Coagulation Parameters Research Articles

Dysregulated Coagulation in Parkinson’s Disease

Parkinson’s disease (PD), a prevalent neurodegenerative disorder characterized by dopaminergic neuron degeneration and α-synuclein accumulation, has been increasingly associated with coagulation dysfunction. This review synthesizes emerging evidence linking dysregulated coagulation to PD pathophysiology. We examine the alterations in coagulation parameters, including elevated fibrinogen levels, impaired fibrinolysis, and platelet dysfunction, which collectively contribute to a hypercoagulable state in PD patients. Epidemiological studies have revealed a higher incidence of thrombotic events, such as deep vein thrombosis (DVT) and stroke, among PD patients, suggesting significant comorbidity between PD and coagulation disorders. This review explores the potential pathophysiological mechanisms underlying this association, focusing on the roles of inflammation and oxidative stress. Additionally, we discuss the limitations of current research and propose future directions. This comprehensive analysis underscores the importance of understanding the coagulation–neurodegeneration axis in PD, which may lead to novel diagnostic and therapeutic strategies for this debilitating condition.

Abstract 4134384: Sotagliflozin, a Dual Inhibitor of Sodium-Glucose Transporters 1 and 2, Elicits Cardioprotective Effects Through Attenuation of Platelet Activation and Thrombosis

Sodium-glucose cotransporter (SGLT) inhibitors are used in the treatment of type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). In the SCORED trial, sotagliflozin (SOTA), a dual SGLT1/2 inhibitor, demonstrated significant reductions in both myocardial infarction (MI) and stroke in patients with T2DM and CKD. These results suggest a cardiovascular (CV) benefit of SOTA in patients with T2DM and CKD who are at increased risk of thromboembolic disease. To investigate the underlying mechanism of CV protection, we evaluated the effects of SOTA on platelet activation and thrombus formation, in both in vivo and ex vivo models, to understand its effects on MI and stroke. Washed human platelets treated with SOTA were stimulated with various agonists and platelet activation was assessed via lumi-aggregometry and flow cytometry. In whole blood, SOTA was evaluated for its potential to reduce platelet adhesion and thrombus formation in the perfusion flow chamber and Total Thrombus formation Analysis System (TTAS) assays. In vivo , mice dosed with SOTA were assessed for thrombus formation at the site of injury in real-time in the cremaster arteriole injury model. To determine the effect of SOTA on hemostasis, we assessed coagulation parameters ex vivo in human whole blood using thromboelastography. Finally, bleeding time was measured in vivo in mice dosed with SOTA using the tail bleeding assay. In washed platelets, SOTA inhibits platelet activation and aggregation in a dose-dependent manner. Similarly, a dose-dependent decrease in platelet adhesion and thrombus formation was observed in whole blood assays. In vivo , platelet accumulation and fibrin formation were decreased in mice dosed with SOTA, however no effect is observed in coagulation parameters or bleeding time. SOTA inhibits platelet activation and thrombus formation with no impact on coagulation parameters or bleeding potential. These findings highlight a potential mechanism through which SOTA reduces the risk of stroke and MI in patients with T2DM and CKD, underscoring the importance of further investigation into the role of SOTA in CV protection, particularly in patients suffering from both T2DM and CKD at high risk of thromboembolic events.

THE IMPACT OF ANTICOAGULANTS ON COAGULATION PARAMETERS IN THE TREATMENT OF PATIENTS WITH COMMUNITY-ACQUIRED PNEUMONIA ASSOCIATED WITH COVID-19

The aim of the study was to evaluate the effect of anticoagulants on coagulation parameters in the treatment of patients with community-acquired pneumonia associated with coronavirus infection. Materials and methods. An open, prospective, observational study was conducted to achieve the research objectives. Between January 2021 and February 2022, 256 patients aged 40 to 65 years with community-acquired pneumonia were examined at the outpatient clinic of the Kherson City Clinical Hospital named after Athanasius and Olga Tropin of the Kherson City Council. Of these, 177 cases were associated with SARS-CoV-2, while 79 patients tested negative for coronavirus infection. Additionally, thirty-five healthy individuals were examined on an outpatient basis. After randomization, 143 hospitalized patients with severe community-acquired pneumonia associated with COVID-19 were divided into subgroups based on the anticoagulant used in their treatment regimen. The first subgroup consisted of 71 patients who received standard heparin infusions, while the second subgroup included 72 patients treated with enoxaparin. Results. The prothrombin time in the group of healthy volunteers was 12.60 [11.80; 13.30] seconds, and the median value was significantly higher by 13.5% compared to both the group of patients with community-acquired pneumonia associated with COVID-19 and the group without COVID-19 (p < 0.05). The median fibrinogen level in patients with COVID-19 and community-acquired pneumonia was 4.80 [4.50; 5.40] g/L, which did not significantly differ from the 4.60 [4.30; 5.40] g/L in the non-COVID-19 pneumonia group (p > 0.05). However, a significant difference was observed when compared to the healthy volunteer group, which had a fibrinogen level of 3.30 [2.50; 3.80] g/L (p < 0.05). After 72 hours of treatment, prothrombin time was significantly higher in the first subgroup (12.00 [11.00; 13.00] seconds) compared to the second subgroup (11.30 [10.00; 12.30] seconds) (p < 0.05). There was also a statistically significant difference in the international normalized ratio (INR) levels between the subgroups after 72 hours of treatment, with the first subgroup showing an INR of 1.20 [1.10; 1.30] U, versus 1.10 [1.00; 1.30] U in the second subgroup (p < 0.05). After 14 days of treatment, fibrinogen levels showed a statistically significant difference: 4.30 [4.10; 4.60] g/L in the first subgroup compared to 4.50 [4.30; 4.90] g/L in the second subgroup (p < 0.05). Conclusion. In patients with community-acquired pneumonia, blood coagulation parameters are disturbed, characterised by a decrease in prothrombin time and activated partial thromboplastin time, as well as an increase in total fibrinogen levels. After 72 hours, heparin demonstrated a more effective effect on prothrombin time and international normalised ratio compared to enoxaparin. When assessing the dynamics of coagulation parameters after 14 days, heparin was found as was more effective in reducing the level of total fibrinogen compared to enoxaparin.

Dabigatran attenuates methotrexate-induced hepatotoxicity by regulating coagulation, endothelial dysfunction, and the NF-kB/IL-1β/MCP-1 and TLR4/NLRP3 signaling pathways.

This study examines Dabigatran's (Dab) capacity to mitigate methotrexate (MTX)-induced coagulation disorders and endothelial dysfunction, while exploring its effects on oxidative stress and inflammatory pathways (NF-kB/IL-1β/MCP-1, TLR4/NLRP3) in reducing hepatotoxicity. Rats were assigned to four groups: a control group receiving saline intraperitoneally (i.p.); an MTX group with a single MTX dose (20 mg/kg, i.p.) to induce hepatotoxicity; and two pretreatment groups receiving Dab orally at 15 mg/kg and 25 mg/kg for seven days before and 4 days after MTX administration. MTX-treated rats showed significant increases in liver enzymes (ALT, AST, ALP) and reductions in antioxidant enzymes (SOD, GSH), along with elevated coagulation parameters (tissue factor (TF), thrombin, fibrin, plasminogen activator inhibitor-1 (PAI-1)), leading to coagulation disorders. Endothelial dysfunction was evident with reduced eNOS expression, while inflammation increased through elevated iNOS, ICAM-1, and pro-inflammatory cytokines (MPO, NF-kB, TNF-α, IL-1β, MCP-1), alongside activation of the TLR4/NLRP3 inflammasome pathway and decreased IL-10 (p < 0.05). Immunohistochemistry revealed increased cytochrome c and caspase-3 expression, with histopathological damage. Dabigatran mitigated these effects, downregulating liver enzymes, modulating coagulation factors, restoring eNOS levels, and reducing histopathological and inflammatory markers. Dabigatran demonstrates significant therapeutic potential in alleviating methotrexate-induced hepatotoxicity through its antioxidant, anti-inflammatory, anticoagulant, and anti-apoptotic effects. Its regulation of coagulation parameters and endothelial function suggests a protective role against tissue damage, warranting further investigation.

The Efficacy of Andexanet Alfa for the Reversal of Factor Xa Inhibitors Is Not Influenced by Hemodilution with Different Volume Expanders

Background: Andexanet alfa is a specific antidote for factor Xa (FXa) inhibitors. It is licensed to treat patients under FXa inhibitor therapy with life-threatening bleeding. Concomitantly, volume expanders are used to compensate for blood loss and maintain circulation. The competitive binding of andexanet to FXa inhibitors may be disrupted due to hemodilution, as shown by laboratory assays with high sample dilution. This study investigated the efficacy of andexanet for the reversal of FXa inhibitors under hemodilution. Methods: Blood from 10 healthy volunteers was anticoagulated with rivaroxaban and subsequently treated with four different volume expanders (Ringer’s solution, 4% gelatine, 5% and 20% human albumin (HA)) at two dilution levels (20% and 50%). After anticoagulation and hemodilution, andexanet was added according to the high-dose protocol. Blood samples were analyzed using a Russell’s viper venom (RVV) test on a Clot Pro® device, a thrombin generation assay, a fully automated coagulation analyzer and a chromogenic anti-FXa activity assay. Results: After anticoagulation, the median rivaroxaban concentration was 272 ng/mL (IQR 254–353). Anticoagulation with rivaroxaban caused a significant impairment of all coagulation parameters, which was further aggravated by hemodilution. After the administration of andexanet, coagulation parameters in anticoagulated samples were reversed to near baseline in all groups. Andexanet administration decreased the rivaroxaban plasma concentration in all groups to a median of &lt;10 ng/mL. In the anticoagulated, non-hemodiluted samples, anti-FXa activity was reduced by 98%. The anti-FXa activity in the anticoagulated, hemodiluted samples was reduced by approximately 96% in the 20% diluted samples and by about 93% in the 50% diluted samples. Conclusions: Our data indicate that FXa inhibitor reversal with andexanet is about 5% less effective with 50% hemodilution than in non-hemodiluted samples.

Enoxaparin Failure in Patient With Cerebral Venous Sinus Thrombosis and Prothrombin G20210A Mutation: Case Report.

Cerebral venous sinus thrombosis (CVST) is a rare, serious, and complex cerebrovascular disease. The prothrombin G20210A mutation is the second most common inherited thrombophilia and is considered to be one of the etiologies of CVST. The optimal heparinoid medication for treatment remains a topic of debate. This case report describes a young woman with CVST who did not respond to low-molecular-weight heparin (LMWH). The patient was initially treated with LMWH; however, her symptoms and clot burden in the sagittal sinus worsened, and coagulation studies showed no evidence of therapeutic anticoagulation despite good compliance. Unfractionated heparin was then initiated, and the patient's symptoms improved dramatically within 24 hours, along with the recanalization of the cerebral venous sinuses. Genetic testing revealed a heterozygous mutation in the prothrombin gene (G20210A). This mutation is a known risk factor for CVST. However, it is unclear why the patient did not respond to LMWH but responded appropriately to unfractionated heparin. This case report highlights the potential for LMWH resistance in patients with CVST and prothrombin gene mutations. These findings also emphasize the importance of close monitoring of coagulation parameters and clinical response in patients with CVST receiving LMWH.

Association Between Laboratory Coagulation Parameters and Postpartum Hemorrhage in Preterm and Term Caesarean Section: A Retrospective Analysis.

Background: Deranged antepartum laboratory parameters may be risk factors for postpartum hemorrhage (PPH). However, whether this is also valid in women who give birth prematurely is currently unknown. Methods: We performed a retrospective single-center study to assess the role of antepartum hemoglobin, platelet count, fibrinogen, activated partial thromboplastin time, and prothrombin time as risk factors for PPH following caesarean section. We defined PPH as documented blood loss of at least 1 L and/or transfusion of red blood cell concentrates. We stratified the included patients according to gestational age: extremely preterm (gestational age < 28 weeks), very preterm (gestational age between 28 and 32 weeks), late and moderate preterm (gestational age between 32 and 37 weeks), and term (gestational age ≥ 37 weeks). Results: We included 1734 patients, 112 (6%) of whom had PPH. In total, 19 patients (10%) were in the extremely preterm group, 13 patients (10%) were in the very preterm group, 44 patients (9%) were in the late and moderate preterm group, and 36 patients (4%) were in the term group. Hemoglobin predicted PPH in all gestational age groups. Platelet count was associated with PPH in term, but not in preterm patients. Fibrinogen was associated with PPH in late prematurity but not in term patients and not in patients with early or extreme prematurity. Conclusions: Antepartum hemoglobin was the only factor predicting PPH in preterm and term caesarean sections. Platelet count and fibrinogen concentration were associated with PPH in term and late prematurity, respectively, but not in earlier stages of prematurity.

Interdependence of coagulation with immunotherapy and BRAF/MEK inhibitor therapy: results from a prospective study

Immune checkpoint inhibitor (ICI) therapies effectively treat a broadening spectrum of cancer entities but induce various immune-related side effects (irAEs). Recent reports suggest a correlation between ICI-induced systemic inflammation and thromboembolic events as well as an increased effectiveness by coadministration of anticoagulants. With cancer patients having a higher risk of thrombotic events per se, it is crucial to dissect and characterize the mechanisms that cause pro-coagulative effects induced by systemic tumor therapies and their potential interplay with anti-tumor response. A total of 31 patients with advanced skin cancer treated with either ICIs (n = 24) or BRAF/MEK inhibitors (n = 7) were longitudinally assessed for blood and coagulation parameters before as well as 7, 20 and 40 days after initiation of systemic tumor therapy. Changes were analyzed and compared between both groups. In addition, the influence of coagulation parameters on progression-free, recurrence-free and overall survival was investigated. The ICI cohort presented significantly increased factor VIII activity after one week of therapy (p 0.0225); while, protein S activity was reduced during the whole observation period. Additionally, von Willebrand factor activity and tissue factor concentrations increased under immunotherapy. Similar changes occurred under BRAF/MEK inhibitor therapy (BRAF/MEKi). Increased baseline levels of von Willebrand factor antigen and factor VIII:C before the start of ICI therapy correlated with a significantly higher risk of recurrence for patients receiving adjuvant immunotherapy. The findings suggest the induction of a pro-coagulant state under ICI and BRAF/MEKi and a role of coagulation parameters in the efficacy of ICI therapies.

In vitro anticoagulant effects of Bungarus venoms on human plasma which are effectively neutralized by the PLA2-inhibitor varespladib.

Bungarus (krait) envenomings are well-known for their life-threatening neurotoxic effects. However, their impact on coagulation remains largely unexplored experimentally or clinically. This study, examined the effect of begins to examine venoms from four Bungarus species-B. caeruleus, B. candidus, B. fasciatus, and B. flaviceps on human platelet poor plasma coagulation parameters using thromboelastography and coagulation inhibition assays. B. flaviceps completely inhibited clotting, while B. caeruleus only delayed clot formation. In contrast, B. candidus and B. fasciatus did not affect clotting. Subsequent examinations into the anticoagulant biochemical mechanisms demonstrated divergent pathphysiological pathways. B. caeruleus venom anticoagulant effects were prevented by the addition of an excess of phospholipids, with anticoagulation thereby the result of phospholipid depletion. In contrast B. flaviceps anticoagulation was not affected by the addition of an excess of phospholipids. Further investigations demonstrated that B. flaviceps mediates its anticoagulant toxicity through the inactivation of coagulation enzymes. The anticoagulant effects of both B. flaviceps and B. caeruleus were nullified by varespladib, a phospholipase A2 (PLA2) inhibitor, revealing the toxin class involved. These results uncover previously unrecognized and unexplored anticoagulant effects of Bungarus venoms.

Effects of Variable Doses of Neurokinin B on Hematological and Coagulation Parameters in Adult Male Rats

Objective: To evaluate the dose-dependent effects of Neurokinin B on hematological and coagulation parameters in adult male Sprague Dawley rats. Study Design: Laboratory-based experimental study Place and Duration of Study: Gomal University and KMU Institute of Medical Sciences from February 2019 to April 2021. Methodology: Adult male Sprague Dawley rats (n=5 per group) were administered intraperitoneally with Neurokinin B at doses of 1 µg, 1 ηg and 1 ρg for 12 days consecutively. Control rats received distilled water injections. After 12 days, rats were sacrificed, and blood samples were collected from the left ventricle for hematological and coagulation analysis. Results: Bleeding time was significantly prolonged in NKB-µg (114±17.10sec) and Neurokinin B -ηg (72±22.25sec) compared to control (33±12.55sec). Clotting time (CT) was also increased (NKB-µg: 111±17.10sec; NKB-ηg: 69±17.10sec, control: 42±12.55sec), as did prothrombin time (PT) [NKB-µg: 93.60±10.92sec; NKB-ηg: 63.40±12.66sec, control: 15±4.12sec] and activated partial thromboplastin time (APTT) [NKB-µg: 94.80±14.04sec; NKB-ηg:68.60±13.74sec, control: 19.40±2.97sec]. Additionally, mean platelet volume [NKB-µg:8.94±0.36fl, control: 8.04±0.48fl] and leukocyte count (×103/µl) [NKB-µg: 12.14±0.69, control: 8.87±1.32] were significantly increased in NKB-treated animals compared to control. There was a significant increase in international normalized ratio in NKB-µg (6.86±0.80) and NKB-ηg (4.65±0.93) compared to control group (1.10±0.30). Conversely, platelet count (×103/µl) was decreased significantly in NKB-µg group (787.80±48.51) compared to the control group (960.60±58.71). Conclusion: NKB administration led to leukocytosis, thromboctopenia, and affected coagulation pathways with prolonged BT, CT, PT, APTT and INR dose-dependently.

Testosterone replacement has a beneficial effect on the hemostatic system by altered gene expression of coagulation factors

This study aimed to investigate the effects of testosterone replacement therapy on hemostasis and some procoagulant gene expression in mice. 42 mice were randomly divided into two groups of non-orchiectomized (non-ORX) and orchiectomized (ORX) with three subgroups (n = 7) each, were subcutaneously administered with sesame oil (control), 2 and 20 mg/kg/week testosterone enanthate. Orchiectomized mice were allowed to recover for one week before treatment. On the 7th week of treatment, blood samples were collected for coagulation parameters analysis and measurement of plasma testosterone levels. Moreover, quantitative real-time PCR analysis was performed on liver samples to assess the expression of factor IX, factor X, and prothrombin genes. The results showed that supraphysiological doses (20 mg/kg) of testosterone significantly increased plasma testosterone levels in all groups, while physiological doses (2 mg/kg) only increased testosterone levels in non-ORX animals. Although testosterone administration had no effect on prothrombin time (PT) and activated partial thromboplastin time (aPTT), supraphysiological doses reduced bleeding time and clotting time. Furthermore, platelet count increased in a dose-dependent manner with testosterone enanthate treatment. The expression of coagulation factors was also decreased with supraphysiological doses of testosterone. In conclusion, testosterone had significant effects on primary hemostasis and common coagulation pathway, including increased platelet number and aggregation, decreased clotting time, and altered gene expression of coagulation factors.

Evaluation of some haematological and coagulation profiles of occupationally heat stress individuals of bakery industries in Kano, Nigeria

Bakers are exposed to heat stress in their work places, which can result in a variety of outcomes ranging from mild heat cramps to heat stroke. There is paucity of published data on the wallop of heat stress on haematologic and haemostatic parameters of individuals occupationally exposed to heat stress from bakery industries. This study attempted to evaluates some haematological and coagulation parameters of bakery workers who are occupationally exposed to heat stress in the baking industries. One hundred (100) individuals who consented to participate among which are: 70 bakers and 30 non-bakers were enrolled into the study. Blood samples were obtained using aseptic venepuncture and assessed for haematologic and haemostatic parameters by Haematology-analyser for full blood count parameters and manual standard coagulation method for Prothrombin time (PT) and activated partial thromboplastin time (aPTT) respectively. The data obtained was analyzed using IBM SPSS version 23. The results are presented as mean and standard deviation and p-value was set at ≤0.05as statistically significant. Platelets, red and white blood cells counts and their indices were counted along with some coagulation parameters (PT and aPTT). A statistically significant increase (p≤0.05) in platelets counts were observed in bakers compared with controls. Similarly, some coagulation parameters were found to be reduced and was statistically significant (p≤0.05) in bakers compared with non bakers as controls. The findings of the study showed insignificant changes in haematologic parameters coupled with altered coagulation parameters. This may be suggestive that individuals occupationally exposed to heat stress are prone to hypercoagulable state and its attending consequences.

Thrombin generation, fibrin clot permeation and lysis in patients with severe mitral regurgitation undergoing transcatheter edge-to-edge mitral valve repair: mitral fibrin study

Abstract Background/Introduction The management of heart failure (HF), particularly in the context of reduced ejection fraction, is further complicated by an increased risk of thromboembolic events. Structural alterations of both left ventricle and mitral valve contribute to mitral regurgitation (MR). However, the body of evidence provides inconclusive insights into the relationship between MR and thromboembolic risk. Purpose This study aimed to investigate the impact of transcatheter edge-to-edge repair (TEER) on thrombin generation, clot permeation and clot lysis time in HF patients with severe MR eligible for mitral TEER. Methods A cohort of 31 HF patients with severe MR undergoing TEER underwent systematic evaluation at three time points. Coagulation parameters, including fibrinogen concentration, thrombin generation, fibrin clot permeability (Ks), and clot lysis time (CLT), were assessed. Comprehensive evaluations also covered echocardiographic, laboratory, and clinical parameters. Results TEER induced changes in fibrinogen levels (p=0.009, visit 3 vs. visit 2) and improved fibrin clot properties over a 50-day follow-up (Ks, p=0.005, visit 3 vs. visit 2). No significant differences were observed among time points in analyzed blood clot parameters. Linear regression, incorporating thrombin generation variables, Ks, and CLT for delta NT-proBNP, highlighted CLT as the sole predictor of NT-proBNP change between visit 2 and visit 1 (p=0.03; R2=0.18). Conclusions MR reduction through TEER led to transient alterations in fibrinogen concentration and improved fibrin clot characteristics. Additionally, baseline CLT emerged as a significant predictor of early NT-proBNP reduction, emphasizing its role as a key indicator of the hemodynamic response to TEER.

Decreased Circulating Red Cell Mass Induced by Intravenous Acepromazine Administration Alters Viscoelastic and Traditional Plasma Coagulation Testing Results in Healthy Horses.

Coagulopathy is common in equine critical illness, with its early recognition being crucial for patient management and prognosis. In vitro viscoelastic (VE) hypercoagulability with decreased RCM/PCV has been demonstrated in dogs but not horses. Our objective was to evaluate the effects of acepromazine-induced (0.1 mg/kg IV) decreased RCM on VE and plasma coagulation parameters using a prospective interventional study of eight adult horses. Complete blood count (CBC), fibrinogen, prothrombin time (PT), partial thromboplastin time (PTT), packed cell volume (PCV), total solids (TS), and VCM Vet™ VE testing performed at baseline (T0), 1 h (T1), and 12 h (T2) post acepromazine administration. Splenic volume was determined ultrasonographically. The results were analyzed using one-way repeated measures ANOVA with Tukey's post hoc HSD test to determine the effect of time (sample). PCV decreased 13% points following acepromazine administration from T0 to T1 (p < 0.001), remaining decreased at T2 (p < 0.001). Splenic volume increased from T0 to T1 (p = 0.04) and was not different from baseline at T2. Maximal clot formation (MCF) increased from T0 (p = 0.03). PTT decreased from T0 to T1 and increased at T2 (p = 0.03). No other coagulation parameters were significantly altered. This study demonstrates a non-inflammatory acute model of anemia in horses that impacts VE and plasma-based testing.

Direct IL-6 inhibition prevents arterial thrombosis by reducing collagen-mediated platelets activation

Abstract Introduction Interleukin 6 (IL-6) has a pivotal role in atherothrombosis. Yet, targeting IL-6 to prevent atherothrombotic events still requires validation of efficacy and safety. The recent phase 2 RESCUE trial reported that direct inhibition of IL-6 ligand by the monoclonal antibody (mAb) Ziltivekimab is safe in patients with elevated cardiovascular risk. Purpose This project investigated the effects of direct IL-6 inhibition on arterial thrombosis, and assessed the underlying cellular mechanisms. Methods Three month old C56Bl/6 male mice received very-low dose LPS i.p. for 4 weeks. During the last week they were randomized to receive in addition either anti-mouse IL-6 mAb 200 μg i.p. every other day or IgG1 isotype control. Then thrombosis of left common carotid artery (LCCA) was induced by laser injury under anesthesia. Platelets of treated mice were isolated and stimulated with either adenosine di-phosphate (ADP), collagen-related peptide (CRP) or thrombin receptor activating peptide (TRAP). Platelets activation was measured by flow-cytometry, as expression of P-selectin and JON/A.The effect of direct IL-6 inhibition was confirmed in patients with stable coronary artery disease (sCAD) by ex-vivo incubation of isolated platelets with either anti-human IL-6 mAb 1.5 μg/mL or IgG1 isotype control. Platelet activation was measured by flow-cytometry, as expression of P-selectin. Results Mice treated with anti-IL6 antibody displayed a significantly longer time-to-occlusion after the LCCA (Figure 1), without any significant difference in coagulation parameters. After stimulation with CRP, platelets were significantly activated in control mice, but not in mice treated with anti-IL6 mAb. Similarly, activation of isolated platelets from patients with sCAD was significantly reduced (Figure 2) by the ex-vivo treatment with anti-IL6 mAb. Conclusion The direct inhibition of IL-6 reduces platelets reactivity to collagen, thereby blunting arterial thrombosis upon endothelial damage. These results provide a potential mechanism to explain the reduction of cardiovascular risk associated to direct IL-6 inhibition. Conclusion The direct inhibition of IL-6 reduces platelets reactivity to collagen, thereby blunting arterial thrombosis upon endothelial damage. These results provide a potential mechanism to explain the reduction of cardiovascular risk associated to direct IL-6 inhibition.Figure 1Figure 2

Is it useful to washing stored red blood cells in cardiopulmonary bypass priming fluid for neonatal cardiac surgery

Abstract Background The small blood volume and immature physiology of neonates necessitate careful consideration of the priming fluid composition during cardiopulmonary bypass (CPB) surgery, as it has a substantial impact on their physiologic stability. This study aimed to investigate the impact of allogeneic stored RBCs processed by an autotransfusion system into the CPB priming fluid for neonatal cardiac surgery. Methods This retrospective cohort study investigated the effects of incorporating unwashed (n=56) or washed (n=45) RBCs into the CPB priming fluid for elective neonatal cardiac surgery. We compared perioperative blood parameters, inflammatory mediators, coagulation indicators, vasoactive inotrope score (VIS), other relevant blood parameters and clinical outcomes between the two groups. The regression models were employed to evaluate the independent association between RBCs washing and prognostic outcomes. Results The autotransfusion system can effectively improve the quality of stored RBCs. During CPB, washed group exhibited higher peak hematocrit (P &amp;lt; 0.01), peak hemoglobin (P = 0.04), increased oxygen delivery index during rewarming (P &amp;lt; 0.05). The washed group exhibited significantly lower early postoperative lactate levels and VIS scores (P &amp;lt; 0.05). Despite demonstrating fluctuations in inflammatory (IL-6, IL-8, IL-10）and coagulation parameters(DD, FIB, FDP) compared to baseline, the two groups exhibited no significant divergence. Notably, the washed group experienced a lower incidence of hyperlactacidemia and delayed sternal closure at weaning from CPB. Conclusions The addition of washed allogeneic stored RBCs to neonatal CPB priming fluid significantly attenuated postoperative lactate elevation and lowered VIS without improving early alterations in the inflammatory and coagulation systems.

Time-Dependent Association of Preinjury Anticoagulation on Traumatic Brain Injury-Induced Coagulopathy: A Retrospective, Multicenter Cohort Study

BACKGROUND AND OBJECTIVES: The impact of preinjury anticoagulation on coagulation parameters over time after traumatic brain injury (TBI) has remained unclear. Based on the hypothesis that preinjury anticoagulation significantly influences the progression and persistence of TBI-induced coagulopathy, we retrospectively examined the association of preinjury anticoagulation with various coagulation parameters during the first 24 hours postinjury in 5 periods. METHODS: Data from the Japanese registry of patients with TBI aged ≥65 years admitted between 2019 and 2021 were used. Time since injury was classified into 5 categories through a graphical analysis of coagulation parameters. We examined the association between preinjury anticoagulation and the platelet count, prothrombin time-international normalized ratio (PT-INR), activated partial thromboplastin time (APTT), D-dimer level, and fibrinogen level during each period by analysis of covariance using 10 clinical factors as confounding factors. RESULTS: Data from 545 patients and 795 blood tests were analyzed. The patients' mean age was 78.9 years, and 87 (16%) received anticoagulation therapy. The preinjury anticoagulation group had significantly greater Rotterdam computed tomography scores and poorer outcomes at discharge than the control group, with significantly lower D-dimer levels and higher fibrinogen levels. Analysis of covariance revealed significant associations between the D-dimer level and preinjury anticoagulation within 2 to 24 hours postinjury, APTT and preinjury anticoagulation within 1 to 24 hours, and PT-INR and preinjury anticoagulation throughout all periods up to 24 hours postinjury. CONCLUSION: Despite more severe TBI signs and poorer outcomes, the preinjury anticoagulation group had significantly lower D-dimer levels, especially within 2 to 24 hours postinjury. Thus, D-dimer levels during this period may not reliably represent TBI severity in patients receiving anticoagulation therapy before injury. Preinjury anticoagulation was also associated with an elevated PT-INR and prolonged APTT from early to 24 hours postinjury, highlighting the importance of aggressive anticoagulant reversal early after injury.

Dan’e fukang decoction reduces hemorrhage in a rat model of mifepristone induced incomplete abortion and may correlate with cell adhesion molecule signaling interference

Ethnopharmacological relevanceDan’e fukang decoction (DFD) is a traditional Chinese medicine formula. DFD obtains 10 herbs, including Salvia yunnanensis C.H.Wright (Zidanshen), Curcuma zedoaria (Christm.) Roscoe (Ezhu), Angelica sinensis (Oliv.) Diels (Danggui), Cyperus rotundus L. (Xiangfuzi), Corydalis yanhusuo (Y.H.Chou & Chun C. Hsu) W.T.Wang ex Z.Y.Su & C.Y.Wu, Bupleurum marginatum Wall. ex DC. (Yanhusuo), Sparganium stoloniferum (Buch.-Ham. ex Graebn.) Buch.-Ham. ex Juz. (Sanleng), Panax notoginseng (Burkill) F.H.Chen (Sanqi), Paeonia lactiflora Pall. (Shaoyao) and Glycyrrhiza uralensis Fisch. (Gancao). DFD is now clinically used for the treatment of menstrual irregularities, dysmenorrhea and menstrual discomfort caused by blood stasis and easing of endometriosis. Based on this, it is reasonable to presume that DFD may be effective in treating incomplete abortion and reducing postpartum bleeding, but no specific studies have been reported so far. Aim of the studyTo investigate the efficacy of Dan’e fukang decoction (DFD) in reducing prolonged vaginal bleeding followed by mifepristone induced incomplete abortion and explore the mechanisms of action of DFD in treating incomplete abortion. MethodsAn incomplete abortion model of rat was established by single intragastrically administered 8.5 mg/kg mifepristone on the 7th day of pregnancy. From the 8th day of pregnancy, the abortive rats were administered solvent, a positive control drug, or different doses of DFD, respectively for seven consecutive days. The efficacy of DFD was assessed by measuring the vaginal bleeding volume of the rats. Four coagulation parameters and platelet counts were measured. Hematoxylin and eosin (HE) staining was performed to evaluate pathological changes in the uterine embryos. Serum levels of progesterone and estrogen were measured using ELISA. Network pharmacology and transcriptomics were used to predict potential targets and pathways for DFD to reduce hemorrhage. The levels of mRNA related to cell adhesion molecules (CAMs) were detected by RT-qPCR. The levels of progesterone and estrogen receptors and the proteins associated with CAMs pathway in uterine tissues were detected by Western Blot. ResultsDFD significantly reduced the volume of vaginal bleeding of the abortive rats and significantly downgraded the pathological scores of uterine embryos. DFD significantly increased serum levels of E2, and had no impact on serum levels of P4 and the protein expression of ER and PR in the uteri of the abortive rats. Pathways in cancer, lipid, focal adhesion and immune-related signaling were predicted to be influenced by DFD via the analysis of network pharmacology. The CAMs signaling was found the most critical pathway regulated by both mifepristone and DFD via RNA-seq assay, followed by axon guidance, basal cell carcinoma, hippo signaling pathway and neuroactive ligand-receptor interaction. Combining the two analytical methods, ICAM-1 was predicted likely the key targeted gene by DFD. Finally, DFD was validated to decrease the protein expression of ICAM-1, ITGB2, ITGB7 and RASSF5 in the uterine tissues, which correlated to suppress the CAMs signaling pathway. ConclusionDFD significantly reduced hemorrhage. DFD significantly increased the serum levels of E2 and inhibited CAMs signaling pathway, which was likely to be involved in the mechanism of action of DFD facilitating residual uterine embryo expulsion in the rat model of incomplete abortion.

The role of post-traumatic antifibrinolysis in the perioperative blood management of elderly patients with intertrochanteric fractures treated with PFNA: A randomised controlled trial

BackgroundThis study aimed to evaluate the efficacy and safety of posttraumatic antifibrinolytic therapy with repeated doses of intravenous tranexamic acid (IV-TXA) in reducing perioperative hidden blood loss (HBL) in elderly intertrochanteric femur fracture (IFF) patients. Method112 elderly IFF patients who were admitted to our department from March 2020 to May 2021 were randomized to receive 100 ml of normal saline (Control group) or 1.5 g of TXA (TXA group) intravenously q12 h from postadmission day 1 (PAD1) to PAD3. Hemoglobin (Hb), hematocrit (Hct), fibrinogen degradation product (FDP), D-dimer (D-D), and coagulation parameters were recorded from PAD1 to postoperative day 3 (POD3). HBL was calculated using the gross formula and recorded as the primary outcome. ResultThe patients in TXA group had lower preoperative hidden blood loss(HBL), decline of hemoglobin(ΔHb), FDP (on PAD3), and D-D (on PAD3) compared with control group, while no difference was found in postoperative HBL, postoperative ΔHb and allogeneic blood transfusion (ABT) rate. In subgroup analyses, it was observed that patients who received the intervention within 24 h of injury and between 24 and 72 h of injury exhibited significantly lower preoperative HBL and ΔHb in the TXA group compared with the control group. Furthermore, the reduction in HBL and ΔHb was more pronounced in the former group. While for patients who received the intervention beyond 72 h after injury, no significant differences were observed in preoperative HBL and ΔHb between the two groups. Similarly, no significant differences were noted in postoperative HBL and ΔHb between the TXA and control groups across all subgroups. Additionally, no significant differences were identified in the incidence of venous thromboembolism (VTE) and mortality within one year between the two groups. ConclusionPost-traumatic antifibrinolytic therapy with repeated doses of intravenous TXA is effective and safe in reducing perioperative HBL for elderly IFF patients, especially for patients injured within 24 h.

The Importance of Coagulation Parameters in Predicting Preterm Birth

The Importance of Coagulation Parameters in Predicting Preterm Birth