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1.
Assessment of Hemostatic Profile in Neonates with Intrauterine Growth Restriction: A Systematic Review of Literature
Karapati E, Sokou R, Iliodromiti Z, Tsaousi M, Sulaj A, Tsantes AG, Petropoulou C, Pouliakis A, Tsantes AE, Boutsikou T, et al
Seminars in thrombosis and hemostasis. 2023
Abstract
Intrauterine growth restriction (IUGR) affects nearly 10 to 15% of pregnancies and is responsible for many short- and long-term adverse consequences, including hemostatic derangement. Both thrombotic and hemorrhagic events are described in the perinatal period in these neonates. The aim of this study was to systematically review the literature on the laboratory studies used to evaluate the hemostatic system of the IUGR small for gestational age neonate. We reviewed the current literature via PubMed and Scopus until September 2022. Following our inclusion/exclusion criteria, we finally included 60 studies in our review. Thrombocytopenia, characterized as hyporegenerative and a kinetic upshot of reduced platelet production due to in utero chronic hypoxia, was the main finding of most studies focusing on growth-restricted neonates, in most cases is mild and usually resolves spontaneously with the first 2 weeks of life. In regard to coagulation, growth-restricted newborns present with prolonged standard coagulation tests. Data regarding coagulation factors, fibrinolytic system, and anticoagulant proteins are scarce and conflicting, mainly due to confounding factors. As thromboelastography/rotational thromboelastometry (TEG/ROTEM) provides a more precise evaluation of the in vivo coagulation process compared with standard coagulation tests, its use in transfusion guidance is fundamental. Only one study regarding TEG/ROTEM was retrieved from this population, where no difference in ROTEM parameters compared with appropriate for gestational age neonates was found. Despite the laboratory aberrations, no correlation could be achieved with clinical manifestations of bleeding or thrombosis in the studies included. More studies are needed to assess hemostasis in IUGR neonates and guide targeted therapeutic interventions.
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Thromboelastography-Guided Therapy Enhances Patient Blood Management in Cirrhotic Patients: A Meta-analysis Based on Randomized Controlled Trials
Hartmann J, Dias JD, Pivalizza EG, Garcia-Tsao G
Seminars in thrombosis and hemostasis. 2022
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Editor's Choice
Abstract
Patients with cirrhosis often have abnormal hemostasis, with increased risk of hemorrhage and thrombosis. Thromboelastography provides a rapid assessment of the coagulation status and can guide product transfusions in adult patients with cirrhosis. This study aimed to determine whether the use of thromboelastography in adult patients with cirrhosis decreases blood product use and impacts adverse events or mortality compared with standard practice. A registered (PROSPERO CRD42020192458) systematic review and meta-analysis was conducted for randomized controlled trials (RCTs) comparing thromboelastography-guided hemostatic management versus standard practice (control). Co-primary outcomes were the number of transfused platelet units and fresh frozen plasma (FFP) units. Secondary outcomes were mortality, adverse events, utilization of individual blood products, blood loss or excessive bleeding events, hospital/intensive care unit stay, and liver transplant/intervention outcomes. The search identified 260 articles, with five RCTs included in the meta-analysis. Platelet use was five times lower with thromboelastography versus the control, with a relative risk of 0.17 (95% confidence interval [CI]: [0.03-0.90]; p = 0.04), but FFP use did not differ significantly. Thromboelastography was associated with less blood product (p < 0.001), FFP + platelets (p < 0.001), and cryoprecipitate (p < 0.001) use. No differences were reported in bleeding rates or longer term mortality between groups, with the thromboelastography group having lower mortality at 7 days versus the control (relative risk [95% CI] = 0.52 [0.30-0.91]; p = 0.02). Thromboelastography-guided therapy in patients with cirrhosis enhances patient blood management by reducing use of blood products without increasing complications.
PICO Summary
Population
Patients with cirrhosis (5 studies, n= 302).
Intervention
Thromboelastography-guided haemostatic management.
Comparison
Standard coagulation testing (standard practice).
Outcome
Platelet use was five times lower with thromboelastography vs. standard practice, with a relative risk of 0.17 (95% confidence interval [CI]: [0.03-0.90]), but fresh frozen plasma (FFP) use did not differ significantly. Thromboelastography was associated with less blood product, FFP + platelets, and cryoprecipitate use. No differences were reported in bleeding rates or longer-term mortality between groups, with the thromboelastography group having lower mortality at 7 days vs. standard practice (relative risk [95% CI] = 0.52 [0.30-0.91]).
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Systematic review and meta-analysis: incidence of variceal hemorrhage in patients with cirrhosis undergoing transesophageal echocardiography
Odewole M, Sen A, Okoruwa E, Lieber SR, Cotter TG, Nguyen AD, Mufti A, Singal AG, Rich NE
Alimentary pharmacology & therapeutics. 2022
Abstract
BACKGROUND The presence of esophageal varices is considered a relative contraindication to transesophageal echocardiography (TEE) by cardiology professional societies, so gastroenterologists are often consulted to perform upper endoscopy prior to TEE in patients with cirrhosis. AIM: To perform a systematic review to quantify the risk of bleeding complications in patients with cirrhosis following TEE. METHODS Two reviewers searched Ovid MEDLINE, MEDLINE In-Process and EMBASE databases from January 1992 to May 2021 for studies reporting bleeding complications from TEE in patients with cirrhosis. We calculated the pooled incidence rate of bleeding events using the metaprop command with a random effect model. RESULTS We identified 21 studies comprising 4050 unique patients with cirrhosis; 9 studies (n = 3015) assessed the risk of intraoperative TEE during liver transplant (LT) and 12 studies (n = 1035) assessed bleeding risk in patients undergoing TEE for other indications. The pooled incidence of bleeding post-TEE was 0.37% (95% CI 0.04-0.94%) across all studies. Bleeding complications were low among patients undergoing TEE during LT as well as those undergoing TEE for other diagnostic reasons (0.97% vs. 0.004%) and among studies with mean MELD >18 compared to those with mean MELD <18 (0.43% vs. 0.08%). Few studies had a comparator arm, and data on patient-level factors impacting bleeding complications (including degree of liver dysfunction and coagulopathy) were limited across studies. CONCLUSIONS The risk of bleeding complications following TEE is low in patients with cirrhosis, suggesting TEE is safe and risk stratification with upper endoscopy may not be necessary.
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Predicting postpartum haemorrhage: A systematic review of prognostic models
Carr BL, Jahangirifar M, Nicholson AE, Li W, Mol BW, Licqurish S
The Australian & New Zealand journal of obstetrics & gynaecology. 2022
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Editor's Choice
Abstract
BACKGROUND Postpartum haemorrhage (PPH) remains a leading cause of maternal mortality and morbidity worldwide, and the rate is increasing. Using a reliable predictive model could identify those at risk, support management and treatment, and improve maternal outcomes. AIMS To systematically identify and appraise existing prognostic models for PPH and ascertain suitability for clinical use. MATERIALS AND METHODS MEDLINE, CINAHL, Embase, and the Cochrane Library were searched using combinations of terms and synonyms, including 'postpartum haemorrhage', 'prognostic model', and 'risk factors'. Observational or experimental studies describing a prognostic model for risk of PPH, published in English, were included. The Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies checklist informed data extraction and the Prediction Model Risk of Bias Assessment Tool guided analysis. RESULTS Sixteen studies met the inclusion criteria after screening 1612 records. All studies were hospital settings from eight different countries. Models were developed for women who experienced vaginal birth (n = 7), caesarean birth (n = 2), any type of birth (n = 2), hypertensive disorders (n = 1) and those with placental abnormalities (n = 4). All studies were at high risk of bias due to use of inappropriate analysis methods or omission of important statistical considerations or suboptimal validation. CONCLUSIONS No existing prognostic models for PPH are ready for clinical application. Future research is needed to externally validate existing models and potentially develop a new model that is reliable and applicable to clinical practice.
PICO Summary
Population
Pregnant women (16 studies from eight different countries).
Intervention
Systematic review to identify and appraise existing prognostic models for post-partum haemorrhage (PPH) and ascertain suitability for clinical use.
Comparison
Various prognostic models for PPH, (e.g., based on prior hospital admissions for chronic diseases, based on medical history and clinical characteristics, using available antenatal and intrapartum variables, using prepartum fibrinogen levels).
Outcome
All studies were hospital settings. Models were developed for women who experienced vaginal birth (n= 7), caesarean birth (n= 2), any type of birth (n= 2), hypertensive disorders (n= 1) and those with placental abnormalities (n= 4). All studies were at high risk of bias due to use of inappropriate analysis methods or omission of important statistical considerations or suboptimal validation.
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5.
Comparison of Risk Scores for Lower Gastrointestinal Bleeding: A Systematic Review and Meta-analysis
Almaghrabi M, Gandhi M, Guizzetti L, Iansavichene A, Yan B, Wilson A, Oakland K, Jairath V, Sey M
JAMA network open. 2022;5(5):e2214253
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Editor's Choice
Abstract
IMPORTANCE Clinical prediction models, or risk scores, can be used to risk stratify patients with lower gastrointestinal bleeding (LGIB), although the most discriminative score is unknown. OBJECTIVE To identify all LGIB risk scores available and compare their prognostic performance. DATA SOURCES A systematic search of Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from January 1, 1990, through August 31, 2021, was conducted. Non-English-language articles were excluded. STUDY SELECTION Observational and interventional studies deriving or validating an LGIB risk score for the prediction of a clinical outcome were included. Studies including patients younger than 16 years or limited to a specific patient population or a specific cause of bleeding were excluded. Two investigators independently screened the studies, and disagreements were resolved by consensus. DATA EXTRACTION AND SYNTHESIS Data were abstracted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline independently by 2 investigators and pooled using random-effects models. MAIN OUTCOMES AND MEASURES Summary diagnostic performance measures (sensitivity, specificity, and area under the receiver operating characteristic curve [AUROC]) determined a priori were calculated for each risk score and outcome combination. RESULTS A total of 3268 citations were identified, of which 9 studies encompassing 12 independent cohorts and 4 risk scores (Oakland, Strate, NOBLADS [nonsteroidal anti-inflammatory drug use, no diarrhea, no abdominal tenderness, blood pressure ≤100 mm Hg, antiplatelet drug use (nonaspirin), albumin <3.0 g/dL, disease score ≥2 (according to the Charlson Comorbidity Index), and syncope], and BLEED [ongoing bleeding, low systolic blood pressure, elevated prothrombin time, erratic mental status, and unstable comorbid disease]) were included in the meta-analysis. For the prediction of safe discharge, the AUROC for the Oakland score was 0.86 (95% CI, 0.82-0.88). For major bleeding, the AUROC was 0.93 (95% CI, 0.90-0.95) for the Oakland score, 0.73 (95% CI, 0.69-0.77) for the Strate score, 0.58 (95% CI, 0.53-0.62) for the NOBLADS score, and 0.65 (95% CI, 0.61-0.69) for the BLEED score. For transfusion, the AUROC was 0.99 (95% CI, 0.98-1.00) for the Oakland score and 0.88 (95% CI, 0.85-0.90) for the NOBLADS score. For hemostasis, the AUROC was 0.36 (95% CI, 0.32-0.40) for the Oakland score, 0.82 (95% CI, 0.79-0.85) for the Strate score, and 0.24 (95% CI, 0.20-0.28) for the NOBLADS score. CONCLUSIONS AND RELEVANCE The Oakland score was the most discriminative LGIB risk score for predicting safe discharge, major bleeding, and need for transfusion, whereas the Strate score was best for predicting need for hemostasis. This study suggests that these scores can be used to predict outcomes from LGIB and guide clinical care accordingly.
PICO Summary
Population
Patients with lower gastrointestinal bleeding (LGIB), (9 studies).
Intervention
Systematic review and meta-analysis to identify all LGIB risk scores available and to compare their prognostic performance.
Comparison
Outcome
Four risk scores were identified: Oakland, Strate, NOBLADS, and BLEED. Summary diagnostic performance measures (sensitivity, specificity, and area under the receiver operating characteristic curve [AUROC]) determined a priori were calculated for each risk score and outcome combination. For the prediction of safe discharge, the AUROC for the Oakland score was 0.86. For major bleeding, the AUROC was 0.93 for the Oakland score, 0.73 for the Strate score, 0.58 for the NOBLADS score, and 0.65 for the BLEED score. For transfusion, the AUROC was 0.99 for the Oakland score and 0.88 for the NOBLADS score. For haemostasis, the AUROC was 0.36 for the Oakland score, 0.82 for the Strate score, and 0.24 for the NOBLADS score.
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6.
Hemostasis in Neonates with Perinatal Hypoxia-Laboratory Approach: A Systematic Review
Tsaousi M, Iliodromiti Z, Iacovidou N, Karapati E, Sulaj A, Tsantes AG, Petropoulou C, Boutsikou T, Tsantes AE, Sokou R
Seminars in thrombosis and hemostasis. 2022
Abstract
Birth asphyxia, with an estimated prevalence of 1 to 6 per 1,000 live births, may lead to multiorgan dysfunction due to impaired oxygen and/or blood supply to various organ systems, including the hemostatic system. Coagulopathy, a common complication of perinatal asphyxia, has been described since the 1960s. The aim of this study was to systematically review the literature for records on the use of hemostasis tests in the evaluation of coagulation disorders, in neonates who had suffered from perinatal hypoxia or asphyxia. We identified published studies by searching PubMed and Scopus, up until April 2022. The literature search retrieved 37 articles fulfilling the inclusion criteria of the review. According to the bibliography, thrombocytopenia is commonly associated with perinatal hypoxia/asphyxia. The thrombocytopenia is usually described as mild and platelets return to normal levels by the 10th day of life. Additionally, hypoxic neonates usually present with a hypocoagulable profile, as reflected by the prolongation of standard coagulation tests, including prothrombin time, activated partial thromboplastin time, and international normalized ratio, findings commonly associated with disseminated intravascular coagulation, and by the reduction of the levels of the physiologic inhibition of coagulation system. A few studies thus far using ROTEM/TEG in hypoxic neonates have come to the same conclusion as well; hypoxic newborns seem to be characterized by a hypocoagulable profile compared with healthy neonates. It should be emphasized, however, that standard coagulation tests provide only a rough estimation of the true bleeding or thrombotic risk of hypoxic neonates. On the contrary, viscoelastic methods seem to be more precise in the early detection of hemostasis disorders in the neonatal population. However, until now, there was uncertainty as to the most appropriate coagulation assays for diagnosis and management of coagulation derangement in neonates with perinatal hypoxia indicating the need for further research on this field.
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Variation of outcome reporting in studies of interventions for heavy menstrual bleeding: a systematic review
Cooper NAM, Papadantonaki R, Yorke S, Khan KS
Facts, views & vision in ObGyn. 2022;14(3):205-218
Abstract
BACKGROUND Heavy menstrual bleeding (HMB) detrimentally effects women. It is important to be able to compare treatments and synthesise data to understand which interventions are most beneficial, however, when there is variation in outcome reporting, this is difficult. OBJECTIVES To identify variation in reported outcomes in clinical studies of interventions for HMB. MATERIALS AND METHODS Searches were performed in medical databases and trial registries, using the terms 'heavy menstrual bleeding', menorrhagia*, hypermenorrhoea*, HMB, "heavy period "period", effective*, therapy*, treatment, intervention, manage* and associated MeSH terms. Two authors independently reviewed and selected citations according to pre-defined selection criteria, including both randomised and observational studies. The following data were extracted- study characteristics, methodology and quality, and all reported outcomes. Analysis considered the frequency of reporting. RESULTS There were 14 individual primary outcomes, however reporting was varied, resulting in 45 specific primary outcomes. There were 165 specific secondary outcomes. The most reported outcomes were menstrual blood loss and adverse events. CONCLUSIONS A core outcome set (COS) would reduce the evident variation in reporting of outcomes in studies of HMB, allowing more complete combination and comparison of study results and preventing reporting bias. WHAT IS NEW? This in-depth review of past research into heavy menstrual bleeding shows that there is the need for a core outcome set for heavy menstrual bleeding.
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Viscoelastic versus conventional coagulation tests to reduce blood product transfusion in patients undergoing liver transplantation: A systematic review and meta-analysis
Aceto P, Punzo G, Di Franco V, Teofili L, Gaspari R, Wolfango Avolio A, Del Tedesco F, Posa D, Lai C, Sollazzi L
European journal of anaesthesiology. 2022
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Editor's Choice
Abstract
BACKGROUND Recent literature suggests viscoelastic test (VET)-guided transfusion management could be associated with reduced blood product administration in patients undergoing liver transplantation. OBJECTIVES To assess the effectiveness of coagulation management guided by VETs compared with conventional coagulation tests (CCTs) in reducing blood product transfusion in patients undergoing liver transplantation. DESIGN Systematic review and meta-analysis of randomised (RCTs) and nonrandomised clinical trials performed according to PRISMA guidelines. The protocol was previously published (PROSPERO CRD42021230213). DATA SOURCES The Cochrane Central Library, PubMed/MEDLINE, Embase and the Transfusion Evidence Library were searched up to 30th January 2022. ELIGIBILITY CRITERIA Setting: operating room. Patients: liver transplantation recipients. Intervention: use of VETs versus CCTs. Main outcome measures: the primary outcome was the mean number of transfused units for each blood product including red blood cells (RBCs), fresh frozen plasma (FFP), platelets (PLTs) and cryoprecipitate. Secondary outcomes included mortality rate, intensive care unit (ICU) and hospital length of stay (LOS). RESULTS Seventeen studies (n = 5345 patients), 15 observational and two RCTs, were included in this review. There was a mean difference reduction in RBCs [mean difference: -1.40, 95% confidence interval (95% CI), -1.87 to -0.92; P < 0.001, I2 = 61%) and FFP units (mean difference: -2.98, 95% CI, -4.61 to -1.35; P = < 0.001; I2 = 98%) transfused in the VETs group compared with the CCTs one. A greater amount of cryoprecipitate was administered in the VETs group (mean difference: 2.71, 95% CI, 0.84 to 4.58; P = 0.005; I2 = 91%). There was no significant difference in the mean number of PLT units, mortality, hospital and ICU-LOS. CONCLUSION Our meta-analysis demonstrated that VETs implementation was associated with reduced RBC and FFP consumption in liver transplantation patients without effects on mortality and hospital and ICU-LOS. The certainty of evidence ranged from moderate to very low. Further well conducted RCTs are needed to improve the certainty of evidence.
PICO Summary
Population
Patients undergoing liver transplantation (17 studies, n= 5,345).
Intervention
Coagulation management guided by viscoelastic tests (VETs group).
Comparison
Conventional coagulation tests (CCTs group).
Outcome
There was a mean difference reduction in red blood cells (mean difference: -1.40, 95% confidence interval (95% CI) -1.87 to -0.92, I2 = 61%) and fresh frozen plasma units (mean difference: -2.98, 95% CI -4.61 to -1.35; I2 = 98%) transfused in the VETs group compared with the CCTs group. A greater amount of cryoprecipitate was administered in the VETs group (mean difference: 2.71, 95% CI, 0.84 to 4.58; I2 = 91%). There was no significant difference in the mean number of platelets units, mortality, hospital and intensive care unit (ICU) and hospital length of stay (LOS).
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9.
What is the optimal management of thromboprophylaxis after liver transplantation regarding prevention of bleeding, hepatic artery or portal vein thrombosis? A systematic review of the literature and expert panel recommendations
Kirchner VA, O'Farrell B, Imber C, McCormack L, Northup PG, Song GW, Spiro M, Raptis DA, Durand F
Clinical transplantation. 2022;:e14629
Abstract
BACKGROUND A key tenet of clinical management of patients post liver transplantation (LT) is the prevention of thrombotic and bleeding complications. This systematic review investigated the optimal management of thromboprophylaxis after LT regarding portal vein thrombosis (PVT) or hepatic artery thrombosis (HAT) and prevention of bleeding. METHODS Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. Seven databases were used to conduct extensive literature searches focusing on the use of anticoagulation in LT and its impact on the following outcomes: PVT, HAT, and bleeding. (CRD42021244288) RESULTS Of the 2,478 articles/abstracts screened, 16 studies were included in the final review. All articles were critically appraised by a panel of independent reviewers. There was wide variation regarding the anticoagulation protocols used. Thromboprophylaxis with therapeutic doses of heparin/Vitamin K antagonist combination did not decrease the risk of de novo or the recurrence of PVT but was associated with an increased risk of bleeding in some studies. Only the use of aspirin resulted in a small but significant decrease in the incidence of HAT post-LT, yet it did not increase the risk of bleeding. CONCLUSIONS Based on existing data and expert opinion, thromboprophylaxis at therapeutic or prophylactic dose is not recommended for prevention of de novo PVT following LT in patients not at high risk. Aspirin should be considered as the standard of care following LT to prevent HAT. Thromboprophylaxis should be strongly considered in recipients at risk of HAT and PVT following LT. This article is protected by copyright. All rights reserved.
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10.
Clinical Outcomes of Negative Balloon-Assisted Enteroscopy for Obscure Gastrointestinal Bleeding: A Systematic Review and Meta-Analysis
Shao XD, Shao HT, Wang L, Zhang YG, Tian Y
Frontiers in medicine. 2022;9:772954
Abstract
BACKGROUND For patients with obscure gastrointestinal bleeding (OGIB), finding the bleeding site is challenging. Balloon-assisted enteroscopy (BAE) has become the preferred diagnostic modality for OGIB. The long-term outcome of patients with negative BAE remains undefined. The present study aimed to evaluate the long-term outcomes of patients with negative BAE results for OGIB and to clarify the effect of further investigations at the time of rebleeding with a systematic review and meta-analysis of the available cohort studies. METHODS Studies were searched through the PubMed, EMBASE, and Cochrane library databases. The following indexes were analyzed: rebleeding rate after negative BAE, rebleeding rate after different follow-up periods, the proportion of patients who underwent further evaluation after rebleeding, the percentage of patients with identified rebleeding sources, and the percentage of patients with rebleeding sources in the small intestine. Heterogeneity was assessed using the I(2) test. RESULTS Twelve studies that involved a total of 407 patients were included in the analysis. The pooled rebleeding rate after negative BAE for OGIB was 29.1% (95% CI: 17.2-42.6%). Heterogeneity was significant among the studies (I(2) = 88%; p < 0.0001). The Chi-squared test did not show a difference in rebleeding rates between the short and long follow-up period groups (p = 0.142). The pooled proportion of patients who underwent further evaluation after rebleeding was 86.1%. Among the patients who underwent further evaluation, rebleeding sources were identified in 73.6% of patients, and 68.8% of the identified rebleeding lesions were in the small intestine. CONCLUSION A negative result of BAE in patients with OGIB indicates a subsequently low risk of rebleeding. Further evaluation should be considered after rebleeding.
