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EClinicalMedicine Oct 2023The optimal duration of anticoagulation in patients with active cancer and venous thromboembolism (VTE) is unknown. Current clinical guidelines advocate anticoagulant...
The risk of recurrent venous thromboembolism after discontinuation of anticoagulant therapy in patients with cancer-associated thrombosis: a systematic review and meta-analysis.
BACKGROUND
The optimal duration of anticoagulation in patients with active cancer and venous thromboembolism (VTE) is unknown. Current clinical guidelines advocate anticoagulant therapy for 3-6 months and to continue anticoagulant therapy for as long as the cancer is active. However, an adequate systematic review on the rate of recurrent VTE after discontinuation of anticoagulant therapy has not been performed.
METHODS
For this systemic review and meta-analysis, we searched Embase.com, Medline (Ovid), Web of Science, Cochrane Library, and Google Scholar, from database inception to February 16, 2023, for studies on anticoagulant therapy in patients with cancer and the recurrence of venous thromboembolism after discontinuation of this therapy. We included randomised controlled trials and cohort studies published in English that reported on patients who met the following: cancer and a first VTE, completed at least 3 months of anticoagulant therapy, were followed after discontinuation of anticoagulant therapy, and with symptomatic recurrent VTE as an outcome during follow-up. Study-level data were requested from study authors. The primary outcome was the rate of recurrent VTE after discontinuation of anticoagulant therapy. A Bayesian random-effects meta-analysis was used to estimate the rate of recurrent VTE per 100 person-years for the pooled studies at different time intervals after discontinuation of anticoagulation therapy. We also calculated the cumulative VTE recurrence rate at different time intervals. Forest plots were mapped and the results were summarized by the median and 95% credible interval (CIs). This study was registered with PROSPERO, CRD42021249060.
FINDINGS
Of 3856 studies identified in our search, 33 studies were identified for inclusion. After requesting study-level data, 14 studies involving 1922 patients with cancer-associated thrombosis were included. The pooled rate of recurrent VTE per 100 person-years after discontinuation of anticoagulant therapy was 14.6 events (95% credible interval 6.5-22.8) in the first three months, decreasing to 1.1 events (95% CI 0.3-2.1) in year 2-3, and 2.2 events (95% CI 0.0-4.4) in year 3-5 after discontinuation of anticoagulant therapy. The cumulative VTE recurrence rate was 28.3% (95% CI 15.6-39.6%) at 1 year; 31.1% (95% CI 16.5-43.8%) at 2 years; 31.9% (95% CI 16.8-45.0%) at 3 years; and 35.0% (95% CI 16.8-47.4%) at 5 years after discontinuation of anticoagulant therapy.
INTERPRETATION
This meta-analysis demonstrates a high rate of recurrent VTE over time after discontinuation of anticoagulant therapy in patients with cancer-associated thrombosis. Our results support the current clinical guidelines to continue anticoagulant therapy in patients with active cancer.
FUNDING
Erasmus MC.
PubMed: 37731937
DOI: 10.1016/j.eclinm.2023.102194 -
Hematology (Amsterdam, Netherlands) Dec 2023Venous thromboembolism (VTE) can occur in children with COVID-19, and the efficacy and safety of prophylactic anticoagulant therapy are uncertain. This study aimed to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Venous thromboembolism (VTE) can occur in children with COVID-19, and the efficacy and safety of prophylactic anticoagulant therapy are uncertain. This study aimed to assess the incidence of VTE in pediatric patients with COVID-19, the association of D-dimer with thrombus formation, and the effectiveness and safety of prophylactic anticoagulation treatment.
METHODS
We systematically searched databases from January 2020 to February 2023. A systematic review and meta-analysis were conducted to determine the incidence of VTE in children and evaluate the efficacy and safety of prophylactic anticoagulant therapy.
RESULTS
Thirteen cohort studies and one clinical trial were included. The pooled incidence rate of VTE in affected children was 1.5% (95% CI 0.4-2.9%). Children with D-dimer levels five times higher than normal had a higher risk of VTE (OR 4.92, 95% CI 1.60-15.11). Prophylactic anticoagulant therapy did not significantly reduce the risk of VTE (OR 1.35, 95% CI 0.74-2.49). The safety of prophylactic anticoagulant therapy was relatively high, with major bleeding and all-cause mortality rates below 0.1% (95% CI 0.0-0.2%).
CONCLUSIONS
The incidence of VTE in children with COVID-19 is low, and prophylaxis based on ISTH standards is reasonable. Low-molecular-weight heparin (LMWH) for VTE prevention has a high level of safety. However, more high-quality studies are needed to understand the impact of anticoagulant therapy on VTE incidence in pediatric patients with COVID-19.
Topics: Humans; Child; Heparin, Low-Molecular-Weight; COVID-19; Venous Thromboembolism; Anticoagulants; Thrombosis; Heparin
PubMed: 37961978
DOI: 10.1080/16078454.2023.2275912 -
British Journal of Haematology Apr 2024The thrombotic risk with haemoglobin C trait (HbAC) or haemoglobin C disease (HbCC) is unclear. However, individuals with HbCC have demonstrated chronic haemolysis,...
The thrombotic risk with haemoglobin C trait (HbAC) or haemoglobin C disease (HbCC) is unclear. However, individuals with HbCC have demonstrated chronic haemolysis, higher blood viscosity and altered rheology when compared to individuals with wild-type haemoglobin (HbAA). These physiological alterations may theoretically translate to increased risk of thrombosis; therefore, a systematic literature review was performed to investigate the possible association between HbAC and/or HbCC and thrombosis. Twenty-two studies met inclusion criteria representing 782 individuals with HbAC (n = 694) or HbCC (n = 88). Fifteen studies described the presence/absence of venous thromboembolism (VTE) in patients with HbAC (n = 685) or HbCC (n = 79), while seven studies described patients with HbAC (n = 9) or HbCC (n = 9) and arterial thrombosis. Most (n = 20) studies were case reports or case series; however, two studies suggested a potential increased VTE risk with HbAC compared to HbAA in (i) all patients (OR 2.2, 95% CI: 0.9-5.5) and in (ii) pregnant individuals (RR 3.7, 95% CI 0.9-16). This review is the largest assessment of patients with HbC trait or disease and thrombosis to date; despite its limitations, the findings suggest HbC may be a predisposing risk factor to thrombosis. Prospective cohort studies are warranted to definitively elucidate the risk of thrombosis in this population.
Topics: Pregnancy; Female; Humans; Hemoglobin C; Hemoglobin C Disease; Venous Thromboembolism; Prospective Studies; Hemoglobinopathies; Thrombosis; Risk Factors
PubMed: 38291731
DOI: 10.1111/bjh.19313 -
Journal of Investigative Medicine : the... Dec 2023We assessed the available evidence regarding adverse effects on surrogate and patient-important health outcomes of third- and fourth-generation combined oral... (Meta-Analysis)
Meta-Analysis Review
We assessed the available evidence regarding adverse effects on surrogate and patient-important health outcomes of third- and fourth-generation combined oral contraceptives among premenopausal women. We performed a systematic review and meta-analysis including randomized controlled trials and observational studies comparing third- and fourth-generation combined oral contraceptives with other generation contraceptives or placebo. Studies that enrolled women aged 15 to 50 years, with at least three cycles of intervention and 6 months of follow-up were included. A total of 33 studies comprising 629,783 women were included. Low-density lipoprotein cholesterol levels were significantly lower in fourth-generation oral contraceptives (mean differences (MD): -0.24 mmol/L; [95% CI -0.39 to -0.08]), while total cholesterol was significantly increased in levonorgestrel users when compared to third-generation oral contraceptives (MD: 0.27 mmol/L; [95% CI 0.04 to 0.50]). A decreased arterial thrombosis incidence was shown in fourth-generation oral contraceptive users, as compared to levonorgestrel (incidence rate ratio (IRR): 0.41; [95% CI 0.19 to 0.86]). No difference was found in the occurrence of deep venous thrombosis between fourth-generation oral contraceptives and levonorgestrel users (IRR: 0.91; [95% CI 0.66 to 1.27]; p = 0.60; I = 0%). Regarding the remaining outcomes, data were heterogeneous and showed no clear difference. In premenopausal women, the use of third- and fourth-generation oral contraceptives is associated with an improved lipid profile and lower risk of arterial thrombosis. Data were inconclusive regarding the rest of outcomes assessed. This review was registered in PROSPERO with CRD42020211133.
Topics: Female; Humans; Contraceptives, Oral, Combined; Levonorgestrel; Thrombosis; Incidence; Cholesterol
PubMed: 37415461
DOI: 10.1177/10815589231184227 -
Thrombosis and Haemostasis Feb 2024To summarize characteristics, complications, and success rates of different catheter-directed thrombolysis (CDT) protocols for the treatment of lower extremity deep... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To summarize characteristics, complications, and success rates of different catheter-directed thrombolysis (CDT) protocols for the treatment of lower extremity deep venous thrombosis (LE-DVT).
METHODS
A systematic review using electronic databases (MEDLINE, Scopus, and Web of Science) was performed to identify randomized controlled trials and observational studies related to LE-DVT treated with CDT. A random-effects model meta-analysis was performed to obtain the pooled proportions of early complications, postthrombotic syndrome (PTS), and venous patency.
RESULTS
Forty-six studies met the inclusion criteria reporting 49 protocols ( = 3,028 participants). In studies that addressed the thrombus location ( = 37), LE-DVT had iliofemoral involvement in 90 ± 23% of the cases. Only four series described CDT as the sole intervention for LE-DVT, while 47% received additional thrombectomy (manual, surgical, aspiration, or pharmacomechanical), and 89% used stenting.Definition of venogram success was highly variable, being the Venous Registry Index the most used method ( = 19). Among those, the minimal thrombolysis rate (<50% lysed thrombus) was 0 to 53%, partial thrombolysis (50-90% lysis) was 10 to 71%, and complete thrombolysis (90-100%) was 0 to 88%. Pooled outcomes were 8.7% (95% confidence interval [CI]: 6.6-10.7) for minor bleeding, 1.2% (95% CI: 0.8-1.7%) for major bleeding, 1.1% (95% CI: 0.6-1.6) for pulmonary embolism, and 0.6% (95% CI: 0.3-0.9) for death. Pooled incidences of PTS and of venous patency at up to 1 year of follow-up were 17.6% (95% CI: 11.8-23.4) and 77.5% (95% CI: 68.1-86.9), respectively.
CONCLUSION
Assessment of the evidence is hampered by the heterogeneity of protocols, which may be reflected in the variation of PTS rates. Despite this, CDT is a low-risk treatment for LE-DVT.
Topics: Humans; Catheters; Femoral Vein; Fibrinolytic Agents; Iliac Vein; Lower Extremity; Postphlebitic Syndrome; Postthrombotic Syndrome; Retrospective Studies; Thrombolytic Therapy; Treatment Outcome; Venous Thrombosis
PubMed: 37279794
DOI: 10.1055/a-2106-3754 -
Journal of Orthopaedic Surgery and... Aug 2023With the increasing prevalence of osteoarthritis of the hip and knee, total joint replacement, the end-stage treatment, provides pain relief and restoration of function,... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
With the increasing prevalence of osteoarthritis of the hip and knee, total joint replacement, the end-stage treatment, provides pain relief and restoration of function, but is often associated with massive blood loss. Tranexamic acid (TXA) has been reported to reduce perioperative blood loss in hip or knee arthroplasty. However, the optimal dose of TXA administration remains controversial. Therefore, we performed a meta-analysis combining data from 5 trials comparing the efficacy and safety of one fixed dose of 1 g intravenously administered TXA with two doses of 1 g each administered intravenously for hip or knee arthroplasty.
METHODS
PubMed, Medline, Embase, Web of Science, and The Cochrane Library were searched from January 2000 to February 2023. Our meta-analysis included randomized controlled trials and cohort studies comparing the efficacy and safety of different doses of intravenous TXA (IV-TXA) for THA or TKA. The observation endpoints included total blood loss, postoperative hemoglobin drop, blood transfusion rate, length of hospital stay, incidence of deep venous thrombosis (DVT), and incidence of pulmonary embolism (PE). Meta-analysis was performed according to Cochrane's guidelines and PRISMA statement. The Danish RevMan5.3 software was used for data merging.
RESULTS
Five cohort studies involving 5542 patients met the inclusion criteria. Our meta-analysis showed that the two groups were significantly higher in total blood loss (mean difference (MD) = - 65.60, 95% confidence interval (CI) [- 131.46, 0.26], P = 0.05); blood transfusion rate (risk difference (RD) = 0.00, 95% CI [- 0.01, 0.02], P = 0.55); postoperative hemoglobin (MD = 0.02, 95% CI [- 0.09, 0.13], P = 0.31); postoperative hospital stay days (MD = - 0.13), 95% CI [- 0.35, 0.09], P = 0.25); DVT (RD = 0.00, 95% CI [- 0.00, 0.01], P = 0.67); PE (RD = 0.00, 95% CI [- 0.01, 0.00], P = 0.79). There was some inherent heterogeneity due to variance in sample size across each major study.
CONCLUSION
1 dose of 1 g and 2 doses of 1 g IV-TXA each time have similar effects on reducing blood loss, blood transfusion rate, postoperative hemoglobin level, and postoperative hospital stay after TKA or THA, without increasing the risk of postoperative complications risk. For patients at high risk of thromboembolic events, one dose of 1 g TXA throughout surgery may be preferred. However, higher-quality RCT is needed to explore the optimal protocol dose to recommend the widespread use of TXA in total joint arthroplasty. Trial registration We conducted literature selection, eligibility criteria evaluation, data extraction and analysis on the research program registered in Prospero (CRD42023405387) on March 16, 2023.
Topics: Humans; Tranexamic Acid; Antifibrinolytic Agents; Arthroplasty, Replacement, Knee; Venous Thrombosis; Blood Loss, Surgical; Arthroplasty, Replacement, Hip; Administration, Intravenous; Pulmonary Embolism; Hemoglobins
PubMed: 37563702
DOI: 10.1186/s13018-023-03929-9 -
European Journal of Vascular and... Nov 2023The objective was to compare technical success, complications, and quality of life after thermal vs. non-thermal endovenous ablation for the treatment of superficial... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The objective was to compare technical success, complications, and quality of life after thermal vs. non-thermal endovenous ablation for the treatment of superficial venous incompetence.
DATA SOURCES
Electronic bibliographic sources (Google Scholar, Pubmed, Cochrane Database, Scopus, Web of Science, and Embase).
REVIEW METHODS
A systematic review and meta-analysis of randomised controlled trials was conducted using terms to identify relevant studies to be included. The primary outcome was vein occlusion rate at up to four weeks and one to two years from procedure. Secondary outcome measures included peri-procedural pain, nerve injury, endothermal heat induced thrombosis, and quality of life.
RESULTS
Eight randomised controlled trials met the selection criteria. These comprised a total of 1 956 patients, of whom 1 042 underwent endovenous thermal ablation and 915 underwent endovenous non-thermal ablation. There was no statistically significant difference in occlusion rate at all time points. Relative risk at four weeks and one to two years was 0.99 (95% CI 0.96 - 1.02) and 0.95 (95% CI 0.88 - 1.01), respectively. Non-thermal ablation was tolerated better and had less risk of nerve injury. There was no statistically significant difference in risk of endothermal heat induced thrombosis (EHIT). There was improvement in quality of life scores post-procedure but there was no statistically significant difference in thermal vs. non-thermal ablation. The quality of evidence assessed using GRADE methodology showed high quality for occlusion rate at four weeks and one to two years, moderate quality for nerve injury and peri-procedural pain, and low quality for EHIT.
CONCLUSION
Vein occlusion rates after thermal vs. non-thermal endovenous ablation are similar. In the early post-operative period, non-thermal endovenous ablation demonstrated the advantages of less pain and less risk of nerve injury. Improvement in quality of life after both thermal and non-thermal endovenous ablation is similar.
Topics: Humans; Pain, Procedural; Quality of Life; Varicose Veins; Saphenous Vein; Thrombosis; Venous Insufficiency; Treatment Outcome; Laser Therapy; Randomized Controlled Trials as Topic
PubMed: 37295602
DOI: 10.1016/j.ejvs.2023.06.002 -
Annals of Surgery Feb 2024To provide procedure-specific estimates of symptomatic venous thromboembolism (VTE) and major bleeding after abdominal surgery. (Meta-Analysis)
Meta-Analysis
Systematic Reviews and Meta-analyses of the Procedure-specific Risks of Thrombosis and Bleeding in General Abdominal, Colorectal, Upper Gastrointestinal, and Hepatopancreatobiliary Surgery.
OBJECTIVE
To provide procedure-specific estimates of symptomatic venous thromboembolism (VTE) and major bleeding after abdominal surgery.
BACKGROUND
The use of pharmacological thromboprophylaxis represents a trade-off that depends on VTE and bleeding risks that vary between procedures; their magnitude remains uncertain.
METHODS
We identified observational studies reporting procedure-specific risks of symptomatic VTE or major bleeding after abdominal surgery, adjusted the reported estimates for thromboprophylaxis and length of follow-up, and estimated cumulative incidence at 4 weeks postsurgery, stratified by VTE risk groups, and rated evidence certainty.
RESULTS
After eligibility screening, 285 studies (8,048,635 patients) reporting on 40 general abdominal, 36 colorectal, 15 upper gastrointestinal, and 24 hepatopancreatobiliary surgery procedures proved eligible. Evidence certainty proved generally moderate or low for VTE and low or very low for bleeding requiring reintervention. The risk of VTE varied substantially among procedures: in general abdominal surgery from a median of <0.1% in laparoscopic cholecystectomy to a median of 3.7% in open small bowel resection, in colorectal from 0.3% in minimally invasive sigmoid colectomy to 10.0% in emergency open total proctocolectomy, and in upper gastrointestinal/hepatopancreatobiliary from 0.2% in laparoscopic sleeve gastrectomy to 6.8% in open distal pancreatectomy for cancer.
CONCLUSIONS
VTE thromboprophylaxis provides net benefit through VTE reduction with a small increase in bleeding in some procedures (eg, open colectomy and open pancreaticoduodenectomy), whereas the opposite is true in others (eg, laparoscopic cholecystectomy and elective groin hernia repairs). In many procedures, thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding VTE and bleeding.
Topics: Humans; Anticoagulants; Colorectal Neoplasms; Hemorrhage; Postoperative Complications; Thrombosis; Venous Thromboembolism
PubMed: 37551583
DOI: 10.1097/SLA.0000000000006059 -
JACC. CardioOncology Feb 2024Current guidelines recommend several direct oral anticoagulant agents (DOACs) equally for managing cancer-associated venous thromboembolism (VTE).
BACKGROUND
Current guidelines recommend several direct oral anticoagulant agents (DOACs) equally for managing cancer-associated venous thromboembolism (VTE).
OBJECTIVES
The aim of this study was to assess the efficacy and safety of DOACs in patients with active cancer.
METHODS
Literature searches were conducted in PubMed, Embase, and Cochrane Central in November 2022. Randomized controlled trials investigating anticoagulation strategies (vitamin K antagonists, parenteral anticoagulation [eg, low-molecular weight heparin], and DOACs) for VTE in patients with active cancer were identified for network meta-analysis. The outcomes included recurrent VTE, recurrent pulmonary embolism, recurrent deep venous thrombosis, major bleeding, clinically relevant nonmajor bleeding (CRNMB), and a composite outcome of major bleeding or CRNMB. Pooled HRs and 95% CIs were estimated using either the HR or relative risk provided from each study. Random-effects models were used for all the analyses.
RESULTS
Seventeen randomized controlled trials involving 6,623 patients with active cancer were included. No significant differences were found among the DOACs for efficacy outcomes (recurrent VTE, pulmonary embolism, and deep venous thrombosis). In terms of major bleeding, apixaban was similarly safe compared with dabigatran and rivaroxaban but was associated with a decreased risk compared with edoxaban (HR: 0.38; 95% CI: 0.15-0.93). Regarding CRNMB, edoxaban was similarly safe compared with apixaban but was associated with a decreased risk compared with rivaroxaban (HR: 0.31; 95% CI: 0.10-0.91). Compared with parenteral anticoagulation, apixaban was associated with a reduced risk for recurrent VTE (HR: 0.60; 95% CI: 0.38-0.93) without increasing bleeding, edoxaban was associated with an increased risk for major bleeding or CRNMB (HR: 1.35; 95% CI: 1.02-1.79), and rivaroxaban was associated with an increased risk for CRNMB (HR: 3.76; 95% CI: 1.43-9.88).
CONCLUSIONS
DOACs demonstrate comparable efficacy but exhibit different safety profiles. Apixaban may confer an antithrombotic benefit without an increased risk for bleeding, distinguishing it from other contemporary anticoagulation strategies in patients with active cancer and VTE.
PubMed: 38510285
DOI: 10.1016/j.jaccao.2023.10.009 -
Archives of Cardiovascular Diseases Jan 2024Patients with cancer are at significantly increased risk of venous thromboembolism (VTE), due both to the impact of malignant disease itself and to the impact of certain... (Review)
Review
Patients with cancer are at significantly increased risk of venous thromboembolism (VTE), due both to the impact of malignant disease itself and to the impact of certain anticancer drugs on haemostasis. This is true both for first episode venous thromboembolism and recurrence. The diagnosis and management of VTE recurrence in patients with cancer poses particular challenges, and these are reviewed in the present article, based on a systematic review of the relevant scientific literature published over the last decade. Furthermore, it is uncertain whether diagnostic algorithms for venous thromboembolism, validated principally in untreated non-cancer patients, are also valid in anticoagulated cancer patients: the available data suggests that clinical decision rules and D-dimer testing perform less well in this clinical setting. In patients with cancer, computed tomography pulmonary angiography and venous ultrasound appear to be the most reliable diagnostic tools for diagnosis of pulmonary embolism and deep vein thrombosis respectively. Options for treatment of venous thromboembolism include low molecular weight heparins (at a therapeutic dose or an increased dose), fondaparinux or oral direct factor Xa inhibitors. The choice of treatment should take into account the nature (pulmonary embolism or VTE) and severity of the recurrent event, the associated bleeding risk, the current anticoagulant treatment (type, dose, adherence and possible drug-drug interactions) and cancer progression.
Topics: Humans; Venous Thromboembolism; Anticoagulants; Pulmonary Embolism; Factor Xa Inhibitors; Neoplasms; Recurrence
PubMed: 38065753
DOI: 10.1016/j.acvd.2023.11.006