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Cartridge-Based Thromboelastography Can Be Used to Monitor and Quantify the Activity of Unfractionated and Low-Molecular-Weight Heparins.

ABSTRACT: Thromboelastography is increasingly utilized in the management of bleeding and thrombotic complications where heparin management remains a cornerstone. This study assessed the feasibility of the cartridge-based TEG ^® 6s system (Haemonetics Corp., Braintree, Massachusetts, United States) to monitor and quantify the effect of unfractionated and low-molecular-weight heparin (UFH and LMWH). Blood samples from healthy donors were spiked with UFH ( n ?=?23; 0-1.0?IU/mL) or LMWH (enoxaparin; n ?=?22; 0-1.5?IU/mL). Functional fibrinogen maximum amplitude (CFF.MA), RapidTEG activated clotting time (CRT.ACT), and kaolin and kaolin with heparinase reaction time (CK.R and CKH.R) were evaluated for their correlation with heparin concentrations, as well as the combination parameters ?CK.R?-?CKH.R, ratio CK.R/CKH.R, and ratio CKH.R/CK.R. Nonlinear mixed-effect modelling was used to study the relationship between concentrations and parameters, and Bayesian classification modelling for the prediction of therapeutic ranges. CK.R and CRT.ACT strongly correlated with the activity of LMWH and UFH ( p ?p ?0.5?IU/mL for UFH and >1.5?IU/mL for LMWH. Combination parameters classified blood samples into subtherapeutic, therapeutic, and supratherapeutic heparin ranges, with an accuracy of >90% for UFH, and >78% for LMWH. This study suggests that TEG 6s can effectively monitor and quantify heparin activity for LMWH and UFH. Additionally, combination parameters can be used to classify blood samples into therapeutic ranges based on heparin activity.

SUBMITTER: Dias JD

PROVIDER: S-EPMC6742498 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Cartridge-Based Thromboelastography Can Be Used to Monitor and Quantify the Activity of Unfractionated and Low-Molecular-Weight Heparins.

Dias João D JD Lopez-Espina Carlos G CG Panigada Mauro M Dalton Heidi J HJ Hartmann Jan J Achneck Hardean E HE

TH open : companion journal to thrombosis and haemostasis 20190701 3

Thromboelastography is increasingly utilized in the management of bleeding and thrombotic complications where heparin management remains a cornerstone. This study assessed the feasibility of the cartridge-based TEG <sup>®</sup> 6s system (Haemonetics Corp., Braintree, Massachusetts, United States) to monitor and quantify the effect of unfractionated and low-molecular-weight heparin (UFH and LMWH). Blood samples from healthy donors were spiked with UFH ( <i>n</i> = 23; 0-1.0 IU/mL) or LMWH (enox ...[more]

PMID: 31523746

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Project description:BackgroundLow-molecular-weight heparins (LMWHs) and heparinoids are anticoagulants that may have more powerful antithrombotic effects than standard unfractionated heparin (UFH) but a lower risk of bleeding complications. This is an update of the original Cochrane Review of these agents, first published in 2001 and last updated in 2008.ObjectivesTo determine whether antithrombotic therapy with LMWHs or heparinoids is associated with a reduction in the proportion of people who are dead or dependent for activities in daily living compared with UFH.Search methodsWe searched the Cochrane Stroke Group Trials Register (last searched February 2017), the Cochrane Central Register of Controlled Trials (CENTRAL: the Cochrane Library Issue 1, 2017), MEDLINE (1966 to February 2017), and Embase (1980 to February 2017). We also searched trials registers to February 2017: ClinicalTrials.gov, EU Clinical Trials Register, Stroke Trials Registry, ISRCTN Registry and the World Health Organization (WHO) International Clinical Trials Registry Platform.Selection criteriaUnconfounded randomised trials comparing LMWH or heparinoids with standard UFH in people with acute ischaemic stroke, in which participants were recruited within 14 days of stroke onset.Data collection and analysisTwo review authors independently chose studies for inclusion, assessed risk of bias and trial quality, extracted and analysed the data. Differences were resolved by discussion.Main resultsWe included nine trials involving 3137 participants. We did not identify any new trials for inclusion in this updated review. None of the studies reported data on the primary outcome in sufficient detail to enable analysis for the review. Overall, there was a moderate risk of bias in the included studies. Compared with UFH, there was no evidence of an effect of LMWH or heparinoids on death from all causes during the treatment period (96/1616 allocated LMWH/heparinoid versus 78/1486 allocated UFH; odds ratio (OR) 1.06, 95% CI 0.78 to 1.47; 8 trials, 3102 participants, low quality evidence). LMWH or heparinoid were associated with a significant reduction in deep vein thrombosis (DVT) compared with UFH (OR 0.55, 95% CI 0.44 to 0.70, 7 trials, 2585 participants, low quality evidence). However, the number of the major clinical events such as pulmonary embolism (PE) and intracranial haemorrhage was too small to provide a reliable estimate of the effects.Authors' conclusionsTreatment with a LMWH or heparinoid after acute ischaemic stroke appears to decrease the occurrence of DVT compared with standard UFH, but there are too few data to provide reliable information on their effects on other important outcomes, including functional outcome, death and intracranial haemorrhage.

Project description:New SARS-CoV-2 variants of concern and waning immunity demonstrate the need for a quick and simple prophylactic agent to prevent infection. Low molecular weight heparins (LMWH) are potent inhibitors of SARS-CoV-2 binding and infection in vitro. The airways are a major route for infection and therefore inhaled LMWH could be a prophylactic treatment against SARS-CoV-2. We investigated the efficacy of in vivo inhalation of LMWH in humans to prevent SARS-CoV-2 attachment to nasal epithelial cells in a single-center, open-label intervention study. Volunteers received enoxaparin in the right and a placebo (NaCl 0.9%) in the left nostril using a nebulizer. After application, nasal epithelial cells were retrieved with a brush for ex-vivo exposure to either SARS-CoV-2 pseudovirus or an authentic SARS-CoV-2 isolate and virus attachment as determined. LMWH inhalation significantly reduced attachment of SARS-CoV-2 pseudovirus as well as authentic SARS-CoV-2 to human nasal cells. Moreover, in vivo inhalation was as efficient as in vitro LMWH application. Cell phenotyping revealed no differences between placebo and treatment groups and no adverse events were observed in the study participants. Our data strongly suggested that inhalation of LMWH was effective to prevent SARS-CoV-2 attachment and subsequent infection. LMWH is ubiquitously available, affordable, and easy to apply, making them suitable candidates for prophylactic treatment against SARS-CoV-2. IMPORTANCE New SARS-CoV-2 variants of concern and waning immunity demonstrate the need for a quick and simple agent to prevent infection. Low molecular weight heparins (LMWH) have been shown to inhibit SARS-CoV-2 in experimental settings. The airways are a major route for SARS-CoV-2 infection and inhaled LMWH could be a prophylactic treatment. We investigated the efficacy of inhalation of the LMWH enoxaparin in humans to prevent SARS-CoV-2 attachment because this is a prerequisite for infection. Volunteers received enoxaparin in the right and a placebo in the left nostril using a nebulizer. Subsequently, nasal epithelial cells were retrieved with a brush and exposed to SARS-CoV-2. LMWH inhalation significantly reduced the binding of SARS-Cov-2 to human nasal cells. Cell phenotyping revealed no differences between placebo and treatment groups and no adverse events were observed in the participants. Our data indicated that LMWH can be used to block SARS-CoV-2 attachment to nasal cells. LMWH was ubiquitously available, affordable, and easily applicable, making them excellent candidates for prophylactic treatment against SARS-CoV-2.

Dataset Information

Cartridge-Based Thromboelastography Can Be Used to Monitor and Quantify the Activity of Unfractionated and Low-Molecular-Weight Heparins.

Publications

Cartridge-Based Thromboelastography Can Be Used to Monitor and Quantify the Activity of Unfractionated and Low-Molecular-Weight Heparins.

Similar Datasets

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