Search Results (10)

This article explores systemic inflammatory response syndrome (SIRS), thromboinflammation, and septic shock in fetuses and neonates, offering a comprehensive examination of their pathophysiology, diagnostic criteria, and clinical implications. It identifies SIRS as an exaggerated response to external stress, disrupting the balance between inflammation and adaptive mechanisms, driven by cytokines such as TNF-α and IL-1. The fetal inflammatory response syndrome (FIRS), a subset of SIRS, is noted for its role in adverse neonatal outcomes, including organ damage, inflammation, and long-term developmental disorders. The article discusses the extensive effects of FIRS on critical systems, including the blood, lungs, central nervous system, and kidneys. It highlights the challenges in diagnosing and managing septic shock in neonates, focusing on the relationship between inflammation and the hemostatic system. Additionally, the paper points out recent advancements, such as the convergent model of coagulation and emerging biomarkers like microRNAs for early detection. Despite this progress, gaps remain in understanding the molecular mechanisms underlying these conditions and in developing effective therapeutic strategies. This highlights the necessity for targeted research to mitigate the morbidity and mortality associated with septic shock in neonates. Full article

Thrombotic microangiopathy (TMA) encompasses a range of disorders characterized by blood clotting in small blood vessels, leading to organ damage. It can manifest as various syndromes, including thrombotic thrombocytopenic purpura (TTP), hemolytic-uremic syndrome (HUS), and others, each with distinct causes and pathophysiology. Thrombo-inflammation plays a significant role in TMA pathogenesis: inflammatory mediators induce endothelial injury and activation of platelet and coagulation cascade, contributing to microvascular thrombosis. Primary TMA, such as TTP, is primarily caused by deficient ADAMTS13 metalloproteinase activity, either due to antibody-mediated inhibition or intrinsic enzyme synthesis defects. In cancer patients, a significant reduction in ADAMTS13 levels and a corresponding increase in VWF levels is observed. Chemotherapy further decreased ADAMTS13 levels and increased VWF levels, leading to an elevated VWF/ADAMTS13 ratio and increased thrombotic risk. Drug-induced TMA (DITMA) can result from immune-mediated or non-immune-mediated mechanisms. Severe cases of COVID-19 may lead to a convergence of syndromes, including disseminated intravascular coagulation (DIC), systemic inflammatory response syndrome (SIRS), and TMA. Treatment of TMA involves identifying the underlying cause, implementing therapies to inhibit complement activation, and providing supportive care to manage complications. Plasmapheresis may be beneficial in conditions like TTP. Prompt diagnosis and treatment are crucial to prevent serious complications and improve outcomes. Full article

Unlike classic APS, CAPS causes multiple microthrombosis due to an increased inflammatory response, known as a “thrombotic storm”. CAPS typically develops after infection, trauma, or surgery and begins with the following symptoms: fever, thrombocytopenia, muscle weakness, visual and cognitive disturbances, abdominal pain, renal failure, and disseminated intravascular coagulation. Although the presence of antiphospholipid antibodies in the blood is one of the diagnostic criteria, the level of these antibodies can fluctuate significantly, which complicates the diagnostic process and can lead to erroneous interpretation of rapidly developing symptoms. Triple therapy is often used to treat CAPS, which includes the use of anticoagulants, plasmapheresis, and high doses of glucocorticosteroids and, in some cases, additional intravenous immunoglobulins. The use of LMWH is recommended as the drug of choice due to its anti-inflammatory and anticoagulant properties. CAPS is a multifactorial disease that requires not only an interdisciplinary approach but also highly qualified medical care, adequate and timely diagnosis, and appropriate prevention in the context of relapse or occurrence of the disease. Improved new clinical protocols and education of medical personnel regarding CAPS can significantly improve the therapeutic approach and reduce mortality rates. Full article

Newborns are the most vulnerable patients for thrombosis development among all children, with critically ill and premature infants being in the highest risk group. The upward trend in the rate of neonatal thrombosis could be attributed to progress in the treatment of severe neonatal conditions and the increased survival in premature babies. There are physiological differences in the hemostatic system between neonates and adults. Neonates differ in concentrations and rate of synthesis of most coagulation factors, turnover rates, the ability to regulate thrombin and plasmin, and in greater variability compared to adults. Natural inhibitors of coagulation (protein C, protein S, antithrombin, heparin cofactor II) and vitamin K-dependent coagulation factors (factors II, VII, IX, X) are low, but factor VIII and von Willebrand factor are elevated. Newborns have decreased fibrinolytic activity. In the healthy neonate, the balance is maintained but appears more easily converted into thrombosis. Neonatal hemostasis has less buffer capacity, and almost 95% of thrombosis is provoked. Different triggering risk factors are responsible for thrombosis in neonates, but the most important risk factors for thrombosis are central catheters, fluid fluctuations, liver dysfunction, and septic and inflammatory conditions. Low-molecular-weight heparins are the agents of choice for anticoagulation. Full article

In some patients, SARS-CoV-2 infection induces cytokine storm, hypercoagulability and endothelial cell activation leading to worsening of COVID-19, intubation and death. Prompt identification of patients at risk of intubation is an urgent need. Objectives. To derive a prognostic score for the risk of intubation or death in patients with COVID-19 admitted in intensive care unit (ICU), by assessing biomarkers of hypercoagulability, endothelial cell activation and inflammation and a large panel of clinical analytes. Design, Setting and Participants. A prospective, observational study enrolled 118 patients with COVID-19 admitted in the ICU. On the first day of ICU admission, all patients were assessed for biomarkers (protein C, protein S, antithrombin, D-Dimer, fibrin monomers, FVIIa, FV, FXII, FXII, FVIII, FvW antigen, fibrinogen, procoagulant phospholipid dependent clotting time, TFPI, thrombomodulin, P-selectin, heparinase, microparticles exposing TF, IL-6, complement C3a, C5a, thrombin generation, PT, aPTT, hemogram, platelet count) and clinical predictors. Main Outcomes and Measures. The clinical outcomes were intubation and mortality during hospitalization in ICU. Results: The intubation and mortality rates were 70% and 18%, respectively. The COMPASS-COVID-19-ICU score composed of P-Selectin, D-Dimer, free TFPI, TF activity, IL-6 and FXII, age and duration of hospitalization predicted the risk of intubation or death with high sensitivity and specificity (0.90 and 0.92, respectively). Conclusions and Relevance. COVID-19 is related to severe endothelial cell activation and hypercoagulability orchestrated in the context of inflammation. The COMPASS-COVID-19-ICU risk assessment model is accurate for the evaluation of the risk of mechanical ventilation and death in patients with critical COVID-19. The COMPASS-COVID-19-ICU score is feasible in tertiary hospitals and could be placed in the diagnostic procedure of personalized medical management and prompt therapeutic intervention. Full article

Biomarkers of hypercoagulability are potential candidates for the evaluation of risk for primary treatment resistance in patients with newly diagnosed multiple myeloma (NDMM). This study aimed to identify the most clinically relevant biomarkers for the evaluation of treatment-resistance risk. NDMM patients (n = 144) were enrolled prior to treatment initiation. Response to treatment was assessed at 3 months. STA-Procoag-PPL^®, factor VIIa factor V, antithrombin, fibrin monomers, soluble thrombomodulin (TM), free TFPI, D-Dimer, P-selectin, heparanase, and thrombin generation (Calibrated Automated Thrombogram^® and PPP-Reagent^®) were measured. In total, 23% (n = 33) of the patients showed a poor response/resistance to treatment (defined as stable disease, minor response, progressive disease). Poor response/treatment resistance was associated with longer Procoag-PPL^® clotting time, higher Peak of thrombin, and higher D-Dimer levels. These biomarkers were included in a prognostic model derived via multivariate analysis. The model had 84% sensitivity and 59% specificity to identify patients at high risk of treatment resistance. The AUC of the ROC analysis for the model was 0.75. In conclusion, Procoag-PPL^®, D-Dimer, and Peak of thrombin generation are clinically relevant for the identification of NDMM patients at risk for poor response to antimyeloma treatment. A prospective multicenter study is necessary for the validation of this new approach. Full article

Background. Hypercoagulable state and endothelial cell activation are common alterations in patients with COVID-19. Nevertheless, the hypothesis of persistent hypercoagulability and endothelial cell activation following recovery from COVID-19 remains an unresolved issue. Objectives. To investigate the persistence of endothelial cell activation and hypercoagulability after recovery from COVID-19. Patients/Methods. COVID-19 survivors (n = 208) and 30 healthy individuals were enrolled in this study. The following biomarkers were measured: procoagulant phospholipid-dependent clotting time (PPL-ct), D-Dimer, fibrin monomers (FM), free Tissue factor pathway inhibitor (free-TFP)I, heparinase, and soluble thrombomodulin (sTM). Antibodies against SARS-CoV-2 (IgG and IgA) were also measured. Results. The median interval between symptom onset and screening for SARS-CoV-2 antibodies was 62 days (IQR = 22 days). Survivors showed significantly higher levels of D-Dimers, FM, TFPI, and heparanase as compared to that of the control group. Survivors had significantly shorter PPL-ct. Elevated D-dimer was associated with older age. Elevated FM was associated with female gender. Elevated heparanase was independently associated with male gender. Decreased Procoag-PPL clotting time was associated with female gender. One out of four of COVID-19 survivors showed increase at least one biomarker of endothelial cell activation or hypercoagulability. Conclusions. Two months after onset of COVID-19, a significant activation of endothelial cells and in vivo thrombin generation persists in at least one out of four survivors of COVID-19. The clinical relevance of these biomarkers in the diagnosis and follow-up of patients with long COVID-19 merits to be evaluated in a prospective clinical study. Full article

Reliable laboratory diagnosis of heparin-induced thrombocytopenia (HIT) remains a major clinical concern. Immunoassays are highly sensitive, while confirmatory functional tests (based on heparin-dependent platelet activation) lack standardization. We evaluated the diagnostic performance of a functional flow cytometric assay (FCA) based on the detection of heparin-dependent platelet activation with an anti-p-selectin. A total of 288 patients were included (131 HIT-positive and 157 HIT-negative) with a HIT diagnosis established by expert opinion adjudication (EOA) considering clinical data and local laboratory results. The FCA was centrally performed in a single laboratory on platelet-rich plasma, using a very simple four-color fluorometer. The results were standardized according to the Heparin Platelet Activation (HEPLA) index. The serotonin release assay (SRA) was performed in the four French reference laboratories. Based on the final HIT diagnosis established by EOA, the sensitivity and specificity of the FCA were 88 and 95%, respectively, values very similar to those of the SRA (88 and 97%, respectively). This study showed that the FCA, based on easily implementable technology, may be routinely used as a reliable confirmatory test for HIT diagnosis. Full article

Background: The role and effect of radiotherapy in the development of VTE has not been extensively explored; Methods: This is a post-hoc analysis from the COMPASS-CAT trial. Patients with breast, lung, colon or ovarian cancer, with early, locally advanced or metastatic disease and receiving chemotherapy were included. Primary endpoint was documented symptomatic VTE; Results: A total of 1355 patients were enrolled between November 2013 and November 2015. Of those, 194 patients were excluded because of missing data or the use of anticoagulation. Of the evaluable patients, 361 patients received radiotherapy (33.6%) At a median follow up of 6 months, 9.1% (n = 33) of patients receiving radiotherapy developed a VTE event (excluding those with missing data on follow up). After applying the competing risk model, radiotherapy remained significantly associated with increased risk for VTE (HR 2.47, 95% CI: 1.47–4.12, p = 0.001). Stratification analysis for the cohort that received radiotherapy revealed an increased risk of VTE in women compared to men (10.8% vs. 2.7%; p = 0.03), in those older than 50 (12.2% vs. 3.7%; p = 0.011); for patients receiving anthracycline chemotherapy (14.4% vs. 2.9%; p < 0.001) and hormonal therapy (12.9% vs. 3.9%; p < 0.001); Conclusions: Analysis from the COMPASS-CAT revealed a significant correlation between radiotherapy and VTE in patients with cancer. Further studies are needed to better understand the potential cellular toxicity associated with radiotherapy. Full article

Advanced age is one of the major determinants of frailty in patients with cancer-associated thrombosis. However, multiple other factors contribute to frailty in these patients. The identification of frailty in patients with cancer-associated thrombosis is critical as it influences the complexity of the anticoagulant treatment in this population at high risk of venous thromboembolism and bleeding. Factors that contribute to frailty in patients with cancer-associated thrombosis include age, type of cancer, comorbidities such as chronic kidney disease, poly-pharmacotherapy, treatment compliance, cognitive impairment, anemia, thrombocytopenia, mobility, nutritional status, Eastern Cooperative Oncology Group grade, risk of falls, and reduced life expectancy. In the absence of specific clinical studies current anticoagulant treatment guidelines for the management are not fully applicable to frail patients with cancer. The anticoagulant treatment should therefore benefit from a tailored approach based on an algorithm that takes into account the specificities of the malignant disease. Full article