Deep vein thrombosis (DVT) is a prevalent complication associated with malignancy. Clinical use of thromboprophylaxis is recommended, however its usage is limited due to bleeding complications, more cost associated, and reluctance to receive anticoagulant injections. Rivaroxaban a relatively easy to administer anticoagulant but it has a risk of bleeding and is expensive. Inflammation is the important factor in pathogenesis of cancer-associated thrombosis. Statins have the anti-inflammatory property that could decrease proinflammatory cytokines. Consequently, statins may be used as thromboprophylaxis for cancer patients receiving chemotherapy.

To provide comparison between atorvastatin and rivaroxaban on affecting inflammatory biomarkers (interleukin 6 [IL-6], C reactive protein [CRP]) and coagulation activation biomarkers (Tissue Factor [TF], prothrombin fragment 1 + 2 [F1 + 2], D-Dimer) in cancer patients at high risk of thrombosis receiving chemotherapy.

A randomized controlled study that was double-blinded and involved high-risk cancer patients undergoing chemotherapy. For up to ninety days, participants were randomized to receiver either atorvastatin 20 mg or rivaroxaban 10 mg daily. The level of plasma of IL-6, CRP, TF, F1 + 2, and D-dimer were assessed 24 h before chemotherapy, 30, 60, and 90 day after chemotherapy. The latest observation carried forward (LOCF) approach was used to examine the data. The laboratory results were evaluated using an independent T test or Mann-Whitney U test prior to and after chemotherapy.

Eighty-six randomized patients were enrolled, although both groups showed a decreasing trend in plasma level of IL-6, CRP, TF, F1 + 2, and D-dimer, there were no significant differences between the two groups (p > 0.05). In the atorvastatin group, there was a significant correlation between delta level of IL-6 and F1 + 2 (r = 0.313, p = 0.043) and delta level of CRP and F1 + 2 (r = 0.398, p = 0.009), whereas in the rivaroxaban group there was a significant correlation between delta CRP and D-dimer level (r = 0.387, p = 0.009).

Atorvastatin decreases IL-6 and CRP level, which also decreases F1 + 2 level. Atorvastatin did not substantially differ from rivaroxaban in decreasing plasma levels of inflammatory biomarkers IL-6, CRP, and coagulation activation biomarkers TF, F1 + 2, D-dimer in high-risk cancer patients undergoing chemotherapy.

ISRCTN71891829, Registration Date: 17/12/2020.

Purpose Owing to the shortage of surgeons and the decrease in medical staff in regional medical care, reducing unnecessary tests can limit the burden on the staff. In this study, we aimed to examine the predictors of deep vein thrombosis (DVT), such as D-dimer levels in patients who underwent surgery at our hospital, and determine the feasibility of screening in these patients. Knowledge of D-dimer levels can indicate the risk of DVT in patients about to undergo surgery. Methods We retrospectively analyzed 310 of 1,059 surgical cases in which preoperative lower extremity ultrasonography was performed in our department between April 2021 and June 2024. We compared 46 patients with thrombi and 264 patients without thrombi. Results Patients with low body mass indices (<18.5 kg/m2) and high D-dimer levels (> 2 μg/mL) had a significantly higher risk of DVT, whereas patients taking oral antiplatelet drugs or anticoagulants had a significantly lower risk of DVT. The area under the curve for D-dimer levels in predicting DVT was 0.779. D-dimer levels of 2 μg/mL had high sensitivity - (1 - specificity). However, there were three false-negative cases, and the highest D-dimer level that resulted in 100% sensitivity was 1.4 μg/mL. Conclusion Predicting DVT using D-dimer levels may be effective, and considering additional testing based on D-dimer levels and patient background may reduce excessive preoperative testing.

Atherosclerosis is a chronic condition characterized by impaired lipid homeostasis and chronic inflammatory pathology in large and mid-sized arteries. Myocardial infarction is caused by coronary artery thrombosis in a ruptured or unstable atherosclerotic plaque. Despite the emphasis on known triggering factors, such as hypertension and dyslipidemia, adverse events following MI, such as recurrence and mortality, are still high. Therefore, it is imperative to assess potential determinants of plaque instability. We evaluated markers of inflammation, extracellular matrix (ECM) remodeling, thrombosis, and lipids in first-time and recurrent MI (RMI).

Two hundred patients diagnosed with MI within the first 24 h of the event were included in the study and categorized as first-time or recurrent MI. Serum levels of NF-κB, hs-CRP, TNF-α, IFN γ, IL-6, VCAM-1,MMP-9, stromelysin, TIMP-1, MCP-1, PAPP-A, vWF, D-dimer, PLA2, PON-1, Apo-B, Apo-A1, ox-LDL, and anti-oxidized LDL antibodies were analyzed by ELISA. We performed a multivariate logistic regression analysis for risk stratification.

The mean age of first-time MI patients was 52.4 ± 25 years and that of recurrent MI patients was 55.9 ± 24.6 years. RMI patients showed significant (p¡0.05) upregulation of markers of inflammation (TNF-α), endothelial adhesion (VCAM-1), ECM remodeling (MMP-9, PAPP-A), and antioxidant PON-1 enzyme. First-time MI patients had significantly higher serum IL-6 and D-dimer levels than RMI patients. Risk categorization for RMI was determined at 0.5 cut-off utilizing proteomic indicators at 95% confidence interval.

Non-lipid factors provide substantial insights into plaque instability. Multiple markers of inflammation, thrombosis, extracellular matrix remodeling, and paroxonase-1 are reliable indicators of recurrent myocardial infarction.

The global burden of atherosclerosis and its implication to cause coronary heart disease and ischemic cardiac problems is the most prevalent cause of morbidity and hospitalization. In the US, there has been an increase in the number of patients with cardiac problems in the last decade, and still remains the primary cause of death in Europe as well as in the US.

Even though therapeutic interventions and early diagnosis the formation of the fatty lesion and its subsequent steps are possible, the therapeutic management of the disease remains questionable when clinical data is observed. There is still scope for proper target identification and biomarker recognition, which can serve as a baseline to develop efficient pharmacological agent and delivery systems so that the disease incidence and prevalence can be controlled. The present article highlights the current pathophysiological state of the disease and emerging strategies that are applied to manage the disease.

This article gives an insight into the limitations of various conventionally used therapeutic agents for disease treatment. The emerging strategies that could prove efficacious in disease treatment. This article also gives an insight into current discoveries in the field of cellular and molecular biology, such as the genetic role in causing dyslipidemia and the role of immune cells and the role of non-coding small RNA, which can set the future direction to develop therapeutics interventions for atherosclerosis.

Hemostasis preserves blood fluidity and prevents its loss after vessel injury. The maintenance of blood fluidity requires a delicate balance between pro-coagulant and fibrinolytic status. Endothelial cells (ECs) in the inner face of blood vessels maintain hemostasis through balancing anti-thrombotic and pro-fibrinolytic activities. Dyslipidemias are linked to hemostatic alterations. Thus, it is necessary a better understanding of the underlying mechanisms linking hemostasis with dyslipidemia. Statins are drugs that decrease cholesterol levels in the blood and are the gold standard for treating hyperlipidemias. Statins can be classified into natural and synthetic molecules, approved for the treatment of hypercholesterolemia. The classical mechanism of action of statins is by competitive inhibition of a key enzyme in the synthesis pathway of cholesterol, the HMG-CoA reductase. Statins are frequently administrated by oral ingestion and its interaction with other drugs and food supplements is associated with altered bioavailability. In this review we deeply discuss the actions of statins beyond the control of dyslipidemias, focusing on the actions in thrombotic modulation, vascular and cardiovascular-related diseases, metabolic diseases including metabolic syndrome, diabetes, hyperlipidemia, and hypertension, and chronic diseases such as cancer, chronic obstructive pulmonary disease, and chronic kidney disease. Furthermore, we were prompted to delved deeper in the molecular mechanisms by means statins regulate coagulation acting on liver, platelets, and endothelium. Clinical evidence show that statins are effective regulators of dyslipidemia with a high impact in hemostasis regulation and its deleterious consequences. However, studies are required to elucidate its underlying molecular mechanism and improving their therapeutical actions.

Rosuvastatin therapy might have an effect on the inflammatory and coagulation biomarkers. However, the evidence about the effect of rosuvastatin therapy on the high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and D-dimer levels among people living with human immunodeficiency virus (PLHIV) is still unclear. Therefore, this study investigated the relational effect of rosuvastatin therapy on serum/plasma hsCRP, IL-6 and D-dimer levels in PLHIV. The literature search was done from Embase, PubMed, and Web of Science databases. The review and meta-analysis included studies written in English language up to January 4, 2020. Random effects model was used to evaluate the pooled standard mean difference with 95% confidence interval. A meta-analysis was performed using nine articles with 392 PLHIV. The result revealed that the plasma/serum levels of IL-6 were significantly reduced after the intervention. However, hsCRP and D-dimer levels showed no significant difference (p > .05) between before and after the intervention. The subgroup analysis showed that there was significant association between PLHIV ages <45 years and cohort studies with IL-6 levels. The current CD4⁺ counts ≥350 cells/mm³ correlated with hsCRP as well as IL-6. Similarly, nadir CD4⁺ counts ≥200 cells/mm³ and duration of HIV diagnosis <10 years also showed significant association with IL-6 and D-dimer levels. It was also indicated that participants who were under antiretroviral drug for <7 years were significantly associated with hsCRP levels. This study established that IL-6 levels were significantly reduced after the intervention while hsCRP and D-dimer levels showed no significant difference between before and after the intervention.

To investigate the protective effect of teprenone on gastric mucosal injury induced by dual antiplatelet therapy in rats.

Healthy, specifically pathogen free SD, rats were selected and divided into 4 groups: Normal group (normal rats, without any treatment), Model group (rats received dual antiplatelet therapy: aspirin and clopidogrel), Teprenone group (rats received dual antiplatelet therapy and teprenone) and Pantoprazole group (rats received dual antiplatelet therapy and pantoprazole). The gastric mucosal blood flow, ulcer index, gastric gel mucus thickness, the levels of gastrin (Gas), prostaglandin (PG), prostaglandin E2 (PGE2), endothelin-1 (ET-1) tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-10 in serum, the levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and myeloperoxidase (MPO) in the gastric mucosa, as well as the expression of vascular endothelial growth factor (VEGF) in the rat's stomach were measured.

Compared with the Normal group, the other groups showed more severe gastric injury, elevated levels of inflammatory factors (TNF-α, IL-1β, IL-6 and IL-10), elevated levels of MDA and MPO, as well as reduced levels of GSH, SOD and VEGF (all P<0.05). Compared with the Model group, the gastric mucosal lesions in the Teprenone group and the Pantoprazole group were improved significantly (both P<0.05). Compared with the Pantoprazole group, the Teprenone group had reduced levels of ET-1 and elevated levels of PG and PGE2 (all P<0.05).

Teprenone protects against gastric mucosal injury induced by dual antiplatelet therapy through inhibiting gastric mucosal inflammation inhibiting oxidative stress and improving gastric mucosa indices.

Patients with familial hypercholesterolemia (FH) are likely at increased risk for COVID-19 complications in the acute phase of the infection, and for a long time thereafter. Because in FH patients the level of low density lipoprotein cholesterol (LDL-C) is elevated from birth and it correlates with the degree of systemic endothelial dysfunction, both heterozygous FH (HeFH) patients and, in particular, homozygous FH (HoFH) patients have a dysfunctional endothelium prone to further damage by the direct viral attack and the hyper-inflammatory reaction typical of severe COVID-19. Evidence to date shows the benefit of statin use in patients with COVID-19. In FH patients, the focus should therefore be on the effective lowering of LDL-C levels, the root cause of the expected excess vulnerability to COVID-19 infection in these patients. Moreover, the ongoing use of statins and other lipid-lowering therapies should be encouraged during the COVID pandemic to mitigate the risk of cardiovascular complications from COVID-19. For the reduction of the excess risk in FH patients with COVID-19, we advocate stringent adherence to the guideline determined LDL-C levels for FH patients, or maybe even to lower levels. Unfortunately, epidemiologic data are lacking on the severity of COVID-19 infections, as well as the number of acute cardiac events that have occurred in FH subjects during the COVID-19 pandemic. Such data need to be urgently gathered to learn how much the risk for, and the severity of COVID-19 in FH are increased.

Background This study was conducted to evaluate the relationship of age-adjusted D-dimer value with different coefficients in diagnosis of pulmonary embolism (PE) in geriatric patients. Methods The emergency admissions of the patients aged 65 and over with suspected PE during 2018 were reviewed retrospectively. The demographic characteristics, laboratory tests and radiologic findings of computed tomography pulmonary angiogram (CTPA) or single photon emission computed tomography ventilation/perfusion scintigraphy (V/Q) were recorded. The characteristics of the patients with PE were statistically compared with the patients without PE. The specificity and sensitivity for higher cut-off levels (age × 10-15) were presented. Results PE was detected in 39.2% (n = 246) of 628 patients aged 65 years and older included in the study. The multivariate analysis revealed that higher D-dimer level (OR = 1,00011; p < 0.001) and BUN level (OR = 1.025; p = 0.013) were independent risk factors for PE diagnosis in elderly patients. Diagnostic statistics for D-dimer cut-off levels selected from ROC analysis and calculated values as 10-15 times of age showed that if the D-dimer cut-off value used is chosen higher, lower sensitivity rates are obtained. Our results also indicated that the patients with malignancy, renal failure, central PE on CTPA and PE with high probability on SPECT VQ were presented with higher D-dimer values. Conclusion Our results do not support the use of higher D-dimer cut-off levels such as 15 times the age in geriatric population. The impact of the location of PE and comorbidities on the outcomes of these patients must be clarified for determining cut-offs with higher specificity.

D-dimer is an essential diagnostic index of thrombotic diseases. Since the existing anti-D-dimer antibodies vary in quality and specificity, a search for alternative anti-D-dimer antibodies is required. The present study aimed to screen a novel monoclonal antibody (mAb) against D-dimer using a light-initiated chemiluminescence assay (LiCA). In this work, mice were immunized with antigen prepared from human plasma by enzyme hydrolysis. After screening, a novel mAb, DD 2G11, was obtained. The results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis indicated that DD 2G11 could be used as a standard marker for D-dimer. The isotype of DD 2G11 was IgG1, the K_a value was 0.646 nM-1, and the K_d value was 50 nM, indicating that the binding affinity to D-dimer was very high. Furthermore, no cross-reactivity between DD 2G11 and other fibrinogen degradation products (FgDPs) was found. Finally, the correlation between DD 2G11 and the reference antibody (commercial antibody) was investigated by analyzing 56 clinical samples using a latex-enhanced turbidimetric immunoassay (LTIA). The R² value of the linear regression was 0.94538, indicating that DD 2G11 met clinical requirements. In conclusion, the present study provides a more expeditious protocol to screen mAbs and provides a clinically usable mAb against D-dimer.

D-dimers are generated during endogenous fibrinolysis of a blood clot and have a central role in diagnostic algorithms to rule out venous thromboembolism. HMG-CoA reductase inhibitors, more commonly called statins, are known to have effects independent of LDL-cholesterol lowering, including antithrombotic properties. An effect of statins on D-dimer levels has been reported in a prior systematic review and meta-analysis, but methodological shortcomings might have led to an overestimated effect. To re-evaluate the association between statins and D-dimer levels, we systematically reviewed all published articles on the influence of statins on D-dimer levels and conducted a novel meta-analysis (PROSPERO registration number CRD42017058932).

We electronically searched EMBASE, Medline Epub, Cochrane, Web of Science and Google Scholar (100 top relevance) (date of last search: 5 October 2017). We included randomized controlled trials, cohort studies and cross-sectional studies. Two reviewers independently screened all articles retrieved and extracted data on study and patient characteristics, study quality and D-dimer levels.

Study-level meta-analysis involving 18,052 study participants showed lower D-dimer levels in those receiving statin treatment than controls (SMD: -0.165, 95% CI -0.234; -0.096, P = <0.001). Sensitivity analyses and additional analyses on treatment duration (<12 weeks vs ≥12 weeks) and type of statin (lipophilic or hydrophilic) did not modify this overall result.

This meta-analysis suggests an association between use of statins and reduction of D-dimer levels, independent of treatment duration and type of statin used. This effect is small but robust, and should be interpreted with caution.

Pulmonary embolism (PE) is an increasingly recognised condition which is associated with significant morbidity and mortality. Despite the better awareness of this serious condition, the diagnosis is still overlooked in many cases with sometimes fatal consequences. Under-diagnosis may be due to several reasons including reliance on non-specific 'classic' symptoms, belief that bedside measurements will likely be abnormal in the setting of acute PE, and confounding factors like co-existent cardiorespiratory diseases or being in an intensive care unit, where the diagnosis may not be considered. At the same time, incidental diagnosis of PE is occurring more often due to frequent use of imaging investigations alongside advancements in CT technology, and dilemma exists as to whether the chance finding of PE requires anticoagulation, especially when identified only at the subsegmental level. This article reviews these two issues of under-diagnosis and over-diagnosis of PE in the current era.

Acute pulmonary embolism may be ruled out by combining nonhigh clinical probability and a normal D-dimer level. Both antiplatelet drugs and HMG-CoA reductase inhibitors (statins) have been associated with effects on thrombus formation, potentially influencing D-dimer levels in this setting, leading to a higher rate of false-negative tests. Therefore, we determined whether D-dimer levels in patients with suspected pulmonary embolism are affected by concomitant use of antiplatelet drugs and/or statins and evaluated whether the effect of antiplatelet drugs or statins might affect diagnostic accuracy.

We performed a posthoc analysis in the YEARS diagnostic study, comparing age- and sex-adjusted D-dimer levels among users of antiplatelet drugs, statins and nonusers. We then reclassified patients within the YEARS algorithm by developing a model in which we adjusted D-dimer cut-offs for statin use and evaluated diagnostic accuracy.

We included 156 statins users, 147 antiplatelet drugs users and 726 nonusers of either drugs, all with suspected pulmonary embolism. Use of antiplatelet drugs did not have a significant effect, whereas statin use was associated with 15% decrease in D-dimer levels (95% CI, -28% to -0.6%). An algorithm with lower D-dimer thresholds in statin users yielded lower specificity (0.42 compared to 0.33) with no difference in false-negative tests.

We conclude that use of statins but not of antiplatelet agents is associated with a modest decrease in D-dimer levels. Adjusting D-dimer cut-offs for statin use did, however, not result in a safer diagnostic strategy in our cohort.