysis of the findings on the biomarkers' outcomes of the studies. We pooled the results using random effects meta-analysis. The meta-analysis was conducted using Review Manager software v5.4. This systematic review is registered in PROSPERO (CRD42018108871).
RESULTS
Of the 3564 studies identified (after duplication removal), 28 were included. PICC-related DVT was associated with higher D-dimers (0.37 μg/mL, 95% CI 0.02, 0.72; = 0.04, I = 92%; for heterogeneity < 0.00001) and with higher platelets (8.76 × 10/L, 95% CI 1.62, 15.91; = 0.02, I = 41%; for heterogeneity = 0.06).
CONCLUSIONS
High levels of D-dimer and platelet were associated with DVT in patients with PICC. However, biomarkers such as APTT, fibrinogen, FDP, glucose, hemoglobin, glycated hemoglobin, INR, prothrombin time, prothrombin fragment 1.2, the thrombin-antithrombin complex, and WBC were not related to the development of DVT associated with PICC.
PubMed: 37445515
DOI: 10.3390/jcm12134480 -
Clinical Therapeutics Feb 2012Activated prothrombin complex concentrate (aPCC) and recombinant Factor VIIa (rFVIIa) are 2 bypassing agents commonly used for treating acute bleeds in hemophiliac... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Activated prothrombin complex concentrate (aPCC) and recombinant Factor VIIa (rFVIIa) are 2 bypassing agents commonly used for treating acute bleeds in hemophiliac patients with inhibitors. A wide range of efficacy rates for aPCC and rFVIIa have been reported in a number of single-armed and randomized controlled comparative studies.
OBJECTIVE
The aims of this study were to compare the clinical efficacy of aPCC and rFVIIa using a classic meta-analytic approach and to explore the role of study characteristics as covariates in a meta-analysis of previously published clinical studies in hemophiliac patients with antibodies to the missing Factor VIII or IX.
METHODS
A systematic search was conducted to identify studies on the efficacy of aPCC and rFVIIa 90 and 270 μg/kg for treating joint bleeds. The efficacy rates with aPCC and rFVIIa were pooled separately, assuming fixed or random effects. Subgroup analyses were conducted to pool the efficacy rates for bleeds evaluated at 8-12, 18-27, and 36-72 hours after the start of the initial infusion. Meta-regression was used to investigate the association between pooled efficacy rates and study characteristics.
RESULTS
Although only 2 studies directly compared the efficacy of aPCC and rFVIIa, data from ~2392 joint bleeding episodes from 19 studies were included. The pooled efficacy rates were 80.8% with aPCC and 68.4% with rFVIIa (90 μg/kg, 72.0%; 270 μg/kg, 55.7%). The pooled efficacy rates with aPCC at 8-12, 18-27, and 36-72 hours were 49.2%, 70.2%, and 90.9%, respectively. The corresponding pooled rates with rFVIIa 90 μg/kg were 66.6%, 70.7%, and 77.7%. No significant differences were found between the pooled efficacy rates with aPCC and rFVIIa overall or at any of the time points evaluated. Positive associations were found between reported efficacy and duration of follow-up and the number of bleeds evaluated.
CONCLUSIONS
Given the paucity of high-quality studies, the findings from the present review and meta-analysis suggest no conclusive evidence that aPCC or rFVIIa is significantly more efficacious than the other in the treatment of joint bleeding episodes in hemophiliac patients with inhibitors.
Topics: Antibodies; Blood Coagulation Factors; Factor IX; Factor VIII; Factor VIIa; Hemophilia A; Humans; Recombinant Proteins
PubMed: 22285208
DOI: 10.1016/j.clinthera.2012.01.001