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The state of the coagulation-fibrinolysis system plays a pivotal role in thrombosis; however, its significance in guiding early revascularization for ischemic stroke remains inadequately understood. To explore the correlation between coagulation activation markers and early neurological function and infarction volume in acute ischemic stroke (AIS), and to evaluate their predictive value for stroke severity. This retrospective cohort study enrolled 135 patients with acute ischemic stroke. Participants were stratified into two groups based on admission National Institutes of Health Stroke Scale (NIHSS)scores: mild stroke group (NIHSS≤3, n=95) and moderate-to-severe stroke group (NIHSS>3, n=40). Five coagulation activation markers were quantified: thrombomodulin (TM), thrombin-antithrombin complex (TAT), plasmin-α2 plasmin inhibitor complex (PIC), tissue plasminogen activator-inhibitor complex (t-PAIC), and D-dimer. The associations between these biomarkers and stroke severity were evaluated using logistic regression models and receiver-operating characteristic (ROC) curve analyses. Infarct volume and its spatial distribution across distinct brain regions were quantified using dedicated neuroimaging software. Subsequently, the correlation between the five coagulation markers and both total infarct volume and region-specific infarction volumes were assessed. Plasma levels of TAT, t-PAIC, and D-dimer were significantly elevated in the moderate-to-severe stroke group compared to the mild stroke group (p<0.05). Multivariate logistic regression analysis identified D-dimer as an independent risk factor for moderate-to-severe stroke (OR=1.002,95% CI:1.000-1.004). The area under the curve (AUC) values for TAT, t-PAIC, and D-dimer in predicting moderate-to-severe stroke were 0.62,0.63, and 0.59, respectively. The combined predictive model achieved an AUC of 0.67. Furthermore, within the moderate-to-severe stroke group, TAT levels demonstrated a positive correlation with anterior circulation cortical infarction volume (R=0.61, p<0.05). Additionally, D-dimer levels exhibited positive correlations with both total infarct volume and anterior circulation cortical infarction volume (R=0.74, p<0.05; R=0.79, p<0.05). TAT, t-PAIC and D-dimer serve as predictors for the severity of acute ischemic stroke, and can be used as a simple and rapid auxiliary tool combined with imaging evaluation to provide synergistic guidance for clinical decision-making.

Antiphospholipid antibodies (aPL) are associated with an increased risk of thrombosis and recurrent miscarriage. We assessed levels of coagulation activation markers and aPL during normal pregnancy and in women with the antiphospholipid syndrome (aPS). Fluctuations in aPL levels were observed in all patients with aPS. No particular pattern of antibody positivity, or fluctuation in aPL level, was associated with poor pregnancy outcome. A significant increase was observed in levels of factor Xlla (FXIIa; P < 0.001), factor VIIa (FVIIa, P < 0.001), thrombin antithrombin complexes (TAT; P < 0.001), prothrombin fragment F1.2 (F1.2; P < 0.001) and D-dimer (DD; P < 0.05) during normal pregnancy. Factor VIIa, TAT, F1.2 and DD increased significantly before 20 weeks gestation, while a statistically significant increase in FXIIa levels was first detected between weeks 20 and 30 of gestation. In pregnant women with aPS, increases in FXIIa were similar to those in normal pregnancy, but increased FVIIa levels were not observed until after 30 weeks gestation. Similar to normal pregnancy, increased levels of TAT and F1.2 were detected in aPS pregnancies before 20 weeks gestation, but increased DD were not observed until after week 20. Surprisingly, women with aPS receiving low molecular weight heparin prophylaxis had significantly higher (P = 0.02) levels of TAT (median 8.6; interquartile range (IQR) 6.5-20.8) between weeks 20 and 30 of gestation compared to the normal pregnant population (median 5.9; IQR 4.7-7.9), thus indicating increased thrombin generation in women with aPS in mid-pregnancy.

Japanese patients experience fewer episodes of postoperative thrombosis than those in certain other countries. To investigate this phenomenon, we measured perioperative coagulation activation markers and conducted thromboelastography (TEG) in 27 Japanese patients undergoing laparoscopic cholecystectomy. D-dimer, thrombin-antithrombin complex (TAT), and prothrombin fragment 1+2 (F1+2) were measured as coagulation activation markers. TEG was performed to measure reaction time (R), clot formation time (K), maximum amplitude (MA), and maximum elastance (ME). These measurements were performed before and after the operation and the day after the operation. Coagulation activation markers increased significantly postoperatively. With respect to TEG, MA and ME increased postoperatively. R and K did not change. Whereas clotting factor activation sthenia is common in Europe and North America, thrombocyte function sthenia occurs in Japanese patients. This difference may account for the differing incidences of phlebothrombosis in Japanese and white populations.

The association of thrombophilia with pregnancy complications has received increasing attention. It is now apparent that thrombophilia is responsible for a large number of the serious complications of pregnancy such as venous thrombosis, pulmonary embolism, fetal loss, pregnancy loss, intrauterine fetal demise, and preeclampsia. The inherited thrombophilia abnormalities, factor V Leiden mutation, prothrombin gene mutation 20210A, and antithrombin III, protein C, and protein S deficiency, and the acquired disorders, the anticardiolipin syndrome and lupus inhibitor, are responsible for a large share of the incidences of premature termination of pregnancy and many of the above complications. The normal physiology of pregnancy may be prothrombotic, with evidence for increased markers of activated coagulation and coagulation factors. There is a decrease in protein S and resistance to activated protein C occurs in a significant number of pregnancies in the absence of the factor V Leiden mutation. In the following article, we review some of the major studies that have correlated the thrombophilia and other acquired disorders that adversely impact pregnancies.

Understanding the pathophysiology of SARS-CoV-2 infection is critical for therapeutic and public health strategies. Viral–host interactions can guide discovery of disease regulators, and protein structure function analysis points to several immune pathways, including complement and coagulation, as targets of coronaviruses. To determine whether conditions associated with dysregulated complement or coagulation systems impact disease, we performed a retrospective observational study and found that history of macular degeneration (a proxy for complement-activation disorders) and history of coagulation disorders (thrombocytopenia, thrombosis and hemorrhage) are risk factors for SARS-CoV-2-associated morbidity and mortality—effects that are independent of age, sex or history of smoking. Transcriptional profiling of nasopharyngeal swabs demonstrated that in addition to type-I interferon and interleukin-6-dependent inflammatory responses, infection results in robust engagement of the complement and coagulation pathways. Finally, in a candidate-driven genetic association study of severe SARS-CoV-2 disease, we identified putative complement and coagulation-associated loci including missense, eQTL and sQTL variants of critical complement and coagulation regulators. In addition to providing evidence that complement function modulates SARS-CoV-2 infection outcome, the data point to putative transcriptional genetic markers of susceptibility. The results highlight the value of using a multimodal analytical approach to reveal determinants and predictors of immunity, susceptibility and clinical outcome associated with infection. A combination of clinical and molecular analyses supports an association between disorders of immune complement or coagulation with poor outcome in patients with SARS-CoV-2 infection.

Aortic aneurysms and vascular malformations are sometimes associated with disseminated intravascular coagulation (DIC). A typical blood coagulation test shows decrease in platelet count and fibrinogen, and increases in fibrin/fibrinogen degradation products (FDP) and D-dimer. The coagulation activation marker thrombin–antithrombin complex (TAT) and the fibrinolysis activation marker plasmin-α2 plasmin inhibitor (PIC) are significantly increased. α2 plasmin inhibitor (α2PI) is significantly reduced. Since no prolongation of prothrombin time (PT) is noticeable and activated partial thromboplastin time (APTT) is shortened in some cases, DIC cannot be diagnosed or ruled out by PT and APTT alone. The cornerstone of treatment for DIC is to treat the underlying disease. However, surgery is not possible in some cases. Follow-up may be appropriate in patients with abnormal results from coagulation tests and no bleeding. However, pharmacotherapy is often required in cases with bleeding. Unfractionated heparin, low molecular weight heparin, protease inhibitors, recombinant thrombomodulin, direct oral anticoagulants, and factor XIII preparations are effective. If PIC is significantly increased and α2PI is significantly decreased, or if the bleeding is severe, tranexamic acid is used as an antifibrinolytic therapy with anticoagulant therapy. In such cases, attention should be paid not only to TAT but also changes in PIC.

Delirium's pathophysiology is poorly understood. We sought to determine if plasma biomarkers of inflammation, coagulation, endothelial activation, and blood brain barrier (BBB) injury were associated with emergency department (ED) delirium duration. We enrolled hospitalized patients who were 65 years or older from the ED. Plasma biomarkers of inflammation (interleukin-6 [IL-6], IL-8, soluble tumor necrosis factor receptor I [sTNFRI]), coagulation (Protein C), endothelial activation (plasminogen activating inhibitor-1 [PAI-1]), and BBB injury (S100B) at were measured using blood obtained at enrollment. The dependent variable was ED delirium duration which was determined by the Brief Confusion Assessment Method assessed in the ED and hospitalization. Proportional odds logistic regression analyses were performed adjusted for relevant confounders and allowing for interaction by baseline dementia status. A total of 156 patients were enrolled. IL-6 (POR = 1.59, 95%CI: 1.09-2.32) and PAI-1 (POR = 2.96, 95%CI: 1.48 to 6.85) were independently associated with more prominent ED delirium duration in subjects without dementia only. No significant associations between IL-8, Protein C, sTNRFI, and S100B and ED delirium duration were observed. Plasma Biomarkers of systemic inflammation and endothelial activation are associated with ED delirium duration in older ED patients without dementia.

Background Early detection of small cell lung cancer (SCLC) crucially demands highly reliable markers. Growing evidence suggests that extracellular vesicles carry tumor cell-specific cargo suitable as protein markers in cancer. Quantitative proteomic profiling of circulating microvesicles and exosomes can be a high-throughput platform for discovery of novel molecular insights and putative markers. Hence, this study aimed to investigate proteome dynamics of plasma-derived microvesicles and exosomes in newly diagnosed SCLC patients to improve early detection. Methods Plasma-derived microvesicles and exosomes from 24 healthy controls and 24 SCLC patients were isolated from plasma by either high-speed- or ultracentrifugation. Proteins derived from these extracellular vesicles were quantified using label-free mass spectrometry and statistical analysis was carried out aiming at identifying significantly altered protein expressions between SCLC patients and healthy controls. Furthermore, significantly expressed proteins were subjected to functional enrichment analysis to identify biological pathways implicated in SCLC pathogenesis. Results Based on fold change (FC) ≥ 2 or ≤ 0.5 and AUC ≥ 0.70 ( p  < 0.05), we identified 10 common and 16 and 17 unique proteins for microvesicles and exosomes, respectively. Among these proteins, we found dysregulation of coagulation factor XIII A (Log 2 FC =  − 1.1, p  = 0.0003, AUC = 0.82, 95% CI: 0.69–0.96) and complement factor H-related protein 4 (Log 2 FC = 1.2, p  = 0.0005, AUC = 0.82, 95% CI; 0.67–0.97) in SCLC patients compared to healthy individuals. Our data may indicate a novel tumor-suppressing role of blood coagulation and involvement of complement activation in SCLC pathogenesis. Conclusions In comparing SCLC patients and healthy individuals, several differentially expressed proteins were identified. This is the first study showing that circulating extracellular vesicles may encompass specific proteins with potential diagnostic attributes for SCLC, thereby opening new opportunities as novel non-invasive markers.

The recommendations for antithrombotic treatment after left atrial appendage closure (LAAC) remain empirical, and no data exist on the changes in hemostatic markers associated with LACC. The objective of the present study is to determine the presence, degree, and timing of changes in the markers of platelet and coagulation activation after LAAC. Forty-three patients (mean age 76 ± 9 years, 23 men) with atrial fibrillation who underwent successful LACC with the Watchman (n = 27) or Amplatzer Cardiac Plug (n = 16) devices were included in the study. Patients received antiplatelet therapy after LAAC (aspirin + clopidogrel: 27 patients; single antiplatelet therapy with aspirin or clopidogrel: 16 patients). Prothrombin fragment 1+2 and thrombin-antithrombin III were used as markers of coagulation activation, and soluble P-selectin and soluble CD40 ligand were used as markers of platelet activation. Measurements of all hemostatic markers were performed at baseline just before the procedure, followed by days 7, 30, and 180 after LAAC. Prothrombin fragment 1+2 and thrombin-antithrombin levels increased from 0.27 nmol/L and 4.68 ng/ml, respectively, at baseline to peak values of 0.43 nmol/L and 9.76 ng/ml, respectively, at 7 days, partially returning to baseline levels at days 30 and 180 after LAAC (p <0.001 for both markers). No clinical or procedural factors were associated with a greater increase in the markers of coagulation activation after LAAC. Levels of soluble P-selectin and soluble CD40 ligand did not change at any time after LAAC. In conclusion, transcatheter LAAC is associated with significant activation of the coagulation system, yet without evidence of significant platelet activation.

Bacterial lipopolysaccharide (LPS) induces general inflammation, by activating pathways involving cytokine production, blood coagulation, complement system activation, and acute phase protein release. The key cellular players are leukocytes and endothelial cells, that lead to tissue injury and organ failure. The aim of this study was to explore the anti-inflammatory, antioxidant, and cytoprotective properties of two bile acids, ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) in LPS-induced endotoxemia in rats. The experiment involved six distinct groups of Wistar rats, each subjected to different pretreatment conditions: control and LPS groups were pretreated with propylene glycol, as a bile acid solvent, while the other groups were pretreated with UDCA or CDCA for 10 days followed by an LPS injection on day 10. The results showed that both UDCA and CDCA reduced the production of pro-inflammatory cytokines: TNF-α, GM-CSF, IL-2, IFNγ, IL-6, and IL-1β and expression of nuclear factor-κB (NF-κB) induced by LPS. In addition, pretreatment with these bile acids showed a positive impact on lipid profiles, a decrease in ICAM levels, an increase in antioxidant activity (SOD, |CAT, GSH), and a decrease in prooxidant markers (H 2 O 2 and O 2 – ). Furthermore, both bile acids alleviated LPS-induced liver injury. While UDCA and CDCA pretreatment attenuated homocysteine levels in LPS-treated rats, only UDCA pretreatment showed reductions in other serum biochemical markers, including creatine kinase, lactate dehydrogenase, and high-sensitivity troponin I. It can be concluded that both, UDCA and CDCA, although exerted slightly different effects, can prevent the inflammatory responses induced by LPS, improve oxidative stress status, and attenuate LPS-induced liver injury.