-
Thrombosis and Haemostasis May 2022Bleeding risk is highly relevant for treatment decisions in cancer-associated thrombosis (CAT). Several risk scores exist, but have never been validated in patients... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Bleeding risk is highly relevant for treatment decisions in cancer-associated thrombosis (CAT). Several risk scores exist, but have never been validated in patients with CAT and are not recommended for practice.
OBJECTIVES
To compare methods of estimating clinically relevant (major and clinically relevant nonmajor) bleeding risk in patients with CAT: (1) existing risk scores for bleeding in venous thromboembolism, (2) pragmatic classification based on cancer type, and (3) new prediction model.
METHODS
In a posthoc analysis of the Hokusai VTE Cancer study, a randomized trial comparing edoxaban with dalteparin for treatment of CAT, seven bleeding risk scores were externally validated (ACCP-VTE, HAS-BLED, Hokusai, Kuijer, Martinez, RIETE, and VTE-BLEED). The predictive performance of these scores was compared with a pragmatic classification based on cancer type (gastrointestinal; genitourinary; other) and a newly derived competing risk-adjusted prediction model based on clinical predictors for clinically relevant bleeding within 6 months after CAT diagnosis with nonbleeding-related mortality as the competing event ("CAT-BLEED").
RESULTS
Data of 1,046 patients (149 events) were analyzed. Predictive performance of existing risk scores was poor to moderate (C-statistics: 0.50-0.57; poor calibration). Internal validation of the pragmatic classification and "CAT-BLEED" showed moderate performance (respective C-statistics: 0.61; 95% confidence interval [CI]: 0.56-0.66, and 0.63; 95% CI 0.58-0.68; good calibration).
CONCLUSION
Existing risk scores for bleeding perform poorly after CAT. Pragmatic classification based on cancer type provides marginally better estimates of clinically relevant bleeding risk. Further improvement may be achieved with "CAT-BLEED," but this requires external validation in practice-based settings and with other DOACs and its clinical usefulness is yet to be demonstrated.
Topics: Anticoagulants; Hemorrhage; Humans; Neoplasms; Risk Factors; Thrombosis; Venous Thromboembolism
PubMed: 34544170
DOI: 10.1055/s-0041-1735251 -
Medicina (Kaunas, Lithuania) Oct 2023: Venous thromboembolism (VTE) is common in cancer patients. Anticoagulant therapy with low-molecular-weight heparins (LMWHs) and direct oral anticoagulants (DOACs),... (Meta-Analysis)
Meta-Analysis Review
: Venous thromboembolism (VTE) is common in cancer patients. Anticoagulant therapy with low-molecular-weight heparins (LMWHs) and direct oral anticoagulants (DOACs), such as dalteparin and apixaban, have demonstrated efficacy and safety. However, more comparative research of these drugs is still needed. This study aimed to synthesize evidence on the efficacy of apixaban compared to dalteparin in reducing recurrent VTE, major bleeding, and clinically relevant non-major bleeding associated with cancer. : We systematically searched the PubMed, Scopus, Web of Science, Embase, Cochrane Library, and ClinicalTrials databases up to 5 January 2023, for randomized controlled trials comparing apixaban versus dalteparin as treatment for cancer-associated VTE. Five studies were included. Effects according to meta-analyses were reported as relative risks (RRs) and their 95% confidence intervals (CIs). : It was found that 33 of 734 (4.5%) patients treated with apixaban and 56 of 767 (7.3%) with dalteparin had recurrent VTE as the efficacy outcome (RR 0.49, 95% CI 0.15-1.58, I 38%). Major bleeding occurred in 25 of 734 patients treated with apixaban (3.4%) and 27 of 767 with dalteparin (3.5%) (RR 1.29, 95% CI 0.31-5.27, I 59%). Likewise, clinically relevant non-major bleeding occurred in 64 of 734 patients treated with apixaban (8.7%) and 46 of 767 (5.9%) with dalteparin (RR 1.52, 95% CI 1.05-2.19, I 0%). : Apixaban showed a lower risk of recurrent VTE than dalteparin in patients with cancer-associated VTE, albeit with no statistical difference. Statistical significance was observed for no major clinically relevant bleeding but not for major bleeding.
Topics: Humans; Dalteparin; Venous Thromboembolism; Anticoagulants; Hemorrhage; Neoplasms
PubMed: 37893585
DOI: 10.3390/medicina59101867 -
RSC Advances Jul 2020Oxytocin (OXT) is a small cyclic peptide that is administered to pregnant women to induce birth in cases where labour is prolonged. It has previously been observed that...
Oxytocin (OXT) is a small cyclic peptide that is administered to pregnant women to induce birth in cases where labour is prolonged. It has previously been observed that patients taking a low molecular weight heparin, dalteparin (DAL), and then prescribed, OXT experienced a swifter labour compared to women given OXT alone. Herein are described the interactions between OXT and a number of heparin-based oligosaccharides; DAL; fondaparinux (FP), which is a synthetic heparin oligosaccharide that represents the predominant antithrombin binding-site, and a family of chemically-derived heparin hexasaccharides. The latter oligosaccharides were chosen as they represent sequences found within the polysaccharide dalteparin. Furthermore, the carbohydrate chemical space was investigated by comparing the interaction between OXT and four chemically derivatived heparin hexasaccharides; I-A (DP6), I-A (DP6-2OH, de-2--sulfated hexasaccharide), I-A (DP6-6OH, de-6--sulfated hexasaccharide) and I-A (DP6-NAc, de--sulfated hexasaccharide). The interactions between the peptide and oligosaccharides were studied using a series of C-H and N-H HSQC NMR experiments, at a range of temperatures. This approach allowed the binding epitopes of the peptide and oligosaccharides to be identified, highlighting that 6-- and -sulfation substituent groups of heparin are important for the interaction between the peptide and carbohydrate. This is an important observation as de--sulfation is a traditional method for decreasing the anticoagulation properties of heparin. Furthermore, low temperature experiments of the OXT : FP complex indicate that hydrogen-bonding is very important for the interaction between the peptide and oligosaccharide.
PubMed: 35519099
DOI: 10.1039/d0ra04204h -
The Lancet. Haematology Oct 2019
Topics: Anniversaries and Special Events; Anticoagulants; Dalteparin; Global Burden of Disease; Humans; Risk Factors; Thrombosis
PubMed: 31561856
DOI: 10.1016/S2352-3026(19)30172-3 -
Innovative Surgical Sciences Dec 2019About 10% of patients taking a chronic, oral anticoagulant therapy require an invasive procedure that can be associated with an increased risk for peri-interventional or... (Review)
Review
About 10% of patients taking a chronic, oral anticoagulant therapy require an invasive procedure that can be associated with an increased risk for peri-interventional or perioperative bleeding. Depending on the risk for thromboembolism and the risk for bleeding, the physician has to decide whether the anticoagulant therapy should be interrupted or continued. Patient characteristics such as age, renal function and drug interactions must be considered. The perioperative handling of the oral anticoagulant therapy differs according to the periprocedural bleeding risk. Patients requiring a procedure with a minor risk for bleeding do not need to pause their anticoagulant therapy. For procedures with an increased risk for perioperative bleeding, the anticoagulant therapy should be adequately paused. For patients on a coumarin derivative with a high risk for a thromboembolic event, a perioperative bridging therapy with a low molecular weight heparin is recommended. Due to an increased risk for perioperative bleeding in patients on a bridging therapy, it is not recommended in patients with a low risk for thromboembolism. For patients taking a non-vitamin K oral anticoagulant, a bridging therapy is not recommended due to the fast onset and offset of the medication.
PubMed: 33977124
DOI: 10.1515/iss-2019-0004