Hemostatic Markers Research Articles

8614 Low Dose Sublingual Estradiol Decreases Protein S, Generating a Potentially Pro-thrombotic Profile: Interim Results of a Controlled Prospective Pilot Study of Treatment-Naïve Trans Women

Abstract Disclosure: S. Bar On: None. I. Yaish: None. M. Barzilai: None. Y. Greenman: None. G. Gindis: None. Y. Moshe: None. K.M. Tordjman: None. Background: Sublingual estradiol (SLE) for gender-affirming hormone therapy (GAHT) of transgender women (TW) might obviate the need for an anti-androgen, and mitigate pro-coagulant changes. We recently showed that 2 mg E, divided into 4 daily sublingual doses, offers no clinical advantage over the same dose given orally in combination with cyproterone acetate (CPA)1. Furthermore, we showed that after each sublingual administration, serum estradiol (sE2) peaked to levels, the likes of which are achieved only during induction of ovulation with gonadotrophins. Hypothesis and Aim: Given the exceedingly high peak sE2 measured under SLE-GAHT, we hypothesized it could lead to partial acquired Protein S deficiency, a recognized pro-thrombotic state and risk factor for venous thromboembolic events (VTE). Our aim was to assess the hemostatic system under SLE in comparison with the standard combined oral (CO) approach. Design and Methods: In this ongoing open label study, treatment-naïve TW are assigned in a 1:1 ratio (15 in each arm) to either standard CO (2 mg E2 with 10 mg CPA once daily), or to SLE with 2 mg sublingual estradiol divided into 4 daily dose for 6 months (6M). An extensive battery of hemostatic biomarkers, including free Protein S antigen (fPS), are assessed at baseline (BL) and at 6M. Results: We herein report on 27 subjects (15 CO/12 SLE) who initiated treatment, 17 of whom have already completed it. The median age of the cohort is 20 y (IQR 19-27; range 18-42]. There were no BL differences between the groups. At 6M, none of the hemostatic markers differed between the groups except for fPS, which was significantly lower in the SLE group 79.7%±11.6% vs. 104.6%±5.6%, P=0.039. By paired comparisons for the entire group, fPS decreased from 104%.2±5.2% at BL to 95.8%±5.9% at 6M, P=0.003. This was entirely accounted for by the change in the SLE group, in which fPS went down from 95.7%±10.3% to 79.7%±11.6%, P<0.001; with some values reaching the fPS deficiency range. In contrast, fPS, remained unchanged under CO 108.9%±5.7% and 104.5%±5.2%, at BL and 6M respectively, P=0.153. Conclusions: The most notable interim finding was a clinically significant decrease in fPS under low dose SLE. Given the extreme peaks of sE2 we previously reported with this protocol, an acquired deficiency of this natural anti-coagulant was expected. These preliminary findings support our hypothesis, and raise the concern that GAHT of TW with chronic SLE might carry an increased long-term risk for VTE. 1 Yaish I, Gindis G, Greenman Y, et al. Sublingual Estradiol Offers no Apparent Advantage Over Combined Oral Estradiol and Cyproterone Acetate for Gender-Affirming Hormone Therapy of Treatment-Naive Trans Women: Results of a Prospective Pilot Study. Transgend Health. 2023;8(6):485-493. Published 2023 Dec 13. doi:10.1089/trgh.2023.0022 Presentation: 6/2/2024

8614 Low Dose Sublingual Estradiol Decreases Protein S, Generating a Potentially Pro-thrombotic Profile: Interim Results of a Controlled Prospective Pilot Study of Treatment-Naïve Trans Women

Abstract Disclosure: S. Bar On: None. I. Yaish: None. M. Barzilai: None. Y. Greenman: None. G. Gindis: None. Y. Moshe: None. K.M. Tordjman: None. Background: Sublingual estradiol (SLE) for gender-affirming hormone therapy (GAHT) of transgender women (TW) might obviate the need for an anti-androgen, and mitigate pro-coagulant changes. We recently showed that 2 mg E, divided into 4 daily sublingual doses, offers no clinical advantage over the same dose given orally in combination with cyproterone acetate (CPA)[1]. Furthermore, we showed that after each sublingual administration, serum estradiol (sE2) peaked to levels, the likes of which are achieved only during induction of ovulation with gonadotrophins. Hypothesis and Aim: Given the exceedingly high peak sE2 measured under SLE-GAHT, we hypothesized it could lead to partial acquired Protein S deficiency, a recognized pro-thrombotic state and risk factor for venous thromboembolic events (VTE). Our aim was to assess the hemostatic system under SLE in comparison with the standard combined oral (CO) approach. Design and Methods: In this ongoing open label study, treatment-naïve TW are assigned in a 1:1 ratio (15 in each arm) to either standard CO (2 mg E2 with 10 mg CPA once daily), or to SLE with 2 mg sublingual estradiol divided into 4 daily dose for 6 months (6M). An extensive battery of hemostatic biomarkers, including free Protein S antigen (fPS), are assessed at baseline (BL) and at 6M. Results: We herein report on 27 subjects (15 CO/12 SLE) who initiated treatment, 17 of whom have already completed it. The median age of the cohort is 20 y (IQR 19-27; range 18-42]. There were no BL differences between the groups. At 6M, none of the hemostatic markers differed between the groups except for fPS, which was significantly lower in the SLE group 79.7%±11.6% vs. 104.6%±5.6%, P=0.039. By paired comparisons for the entire group, fPS decreased from 104%.2±5.2% at BL to 95.8%±5.9% at 6M, P=0.003. This was entirely accounted for by the change in the SLE group, in which fPS went down from 95.7%±10.3% to 79.7%±11.6%, P<0.001; with some values reaching the fPS deficiency range. In contrast, fPS, remained unchanged under CO 108.9%±5.7% and 104.5%±5.2%, at BL and 6M respectively, P=0.153. Conclusions: The most notable interim finding was a clinically significant decrease in fPS under low dose SLE. Given the extreme peaks of sE2 we previously reported with this protocol, an acquired deficiency of this natural anti-coagulant was expected. These preliminary findings support our hypothesis, and raise the concern that GAHT of TW with chronic SLE might carry an increased long-term risk for VTE. [1] Yaish I, Gindis G, Greenman Y, et al. Sublingual Estradiol Offers no Apparent Advantage Over Combined Oral Estradiol and Cyproterone Acetate for Gender-Affirming Hormone Therapy of Treatment-Naive Trans Women: Results of a Prospective Pilot Study. Transgend Health. 2023;8(6): 485-493. Published 2023 Dec 13. doi:10.1089/trgh.2023.0022 Presentation: 6/2/2024

Relacorilant or surgery improved hemostatic markers in Cushing syndrome

Relacorilant or surgery improved hemostatic markers in Cushing syndrome

Dysregulated neutrophil extracellular traps and haemostatic biomarkers as diagnostic tools and therapeutic targets in periprosthetic joint infection.

Bacterial infection activates neutrophils to release neutrophil extracellular traps (NETs) in bacterial biofilms of periprosthetic joint infections (PJIs). The aim of this study was to evaluate the increase in NET activation and release (NETosis) and haemostasis markers in the plasma of patients with PJI, to evaluate whether such plasma induces the activation of neutrophils, to ascertain whether increased NETosis is also mediated by reduced DNaseI activity, to explore novel therapeutic interventions for NETosis in PJI in vitro, and to evaluate the potential diagnostic use of these markers. We prospectively recruited 107 patients in the preoperative period of prosthetic surgery, 71 with a suspicion of PJI and 36 who underwent arthroplasty for non-septic indications as controls, and obtained citrated plasma. PJI was confirmed in 50 patients. We measured NET markers, inflammation markers, DNaseI activity, haemostatic markers, and the thrombin generation test (TGT). We analyzed the ability of plasma from confirmed PJI and controls to induce NETosis and to degrade in vitro-generated NETs, and explored the therapeutic restoration of the impairment to degrade NETs of PJI plasma with recombinant human DNaseI. Finally, we assessed the contribution of these markers to the diagnosis of PJI. Patients with confirmed PJI had significantly increased levels of NET markers (cfDNA (p < 0.001), calprotectin (p < 0.001), and neutrophil elastase (p = 0.022)) and inflammation markers (IL-6; p < 0.001) in plasma. Moreover, the plasma of patients with PJI induced significantly more neutrophil activation than the plasma of the controls (p < 0.001) independently of tumour necrosis factor alpha. Patients with PJI also had a reduced DNaseI activity in plasma (p < 0.001), leading to a significantly impaired degradation of NETs (p < 0.001). This could be therapeutically restored with recombinant human DNaseI to the level in the controls. We developed a model to improve the diagnosis of PJI with cfDNA, calprotectin, and the start tail of TGT as predictors, though cfDNA alone achieved a good prediction and is simpler to measure. We confirmed that patients with PJI have an increased level of NETosis in plasma. Their plasma both induced NET release and had an impaired ability to degrade NETs mediated by a reduced DNaseI activity. This can be therapeutically restored in vitro with the approved Dornase alfa, Pulmozyme, which may allow novel methods of treatment. A combination of NETs and haemostatic biomarkers could improve the diagnosis of PJI, especially those patients in whom this diagnosis is uncertain.

Assessment of metabolic and hemostatic profile of apheresis platelet concentrates: does the storage medium play a role?

The impact of pathogen reduction technology (PRT) on metabolic and haemostatic profile of treated platelets remains a subject of debate. Platelets Additive Solutions (PASs) are suggested as more appropriate storage medium compared to plasma. To investigate this in terms of zero heterogeneity PRT-treated and control apheresis platelet concentrates (PCs), collected from the same donors and stored in PAS and plasma respectively, were analyzed. In the first arm of the study six double dose-apheresis PCs were produced, split and stored in plasma, while in the second arm six split double dose-apheresis PCs from the same donors, were produced and stored in PAS. Control and PRT-treated PCs resulted in both arms. Metabolic and haemostatic markers were evaluated in all the examined groups on days 1, 3 and 5. A time dependent increased metabolism both in PAS and plasma-stored PCs was evident in PRT-treated PCs. However, the metabolic profile was better preserved in PCs stored in PAS, as higher pH (6.8 vs 6.5, p=0.007) and lower lactate levels (12.6 vs 17.8 mmol/L, p=0.009) were documented in PRT-treated PAS-PCs compared to plasma-PCs, on day 5. A time dependent decreased hemostatic capacity regardless the storage medium was evident in PRT-treated PCs, (PAS-PCs MCF, p=0.004 and plasma-PCs MCF, p=0.007). Similar results were obtained in control PCs. The use of PAS preserves the metabolic profile of PCs more adequately compared to plasma but has no effect on the haemostatic profile. The clinical relevance of these findings needs further investigation.

Daytime plasma cortisol and cortisol response to dexamethasone suppression are associated with a prothrombotic state in hypertension.

A prothrombotic state was demonstrated in patients with Cushing's syndrome and is involved in the development and progression of cardiovascular and renal damage in hypertensive patients. This study was designed to examine the relationships between cortisol secretion and the hemostatic and fibrinolytic systems in hypertension. In 149 middle-aged, nondiabetic, essential hypertensive patients free of cardiovascular and renal complications, we measured hemostatic markers that express the spontaneous activation of the coagulation and fibrinolytic systems and assessed daily cortisol levels (8 AM, 3 PM, 12 AM; area under the curve, AUC-cortisol) together with the cortisol response to dexamethasone overnight suppression (DST-cortisol). Plasma levels of D-dimer (D-dim), prothrombin fragment 1+2 (F1+2), and von Willebrand factor (vWF) were progressively and significantly higher across tertiles of AUC-cortisol and DST-cortisol, whereas no differences were observed in fibrinogen, tissue plasminogen activator, plasminogen activator inhibitor-1, antithrombin III, protein C, and protein S. D-dim, F1+2, and vWF were significantly and directly correlated with age and both AUC-cortisol and DST-cortisol. Multivariate regression analysis showed that both AUC-cortisol and DST-cortisol were related to plasma D-dim, F1+2, and vWF independently of age, body mass index, blood pressure, and renal function. Greater daily cortisol profile and cortisol response to overnight suppression are independently associated with a prothrombotic state in hypertensive patients and might contribute to the development of organ damage and higher risk of cardiovascular complications.

Assessment of Factor VIII Activity and D-Dimer Levels in the Post-COVID Period.

Changes in the hemostatic system during COVID infection lead to hypercoagulability. Numerous studies have evaluated hemostatic abnormalities in COVID patients during acute infection, in the period of hospitalization. However, the hemostatic status following hospital discharge has not been sufficiently assessed. Considering the importance of FVIII and D-dimer levels as markers for the assessment of thrombosis, our study aimed to evaluate changes in these markers, as well as the influence of patient's age and clinical presentation of COVID infection on those hemostatic markers in the post-COVID phase. This prospective study (July 2020 to December 2022) included 115 COVID patients, 68 (59%) with asymptomatic/mild and 47 (41%) with moderate/severe clinical presentation. Patient follow-up included laboratory evaluation of FVIII and D-dimer levels at 1, 3, and 6 months following the COVID infection. Three months after the COVID infection, elevated FVIII was recorded in 44% of younger versus 65% of older individuals, p = 0.05, respectively, and 30 versus 57% (p = 0.008) 6 months post-COVID infection. With a focus on clinical presentation, a higher number of patients with moderate/severe COVID had elevated FVIII activity, but a statistically significant difference was observed only for the 6 months (32% mild vs. 53% moderate/severe, p = 0.041) post-infection time point. Following a COVID infection, an increase in FVIII activity suggests a continued hypercoagulable state in the post-COVID period and correlates with elevated D-dimer levels. This increase in FVIII is more pronounced in patients with moderate/severe clinical picture and those patients older than 50 years.

Alterations of Hemostatic Molecular Markers During Acute Large Vessel Occlusion Stroke.

This study aimed to investigate regional levels of TAT (thrombin-antithrombin complex), PIC (plasmin-α2 plasmin inhibitor complex), t-PAIC (tissue plasminogen activator-plasminogen activator inhibitor complex), sTM (soluble thrombomodulin), and D-dimer, along with their associations with clinical and procedural characteristics in patients with acute ischemic stroke undergoing endovascular thrombectomy. We retrospectively analyzed 166 consecutive patients with acute ischemic stroke (62±11.54 years of age, 34.3% women) using prospectively maintained clinical databases and blood samples from local ischemic (proximal to thrombus) and systemic (femoral artery, self-control) arterial compartments. Levels of TAT, PIC, t-PAIC, and D-dimer were significantly elevated, whereas sTM was significantly reduced, in local ischemic regions compared with their systemic levels. Each 1-unit increase in ischemic TAT (adjusted odds ratio [aOR], 1.086 [95% CI, 1.03-1.145]; P=0.002; area under the curve [AUC], 0.833) and PIC (aOR, 1.337 [95% CI, 1.087-1.644]; P=0.006; AUC, 0.771) correlated significantly with higher symptomatic intracranial hemorrhage risk. Additionally, each 1-unit increase in ischemic TAT (aOR, 1.076 [95% CI, 1.016-1.139]; P=0.013; AUC, 0.797), PIC (aOR, 1.554 [95% CI, 1.194-2.022]; P=0.001; AUC, 0.798), and sTM (aOR, 0.769 [95% CI, 0.615-0.961]; P=0.021; AUC, 0.756) was significantly associated with an increased risk of an unfavorable 90-day outcome (modified Rankin scale of 3-6). These hemostatic molecules, individually or combined, significantly improved the predictive power of conventional risk factors, as evidenced by significant increases in net reclassification improvement and integrated discrimination improvement (all P<0.01). We observed a hyperactive state of the coagulation-fibrinolysis system within the local ischemic region during hyperacute stroke. Rapid automated measurement of hemostatic molecular markers, particularly TAT, PIC, and sTM, during intra-arterial procedures may provide additional information for stroke risk stratification and therapeutic decision-making, and warrants further investigation.

Abstract 13838: Hemostatic Disorder During Left Ventricular Assist Device Implantation in Swine

Introduction: Implantation of left ventricular assist devices (LVAD) conventionally requires the use of cardiopulmonary bypass (CPB). Among others, mechanical circulatory support devices favor intraoperative hemostatic disorder. Hypothesis: Despite the high risk of severe bleeding and thromboembolic complications, little is known about the intraoperative extent of hemostatic disorder during LVAD implantation.This study aimed to determine the extent of hemostatic disorder during LVAD implantation in a porcine model under CPB and LVAD support, separately. Methods: We performed LVAD implantation in 10 female German Landrace pigs (body weight 104 ± 13 kg). Blood samples were collected three times: at (1) Baseline, (2) after CPB and (3) after LVAD. For CPB, cannulation of the left jugular vein and right femoral artery was performed. After sternotomy and pericardiotomy, apical coring was performed under CPB. A continuous-flow LVAD with transventricular outflow graft was implanted. For CPB and LVAD, a flow rate of 3-7 L/min and a rotational speed of 4000 to 7200 rpm were aimed, respectively. Hemostatic laboratory markers from all times were compared by Wilcoxon signed rank test. Results: Compared to Baseline, CPB led to a significant decrease of fibrinogen and antithrombin as well as an increase of von Willebrand factor (vWF) ratio and D dimer (DD). Compared to after CPB, there was a continued decrease of antithrombin and an increase of DD, as well as a significant increase of vWF and vWF activity under LVAD support. Conclusion: Among others, CPB and LVAD separately contribute to hemostatic disorder during LVAD implantation. Human laboratory markers allowed early detection of intraoperative hemostatic changes in pigs. Further studies are needed to investigate whether off-pump LVAD implantation reduces perioperative hemostatic disorder.

PB1517 Effect of Uteroplacental Manipulation on Hemostatic Markers during Cesarean Delivery and Hysterectomy for Placenta Accreta Spectrum

PB1517 Effect of Uteroplacental Manipulation on Hemostatic Markers during Cesarean Delivery and Hysterectomy for Placenta Accreta Spectrum

Increased thromboinflammatory load in hereditary angioedema.

C1 inhibitor (C1Inh) is a serine protease inhibitor involved in the kallikrein-kinin system, the complement system, the coagulation system, and the fibrinolytic system. In addition to the plasma leakage observed in hereditary angioedema (HAE), C1Inh deficiency may also affect these systems, which are important for thrombosis and inflammation. The aim of this study was to investigate the thromboinflammatory load in C1Inh deficiency. We measured 27 cytokines including interleukins, chemokines, interferons, growth factors, and regulators using multiplex technology. Complement activation (C4d, C3bc, and sC5b-C9/TCC), haemostatic markers (β-thromboglobulin (β-TG), thrombin-antithrombin complexes (TAT), prothrombin fragment 1 + 2 (F1 + 2), active plasminogen activator inhibitor-1 (PAI-1), and the neutrophil activation marker myeloperoxidase (MPO) were measured by enzyme immunoassays. Plasma and serum samples were collected from 20 patients with HAE type 1 or 2 in clinical remission and compared with 20 healthy age- and sex-matched controls. Compared to healthy controls, HAE patients had significantly higher levels of tumour necrosis factor (TNF), interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-7, IL-9, IL-12, and IL-17A, chemokine ligand (CXCL) 8, chemokine ligand (CCL) 3, CCL4, IL-1 receptor antagonist (IL-1RA), granulocyte-macrophage colony-stimulating factor (GM-CSF), fibroblast growth factor (FGF) 2 and platelet-derived growth factor (PDGF)-BB. HAE patients also had higher levels of TAT and F1 + 2. Although granulocyte colony-stimulating factor (G-CSF), β-TG and PAI-1 were higher in HAE patients, the differences did not reach statistical significance after correction for multiple testing. In conclusion, C1Inh deficiency is associated with an increased baseline thromboinflammatory load. These findings may reflect that HAE patients are in a subclinical attack state outside of clinically apparent oedema attacks.

Association between fatty liver index and blood coagulation markers: a population-based study

BackgroundPopulation-based studies investigating the association between blood coagulation markers and non-alcoholic fatty liver disease (NAFLD) are rare. Thus, we aimed to investigate the relationship between the Fatty Liver Index (FLI) as a measure of hepatic steatosis and plasma concentrations of antithrombin III, D-dimer, fibrinogen D, protein C, protein S, factor VIII, activated partial thromboplastin time (aPTT), quick value and international thromboplastin time (INR) in the general population.MethodsAfter the exclusion of participants with anticoagulative treatment, 776 participants (420 women and 356 men, aged 54–74 years) of the population-based KORA Fit study with analytic data on hemostatic factors were included in the present analysis. Linear regression models were used to explore the associations between FLI and hemostatic markers, adjusted for sex, age, alcohol consumption, education, smoking status, and physical activity. In a second model, additional adjustments were made for the history of stroke, hypertension, myocardial infarction, serum non-HDL cholesterol levels, and diabetes status. In addition, analyses were stratified by diabetes status.ResultsIn the multivariable models (with or without health conditions), significantly positive associations with FLI were obtained for plasma concentrations of D-dimers, factor VIII, fibrinogen D, protein C, protein S, and quick value, while INR and antithrombin III were inversely associated. These associations were weaker in pre-diabetic subjects and largely disappeared in diabetic patients.ConclusionIn this population-based study, an increased FLI is clearly related to changes in the blood coagulation system, possibly increasing the risk of thrombotic events. Due to a generally more pro-coagulative profile of hemostatic factors, such an association is not visible in diabetic subjects.

Incident CHD and ischemic stroke associated with lipoprotein(a) by levels of Factor VIII and inflammation

Inflammation and coagulation may contribute to the increased risk for atherosclerotic cardiovascular disease (ASCVD) associated with high lipoprotein(a). The association of lipoprotein(a) with ASCVD is stronger in individuals with high versus low high-sensitivity C-reactive protein (hs-CRP), a marker of inflammation. Determine the association of lipoprotein(a) with incident ASCVD by levels of coagulation Factor VIII controlling for hs-CRP. We analyzed data from 6,495 men and women 45 to 84 years of age in the Multi-Ethnic Study of Atherosclerosis (MESA) without prevalent ASCVD at baseline (2000-2002). Lipoprotein(a) mass concentration, Factor VIII coagulant activity, and hs-CRP were measured at baseline and categorized as high or low (≥75th or <75th percentile of the distribution). Participants were followed for incident coronary heart disease (CHD) and ischemic stroke through 2015. Over a median follow-up of 13.9 years, there were 390 CHD and 247 ischemic stroke events. The hazard ratio (95%CI) for CHD associated with high lipoprotein(a) (≥40.1 versus <40.1 mg/dL) including adjustment for hs-CRP among participants with low and high Factor VIII was 1.07 (0.80-1.44) and 2.00 (1.33-3.01), respectively (p-value for interaction 0.016). The hazard ratio (95%CI) for CHD associated with high lipoprotein(a) including adjustment for Factor VIII was 1.16 (0.87-1.54) and 2.00 (1.29-3.09) among participants with low and high hs-CRP, respectively (p-value for interaction 0.042). Lp(a) was not associated with ischemic stroke regardless of Factor VIII or hs-CRP levels. High lipoprotein(a) is a risk factor for CHD in adults with high levels of hemostatic or inflammatory markers.

Study of C - reactive protein, D-dimer in correlation with HbA1C levels in patients with diabetes mellitus type 2

: Diabetes Mellitus is a chronic metabolic disease presented with chronic hyperglycemia, which causes abnormalities in the endothelial cells, proinflammatory state, altered platelet function &amp; plasma coagulation factors that lead to a hypercoagulable state &amp; thrombotic incidents. D-dimer is an indirect marker of thrombotic activity. C-reactive protein (CRP) is an important risk factor for systemic inflammation, so the present study aimed to determine the relationship between CRP, D-dimer in correlation with HbA1C in patients with Diabetes Mellitus. The present study is undertaken to evaluate the study of D-dimer, C-reactive protein in correlation with HbA1C levels in Type 2 Diabetes Mellitus. : A total of one hundred &amp; twenty subjects aged 30-70 years were included. The patients were selected from those who attended the medical OPD at Gandhi Medical College &amp; hospital, Secunderabad, &amp; their samples are analyzed by Beckmann Coulter Fully Automatic Analyzer AU5800. CRP is estimated by rate turbidimetry method &amp; D-dimer is estimated by rate turbidimetry method. HbA1C by HPLC in Bio-rad-D-10: The prospective of elevated D-dimer, CRP levels are in correlation with increased HbA1C levels. So screening of inflammatory &amp; hemostatic markers must be done in patients with uncontrolled Diabetes Mellitus.

Targeted Blood Plasma Proteomics and Hemostasis Assessment of Post COVID-19 Patients with Acute Myocardial Infarction

The molecular mechanisms underlying cardiovascular complications after the SARS-CoV-2 infection remain unknown. The goal of our study was to analyze the features of blood coagulation, platelet aggregation, and plasma proteomics in COVID-19 convalescents with AMI. The study included 66 AMI patients and 58 healthy volunteers. The groups were divided according to the anti-N IgG levels (AMI post-COVID (n = 44), AMI control (n = 22), control post-COVID (n = 31), and control (n = 27)). All participants underwent rotational thromboelastometry, thrombodynamics, impedance aggregometry, and blood plasma proteomics analysis. Both AMI groups of patients demonstrated higher values of clot growth rates, thrombus size and density, as well as the elevated levels of components of the complement system, proteins modifying the state of endothelium, acute-phase and procoagulant proteins. In comparison with AMI control, AMI post-COVID patients demonstrated decreased levels of proteins connected to inflammation and hemostasis (lipopolysaccharide-binding protein, C4b-binding protein alpha-chain, plasma protease C1 inhibitor, fibrinogen beta-chain, vitamin K-dependent protein S), and altered correlations between inflammation and fibrinolysis. A new finding is that AMI post-COVID patients opposite the AMI control group, are characterized by a less noticeable growth of acute-phase proteins and hemostatic markers that could be explained by prolonged immune system alteration after COVID-19.

Body Mass Index and Waist Circumference as Determinants of Hemostatic Factors in Participants of a Population-Based Study.

Background: In contrast to studies in patients, an association between obesity and blood coagulation factors has not been established in the population. If confirmed it could become a target for primary prevention. Objective: To investigate the relationship between Body Mass Index (BMI) and waist circumference (WC) with plasma concentrations of antithrombin III, D-dimers, fibrinogen D, protein S, factor VIII, activated partial thromboplastin time (aPTT), quick value, and international normalized ratio (INR) in the general population. Materials and Methods: Participants of the Cooperative Health Research in the Region of Augsburg (KORA) S4 study who took part in the KORA Fit follow-up (2018-2019, aged 54-74 years) examination were eligible. Citrate plasma samples were collected in fasted participants. After the exclusion of participants with anticoagulative treatment, 776 participants (420 women and 356 men) with analytic data on hemostatic factors were included in the present analysis. Linear regression models were used to explore the association between BMI or WC with hemostatic markers, adjusted for sex, age, alcohol consumption, education, smoking status, and physical activity. In a second model, additional adjustments were made for the prevalence of stroke, hypertension, myocardial infarction, serum non-HDL cholesterol, and serum triglycerides. Results: In the multivariable models (with or without health conditions), significant positive associations with BMI were obtained for plasma concentrations of D-dimers, factor VIII, fibrinogen D, protein S, and quick value, while INR and antithrombin III were inversely associated. Similar to BMI, WC was significantly associated with all hemostatic factors, except for aPTT. Conclusion: In this population-based study, both increasing BMI and WC affect the blood coagulation system. Thus, modification of a prothrombotic coagulation profile emerged as a potential target for primary prevention in obese subjects.

Dexmedetomidine induced hypotension and hemostatic markers.

The hemostatic system undergoes extensive alterations following surgical trauma leading to a hypercoagulable state. We assessed and compared the changes in platelet aggregation, coagulation, and fibrinolysis status during normotensive and dexmedetomidine-induced hypotensive anesthesia in patients undergoing spine surgery. Sixty patients undergoing spine surgery were randomly allocated into two groups: normotensive and dexmedetomidine-induced hypotensive groups. Platelet aggregation was assessed preoperatively, 15 min after induction, 60 min, and 120 min after skin incision, at the end of surgery, 2 h and 24 h postoperatively. Prothrombin time (PT), activated partial thromboplastin time (aPTT), platelet count, antithrombin III, fibrinogen, and D-dimer levels were measured preoperatively, 2 h and 24 h postoperatively. Preoperative platelet aggregation (%) was comparable between both groups. Platelet aggregation significantly increased intraoperative at 120 min after skin incision and postoperatively in the normotensive group compared to the preoperative value (P < 0.05) but it was insignificantly decreased during the intraoperative induced hypotensive period in the dexmedetomidine-induced hypotensive group (P > 0.05). Postoperative PT, aPTT significantly increased and platelet count, and antithrombin III significantly decreased in the normotensive group compared to the preoperative value (P < 0.05) but they were not significantly changed in the hypotensive group (P > 0.05). Postoperative D-dimer significantly increased in the two groups compared to the preoperative value (P < 0.05). Intraoperative and postoperative platelet aggregation significantly increased in the normotensive group with significant alterations of the coagulation markers. Dexmedetomidine-induced hypotensive anesthesia prevented the increased platelet aggregation that occurred in the normotensive group with better preservation of platelet and coagulation factors.

Prothrombin Time and Coagulation Factor IX as Hemostatic Risk Markers for Legg- Calvé-Perthes Disease.

Legg-Calvé-Perthes disease (LCPD) is a pediatric disorder that occurs due to the avascular necrosis of the femoral head and affects the range of motion of the hip in various degrees. Its etiology is still unknown, although it has been associated with coagulation abnormalities, however, the lack of reproducibility in the results in various studies has created a controversy as to whether hemostasis disorders are related to LCPD. On the other hand, there is little information on laboratory studies that could facilitate the diagnosis and treatment of LCPD. Blood and plasma samples were tested from 25 patients with LCPD and 50 healthy controls, matched by sex and age. Cellular markers were evaluated through complete blood count, as well as coagulation times, coagulation factors activity, antithrombotic proteins, and homocysteine concentration. After assessing activity value frequencies in each group, the results showed more significant activity in some of the biological risk markers of thrombophilia, presenting a substantial difference in prothrombin time↘, FV↗, FVIII↗, FIX↗, and Hcy↗. These values imply that there may be hypercoagulable states in patients, which can cause thrombotic events. Diminished prothrombin time and increase in FV activity, FVIII, FIX, and Hcy concentration support the hypothesis that microthrombi formation in small-caliber vessels could be causing avascularity and femoral necrosis, which are traits of LCPD. In addition, based on our results, we believe that the laboratory studies carried out are very useful in the diagnosis and treatment of LCPD.

Sepsis-induced Coagulopathy: The Different Prognosis in Severe Pneumonia and Bacteremia Infection Patients.

Sepsis-induced coagulopathy (SIC) is a critical condition in sepsis patients, with varying outcomes depending on the type of infection. This study aims to analyze the prognosis of different infections in SIC cohort. A retrospective cohort study was conducted on 525 patients diagnosed with SIC in the intensive care unit from December 2013 to December 2022. These patients were divided into four groups: a non-pneumonia or bacteremia group, a severe pneumonia group, a bacteremia group, and a severe pneumonia concomitant with bacteremia group. The 28-day mortality was 18% (49/271) in the other infections group, 31% (33/106) in the lung infections group, 23% (29/126) in the blood infections group and 36% (8/36) in the lung and blood co-infections group, respectively. Pearson correlation analysis showed that procalcitonin (PCT) correlated strongly with all detected hemostatic markers (p < 0.001). The 28-day mortality rate in Lung infections group was significantly higher (p = 0.019), while Blood infections group had a higher incidence of disseminated intravascular coagulation (p = 0.011). By multivariable model analyses, longer duration of ventilation (p = 0.039) and severe pneumonia (p = 0.040) are risk factors associated with mortality. Different infections, including Lung and Blood infections, indicated different conditions in vivo. Longer duration of ventilation is associated with mortality, while Lung infections indicated higher 28-day mortality rate.

Inflammation-mediated changes in haemostatic variables of pulmonary tuberculosis patients during treatment

Tuberculosis (TB) disease is usually marked by inflammation which is closely linked to haemostasis both in health and disease. Close monitoring of haemostatic response to inflammatory changes during treatment is important to improve TB management. Here we studied associations between haemostatic markers and inflammatory cytokines in 60 TB-infected individuals, aged 18–65 years who received anti-TB therapy. They were recruited before commencement of therapy and followed up till completion of therapy after 6-months. The TNF-α, IL-6, IL-2 (pro-inflammatory cytokines) and P-selectin, GP IIb/IIIa, thrombopoietin (haemostatic variables) were significantly increased at 2 month into therapy compared to pre-treatment values and decreased at 6 month into therapy. Also at 6 month into therapy in comparison to 2-month into therapy, there were significant increase in IL-10 and TGF-β (anti-inflammatory cytokines) as well as a significant decline in PF-4. There were significant positive correlations between GP IIb/IIIa and TNF-α, IL-6 and PSEL, IL-6 and TPO, PF4 and TGF-β. Conclusively, the changes in the TNF-α, IL-6, IL-2 aligned with changes in the levels of P-selectin, GP IIb/IIIa, and TPO in the course of TB therapy. This may suggest that the levels of inflammatory cytokines are linked to the levels of these haemostatic variables in TB individuals.