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Clinical Pharmacokinetics Mar 2024Investigations into the rivaroxaban response from the perspective of genetic variation have been relatively recent and wide in scope, whereas there is no consensus on...
BACKGROUND
Investigations into the rivaroxaban response from the perspective of genetic variation have been relatively recent and wide in scope, whereas there is no consensus on the necessity of genetic testing of rivaroxaban. Thus, this systematic review aims to thoroughly evaluate the relationship between genetic polymorphisms and rivaroxaban outcomes.
METHODS
The PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Chinese databases were searched to 23 October 2022. We included cohort studies reporting the pharmacogenetic correlation of rivaroxaban. Outcomes measured included efficacy (all-cause mortality, thromboembolic events and coagulation-related tests), safety (major bleeding, clinically relevant non-major bleeding [CRNMB] and any hemorrhage), and pharmacokinetic outcomes. A narrative synthesis was performed to summarize findings from individual studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the reporting guideline for Synthesis Without Meta-Analysis.
RESULTS
A total of 12 studies published between 2019 and 2022 involving 1364 patients were included. Ten, one, and six studies focused on the ABCB1, ABCG2, and CYP gene polymorphisms, respectively. Pharmacokinetic outcomes accounted for the majority of the outcomes reported (n = 11), followed by efficacy (n = 5) [including prothrombin time (PT) or international normalized ratio (n = 3), platelet inhibition rate (PIR) or platelet reactivity units (PRUs; n = 1), thromboembolic events (n = 1)], and safety (n = 5) [including major bleeding (n = 2), CRNMB (n = 2), any hemorrhage (n = 1)]. For ABCB1 gene polymorphism, the relationship between PT and ABCB1 rs1045642 was inconsistent across studies, however there was no pharmacogenetic relationship with other efficacy outcomes. Safety associations were found in ABCB1 rs4148738 and major bleeding, ABCB1 rs4148738 and CRNMB, ABCB1 rs1045642 and CRNMB, and ABCB1 rs2032582 and hemorrhage. Pharmacokinetic results were inconsistent among studies. For ABCG2 gene polymorphism, no correlation was observed between ABCG2 rs2231142 and dose-adjusted trough concentration (C/D). For CYP gene polymorphisms, PIR or PRUs have a relationship with CYP2C19 rs12248560, however bleeding or pharmacokinetic effects did not show similar results.
CONCLUSIONS
Currently available data are insufficient to confirm the relationship between clinical or pharmacokinetic outcomes of rivaroxaban and gene polymorphisms. Proactive strategies are advised as a priority in clinical practice rather than detection of SNP genotyping.
CLINICAL TRIALS REGISTRATION
PROSPERO registration number CRD42022347907.
Topics: Humans; Rivaroxaban; Polymorphism, Genetic; Hemorrhage; Genetic Testing; Anticoagulants
PubMed: 38460105
DOI: 10.1007/s40262-024-01358-3 -
American Journal of Health-system... May 2024The purpose of this review is to evaluate current literature on the treatment of factor Xa inhibitor-associated bleeds with 4-factor prothrombin complex concentrate... (Comparative Study)
Comparative Study
PURPOSE
The purpose of this review is to evaluate current literature on the treatment of factor Xa inhibitor-associated bleeds with 4-factor prothrombin complex concentrate (4F-PCC), with a focus on the effect of low versus high dosing of 4F-PCC on hemostatic efficacy and safety outcomes.
SUMMARY
A search of PubMed and EBSCOhost was performed to identify studies evaluating patients with a factor Xa inhibitor-bleed treated with 4F-PCC at either low or high doses. Studies of patients receiving alternative reversal agents such as fresh frozen plasma and andexanet alfa or where no comparator group was evaluated were excluded from the analysis. To assess the effect of these 4F-PCC dosing strategies, the primary outcome of interest was hemostatic efficacy. Four studies meeting inclusion criteria were included in this review. In each of the included studies, similar rates of hemostatic efficacy, hospital mortality, and venous thromboembolism were observed in the low- and high-dose cohorts.
CONCLUSION
These results suggest low- and high-dose 4F-PCC may confer similar clinical effectiveness and safety; however, these findings should be evaluated and confirmed with future prospective studies.
Topics: Humans; Blood Coagulation Factors; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Hemorrhage; Treatment Outcome
PubMed: 38430127
DOI: 10.1093/ajhp/zxae009 -
Medicine Mar 2024This systematic review and meta-analysis aimed to evaluate the effects of Taohong Siwu Decoction (THSWD) combined with low molecular weight heparin (LMWH), as well as... (Meta-Analysis)
Meta-Analysis
Effectiveness of Taohong Siwu decoction in the prevention of deep vein thrombosis in hip surgery patients: A systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
This systematic review and meta-analysis aimed to evaluate the effects of Taohong Siwu Decoction (THSWD) combined with low molecular weight heparin (LMWH), as well as THSWD alone, on the incidence of Deep vein thrombosis (DVT), D-dimer levels, prothrombin time (PT), activated partial thromboplastin time (APTT), visual analogue scale (VAS) pain score, and calf swelling in patients undergoing hip fracture or replacement surgery, compared to LMWH.
METHODS
According to the predefined inclusion criteria, we conducted a comprehensive search for randomized controlled trials (RCTs) examining the efficacy of THSWD combined with LMWH or THSWD compared to LMWH in patients with hip fractures or undergoing replacement surgery. The search was performed across multiple databases including China National Knowledge Internet, WanFang, Sinomed, Duxiu, PubMed, Embase, Google Scholar, Cochrane, and Web of Science from their inception until December 2023. Additionally, relevant literature references were retrieved and hand searching of pertinent journals was conducted. The methodological quality assessment of the included trials was carried out following the guidelines outlined in the Cochrane Handbook. Review Manager 5.4 was applied in analyzing and synthesizing.
RESULTS
A total of 18 RCTs with 1353 patients were included. The results of meta-analysis showed that compared with the control group, the combined group had a better effect on the incidence of DVT [RR = 0.32, 95% CI(0.17, 0.58; P = .0002], D-dimer [SMD = -5.88, 95% CI(-7.66, -4.11); P < .00001], VAS [MD = -1.16, 95% CI(-1.81, -0.50); P = .0005], Calf circumference difference [MD = -0.56, 95% CI(-1.05, -0.08); P = .02]. There was no significant difference in PT and APTT between the combined group and the control group. Meta-analysis results show that the D-dimer, incidence of DVT, PT, and APTT did not significantly differ between the THSWD and the LMWH groups.
CONCLUSION
This meta-analysis shows that compared with LMWH, THSWD combined with LMWH has a better efficacy in the treatment of DVT after hip surgery, without a significant increase in the incidence of adverse events. Additionally, the combined therapy can also reduce D-dimer, VAS, and swelling. However, due to the limitations of the included studies (such as small sample size and low-quality evidence), the results need to be further verified in more rigorous multicenter clinical trials with a large sample size.
Topics: Humans; Anticoagulants; Randomized Controlled Trials as Topic; Heparin, Low-Molecular-Weight; Venous Thrombosis; Multicenter Studies as Topic; Drugs, Chinese Herbal
PubMed: 38428876
DOI: 10.1097/MD.0000000000037241 -
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 -
Critical Care Medicine May 2024Four-factor prothrombin complex concentrate (4-PCC) is recommended for rapid reversal of vitamin K antagonists (VKAs) such as warfarin, yet optimal dosing remains... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Four-factor prothrombin complex concentrate (4-PCC) is recommended for rapid reversal of vitamin K antagonists (VKAs) such as warfarin, yet optimal dosing remains uncertain.
DATA SOURCES
A systematic review was conducted of PubMed, Embase, and Ovid MEDLINE (Wolters Kluwer) databases from January 2000 to August 2023 for clinical studies comparing fixed- vs. variable-dose 4-PCC for emergent VKA reversal with at least one reported clinical outcome.
STUDY SELECTION
Abstracts and full texts were assessed independently and in duplicate by two reviewers.
DATA EXTRACTION
Data were extracted independently and in duplicate by two reviewers using predefined extraction forms.
DATA SYNTHESIS
The analysis comprised three randomized trials and 16 cohort studies comprising a total of 323 participants in randomized trials (161 in fixed dosage and 162 in variable dosage) and 1912 patients in cohort studies (858 in fixed-dose and 1054 in variable dose). Extracranial bleeding was the predominant indication, while intracranial hemorrhage varied. Overall, a fixed-dose regimen may be associated with a lower dose of 4-PCC and results in a reduction in 4-PCC administration time compared with a variable-dose regimen. A fixed-dose regimen also likely results in increased clinical hemostasis. While there is no clear difference between the two regimens in terms of achieving a goal international normalized ratio (INR) less than 2, a fixed-dose regimen is less likely to achieve a goal INR less than 1.5. High certainty evidence indicates that the fixed-dose regimen reduces both mortality and the occurrence of thromboembolic events. Additional subgroup analyses provides exploratory data to guide future studies.
CONCLUSIONS
A fixed-dose regimen for 4-PCC administration provides benefits over a variable-dose regimen in terms of dose reduction, faster administration time, improved clinical hemostasis, and reduced mortality and thromboembolic events. Further studies are warranted to better refine the optimal fixed-dose regimen.
Topics: Humans; Blood Coagulation Factors; Anticoagulants; Hemorrhage; Thromboembolism; International Normalized Ratio; Fibrinolytic Agents; Vitamin K; Retrospective Studies
PubMed: 38353592
DOI: 10.1097/CCM.0000000000006212 -
American Journal of Hematology Apr 2024In the general population, individuals with an inherited thrombophilia have a higher risk of thrombosis, but the effect of inherited thrombophilia on the risk of... (Meta-Analysis)
Meta-Analysis
In the general population, individuals with an inherited thrombophilia have a higher risk of thrombosis, but the effect of inherited thrombophilia on the risk of cancer-associated venous thromboembolism (VTE) remains controversial. Our objective was to determine the risk of VTE in cancer patients with inherited thrombophilia. We conducted a systematic review and meta-analysis of studies reporting on VTE after a cancer diagnosis in adult patients who were tested for inherited thrombophilia. In September 2022, we searched Medline, EMBASE, and Cochrane Central. Two reviewers screened the abstracts/full texts and assessed study quality using the Quality in Prognostic Studies tool. We used Mantel-Haenszel random-effects models to estimate pooled odds ratios (OR) of VTE and 95% confidence intervals (95%CI). We included 37 and 28 studies in the systematic review and meta-analysis, respectively. Most studies focused on specific cancer types and hematologic malignancies were rare. The risk of VTE was significantly higher in cancer patients with non-O (compared with O) blood types (OR: 1.56 [95% CI: 1.28-1.90]), Factor V Leiden, and Prothrombin Factor II G20210A mutations compared with wild types (OR: 2.28 [95% CI: 1.51-3.48] and 2.14 [95% CI: 1.14-4.03], respectively). Additionally, heterozygous and homozygous methylenetetrahydrofolate reductase C677T had ORs of 1.50 (95% CI: 1.00-2.24) and 1.38 (95% CI: 0.87-2.22), respectively. Among those with Plasminogen-Activator Inhibitor-1 4G/5G, Vascular Endothelial Growth Factor (VEGF) A C634G, and VEGF C2578A mutations, there was no significant association with VTE. In conclusion, this meta-analysis provided evidence that non-O blood types, Factor V Leiden, and Prothrombin Factor II G20210A mutations are important genetic risk factors for VTE in cancer patients.
Topics: Adult; Humans; Venous Thromboembolism; Vascular Endothelial Growth Factor A; Prothrombin; Thrombophilia; Mutation; Neoplasms; Factor V; Risk Factors
PubMed: 38291601
DOI: 10.1002/ajh.27222 -
Frontiers in Medicine 2023This systematic review aimed to compare liver venous deprivation (LVD) with portal vein embolization (PVE) in terms of future liver volume, postoperative outcomes, and...
A systematic review and meta-analysis of liver venous deprivation versus portal vein embolization before hepatectomy: future liver volume, postoperative outcomes, and oncological safety.
INTRODUCTION
This systematic review aimed to compare liver venous deprivation (LVD) with portal vein embolization (PVE) in terms of future liver volume, postoperative outcomes, and oncological safety before major hepatectomy.
METHODS
We conducted this systematic review and meta-analysis following the PRISMA guidelines 2020 and AMSTAR 2 guidelines. Comparative articles published before November 2022 were retained.
RESULTS
The literature search identified nine eligible comparative studies. They included 557 patients, 207 in the LVD group and 350 in the PVE group. This systematic review and meta-analysis concluded that LVD was associated with higher future liver remnant (FLR) volume after embolization, percentage of FLR hypertrophy, lower failure of resection due to low FLR, faster kinetic growth, higher day 5 prothrombin time, and higher 3 years' disease-free survival. This study did not find any difference between the LVD and PVE groups in terms of complications related to embolization, FLR percentage of hypertrophy after embolization, failure of resection, 3-month mortality, overall morbidity, major complications, operative time, blood loss, bile leak, ascites, post hepatectomy liver failure, day 5 bilirubin level, hospital stay, and three years' overall survival.
CONCLUSION
LVD is as feasible and safe as PVE with encouraging results making some selected patients more suitable for surgery, even with a small FLR.
SYSTEMATIC REVIEW REGISTRATION
The review protocol was registered in PROSPERO before conducting the study (CRD42021287628).
PubMed: 38269320
DOI: 10.3389/fmed.2023.1334661 -
Phytomedicine : International Journal... Mar 2024Panax notoginseng saponins (PNS) are the primary active components of an ancient Chinese herb Panax notoginseng. Hypercoagulable state of blood (HCS) is an independent... (Meta-Analysis)
Meta-Analysis
Clinical efficacy and safety of Panax notoginseng saponins in treating chronic obstructive pulmonary disease with blood hypercoagulability: A meta-analysis of randomized controlled trials.
BACKGROUND
Panax notoginseng saponins (PNS) are the primary active components of an ancient Chinese herb Panax notoginseng. Hypercoagulable state of blood (HCS) is an independent risk factor and a cause of death in chronic obstructive pulmonary disease (COPD). Several vivo studies have demonstrated the use of PNS preparations for treating COPD with HCS.
PURPOSE
This study aimed to systematically evaluate the clinical efficacy and safety of PNS preparations in treating COPD with HCS.
STUDY DESIGN
Meta-analysis of the randomized controlled trials (RCTs) was conducted to review data.
METHODS
RCTs on the treatment of COPD with HCS and PNS preparations were searched from PubMed, Cochrane Library, Embase, Web of Science, Chinese National Knowledge Infrastructure, Vip Information Database, Wanfang data, and Chinese Biomedical Literature Database. Relevant data were extracted from the included studies and methodological quality evaluation was performed. R language (version 4.2.3) was applied for the meta-analysis.
RESULTS
Twenty RCTs involving 1831 patients were analyzed. The results revealed that PNS preparations considerably increased the total clinical efficiency, improved forced expiratory volume in one second percent of predicted, and forced expiratory volume/forced vital capacity ratio. Further, PNS preparations improved fibrinogen, plasma d-dimer, whole blood viscosity at high cut, whole blood viscosity at low cut, and plasma viscosity levels. The results obtained for activated partial thromboplastin and prothrombin times were not statistically significant. Finally, PNS preparations increased partial pressure of oxygen and decreased carbon dioxide pressure.
CONCLUSION
This is the first relatively comprehensive systematic review of the clinical efficacy and safety of PNS preparations for treating COPD with HCS. The study revealed that PNS preparations considerably improve lung function, hypoxia, and blood hypercoagulability in patients with COPD and HCS without increasing the risk of hemorrhage and has a good safety profile; therefore, it can be used as a new modulating agent and anticoagulant.
Topics: Humans; Panax notoginseng; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Saponins; Thrombophilia; Treatment Outcome
PubMed: 38216446
DOI: 10.1016/j.phymed.2023.155244 -
The American Journal of Emergency... Mar 2024Four-factor prothrombin complex concentrate (4F-PCC) is standard of care for emergent vitamin K antagonist (VKA) reversal but optimal dosing is uncertain. This... (Meta-Analysis)
Meta-Analysis
STUDY OBJECTIVE
Four-factor prothrombin complex concentrate (4F-PCC) is standard of care for emergent vitamin K antagonist (VKA) reversal but optimal dosing is uncertain. This meta-analysis estimated the proportion of patients treated with fixed dose (FD) 4F-PCC who achieved adequate reversal and compared safety and efficacy of FD versus weight-based dose (WB) strategies.
METHODS
This review was conducted according to PRISMA guidelines. Medline and Scopus were searched and included studies evaluating FD regimens and comparing FD and WB for emergent VKA reversal. Data was pooled using random effects. Subgroup analyses examined heterogeneity. Risk of bias was assessed with Newcastle-Ottawa Scale and RoB2 score.
RESULTS
Twenty-three studies (n = 2055) were included with twelve (n = 1143) comparing FD versus WB. The proportion of patients achieving goal INR with FD varied depending on the INR target, being significantly higher for INR <2 (90.9%, 95% Confidence Interval (CI) 87.2, 94.06) compared to INR <1.6 (70.97%, 95%CI 65.33, 76.31). Compared to WB, FD was less likely to achieve a goal INR <1.6 (Risk Difference (RD) -13%, 95% CI -21, -4) but achieved similar reversal for a goal INR <2.0, (RD -1%, 95%CI -7, 4). There was no difference in hospital mortality (RD 4%, 95%CI -2, 9) or thrombosis (RD 0.0%, 95%CI -3, 3).
CONCLUSION
FD VKA reversal was associated with significantly lower attainment of goal INR compared to WB with lower INR targets. This did not translate to differences in hospital mortality, but these results should be interpreted cautiously in light of the observational nature of the included studies.
Topics: Humans; Vitamin K; International Normalized Ratio; Blood Coagulation Factors; Anticoagulants; Fibrinolytic Agents; Retrospective Studies
PubMed: 38118388
DOI: 10.1016/j.ajem.2023.11.066 -
Advanced Pharmaceutical Bulletin Nov 2023Several vaccine-induced thrombotic thrombocytopenia syndrome (VITTS) cases have been reported after the ChAdOx1 nCov-19 vaccination. The current study systematically... (Review)
Review
Several vaccine-induced thrombotic thrombocytopenia syndrome (VITTS) cases have been reported after the ChAdOx1 nCov-19 vaccination. The current study systematically reviewed the reported post-ChAdOx1 nCoV-19 vaccination thrombotic thrombocytopenia cases. Their laboratory and clinical features, as well as the diagnostic and therapeutic measures, were investigated. Online databases were searched until 25 August 2021. Studies reporting post-ChAdOx1 nCov-19 vaccination thrombotic thrombocytopenia syndrome (TTS) were included. Overall, 167 cases (21-77 years old) from 53 publications were included showing a female dominance of 1.75 times. About 85% of the cases exhibited the primary symptoms within the first two weeks post-vaccination. Headache was the most common initial symptom (>44.2%), and hemorrhage/thrombotic problems (22.46%), as well as discoordination/weakness/numbness/ hemiparesis/cyanotic toes (19.6%), were the most prevalent uncommon initial symptoms. Prothrombin time (PT), D-dimers, and C-reactive protein were the most remarkable increased laboratory parameters in 50.6%, 99.1%, and 55.6% of cases, respectively. In comparison, platelet and fibrinogen were the most remarkable decreased laboratory parameters in 92.7% and 50.5% of cases, respectively. Most VITT cases presented with cerebral venous thrombosis/cerebral venous sinus thrombosis, supraventricular tachycardia, transverse sinus/cerebral thrombosis, pulmonary embolism, and cerebral hemorrhage. Anti-PF4 antibody measurement through immunoassays and functional assays were positive in 86.2% and 73% of cases, respectively. About 31% of the cases died. Early diagnosis and proper therapeutic measures are important in ChAdOx1 nCov-19 vaccine-induced VITTS patients. Therefore, experts are recommended to know the corresponding clinical and laboratory features, as well as diagnostic methods. Elucidation of the pathophysiologic mechanism of ChAdOx1 nCov-19 vaccine-induced TTS deserves further investigation.
PubMed: 38022808
DOI: 10.34172/apb.2023.081