A relatively high mortality of severe coronavirus disease 2019 (COVID-19) is worrying, and the application of heparin in COVID-19 has been recommended by some expert consensus because of the risk of ...disseminated intravascular coagulation and venous thromboembolism. However, its efficacy remains to be validated.
Coagulation results, medications, and outcomes of consecutive patients being classified as having severe COVID-19 in Tongji hospital were retrospectively analyzed. The 28-day mortality between heparin users and nonusers were compared, as was a different risk of coagulopathy, which was stratified by the sepsis-induced coagulopathy (SIC) score or D-dimer result.
There were 449 patients with severe COVID-19 enrolled into the study, 99 of them received heparin (mainly with low molecular weight heparin) for 7 days or longer. D-dimer, prothrombin time, and age were positively, and platelet count was negatively, correlated with 28-day mortality in multivariate analysis. No difference in 28-day mortality was found between heparin users and nonusers (30.3% vs 29.7%, P = .910). But the 28-day mortality of heparin users was lower than nonusers in patients with SIC score ≥4 (40.0% vs 64.2%, P = .029), or D-dimer >6-fold of upper limit of normal (32.8% vs 52.4%, P = .017).
Anticoagulant therapy mainly with low molecular weight heparin appears to be associated with better prognosis in severe COVID-19 patients meeting SIC criteria or with markedly elevated D-dimer.
Anticoagulants and Osteoporosis Signorelli, Salvatore Santo; Scuto, Salvatore; Marino, Elisa ...
International journal of molecular sciences,
10/2019, Volume:
20, Issue:
21
Journal Article
Peer reviewed
Open access
Anticoagulant agents are widely used in the treatment of thromboembolic events and in stroke prevention. Data about their effects on bone tissue are in some cases limited or inconsistent (oral ...anti-vitamin K agents), and in others are sufficiently strong (heparins) to suggest caution in their use in subjects at risk of osteoporosis. This review analyses the effects of this group of drugs on bone metabolism, on bone mineral density, and on fragility fractures. A literature search strategy was developed by an experienced team of specialists by consulting the MEDLINE platform, including published papers and reviews updated to March 2019. Literature supports a detrimental effect of heparin on bone, with an increase in fracture rate. Low molecular weight heparins (LMWHs) seem to be safer than heparin. Although anti-vitamin K agents (VKAs) have a significant impact on bone metabolism, and in particular, on osteocalcin, data on bone mineral density (BMD) and fractures are contrasting. To date, the new direct oral anticoagulants (DOACs) are found to safe for bone health.
It is unclear if direct oral anticoagulants (DOACs) are effective and safe alternatives to low-molecular-weight heparin (LMWHs) for the treatment of cancer-associated venous thromboembolism (VTE). We ...aim to synthesize existing literature that compared DOACs versus LMWHs in this high-risk population.
We conducted a systematic review using EMBASE, MEDLINE and CENTRAL for all observational studies and randomized controlled trials (RCTs) (PROSPERO: CRD42017080898). Two authors independently reviewed study eligibility, extracted data, and assessed bias. Primary outcomes included 6-month recurrent VTE and major bleeding. Secondary outcomes included clinically relevant non-major bleeding (CRNMB) and mortality.
We screened 426 articles, reviewed 25 in full-text, and selected 13 and 2 for qualitative and quantitative synthesis, respectively. Based on a meta-analysis of the 2 RCTs, DOACs had lower 6-month recurrent VTE (42/725) when compared to LMWH (64/727) (RR: 0.65 (0.42–1.01)). However, DOACs had higher major bleeding (40/725) when compared to LMWH (23/727) (RR 1.74 (1.05–2.88)). Similarly, CRNMB was higher (RR 2.31 (0.85–6.28)) for patients receiving DOACs. There was no difference in mortality (RR 1.03 (0.85–1.26)). Observational studies were heterogeneous with high risks of bias but showed recurrent VTE rates consistent with the meta-analysis.
DOACs were more effective than LMWHs to prevent recurrent VTE but were associated with a significantly increased risk of major bleeding as well as a trend toward more CRNMB. The absolute risk differences were small (2–3%) for both primary outcomes and may reflect better compliance with DOACs than LMWHs.
•LMWHs have been the treatment of choice for cancer associated VTE.•DOACs are more effective than LMWHs to prevent recurrent VTE in cancer patients.•DOACs are associated with a higher risk of major bleeding compared to LMWHs.•Effectiveness and safety may reflect better compliance with DOACs compared to LMWHs.
Ultralow molecular weight (ULAAW) heparins are sulfated glycans that are clinically used to treat thrombotic disorders. ULMW heparins range from 1500 to 3000 daltons, corresponding from 5 to 10 ...saccharide units. The commercial drug Arixtra (fondaparinux sodium) is a structurally homogeneous ULMW heparin pentasaccharide that is synthesized through a lengthy chemical process. Here, we report 10- and 12-step chemoenzymatic syntheses of two structurally homogeneous ULMW heparins (MW = 1778.5 and 1816.5) in 45 and 37% overall yield, respectively, starting from a simple disaccharide. These ULMW heparins display excellent in vitro anticoagulant activity and comparable pharmacokinetic properties to Arixtra, as demonstrated in a rabbit model. The chemoenzymatic approach is scalable and shows promise for a more efficient route to synthesize this important class of medicinal agent.
The breadth and the shape of molecular weight distributions can significantly influence fundamental polymer properties that are critical for various applications. However, current approaches require ...the extensive synthesis of multiple polymers, are limited in dispersity precision and are typically incapable of simultaneously controlling both the dispersity and the shape of molecular weight distributions. Here we report a simplified approach, whereby on mixing two polymers (one of high Đ and one of low Đ), any intermediate dispersity value can be obtained (e.g. from 1.08 to 1.84). Unrivalled precision is achieved, with dispersity values obtained to even the nearest 0.01 (e.g. 1.37→1.38→1.39→1.40→1.41→1.42→1.43→1.44→1.45), while maintaining fairly monomodal molecular weight distributions. This approach was also employed to control the shape of molecular weight distributions and to obtain diblock copolymers with high dispersity accuracy. The straightforward nature of our methodology alongside its compatibility with a wide range of polymerisation protocols (e.g. ATRP, RAFT), significantly expands the toolbox of tailored polymeric materials and makes them accessible to all researchers.
Tuning dispersity and molecular weight distribution shape significantly impacts polymer properties. Herein, we report a straight‐forward approach, wherein blending just two polymers allows for unrivalled precision in tuning molecular weight distributions.
The tensile properties of ultra‐high molecular weight polyethylene (UHMWPE) fibers obtained from mixed solvents are addressed by virtue of improved solubility. In this work, olive oil (OO) was ...introduced as a poor solvent for the pre‐swelling of UHMWPE in decalin, and its mass percentage was intended to be 10, 20, 30, and 40 wt% of UHMWPE. Then UHMWPE fibers with high molecular weight retention and low entanglement were prepared with paraffin oil as spinning solvent by gel‐spinning and hot‐drawing. Unlike other samples, there is a more significant molecular chain disentanglement and higher molecular weight retention for UHMWPE fibers as OO addition is 20 wt%. Surprisingly, obtained UHMWPE fibers exhibit tensile strength up to 33.85 cN/dtex and tensile modulus of 1673.27 cN/dtex, with an increase of 24.0% and 32.3%, respectively, compared with that of UHMWPE fibers without decalin/OO pre‐swelling. Furthermore, the obtained UHMWPE fibers are accompanied by a marked improvement in melting temperature, crystallization and orientation.
In this study, decalin/olive oil mixed solvent was introduced as the pre‐swelling solvent and we regulated the dissolving system of UHMWPE to improve the solubility of UHMWPE in paraffin oil without severe degradation so as to prepare UHMWPE fibers with high molecular weight retention and low entanglement. The tensile strength of UHMWPE fibers prepared after swelling is able to attain 33.85 cN/dtex, increased by 24.0% in comparison to neat UHMWPE fibers.
The width and shape of molecular weight distributions can significantly affect the properties of polymeric materials and thus are key parameters to control. This mini-review aims to critically ...summarise recent approaches developed to tailor molecular weight distributions and highlights the strengths and limitations of each technique. Special emphasis will also be given to applications where tuning the molecular weight distribution has been used as a strategy to not only enhance polymer properties but also to increase the fundamental understanding behind complex mechanisms and phenomena.
This review explores the different synthetic methods by which dispersity and MWD shape can be tuned and discusses the different properties and applications where this variation is beneficial.
Essentials Intracranial hemorrhage (ICH) is common in patients with brain tumors. We compared rates of ICH with DOACs and low molecular weight heparin. DOACs were associated with a lower incidence of ...ICH in primary brain tumors. DOACs appear safe to administer to patients with brain tumors. SUMMARY: Background Direct oral anticoagulants (DOACs) are efficacious in the treatment of cancer-associated thrombosis but are associated with an increased risk of hemorrhage compared with low-molecular-weight heparin in certain malignancies. Whether the DOACs increase the incidence of intracranial hemorrhage (ICH) in patients with brain tumors is not established. Objectives To determine the cumulative incidence of ICH in DOACs compared with Low-molecular-weight heparin (LMWH) in patients with brain tumors and venous thromboembolism. Patients and methods A retrospective comparative cohort study was performed. Radiographic images for all ICH events were reviewed and the primary endpoint was cumulative incidence of ICH at 12 months following initiation of anticoagulation. Results and conclusions A total of 172 patients with brain tumors were evaluated (42 DOAC and 131 LMWH). In the primary brain tumor cohort (n = 67), the cumulative incidence of any ICH was 0% in patients receiving DOACs vs. 36.8% (95% confidence interval CI, 22.3-51.3%) in those treated with LMWH, with a major ICH incidence of 18.2% (95% CI, 8.4-31.0). In the brain metastases cohort (n = 105), DOACs did not increase the risk of any ICH relative to enoxaparin, with an incidence of 27.8% (95% CI, 5.5-56.7%) compared with 52.9% (95% CI, 37.4-66.2%). Similarly, DOAC did not increase the incidence of major ICH in brain metastases, with a cumulative incidence 11.1% (95% CI, 0.5-40.6%) vs. 17.8% (95% CI, 10.2-27.2%). We conclude that DOACs are not associated with an increased incidence of ICH relative to LMWH in patients with brain metastases or primary brain tumors.
Low molecular weight (LWM) hyaluronic acid (HA) and chondroitin sulfate (CS) have a wide range of applications. To determine their molecular weight (MW), we developed a gel permeation chromatography ...(GPC) method, which is calibrated based on serrated peaks in the chromatograms. MW calibrants were obtained from the enzymolysis of HA and CS using hyaluronidase. The identical structure of calibrants and samples ensured the soundness of the method. The highest confidence MWs were up to 14,454 and 14,605 for HA and CS, respectively, and the standard curves showed very high correlation coefficients. Thanks to the changeless relationship between MW and its contribution to the GPC integral, the second calibration curves could be derived via one GPC column, also embodied correlation coefficients of >0.9999. The discrepancies of MW values were minuscule, and the measurement of a sample could be conducted in <30 min. The accuracy of the method was verified using LWM heparins, and the measured Mw values showed a 1.2 %–2.0 % error relative to pharmacopeia results. The MW results obtained for LWM-HA and LWM-CS samples were also consistent with the results obtained by multiangle laser light scattering. The method was also verified be able to measure the very low MWs.
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Low-molecular-weight heparin (LMWH) is usually recommended for the treatment of cancer-associated thrombosis (CAT) but this treatment requires burdensome daily injections. We did a systematic review ...to compare the efficacy and safety of direct oral anticoagulants (DOAC), vitamin K antagonists (VKA) and LMWH in patients with CAT.
We searched Pubmed, Embase and CENTRAL for randomised controlled trials comparing DOAC, VKA and LMWH in patients with CAT. Pairwise and network meta-analyses were computed for venous thromboembolism (VTE) recurrence and bleeding complications.
We identified 14 studies, including 4,661 patients. In pairwise comparison, DOAC were superior to LMWH to prevent VTE recurrence (HR 0.63; 95% CI 0.42-0.96) and LMWH was superior to VKA (HR 0.53; 95% CI 0.40-0.70). The rate of major bleeding was higher with DOAC compared to LMWH (HR 1.78; 95% CI 1.11-2.87). In the network meta-analysis, DOAC had a lower, but non-significant, rate of VTE recurrence compared to LMWH (HR 0.74; 95% CI 0.54-1.01). Both DOAC (HR 0.42; 95% CI 0.29-0.61) and LMWH (HR 0.57; 95% CI 0.44-0.75) were associated with lower rates of recurrence compared to VKA. No significant difference in major bleeding rate was observed in the network meta-analysis. Inconsistency was observed between pairwise and network meta-analysis comparisons for major bleeding.
DOAC are effective to prevent VTE recurrence in patients with CAT but are associated with an increased risk of bleeding compared to LMWH. The choice of anticoagulant should be personalised, taking into account the patient's bleeding risk, including cancer site, and patient's values and preferences.
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