Differentiation of parenteral anticoagulants in the prevention and treatment of venous thromboembolism

<p>Abstract</p> <p>Background</p> <p>The prevention of venous thromboembolism has been identified as a leading priority in hospital safety. Recommended parenteral anticoagulant agents with different indications for the prevention and treatment of venous thromboembolism include unfractionated heparin, low-molecular-weight heparins and fondaparinux. Prescribing decisions in venous thromboembolism management may seem complex due to the large range of clinical indications and patient types, and the range of anticoagulants available.</p> <p>Methods</p> <p>MEDLINE and EMBASE databases were searched to identify relevant original articles.</p> <p>Results</p> <p>Low-molecular-weight heparins have nearly replaced unfractionated heparin as the gold standard antithrombotic agent. Low-molecular-weight heparins currently available in the US are enoxaparin, dalteparin, and tinzaparin. Each low-molecular-weight heparin is a distinct pharmacological entity with different licensed indications and available clinical evidence. Enoxaparin is the only low-molecular-weight heparin that is licensed for both venous thromboembolism prophylaxis and treatment. Enoxaparin also has the largest body of clinical evidence supporting its use across the spectrum of venous thromboembolism management and has been used as the reference standard comparator anticoagulant in trials of new anticoagulants. As well as novel oral anticoagulant agents, biosimilar and/or generic low-molecular-weight heparins are now commercially available. Despite similar anticoagulant properties, studies report differences between the branded and biosimilar and/or generic agents and further clinical studies are required to support the use of biosimilar low-molecular-weight heparins. The newer parenteral anticoagulant, fondaparinux, is now also licensed for venous thromboembolism prophylaxis in surgical patients and the treatment of acute deep-vein thrombosis; clinical experience with this anticoagulant is expanding.</p> <p>Conclusions</p> <p>Parenteral anticoagulants should be prescribed in accordance with recommended dose regimens for each clinical indication, based on the available clinical evidence for each agent to assure optimal safety and efficacy.</p

Teaching English Language at SSC Level in Private Non-Elite Schools in Pakistan: Practices and Problems

English language is taught as a compulsory subject up to graduate level in Pakistani educational system. Despite studying English for over 14 years, majority of students coming from non-elite schools, lack required command in English language skills to pursue their higher education and professional careers. With this background in mind, the current research focused on teaching English reading and writing skills and the problems faced while teaching these skills at Secondary School Certificate (SSC) level in private non-elite schools in Karachi. The sample of the study comprised 20 SSC level students, 12 SSC level English language teachers of non-elite private schools and 5 student notebooks. Data were collected through open-ended questionnaires, group interviews and notebook analysis. Data were examined using thematic analysis. The findings revealed that teaching English language reading practices include reading the text aloud, translating the chapter, providing the central idea and meanings of difficult words to the students. The major problems faced by the teachers in teaching reading skills are learners’ lack of interest in reading, lack of concentration and low reading comprehension skills. The study also revealed practices of teaching writing skills such as provision of model texts and relevant vocabulary items. The major problems while teaching writing skills are lack of pre-writing activities, learners’ deficient command over vocabulary, grammar, spellings and punctuation, lengthy syllabus and limited time

International Normalized Ratio Relevance to the Observed Coagulation Abnormalities in Warfarin Treatment and Disseminated Intravascular Coagulation

The development of coagulation abnormalities is common in patients with sepsis. Sepsis-associated coagulopathy (SAC) is typically diagnosed by prothrombin time (PT) prolongation or elevated international normalized ratio (INR) in conjunction with reduced platelet count. INR is also used to monitor warfarin-treated patients. However, due to the different natures of SAC and warfarin anticoagulation, it is likely that the same INR value provides different information in these two patient populations. The purpose of this study was to compare measures of coagulation function and clotting factor levels in patients with SAC to those observed in patients receiving warfarin anticoagulation. Deidentified plasma samples were collected at baseline from patients diagnosed with SAC and from patients receiving warfarin. These plasma samples were evaluated for PT/INR, activated partial thromboplastin time (aPTT), fibrinogen, and functional and immunologic levels of factors VII, IX, and X. Both aPTT and fibrinogen correlated with INR in patients with SAC, but not in patients treated with warfarin. Factors VII, IX, and X showed an inverse relationship with INR in the anticoagulated patients; however, no relationship between factor level and INR was observed in patients with SAC. Distinct patterns of coagulopathy were observed in patients with SAC and patients receiving warfarin anticoagulation, and equivalent INR values were associated with distinct coagulation profiles in the two patient groups. These results suggest that an abnormal INR provides different information about the coagulation status in patients with disseminated intravascular coagulation than in patients receiving warfarin. This may indicate that an equivalently increased INR predicts different bleeding risks in these two patient groups

Heparan sulphate inhibition of cell proliferation induced by TGFβ and PDGF

The effect of glycosaminoglycans (GAGs) on the proliferation of smooth muscle cells (SMC) and fibroblasts was assessed by culturing cells with or without GAGs. Porcine heparan sulphate (HS) inhibited proliferation in a dose dependent manner. At 167 μg/ml of HS this reached 88% and 72% inhibition of SMC and fibroblast growth, respectively. Pig and beef mucosal heparins also blocked proliferation, but to a lesser extent. In contrast, beef lung heparin, chondroitin sulphate, and dermatan sulphate failed to block growth factor induced proliferation. Continuous presence of HS was not required, suggesting that the inhibitory effects resulted from a direct effect on the cell rather than an interaction of the GAG with growth factors. The mechanism by which GAGs inhibit proliferation will be addressed in future studies

Utility of Blood Cellular Indices in the Risk Stratification of Patients Presenting with Acute Pulmonary Embolism.

Pulmonary embolism (PE) clinical manifestations vary widely, and that scope is not fully captured by current all-cause mortality risk models. PE is associated with inflammatory, coagulation, and hemostatic imbalances so blood cellular indices may be prognostically useful. Complete blood count (CBC) data may improve current risk models like the simplified pulmonary embolism severity index (sPESI) for all-cause mortality, offering greater accuracy and analytic ability. Acute PE patients (n = 228) with confirmatory diagnostic imaging were followed for all-cause mortality. Blood cellular indices were assessed for association to all-cause mortality and were supplemented into sPESI using multivariate logistic regression. Multiple blood cellular indices were found to be significantly associated with all-cause mortality in acute PE. sPESI including red cell distribution width, hematocrit and neutrophil-lymphocyte ratio had better predictive ability as compared to sPESI alone (AUC: 0.852 vs 0.754). Blood cellular indices contribute an inflammatory and hemodynamic perspective not currently included in sPESI. CBC with differential is a widely used, low-cost test that can augment current risk stratification tools for all-cause mortality in acute PE patients

Response to Maccio et al, - Multifactorial pathogenesis of COVID- 19- related coagulopathy: Can defibrotide have a role in the early phases of coagulation disorders?-

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163392/2/jth15088_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163392/1/jth15088.pd

Dysregulation of Biomarkers of Hemostatic Activation and Inflammatory Processes are Associated with Adverse Outcomes in Pulmonary Embolism

Introduction: The pathophysiology of pulmonary embolism (PE) represents complex, multifactorial processes involving blood cells, vascular endothelium, and the activation of inflammatory pathways. Platelet (P), endothelial (E), and leukocyte (L)-selectin molecules may play an important role in PE pathophysiology. We aimed to profile the biomarkers of inflammation, including selectins in PE patients, and compare them to healthy individuals. Materials and methods: 100 acute PE patients and 50 controls were included in this case control study. ELISA methods were used to quantify levels of selectins, inflammatory, and hemostatic biomarkers. Results: In PE patients, levels of selectin molecules as compared to controls convey increased P-selectin levels (95 ng/mL vs 40 ng/mL, p \u3c .0001) and decreased L-selectin levels (1468 ng/mL vs 1934 ng/mL, p \u3c .0001). Significant correlations were found between selectins and Plasminogen Activating Inhibitor-1 (PAI-1), Tumor Necrosis Factor-a (TNFa), and D-dimer. Fold change between selectins and controls is compared to other biomarkers, illustrating degrees of change comparable to TNFa, alpha-2-antiplasmin, and microparticles. L-selectin levels are inversely associated with all-cause-mortality in PE patients, (p = .040). Conclusion: These studies suggest that various thrombo-inflammatory biomarkers are elevated in PE patients. Furthermore, L-selectin levels are inversely associated with mortality outcomes

Upregulation of Inflammatory Cytokines in Pulmonary Embolism Using Biochip-Array Profiling.

The complex pathophysiology of pulmonary embolism (PE) involves hemostatic activation, inflammatory processes, cellular dysfunction, and hemodynamic derangements. Due to the heterogeneity of this disease, risk stratification and diagnosis remains challenging. Biochip-array technology provides an integrated high throughput method for analyzing blood plasma samples for the simultaneous measurement of multiple biomarkers for potential risk stratification. Using biochip-array method, this study aimed to quantify the inflammatory biomarkers such as interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, vascular endothelial growth factor (VEGF), interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and epidermal growth factor (EGF) in 109 clinically confirmed PE patients in comparison to the control group comprised of plasma samples collected from 48 healthy subjects. Cytokines IL-4, IL-6, IL-8, IL-10, IL-1β, and MCP-1 demonstrated varying level of significant increase (P \u3c 0.05) in massive-risk PE patients compared to submassive- and low-risk PE patients. The upregulation of inflammatory cytokines in PE patients observed in this study suggest that inflammation plays an important role in the overall pathophysiology of this disease. The application of biochip-array technology may provide a useful approach to evaluate these biomarkers to understand the pathogenesis and risk stratification of PE patients

Synthetic oligosaccharides can replace animal-sourced low–molecular weight heparins

Full-sized and low–molecular weight heparins are widely used to treat a variety of clotting disorders. Although low–molecular weight heparins are safer and more convenient to use than full-size heparin, they are still animal-derived products that present a risk of contamination and supply chain interruptions and are limited with respect to standardization and reversibility of anticoagulation. A method developed by Xu et al . offers a potential alternative to animal-sourced heparins in the form of a chemical synthesis process that can be scaled up to produce heparin dodecasaccharides with reversible activity in adequate quantities for potential therapeutic use