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World Neurosurgery Jul 2020The chronic subdural hematoma (cSDH)-Drain trial compared recurrence rates and clinical outcome associated with the use of subperiosteal drain (SPD) and subdural drain... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The chronic subdural hematoma (cSDH)-Drain trial compared recurrence rates and clinical outcome associated with the use of subperiosteal drain (SPD) and subdural drain (SDD) after burr-hole drainage for cSDH. This subgroup analysis aimed to determine whether one drain type is preferable for patients treated with platelet inhibitors (PI) or anticoagulants (AC).
METHODS
This subanalysis included 133 patients treated with PI/AC of the 220 patients from the preceding cSDH-Drain trial. For these patients the association between the drain type used and recurrence rates, mortality, as well as clinical outcome at 6 weeks and 12 months follow-up were analyzed using a logistic regression analysis model. Additionally, recurrence rates, clinical outcome, and mortality were assessed for each PI or AC type separately.
RESULTS
The insertion of SPD was associated with 7.35% recurrence rates compared to 13.85% with SDD in patients treated with PI or AC (OR 0.41, 95% CI 0.06-2.65, P = 0.36). Outcome measurements and mortality did not differ significantly between both groups at 6-week and 12-month follow-up. In addition, there was no statistically significant association between drain type and recurrence rate or mortality when comparing data for each PI or AC type. At 24 hours postoperatively, significantly more patients under phenprocoumon and natrium-dalteparin had a Glasgow Coma Scale score between 13 and 15 in the SDD group compared with the SPD group (P = 0.006), whereaas at 6-week follow-up significantly more patients in the SDD group treated with ASA had a good modified Rankin scale score (P = 0.01). At 12 months, no significant difference in outcome measurements was seen for all PI and AC types.
CONCLUSIONS
In patients treated with PI or AC, the insertion of SPD after burr-hole drainage of cSDH showed comparable recurrence, mortality, and long term outcome rates when compared with SDD.
Topics: Aged; Aged, 80 and over; Anticoagulants; Drainage; Female; Hematoma, Subdural, Chronic; Humans; Male; Periosteum; Platelet Aggregation Inhibitors; Recurrence; Subdural Space; Treatment Outcome; Trephining
PubMed: 32247794
DOI: 10.1016/j.wneu.2020.03.134 -
Thrombosis Journal 2020Advanced pancreatic ductal adenocarcinoma (aPDAC) patients have a lifetime all type thromboembolic event (ATTE) rate of 25-35%. Efficacy and safety of increased dose...
BACKGROUND
Advanced pancreatic ductal adenocarcinoma (aPDAC) patients have a lifetime all type thromboembolic event (ATTE) rate of 25-35%. Efficacy and safety of increased dose primary thromboprophylaxis (IDPTP) with low molecular heparin (LMWH) given for 3 months has been shown in two prospective randomized trials.
OBJECTIVES
To report on efficacy -reduction of all type thromboembolic events (ATTE)-, safety -incidence of Major Bleeding (MB)- and compliance in a single-centre cohort of aPDAC patients receiving first line chemotherapy and LMWH-IDPTP.
METHODS
From May 2009 to October 2016, 82 patients received IDPTP -LMWH with dalteparin. Schedule: 55 kg and below: 7500 IU, between 55 and 80 kg: 10,000 IU, above 80 kg: 12,500 IU. MB is reported using the International Society of Thrombosis and Haemostasis (ISTH) criteria. ATTE was defined as any arterial or venous event, incidental or clinically symptomatic, including visceral VTE.
RESULTS
Mean and median time on dalteparin was 10.2 (95%CI 8.1, 12.4) and 8.0 (95%CI 6.2, 9.7) months respectively. ATTE was observed in 7 (8.5%) of patients, with a median time on IDPTP of 6.2 months (95% CI 10.0, 13.2). MB was seen in 10 (12.2%) patients with a median time on IDPTP of 4.5 months (95% CI 1.6, 7.4). Six major bleeds (60%) were the direct or indirect result of aPDAC. Eighty-one patients had died at the time of data collection with a median overall survival time of 8.7 months (95%CI 6.4, 11.0). Thromboembolism and bleeding were late events. No impact of thromboembolism or bleeding on overall survival was observed.
CONCLUSIONS
IDPTP-dalteparin was associated with lower ATTE occurrence rates than expected and comparable major bleeding rates. ATTE and MB were late events, the majority of MB was from direct or indirect result of locally progressing aPDAC. Since these conditions can frequently arise in aPDAC, IDPTP should be regularly reviewed beyond 3 months.
PubMed: 32514256
DOI: 10.1186/s12959-020-00222-1 -
JACC. CardioOncology Sep 2020Many patients with cancer have a hypercoagulable state and an increased risk of developing venous thromboembolism (VTE), arterial occlusion, and pulmonary emboli....
BACKGROUND
Many patients with cancer have a hypercoagulable state and an increased risk of developing venous thromboembolism (VTE), arterial occlusion, and pulmonary emboli. Patients with cancer may also have an increased risk of bleeding with anticoagulant treatment. Recent trials have reported that direct oral anticoagulants (DOACs) are noninferior to the low-molecular-weight heparin, dalteparin, in preventing VTE, but have a higher bleeding rate.
OBJECTIVES
This study compared the efficacy and risks of DOACs versus dalteparin in patients with cancer-related VTEs across all randomized controlled trials (RCTs).
METHODS
This study performed a systematic analysis of RCTs published in PubMed, SCOPUS, and Google Scholar from September 1, 2007 through March 31, 2020 that reported clinical outcomes of treatment with DOACs versus dalteparin in patients with cancer with acute VTE. Two investigators independently performed study selection and data extraction. Extracted data were recorded and exported to statistical software for all analyses (OpenMetaAnalyst).
RESULTS
This study included 4 randomized trials (N = 2,907). Compared with DOACs, dalteparin was associated with higher VTE recurrence (risk ratio [RR]: 1.55; 95% confidence interval [CI]: 1.19 to 2.03; p = 0.001), whereas clinically relevant nonmajor bleeding (CRNMB) was significantly less frequent with dalteparin than that with DOACs (RR: 0.68; 95% CI: 0.54 to 0.86; p = 0.001). The risk of CRNMB was largely observed with patients with gastrointestinal malignancies. No significant differences were observed in major bleeding (RR: 0.74; 95% CI: 0.52 to 1.06; p = 0.11).
CONCLUSIONS
DOACs were noninferior to dalteparin in preventing VTE recurrence in patients with cancer without a significantly increased risk of major bleeding. However, DOACs were associated with higher rates of CRNMB compared with dalteparin, primarily in patients with gastrointestinal malignancies.
PubMed: 34396250
DOI: 10.1016/j.jaccao.2020.06.001 -
Journal of Oncology Pharmacy Practice :... Jan 2019Patients with cancer have an elevated risk of venous thromboembolism. Importantly, patients with cancer, who have metastatic disease, renal insufficiency, or are...
Low-molecular-weight heparins for the prevention of recurrent venous thromboembolism in patients with cancer: A systematic literature review of efficacy and cost-effectiveness.
BACKGROUND
Patients with cancer have an elevated risk of venous thromboembolism. Importantly, patients with cancer, who have metastatic disease, renal insufficiency, or are receiving anticancer therapy, have an even higher risk of a recurrent event. Similarly, the risk of recurrent venous thromboembolism is higher than the risk of an initial event. To reduce the risk, extended duration of prophylaxis for up to six months with low-molecular-weight heparins such as dalteparin, enoxaparin, nadroparin, and tinzaparin is recommended by international guidelines. In this paper, the clinical and economic literature is reviewed to provide evidenced based recommendations based on clinical benefit and economic value.
METHODS
A systematic review of major databases was conducted from January 1996 to October 2016 for randomized controlled trials evaluating the four distinct low-molecular-weight heparins against a vitamin K antagonists control group for the prevention of recurrent venous thromboembolism in patients with active cancer. This was then followed by the application of the National Institute of Health and Clinical Excellence guidance to assess the quality of all trials that met the inclusion criteria. Finally, the cost-effectiveness literature supporting the value proposition of each product was reviewed.
RESULTS
Six randomized trials met the inclusion criteria. There were one, two, and three trials that compared dalteparin, tinzaparin, and enoxaparin to a vitamin K antagonists control group. However, there were no trials for nadroparin in the setting of secondary venous thromboembolism prevention. In addition, only the dalteparin and one of the tinzaparin trials were of high quality and adequately powered. Of the two studies, only the dalteparin trial reported a statistically significant benefit in terms of venous thromboembolism absolute risk reduction when compared to a vitamin K antagonists control group (HR = 0.48; p = 0.002). In addition, there was robust pharmacoeconomic data from Canada, the Netherlands, France, and Austria supporting the cost-effectiveness of dalteparin for this indication. There were no such studies for any of the other agents.
CONCLUSIONS
The totality of high-quality clinical and cost-effectiveness data supports the use of dalteparin over other low-molecular-weight heparins for preventing recurrent venous thromboembolism in patients with cancer.
Topics: Anticoagulants; Cost-Benefit Analysis; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Secondary Prevention; Treatment Outcome; Venous Thromboembolism
PubMed: 28857713
DOI: 10.1177/1078155217727140 -
BMC Musculoskeletal Disorders Jan 2023Tranexamic acid (TXA) has been widely applied in total knee arthroplasty (TKA) to significantly reduce perioperative blood loss and improve knee function recovery in... (Randomized Controlled Trial)
Randomized Controlled Trial
Effectiveness of different antithrombotic agents in combination with tranexamic acid for venous thromboembolism prophylaxis and blood management after total knee replacement: a prospective randomized study.
BACKGROUND
Tranexamic acid (TXA) has been widely applied in total knee arthroplasty (TKA) to significantly reduce perioperative blood loss and improve knee function recovery in patients after surgery. The choice of antithrombotic agents for venous thromboembolism (VTE) prevention after TKA is controversial. Therefore, this study aimed to compare the effects of different antithrombotic agents on patients after primary unilateral TKA in the context of applied TXA.
METHODS
A total of 180 patients undergoing primary unilateral TKA from October 2020 to December 2021 were included in this study. All patients were given an intraoperative drip of 60 mg/kg TXA. Thereafter, patients were divided into three groups (n = 60 each). Baseline data were comparable among the three groups. The average follow-up time was 3.02 ± 0.09 months. Group 1 enrolled patients receiving oral rivaroxaban (RA) at 10 mg, Group 2 included patients who received subcutaneous Dalteparin sodium at 2500 IU, while Group 3 included patients taking oral aspirin (ASA) at 100 mg. Patients in all the three groups received treatment once a day for 30 days at 12 h postoperatively. The primary outcomes in this study were post-treatment drainage volume and thrombotic complication rate. The secondary outcomes included hematologic parameters, transfusion rate, intraoperative blood loss, total blood loss (TBL), and bleeding complication rate.
RESULTS
The average drainage volume after treatment was significantly lower in Group 3 than in Group 1 and Group 2 (205.2 ± 69.0 vs 243.4 ± 72.5 vs 295.4 ± 72.5 ml, P < 0.001), and there was a significant difference between Group 1 and Group 2 (243.4 ± 72.5 mL vs 295.4 ± 72.5 mL, P < 0.001). The blood transfusion rate of Group 2 dramatically increased compared with Group 1 and Group 3 (20.0% vs 6.7% vs 5.0%, P = 0.01). The bleeding complication rate in Group 1 apparently increased relative to Group 2 and Group 3 (26.7% vs 10.0% vs 8.3%, P = 0.008). Besides, there was no significant difference in the thrombotic complication rate among the three groups.
CONCLUSION
Under the background of TXA application, ASA, RA, and Dalteparin sodium were all effective on preventing VTE after TKA. In addition, ASA effectively reduced post-treatment Hemoglobin (Hb) loss, drainage volume, TBL, transfusion rate, and bleeding complications compared with RA and Dalteparin sodium.
TRIAL REGISTRATION
The trial was registered at the Chinese Clinical Trial Registry (ChiCTR2200060169). Date of Registration: 21/05/2022.
Topics: Humans; Tranexamic Acid; Arthroplasty, Replacement, Knee; Venous Thromboembolism; Fibrinolytic Agents; Antifibrinolytic Agents; Dalteparin; Prospective Studies; Blood Loss, Surgical; Rivaroxaban; Anticoagulants; Postoperative Hemorrhage
PubMed: 36600227
DOI: 10.1186/s12891-022-06117-8 -
Biology of Reproduction Nov 2018Low molecular weight heparin (LMWH) is being investigated as a potential preventative therapy against preeclampsia. There is evidence suggesting that LMWH may prevent...
Low molecular weight heparin (LMWH) is being investigated as a potential preventative therapy against preeclampsia. There is evidence suggesting that LMWH may prevent preeclampsia through anticoagulation-independent mechanisms. In this study, we compared the in vitro placental, endothelial, and anti-inflammatory effects of an LMWH (dalteparin) with a nonanticoagulant, glycol-split heparin derivative (gsHep). In contrast with dalteparin, gsHep did not interact with antithrombin III, possess significant anti-Factor Xa activity, or significantly prolong in vitro plasma clotting time. However, dalteparin and gsHep were otherwise mechanistically similar, both interacting with soluble fms-like tyrosine kinase-1 (sFlt1) and promoting release of the pro-angiogenic protein placental growth factor, but not the antiangiogenic sFlt1, from healthy placental villous explants. Placental explant media pretreated with dalteparin or gsHep significantly stimulated endothelial cell tube formation compared to untreated explants. Lastly, dalteparin and gsHep both significantly suppressed inflammation by inhibiting complement activation and leukocyte adhesion to endothelial cells that were activated using serum from preeclamptic women. Our data suggest that nonanticoagulant heparin derivatives may be utilized as a tool to distinguish the anticoagulation-independent mechanisms of LMWH, and provide insight into the role of anticoagulation in the prevention of preeclampsia.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Cell Adhesion; Complement Activation; Dalteparin; Factor Xa; Female; Glycols; Heparin, Low-Molecular-Weight; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Placenta; Pre-Eclampsia; Pregnancy; Signal Transduction; Vascular Endothelial Growth Factor Receptor-1
PubMed: 29860275
DOI: 10.1093/biolre/ioy127 -
Scientific Reports Apr 2019The bidirectional association between coagulation and cancer has been established. However, anticoagulant therapies have been reported to have beneficial outcomes by...
The bidirectional association between coagulation and cancer has been established. However, anticoagulant therapies have been reported to have beneficial outcomes by influencing the vascularisation of the tumours. In this study the influence of a set of anticoagulants on tumour formation, invasion and vascularisation was examined. WM-266-4 melanoma and AsPC-1 pancreatic cancer cell lines were treated with LMWH (Tinzaparin and Dalteparin), and DOAC (Apixaban and Rivaroxaban) and the rate of tumour formation, growth and invasion were measured in vitro. In addition, the influence of these anticoagulants on vascularisation was examined using the chorioallantoic membrane assay (CAM) model and compared to the outcome of treatment with Bevacizumab. Using this model the influence of pharmacological concentrations of the anticoagulant on the growth, invasion and vascularisation of tumours derived from WM-266-4 and AsPC-1 cells was also measured in vivo. Tinzaparin and Daltepain reduced tumour formation and invasion by the cell lines in vitro, but with dissimilar potencies. In addition, treatment of CAM with LMWH reduced the local vascular density beyond that achievable with Bevacizumab, particularly suppressing the formation of larger-diameter blood vessels. In contrast, treatment with DOAC was largely ineffective. Treatment of CAM-implanted tumours with LMWH also reduced tumour vascularisation, while treatment of tumours with Apixaban reduced tumour growth in vivo. In conclusion, LMWH and DOAC appear to have anti-cancer properties that are exerted through different mechanisms.
Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Tests; Cell Line, Tumor; Cell Proliferation; Factor Xa Inhibitors; Heparin, Low-Molecular-Weight; Humans; Melanoma; Neoplasm Invasiveness; Neovascularization, Pathologic; Pancreatic Neoplasms
PubMed: 31000751
DOI: 10.1038/s41598-019-42738-1 -
BMJ Case Reports Oct 2016Drug fever caused by dalteparin-sodium (DS), a low-molecular-weight derivative of heparin, is neither listed in the official drug information and nor published as a case...
Drug fever caused by dalteparin-sodium (DS), a low-molecular-weight derivative of heparin, is neither listed in the official drug information and nor published as a case report until today. A preterm infant, born at 26 weeks of gestation, developed fever 2 days after starting a treatment with DS for an intracardial thrombus. The fever reverses soon after changing the treatment to unfractionated heparin and reappeared after reintroduction of DS. Once again, after discontinuing DS, the infant regained normothermia. Bacterial and viral infections, tissue damage, impaired liver or kidney function, preservative agents and comedications could be ruled out as fever origin. By using the Naranjo adverse drug reaction (ADR) probability scale and the Liverpool ADR causality assessment tool, this case can be classified as 'probable ADR' and 'definite ADR'. This is the first case report of a drug fever caused by the low-molecular-weight heparin DS in a preterm infant.
Topics: Anticoagulants; Dalteparin; Fever; Heart Diseases; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Thrombosis
PubMed: 27737872
DOI: 10.1136/bcr-2016-217621 -
Haematologica Jul 2022The effect of renal impairment (RI) on risk of bleeding and recurrent thrombosis in cancer patients treated with direct oral anticoagulants for venous thromboembolism... (Randomized Controlled Trial)
Randomized Controlled Trial
Renal function and clinical outcome of patients with cancer-associated venous thromboembolism randomized to receive apixaban or dalteparin. Results from the Caravaggio trial.
The effect of renal impairment (RI) on risk of bleeding and recurrent thrombosis in cancer patients treated with direct oral anticoagulants for venous thromboembolism (VTE) is undefined. We ran a prespecified analysis of the randomized Caravaggio study to evaluate the role of RI as a risk factor for bleeding or recurrence in patients treated with dalteparin or apixaban for cancerassociated VTE. RI was graded as moderate (creatinine clearance between 30-59 mL/minute; 275 patients) and mild (between 60- 89 mL/minute; 444 patients). In the 1142 patients included in this analysis, the incidence of major bleeding was similar in patients with moderate vs. no or mild RI (HR 1.06-95% CI: 0.53-2.11), with no difference in the relative safety of apixaban and dalteparin. Recurrent VTE was not different in moderate vs. no or mild RI (HR=0.67, 95% CI: 0.38-1.20); in moderate RI, apixaban reduced recurrent VTE compared to dalteparin (HR=0.27, 95% CI: 0.08-0.96; P for interaction 0.1085). At multivariate analysis, no association was found between variation of renal function over time and major bleeding or recurrent VTE. Advanced or metastatic cancer was the only independent predictor of major bleeding (HR=2.84, 95% CI: 1.20-6.71), with no effect of treatment with apixaban or dalteparin. In our study, in cancer patients treated with apixaban or dalteparin, moderate RI was not associated with major bleeding or recurrent VTE. In patients with moderate renal failure, the safety profile of apixaban was confirmed with the potential for improved efficacy in comparison to dalteparin. ClinicalTrials.gov identifier: NCT03045406.
Topics: Anticoagulants; Dalteparin; Hemorrhage; Humans; Kidney; Neoplasms; Pyrazoles; Pyridones; Venous Thromboembolism
PubMed: 34382385
DOI: 10.3324/haematol.2021.279072 -
Journal of Thrombosis and Haemostasis :... Dec 2020Inflammation with leukocyte activation is a hallmark of cancer-associated thrombosis (CAT), and elevated leukocytes predict venous thromboembolism in cancer outpatients....
BACKGROUND
Inflammation with leukocyte activation is a hallmark of cancer-associated thrombosis (CAT), and elevated leukocytes predict venous thromboembolism in cancer outpatients. In a recent trial, rivaroxaban was more efficacious than dalteparin in preventing CAT recurrence.
OBJECTIVES
In a proof-of-concept study, we aimed to provide a mechanistic basis for improved efficacy of rivaroxaban compared to low molecular weight heparin in CAT treatment.
METHODS
We studied the effects of rivaroxaban, dalteparin, and tinzaparin at peak and trough levels on tumor cell-induced procoagulant activity and platelet aggregation in the presence or absence of the cationic leukocyte-derived enzyme, myeloperoxidase (MPO). Furthermore, pro-inflammatory conditions were generated by stimulating whole blood with lipopolysaccharide (LPS) or phorbol-myristate-acetate (PMA), before measuring thrombin generation in plasma supernatants.
RESULTS
All three anticoagulants inhibited thrombin generation, fibrin clot formation, and platelet aggregation induced by the tissue factor-expressing prostate carcinoma cell line, 22Rv1. Pre-incubation with MPO partially attenuated the anticoagulant activity of dalteparin and tinzaparin, but not rivaroxaban, at trough levels. The effect of MPO did not involve the enzyme's catalytic properties, but required its structural integrity, as indicated by heat denaturation. In plasma obtained from LPS- or PMA-stimulated whole blood, elevated MPO antigen levels inversely correlated with the ability of tinzaparin to inhibit 22Rv1-induced thrombin generation.
CONCLUSIONS
Myeloperoxidase release may partially attenuate the anticoagulant activity of trough levels of dalteparin and tinzaparin in the context of paraneoplastic leukocyte activation. However, this effect is likely not sufficient to explain the improved efficacy of rivaroxaban, and possibly other oral factor Xa inhibitors, in CAT treatment.
Topics: Anticoagulants; Factor Xa Inhibitors; Heparin, Low-Molecular-Weight; Humans; Male; Neoplasms; Peroxidase; Rivaroxaban
PubMed: 32865287
DOI: 10.1111/jth.15075