-
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 -
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 -
Clinical and Applied... Jul 2018Anticoagulation therapy is administered to patients to prevent or stop thrombin generation in vivo. Although plasma tests of in vivo thrombin generation have been... (Review)
Review
Anticoagulation therapy is administered to patients to prevent or stop thrombin generation in vivo. Although plasma tests of in vivo thrombin generation have been available for more than 2 decades, they are not routinely used in clinical trials or practice to monitor anticoagulation therapy. We observed a fall in one such marker, the D-dimer antigen, in patients receiving anticoagulation therapy. We therefore conducted a systematic review of the medical literature to document the change in serum biomarkers of thrombin generation following the initiation of anticoagulation therapy. Using a defined search strategy, we screened PubMed and Embase citations and identified full-length articles published in English. Eighteen articles containing serial changes in 1 of 3 markers of thrombin generation (D-dimer antigen, thrombin-antithrombin complexes, and prothrombin fragment 1+2 antigen levels) in the 14 days following the initiation of anticoagulation were identified. Even though the assays used varied considerably, each of the 3 markers of thrombin generation declined in the initial period of anticoagulation therapy, with changes evident as early as 1 day after beginning therapy. These observations provide a rationale for further exploration of these markers as measures of the adequacy of anticoagulation using classic as well as novel anticoagulants. Particular patient groups that would benefit from additional means of monitoring anticoagulation therapy are discussed.
Topics: Anticoagulants; Biomarkers; Drug Monitoring; Humans; Infusions, Parenteral; Thrombin
PubMed: 29439639
DOI: 10.1177/1076029617746506 -
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 -
Thrombosis Research Mar 2018Despite high rates of venous thromboembolism (VTE) among patients with hematologic malignancies, few tools exist to assist providers in identifying those patients at... (Review)
Review
INTRODUCTION
Despite high rates of venous thromboembolism (VTE) among patients with hematologic malignancies, few tools exist to assist providers in identifying those patients at highest risk for this potentially fatal complication. Laboratory biomarkers, such as d-dimer, have demonstrated utility in some clinical settings to distinguish patients at increased risk.
MATERIALS AND METHODS
We performed a systematic review of the literature utilizing search terms including "biomarker", "venous thromboembolism", "hematologic malignancy", "lymphoma", "myeloma" and "leukemia" in the Medline database. A total of 25 studies investigating laboratory biomarkers of increased thrombotic risk in the setting of hematologic malignancy were identified and included in this review.
RESULTS AND CONCLUSIONS
The most studied biomarkers, d-dimer and fibrinogen, demonstrated some degree of efficacy in identifying high-risk patients at levels >4.0 mg/L or <1.0 g/L respectively. Additional markers which demonstrated promise included thrombin generation, mean platelet volume, soluble VEGF, soluble P-selectin and extracellular vesicles. Other biomarkers reviewed, which did not consistently demonstrate significant associations with VTE included prothrombin fragments F1 + 2, factor VIII, protein C, protein S, von Willebrand antigen and activity, antithrombin, thrombin antithrombin complex, antiphospholopid antibody, plasminogen activator inhibitor, tissue factor pathway inhibitor and several variants associated with known hypercoagulable states (factor V Leiden, prothrombin gene variant, methylenetetrahydrofolate reductase variant). Data to support any of the biomarkers discussed here in routine clinical decision-making are currently lacking, but additional investigation in clinical studies, ideally in combination with clinical factors known to be associated with increased thrombotic risk, is warranted.
Topics: Biomarkers; Female; Hematologic Neoplasms; Humans; Male; Risk Factors; Venous Thromboembolism
PubMed: 29407626
DOI: 10.1016/j.thromres.2018.01.037 -
The Cochrane Database of Systematic... Jul 2015Fresh frozen plasma (FFP) is a blood component containing procoagulant factors, which is sometimes used in cardiovascular surgery with the aim of reducing the risk of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fresh frozen plasma (FFP) is a blood component containing procoagulant factors, which is sometimes used in cardiovascular surgery with the aim of reducing the risk of bleeding. The purpose of this review is to assess the risk of mortality for patients undergoing cardiovascular surgery who receive FFP.
OBJECTIVES
To evaluate the risk to benefit ratio of FFP transfusion in cardiovascular surgery for the treatment of bleeding patients or for prophylaxis against bleeding.
SEARCH METHODS
We searched 11 bibliographic databases and four ongoing trials databases including the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, 2015), MEDLINE (OvidSP, 1946 to 21 April 2015), EMBASE (OvidSP, 1974 to 21 April 2015), PubMed (e-publications only: searched 21 April 2015), ClinicalTrials.gov, World Health Organization (WHO) ICTRP and the ISRCTN Register (searched 21 April 2015). We also searched the references of all identified trials and relevant review articles. We did not limit the searches by language or publication status.
SELECTION CRITERIA
We included randomised controlled trials in patients undergoing major cardiac or vascular surgery who were allocated to a FFP group or a comparator (no plasma or an active comparator, either clinical plasma (any type) or a plasma-derived blood product). We included participants of any age (neonates, children and adults). We excluded studies of plasmapheresis and plasma exchange.
DATA COLLECTION AND ANALYSIS
Two authors screened all electronically derived citations and abstracts of papers identified by the review search strategy. Two authors assessed risk of bias in the included studies and extracted data independently. We took care to note whether FFP was used therapeutically or prophylactically within each trial.
MAIN RESULTS
We included 15 trials, with a total of 755 participants for analysis in the review. Fourteen trials compared prophylactic use of FFP against no FFP. One study compared therapeutic use of two types of plasma. The timing of intervention varied, including FFP transfusion at the time of heparin neutralisation and stopping cardiopulmonary bypass (CPB) (seven trials), with CPB priming (four trials), after anaesthesia induction (one trial) and postoperatively (two trials). Twelve trials excluded patients having emergency surgery and nine excluded patients with coagulopathies.Overall the trials were small, with only four reporting an a priori sample size calculation. No trial was powered to determine changes in mortality as a primary outcome. There was either high risk of bias, or unclear risk, in the majority of trials included in this review.There was no difference in the number of deaths between the intervention arms in the six trials (with 287 patients) reporting mortality (very low quality evidence). There was also no difference in blood loss in the first 24 hours for neonatal/paediatric patients (four trials with 138 patients; low quality evidence): mean difference (MD) -1.46 ml/kg (95% confidence interval (CI) -4.7 to 1.78 ml/kg); or adult patients (one trial with 120 patients): MD -12.00 ml (95% CI -101.16 to 77.16 ml).Transfusion with FFP was inferior to control for preventing patients receiving any red cell transfusion: Peto odds ratio (OR) 2.57 (95% CI 1.30 to 5.08; moderate quality evidence). There was a difference in prothrombin time within two hours of FFP transfusion in eight trials (with 210 patients; moderate quality evidence) favouring the FFP arm: MD -0.71 seconds (95% CI -1.28 to -0.13 seconds). There was no difference in the risk of returning to theatre for reoperation (eight trials with 398 patients; moderate quality evidence): Peto OR 0.81 (95% CI 0.26 to 2.57). Only one included study reported adverse events as an outcome and reported no significant adverse events following FFP transfusion.
AUTHORS' CONCLUSIONS
This review has found no evidence to support the prophylactic administration of FFP to patients without coagulopathy undergoing elective cardiac surgery. There was insufficient evidence about treatment of patients with coagulopathies or those who are undergoing emergency surgery. There were no reported adverse events attributable to FFP transfusion, although there was a significant increase in the number of patients requiring red cell transfusion who were randomised to FFP. Variability in outcome reporting between trials precluded meta-analysis for many outcomes across all trials, and there was evidence of a high risk of bias in most of the studies. Further adequately powered studies of FFP, or comparable pro-haemostatic agents, are required to assess whether larger reductions in prothrombin time translate into clinical benefits. Overall the evidence from randomised controlled trials for the safety and efficacy of prophylactic transfusion of FFP for cardiac surgery is insufficient.
Topics: Adult; Blood Loss, Surgical; Cardiovascular Surgical Procedures; Child; Elective Surgical Procedures; Erythrocyte Transfusion; Hemostasis, Surgical; Humans; Infant, Newborn; Plasma; Randomized Controlled Trials as Topic; Risk Assessment
PubMed: 26171897
DOI: 10.1002/14651858.CD007614.pub2 -
The Turkish Journal of Gastroenterology... Nov 2016The therapeutic efficacy of stem cell transplantation in liver diseases has not yet been determined. The objective of this study was to conduct a meta-analysis to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND/AIMS
The therapeutic efficacy of stem cell transplantation in liver diseases has not yet been determined. The objective of this study was to conduct a meta-analysis to evaluate changes in liver function and clinical outcome following stem cell transplantation in patients with liver disease.
MATERIALS AND METHODS
A literature review of NCBI, Cochrane Library, and MEDLINE was performed. Eligible studies reported liver function indices and prothrombin time (PT) before and after transplantation. The weighted mean difference (WMD) was defined by the distinction before and after stem cell transplantation. Either a fixed-effects model or random-effects model was used to analyze the data.
RESULTS
A total of 17 publications involving 21 original studies were included. We found that the levels of serum albumin significantly increased at 4, 8, 12, 24, and 48 weeks after stem cell transplantation compared with that at baseline. Serum alanine aminotransferase levels notably decreased at 1, 3, 4, 12, 24, and 48 weeks after stem cell transplantation. Aspartate aminotransferase levels significantly decreased at 4, 8, 12, and 48 weeks after transplantation. Total bilirubin levels significantly decreased at 4, 12, 24, and 48 weeks after transplantation. PT decreased at 4, 12, 24, and 48 weeks after transplantation. The MELD score significantly decreased at 24 weeks after transplantation. Stem cell infusion through the hepatic artery had better biochemical outcomes than an injection through the portal vein.
CONCLUSION
Our meta-analysis verified that there are clinical and biochemical improvements in patients who suffered from liver diseases after stem cell transplantation, suggesting that stem cell transplantation may be a viable clinical solution for treating such patients.
Topics: Alanine Transaminase; Aspartate Aminotransferases; Bilirubin; End Stage Liver Disease; Humans; Liver Diseases; Prothrombin Time; Serum Albumin; Severity of Illness Index; Stem Cell Transplantation
PubMed: 27852540
DOI: 10.5152/tjg.2016.16398 -
JAMA Network Open May 2022Clinical prediction models, or risk scores, can be used to risk stratify patients with lower gastrointestinal bleeding (LGIB), although the most discriminative score is... (Meta-Analysis)
Meta-Analysis
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.
Topics: Area Under Curve; Gastrointestinal Hemorrhage; Humans; ROC Curve; Risk Assessment; Risk Factors
PubMed: 35622365
DOI: 10.1001/jamanetworkopen.2022.14253 -
Archives of Medical Science : AMS 2022The role of low-dose aspirin combined with low-molecular-weight heparin (LMWH) in the treatment of preeclampsia (PE) remains unclear. We aimed to assess the efficacy and... (Review)
Review
INTRODUCTION
The role of low-dose aspirin combined with low-molecular-weight heparin (LMWH) in the treatment of preeclampsia (PE) remains unclear. We aimed to assess the efficacy and safety of low-dose aspirin combined with LMWH in PE treatment, to provide evidence for clinical PE management.
MATERIAL AND METHODS
We searched PubMed and other databases for randomized controlled trials (RCTs) on the effects and safety of low-dose aspirin and LMWH in the treatment of PE up to January 31, 2021. Two researchers strictly followed the inclusion and exclusion criteria to independently conduct the literature screening, data extraction and quality evaluation. We used RevMan 5.3 statistical software for synthesized analysis.
RESULTS
A total of 8 RCTs involving 861 patients were included. The synthesized outcome indicated that the differences in systolic blood pressure (MD = -10.61, 95% CI: -13.19 - -8.02), diastolic blood pressure (MD = -9.24, 95% CI: -14.49- -4.00), 24-hour urinary protein (MD = -2.24, 95% CI: -3.97- -0.50), prothrombin time (MD = 1.42, 95% CI: 0.53-2.32), activated partial thromboplastin time (MD = 2.91, 95% CI: 2.06-3.75), FIB (MD = -1.24, 95% CI: -1.32- -1.15), and adverse perinatal outcomes (MD = 0.41, 95% CI: 0.20-0.85) between the two groups were statistically significant (all < 0.05), while the difference in the adverse reactions of pregnant women (MD = 0.44, 95% CI: 0.18-1.10) between the two groups was not statistically significant ( = 0.08). No publication bias was detected in all the synthesized outcomes (all > 0.05).
CONCLUSIONS
Low-dose aspirin combined with LMWH treatment of PE may be advantageous to improve blood pressure, 24-hour proteinuria and coagulation function, and it may reduce the adverse reactions in pregnant women without increasing adverse perinatal outcomes.
PubMed: 36457979
DOI: 10.5114/aoms/136518 -
Journal of Personalized Medicine Sep 2022Vitamin K antagonists (VKAs) are used in the prophylaxis and treatment of thromboembolic disorders. Despite a high efficacy, their narrow therapeutic window and high... (Review)
Review
Vitamin K antagonists (VKAs) are used in the prophylaxis and treatment of thromboembolic disorders. Despite a high efficacy, their narrow therapeutic window and high response variability hamper their management. Several patients experience fluctuations in dose−response and are at increased risk of over- or under-anticoagulation. Therefore, it is essential to monitor the prothrombin time/international normalized ratio to determine the so-called stable dose and to adjust the dosage accordingly. Three polymorphisms, CYP2C9∗2, CYP2C9∗3 and VKORC1-1639G>A, are associated with increased sensitivity to VKAs. Other polymorphisms are associated with a request for a higher dose and VKA resistance. We described the clinical cases of two patients who were referred to the Clinical Pharmacology and Pharmacogenetics Unit of the University Hospital of Salerno for pharmacological counseling. One of them showed hypersensitivity and the other one was resistant to VKAs. A systematic review was performed to identify randomized clinical trials investigating the impact of pharmacogenetic testing on increased sensitivity and resistance to VKAs. Although international guidelines are available and information on the genotype-guided dosing approach has been included in VKA drug labels, VKA pharmacogenetic testing is not commonly required. The clinical cases and the results of the systematically reviewed RCTs demonstrate that the pharmacogenetic-based VKA dosing model represents a valuable resource for reducing VKA-associated adverse events.
PubMed: 36294717
DOI: 10.3390/jpm12101578