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Experimental Hematology & Oncology Oct 2022Cancer-associated thrombosis (CAT) poses a significant disease burden and the incidence in Asian populations is increasing. Anticoagulation is the cornerstone of... (Review)
Review
Cancer-associated thrombosis (CAT) poses a significant disease burden and the incidence in Asian populations is increasing. Anticoagulation is the cornerstone of treatment, but can be challenging due to the high bleeding risk in some cancers and the high risk of recurrent venous thromboembolism (VTE) in patients with malignancies. Direct oral anticoagulants (DOACs) are well established as first-choice treatments for VTE in non-cancer patients, offering a more convenient and less invasive treatment option than low-molecular-weight heparin (LMWH). Asian patients have exhibited comparable efficacy and safety outcomes with other races in trials of DOACs for VTE in the general population. Although no specific data are available in Asian patients with CAT, results from randomized controlled trials of apixaban, edoxaban, or rivaroxaban versus the LMWH, dalteparin, indicate that DOACs are a reasonable alternative to LMWH for anticoagulation in Asian patients with CAT. This is further supported by analyses of real-world data in Asian populations demonstrating the efficacy and safety of DOACs in Asian patients with CAT. Apixaban, edoxaban, or rivaroxaban are recommended in the most recently updated international guidelines as first-line therapy for CAT in patients without gastrointestinal or genitourinary cancers and at low risk of bleeding. An increased risk of major gastrointestinal bleeding was evident with edoxaban or rivaroxaban, but not apixaban, versus dalteparin in the clinical trials, suggesting that apixaban could be a safe alternative to LMWH in patients with gastrointestinal malignancies. Determining the optimal anticoagulant therapy for patients with CAT requires careful consideration of bleeding risk, tumor type, renal function, drug-drug interactions, financial costs, and patients' needs and preferences.
PubMed: 36303259
DOI: 10.1186/s40164-022-00331-9 -
BMC Pregnancy and Childbirth Jan 2024To systematically evaluate the efficacy of low molecular weight heparin (LMWH) to prevent preeclampsia in high risk pregnant women without thrombophilia. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To systematically evaluate the efficacy of low molecular weight heparin (LMWH) to prevent preeclampsia in high risk pregnant women without thrombophilia.
SEARCH STRATEGY
PubMed, Embase and the Cochrane library were searched for articles published before 1st August 2022 using the combination keywords "preeclampsia", "Low Molecular Weight Heparin", "LMWH", "Heparin, Low Molecular Weight", "Dalteparin", "Nadroparin", and "Tinzaparin".
SELECTION CRITERIA
Randomized controlled trials evaluating the use of LMWH in pregnant women at high risk of preeclampsia without thrombophilia.
DATA COLLECTION AND ANALYSIS
Ten studies were included in the meta-analysis (1758 patients in total). Outcomes were expressed as relative risk (RR) with 95% confidence intervals (CI).
RESULTS
LMWH reduced the incidence of PE (RR = 0.67; 95% CI = 0.50-0.90; P = 0.009) in high risk pregnant women without thrombophilia. Subgroup analysis found that the prophylactic effect of LMWH was only significant in studies using low-dose aspirin (LDA) as the primary intervention. The combination of LMWH and LDA was also effective for the prevention of preterm birth and fetal growth restriction, but had no effect on the incidence of placenta abruption.
CONCLUSION
For women at high risk of developing preeclampsia without thrombophilia, the combination of LMWH and low-dose aspirin is effective for the prevention of preeclampsia, preterm birth and fetal growth restriction and is superior to LDA alone.
Topics: Female; Infant, Newborn; Humans; Pregnancy; Heparin, Low-Molecular-Weight; Pre-Eclampsia; Pregnancy, High-Risk; Premature Birth; Fetal Growth Retardation; Aspirin; Heparin; Nadroparin; Thrombophilia; Anticoagulants
PubMed: 38233773
DOI: 10.1186/s12884-023-06218-9 -
Cureus May 2023Spontaneous retroperitoneal hematomas are a rare yet potentially devastating occurrence associated with antiplatelet and anticoagulant therapies. We present a case of a...
Spontaneous retroperitoneal hematomas are a rare yet potentially devastating occurrence associated with antiplatelet and anticoagulant therapies. We present a case of a spontaneous retroperitoneal hematoma post-operatively after a total hip arthroplasty surgery performed under a midline approach spinal anesthetic. A 79-year-old male with a BMI of 25.72 kg/m presented for anterior total hip arthroplasty. A midline approach with an uncomplicated spinal anesthetic was performed. On the night of postoperative day 0, the patient received a prophylactic dose of dalteparin. The patient reported back pain, contralateral leg numbness, and weakness that began overnight on postoperative day 0. A computed tomography (CT) scan confirmed a 10 cm, contralateral retroperitoneal hematoma. The patient underwent interventional radiology embolization followed by surgical evacuation and demonstrated improvement in the neurologic function of his affected leg. Despite the rarity of a spontaneous retroperitoneal hematoma formation in the perioperative period, it could be simultaneously evaluated when performing an MRI to rule out spinal hematoma if a patient suffers a post-op neurologic deficit after a neuraxial technique. Understanding the evaluation and timely treatment of patients at risk for a perioperative retroperitoneal hematoma could help clinicians prevent a permanent neurologic deficit.
PubMed: 37193095
DOI: 10.7759/cureus.38971 -
Blood Mar 2022Venous thromboembolism (VTE) is a common complication occurring in 5% to 10% of patients with lymphoma. As the complexity of lymphoma management has increased with novel...
Venous thromboembolism (VTE) is a common complication occurring in 5% to 10% of patients with lymphoma. As the complexity of lymphoma management has increased with novel therapies, so too has the treatment of VTE. Therapeutic options for the treatment of cancer-associated VTE have expanded from only warfarin and low-molecular-weight heparins (LMWHs) to include the direct oral anticoagulants (DOACs) apixaban, edoxaban and rivaroxaban. There have been no head-to-head trials comparing different DOACs in this setting, and randomized trials comparing a DOAC with LMWH dalteparin differ in trial design and results. Drug-drug interactions, drug-specific side effects, and patient selection are important considerations when prescribing anticoagulant therapy. In all patients, the relative risks of thrombosis and bleeding, the availability of the anticoagulant, and the life expectancy of the patient are vital elements in selecting the most appropriate anticoagulant (which can vary over time) for the individual patient. We describe the intricacies and challenges of treating thrombotic complications in patients with lymphoma with an emphasis on evidence and guideline-based care.
Topics: Administration, Oral; Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Lymphoma; Neoplasms; Thrombosis; Venous Thromboembolism
PubMed: 34479364
DOI: 10.1182/blood.2019003689 -
Analytical Chemistry Sep 2022In this work, the first version of "Glycomapping" software is developed for the analysis of the most common low-molecular-weight heparin (LMWH), enoxaparin. Using...
In this work, the first version of "Glycomapping" software is developed for the analysis of the most common low-molecular-weight heparin (LMWH), enoxaparin. Using ultrahigh-performance liquid chromatography-mass spectrometry, size exclusion chromatography is applied, and a virtual database of glycans in enoxaparin is established for the initial searching. With "Glycomapping", a complex chromatogram can be fitted, significantly improving resolution and confirming an accurate distribution range for each size of glycan within enoxaparin. In addition, randomly matched MS data can be corrected, with the constraint of the corresponding chromatographic retention time range, to remove most false positive data. The analytical stability of "Glycomapping" software was confirmed. Enoxaparin, prepared by different manufacturers and from different animal sources, was analyzed using "Glycomapping." Compared to raw data, data processed with "Glycomapping" are more robust and accurate. Another two LMWHs, nadroparin and dalteparin could also be analyzed with this software. This work lays a solid foundation for the automated analysis of heterogeneous mixtures of natural glycans, such as LMWHs and other complex oligosaccharides and polysaccharides.
Topics: Animals; Anticoagulants; Chromatography, Liquid; Dalteparin; Enoxaparin; Heparin; Heparin, Low-Molecular-Weight; Nadroparin; Software
PubMed: 36102213
DOI: 10.1021/acs.analchem.2c01579 -
Journal of Gynecologic Oncology Jan 2020
Topics: Anticoagulants; Dalteparin; Female; Humans; Neoplasm Recurrence, Local; Rivaroxaban; Venous Thromboembolism
PubMed: 31833262
DOI: 10.3802/jgo.2020.31.e40 -
Journal of Diabetes and Metabolic... Dec 2022Coronavirus Disease 2019 (COVID-19) is a recent public health issue worldwide. Also, diabetes is a frequent condition with high mortality. There is a strong relationship... (Review)
Review
Coronavirus Disease 2019 (COVID-19) is a recent public health issue worldwide. Also, diabetes is a frequent condition with high mortality. There is a strong relationship between COVID-19 and diabetes. This article analyses the intricate relationship between COVID-19 and hepcidin. Hepcidin increases in aged non-insulin diabetic patients. Hepcidin is the last target treatment of several medications commonly used. Viral diseases, especially SARS-CoV19, can activate the hepcidin pathway leading to an elevation in the iron load. This increased iron is released into the bloodstream and results in cell death through ferroptosis, like free iron. Excess iron has pro-coagulative and toxic effects. Hepcidin overexpression and iron overload are associated with COVID-19 infection and can be considered potential targets for treatment. Several studies have shown dalteparin (anti-Hepcidin) could improve the symptoms of COVID-19 in diabetics by appropriately modulating and decreasing oxidative stress and inflammation. This finding can be leading to enhancing the existing knowledge about Therapeutic measures for reducing Covid-19 impairments in diabetics and is suggested as a possible therapeutic agent in diabetes.
PubMed: 35812243
DOI: 10.1007/s40200-022-01053-9 -
The Journal of Allergy and Clinical... Nov 2022Heparin allergy most frequently manifests as delayed-type hypersensitivity (DTH) causing an itchy inflammatory skin reaction at the site of subcutaneous injection. An...
BACKGROUND
Heparin allergy most frequently manifests as delayed-type hypersensitivity (DTH) causing an itchy inflammatory skin reaction at the site of subcutaneous injection. An important differential diagnosis is circumscribed skin necrosis due to heparin-induced thrombocytopenia.
OBJECTIVES
An inflammatory skin reaction to subcutaneously injected heparin generally entails the quest for alternative anticoagulation; concerns may particularly arise in an emergency situation requiring intravenous heparin administration.
METHODS
All heparin DTH cases seen in our department over the last 17 years underwent standardized allergy diagnostics including challenge testing, that is, subcutaneous injection of fondaparinux and intravenous administration of unfractionated heparin (UFH).
RESULTS
Of a total of 50 patients with confirmed heparin allergy, DTH was found in 48 (96.0%), and immediate-type, presumably IgE-mediated hypersensitivity was diagnosed in only 2 (4.0%). In the 48 DTH cases, intradermal testing revealed broad cross-reactivity between UFH and low-molecular-weight heparins (LMWH) including nadroparin, dalteparin, and enoxaparin. Cross-reactivity with (or concomitant sensitization to) fondaparinux was seen in only 3 (6.3%) cases. Intravenous administration of UFH was tolerated by all 45 patients challenged, despite DTH to UFH and LMWH as demonstrated by intradermal testing.
CONCLUSIONS
If an inflammatory skin reaction at the site of subcutaneously injected heparin is observed or reported without any evidence of skin necrosis or thrombocytopenia, intravenous administration of UFH seems to be sufficiently safe and may be considered without allergy testing if urgently indicated in an emergency situation. Fondaparinux is the most suitable alternative for subcutaneous application.
Topics: Humans; Heparin; Fondaparinux; Heparin, Low-Molecular-Weight; Anticoagulants; Skin Tests; Drug Hypersensitivity; Injections, Subcutaneous; Administration, Intravenous; Necrosis
PubMed: 35788063
DOI: 10.1016/j.jaip.2022.06.030 -
Critical Care (London, England) Nov 2020A substantial proportion of critically ill COVID-19 patients develop thromboembolic complications, but it is unclear whether higher doses of thromboprophylaxis are...
BACKGROUND
A substantial proportion of critically ill COVID-19 patients develop thromboembolic complications, but it is unclear whether higher doses of thromboprophylaxis are associated with lower mortality rates. The purpose of the study was to evaluate the association between initial dosing strategy of thromboprophylaxis in critically ill COVID-19 patients and the risk of death, thromboembolism, and bleeding.
METHOD
In this retrospective study, all critically ill COVID-19 patients admitted to two intensive care units in March and April 2020 were eligible. Patients were categorized into three groups according to initial daily dose of thromboprophylaxis: low (2500-4500 IU tinzaparin or 2500-5000 IU dalteparin), medium (> 4500 IU but < 175 IU/kilogram, kg, of body weight tinzaparin or > 5000 IU but < 200 IU/kg of body weight dalteparin), and high dose (≥ 175 IU/kg of body weight tinzaparin or ≥ 200 IU/kg of body weight dalteparin). Thromboprophylaxis dosage was based on local standardized recommendations, not on degree of critical illness or risk of thrombosis. Cox proportional hazards regression was used to estimate hazard ratios with corresponding 95% confidence intervals of death within 28 days from ICU admission. Multivariable models were adjusted for sex, age, body mass index, Simplified Acute Physiology Score III, invasive respiratory support, and initial dosing strategy of thromboprophylaxis.
RESULTS
A total of 152 patients were included: 67 received low-, 48 medium-, and 37 high-dose thromboprophylaxis. Baseline characteristics did not differ between groups. For patients who received high-dose prophylaxis, mortality was lower (13.5%) compared to those who received medium dose (25.0%) or low dose (38.8%), p = 0.02. The hazard ratio of death was 0.33 (95% confidence intervals 0.13-0.87) among those who received high dose, and 0.88 (95% confidence intervals 0.43-1.83) among those who received medium dose, as compared to those who received low-dose thromboprophylaxis. There were fewer thromboembolic events in the high (2.7%) vs medium (18.8%) and low-dose thromboprophylaxis (17.9%) groups, p = 0.04.
CONCLUSIONS
Among critically ill COVID-19 patients with respiratory failure, high-dose thromboprophylaxis was associated with a lower risk of death and a lower cumulative incidence of thromboembolic events compared with lower doses.
TRIAL REGISTRATION
Clinicaltrials.gov NCT04412304 June 2, 2020, retrospectively registered.
Topics: APACHE; Aged; Anticoagulants; COVID-19; Critical Illness; Dalteparin; Female; Humans; Intensive Care Units; Male; Middle Aged; Retrospective Studies; SARS-CoV-2; Sweden; Thrombosis; Tinzaparin
PubMed: 33225952
DOI: 10.1186/s13054-020-03375-7 -
Neonatology 2021Neonatal thrombosis is a frequently encountered complication in a neonatal intensive care unit. Dalteparin can be used to treat thrombosis in newborn infants.
BACKGROUND
Neonatal thrombosis is a frequently encountered complication in a neonatal intensive care unit. Dalteparin can be used to treat thrombosis in newborn infants.
OBJECTIVES
In this study, we evaluate the current recommended starting dose of 129 ± 43 U/kg/24 h, hypothesizing that this dose is too low to reach therapeutic anti-Xa levels.
METHODS
From 2008 until 2017, all infants treated with dalteparin in the University Medical Centre Utrecht were included in this study. In this retrospective cohort study, the correlation between dose and anti-Xa level was observed.
RESULTS
Sixty-six infants were included. The most common thrombus types were catheter-related (29 patients, 44%) and venous sinus thrombosis (28 patients, 43%). The mean dalteparin dose needed for the first adequate anti-Xa level (0.5-1.0 IU/mL) was 297.6 U/kg/12 h. Two infants developed a first bleeding episode under dalteparin therapy; they both had anti-Xa levels in the therapeutic range.
CONCLUSION
The increase of the starting dose of dalteparin will lead to earlier therapeutic levels of anti-Xa in the studied population and appears to be safe. However, this needs to be evaluated in further study.
Topics: Anticoagulants; Dalteparin; Humans; Infant; Infant, Newborn; Retrospective Studies; Thrombosis; Treatment Outcome
PubMed: 33735895
DOI: 10.1159/000513784