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- Chacma baboon natural anticoagulants and factor VIII activities: implications for thrombin generation and haemostatic disease models (Exhibition Hall) - May 17, 2024 - Abstract #ISTH2024ISTH_1001;
APC (baboon: 111
- rivaroxaban / Generic mfg.
New coagulation factor V mutant for measurement of protein S activity (Exhibition Hall) - May 17, 2024 - Abstract #ISTH2024ISTH_998;
We measured 160 plasma samples purposively selected from the Biobank of the National Cerebral and Cardiovascular Center. The correlation between the FVm-cleavage PS activities and free PS antigen levels was the relatively weak (R2=0.378).
- SR604 / Equilibra Biosci
Safety and efficacy of anti-human activated protein C antibody SR604 for prophylaxis of congenital factor deficiencies (Exhibition Hall) - May 17, 2024 - Abstract #ISTH2024ISTH_997;
SR604 exhibited prophylactic and therapeutic efficacy in the tail bleeding and knee injury models of hemophilia A and B mice expressing human APC (humanized hemophilia mice). SR604 did not interfere with the cyto-protection and endothelial barrier function of APC nor have obvious toxicity effects in humanized hemophilia mice.
- ASSESSMENT OF THROMBIN GENERATION TEST USING ST-GENESIA () - May 15, 2024 - Abstract #EHA2024EHA_3307;
Also 50 control specimens wereanalyzed. Table 1 shows the results obtained for the various TGT-TS parameters assayed and patientcharacteristics in both groups.
- IMPACT OF LABORATORY MARKERS AND CARDIOVASCULAR RISK FACTORS ON THROMBOSIS IN ESSENTIAL THROMBOCYTHEMIA () - May 15, 2024 - Abstract #EHA2024EHA_2878;
Cardiovascular risk factors and hyperlipoproteinemia significantly influencethe occurrence of thrombotic complications at diagnosis, especially arterial thrombosis. White blood cell count,platelet count, genetic mutations for inherited thrombophilia, and other markers of thrombophilia did not havea role in the occurrence of thrombotic complications during follow-up in our group of patients with ET.
- Identification of pro-and anticoagulant mechanisms of thrombin formation in patients with multiple myeloma (Grand Hall) - May 9, 2024 - Abstract #ISLH2024ISLH_68;
In MM patients, APC had no inhibitory effect on thrombin generation. However, isolated monoclonal IgG was found to be capable of inhibiting both thrombin and fibrin formation.
- ||| hydrocortisone / Generic mfg.
P3 data, Journal: Hydrocortisone plus fludrocortisone for community acquired pneumonia-related septic shock: a subgroup analysis of the APROCCHSS phase 3 randomised trial. (Pubmed Central) - May 2, 2024
P3
Although a large proportion of patients with CAP also met criteria for ARDS, the subgroup analysis was underpowered to fully discriminate between ARDS and CAP modifying effects on mortality reduction with corticosteroids. There was no evidence of a significant treatment effect of corticosteroids in the non-CAP subgroup.
- || Review, Journal: Thrombin Generation Assay in Antiphospholipid Antibodies Positive Subjects as a Personalized Thrombotic Risk Assessment: State of the Art and Perspectives. (Pubmed Central) - May 1, 2024
Only one prospective cohort had investigated the prognostic impact of APC resistance in aPL?+?subjects, with a positive and significant correlation between APC sensitivity and the risk of thrombosis during the follow up (hazard ratio, 6.07 [95% CI, 1.69-21.87]). APC resistance assessed with TGA could be associated with thrombotic events in aPL?+?subjects.
- Donesta (estetrol) / Mithra, Pantarhei
Safety, compliance and pharmacokinetics of E4/DRSP in post-menarchal female adolescents (ROOM 0A) - Apr 29, 2024 - Abstract #ESCRH2024ESCRH_124;
P3
APC resistance assessed with TGA could be associated with thrombotic events in aPL?+?subjects. This study will provide crucial insights into E4/DRSP's safety, compliance, and bleeding profiles in post-menarchal adolescents, commonly prescribed COC for non-contraceptive purposes.
- estradiol valerate / Generic mfg.
Is there a physiological explanation to VTE risk observed in epidemiological studies? (ROOM 0B) - Apr 29, 2024 - Abstract #ESCRH2024ESCRH_40;
A significant portion of the analysis is dedicated to contrasting contraceptives containing EE with those comprising estradiol (E2) or estradiol valerate (E2V), suggesting that natural estrogens may offer a reduced risk of VTE, due to their lower impact on hepatic protein synthesis...The clinical and ethical considerations in the prescription of COCs will be addressed, advocating for informed patient decisions and highlighting the potential of newer estrogen compounds, such as E2 and E4 containing pills, in diminishing thrombotic risks. The imperative for post-authorization safety studies (PASS) to monitor novel COCs is challenged and the call for a reevaluation of COC classifications based on the most recent scientific evidence are emphasized, indicating the continual need for vigilance in enhancing contraceptive safety.
- | Journal: Study on the active components and mechanism of Atractylodis Macrocephalae Rhizoma for invigorating the spleen and tonifying qi based on spectrum-effect relationship and network pharmacology. (Pubmed Central) - Apr 25, 2024
In summary, our study has identified the primary active components associated with the efficacy of AMR and has provided an initial exploration of its mechanism of action. This offers a theoretical foundation for future investigations into the material basis and molecular mechanisms underlying the pharmacodynamics of AMR.
- | tamoxifen / Generic mfg.
Observational data, Journal: Hemostatic imbalance induced by tamoxifen in estrogen receptor-positive breast cancer patients: An observational study. (Pubmed Central) - Apr 23, 2024
This observational study showed that patients in remission from ER+ breast cancer taking tamoxifen had altered thrombin generation, as well as an acquired APC resistance. Moreover, this is the first study using the validated ETP-based APC resistance assay in tamoxifen-treated patients.
- | Journal: Activated protein C-released endothelial extracellular vesicles: A potential mechanism for their cytoprotective effects. (Pubmed Central) - Apr 19, 2024
Our study demonstrates that the cytoprotective effects of APC-released EVs are independent of APC. APC-released EVs carry anti-inflammatory microRNAs in their cargo.
- | Journal: In-depth structure-function profiling of the complex formation between clotting factor VIII and heme. (Pubmed Central) - Apr 17, 2024
APC-released EVs carry anti-inflammatory microRNAs in their cargo. Our study provides not only novel molecular insights into the FVIII-heme interaction and its physiological relevance, but also strongly suggests the reduction of the intrinsic pathway and the accentuation of the final clotting step (by, for example, fibrinogen crosslinking) in hemolytic conditions as well as a future perspective in the context of FVIII substitution therapy of hemorrhagic events in hemophilia A patients.
- || Review, Journal: The natural anticoagulant protein S; hemostatic functions and deficiency. (Pubmed Central) - Apr 15, 2024
This paper will provide an in-depth review of the molecular structure of protein S and its hemostatic effects. Furthermore, we shall address the insufficiency of protein S and its methods of diagnosis and treatment.
- || Review, Journal: Endothelial Protein C Receptor and Its Impact on Rheumatic Disease. (Pubmed Central) - Apr 13, 2024
Rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus are autoimmune/inflammatory conditions that are associated with elevated EPCR levels and disease activity, potentially driven by EPCR. This review highlights the functions of EPCR and its contribution to rheumatic diseases.
- | Biomarker, Journal: Fibrinolysis biomarker, thrombin, and activated protein C level alterations after coagulation activation depend on type of thrombophilia and clinical phenotype. (Pubmed Central) - Mar 15, 2024
rFVIIa-induced thrombin formation is associated with fibrinolysis parameter changes outlasting the concomitant anticoagulant response. Both correlate with thrombosis history in FV Leiden and might help explain its variable clinical expressivity.
- || Review, Journal: Deficiency of protein C or protein S as a possible cause of osteoporosis. (Pubmed Central) - Mar 14, 2024
Moreover, when secondary causes of protein C and S deficiency are also considered, the proportion likely further increases. In this paper, we discuss the pathophysiological background of the potential relationship between protein C and S deficiency and the genesis of osteoporosis.
- | Visanne (dienogest) / Mochida, Bayer
Journal: The effects of dienogest and combined oral contraceptives on protein S-specific activity in endometriosis patients. (Pubmed Central) - Mar 13, 2024
The effects of DNG on protein S were negligible, though both total protein S activity and antigen levels decreased soon after COC treatment began and remained low. As there was no VTE event during the study, further studies with larger numbers of patients will be needed to confirm that protein S-specific activity can be a surrogate maker of VTE risk.
- | Donesta (estetrol) / Mithra, Pantarhei
Journal: Low thrombin generation in postmenopausal women using estetrol. (Pubmed Central) - Mar 13, 2024
P2
As there was no VTE event during the study, further studies with larger numbers of patients will be needed to confirm that protein S-specific activity can be a surrogate maker of VTE risk. After 12?weeks of treatment, all treatment groups showed a mean thrombogram (
- | Journal: Single-Cell RNA-seq reveals transcriptomic modulation of Alzheimer's disease by activated protein C. (Pubmed Central) - Mar 6, 2024
burden and improved cognitive function of 5xFAD mice. The downregulation of highly expressed AD biomarkers in 5xFAD could provide insight into the mechanisms by which APC administration benefits AD.
- | Journal: Activated protein C and free protein S in patients with mild to moderate bleeding disorders. (Pubmed Central) - Mar 4, 2024
The downregulation of highly expressed AD biomarkers in 5xFAD could provide insight into the mechanisms by which APC administration benefits AD. Our data demonstrate increased antigen levels of APC in BDUC, which might contribute to the bleeding tendency in some patients and could be a future therapeutic target in BDUC.
- INTRINSIC XASE LIGAND INTERACTIONS IMPACT FVIIIA REGULATION (Sheraton Ballroom I-II; Virtual) - Mar 2, 2024 - Abstract #THSNA2024THSNA_184;
Our data demonstrate increased antigen levels of APC in BDUC, which might contribute to the bleeding tendency in some patients and could be a future therapeutic target in BDUC. These data suggest that both A2-domain dissociation and APC cleavage meaningfully contribute to FVIIIa regulation under physiologic conditions and highlight the potential benefit of FVIII transgenes resistant to inactivation for HA gene therapy.
- UNRAVELING THE ANTICOAGULANT FUNCTIONS OF FV USING MONOCLONAL ANTIBODIES (Sheraton Ballroom IV-V; Virtual) - Mar 2, 2024 - Abstract #THSNA2024THSNA_61;
pathways and are useful tools to better investigate the anticoagulant properties of FV. These antibodies may be useful for rebalancing coagulation via FV
- VGA039 / Vega Therap
PROPHYLACTIC TREATMENT OF ACQUIRED VON WILLEBRAND DISEASE IN NON-HUMAN PRIMATES WITH VGA039, AN ANTI-PROTEIN S MONOCLONAL ANTIBODY (Chicago Ballroom VII; Virtual) - Mar 2, 2024 - Abstract #THSNA2024THSNA_55;
Efficacy of VGA039 was demonstrated in a novel NHP model of acquired VWD. This proof-of-concept study supports clinical evaluation of VGA039 for the treatment of VWD.
- | Journal: Factor V variants in bleeding and thrombosis. (Pubmed Central) - Feb 26, 2024
In particular, we discuss our current understanding of the 3 main pathological conditions related to FV, namely FV deficiency, activated protein C resistance, and the overexpression of FV-short, a minor splicing isoform of FV with tissue factor pathway inhibitor ?-dependent anticoagulant properties and an emerging role as a key regulator of the initiation of coagulation. Finally, we summarize relevant new data on this topic presented during the 2023 ISTH Congress.
- bleomycin / Generic mfg.
Potential Role of Extracellular Vesicles in the Pathogenesis of Pleural Fibrosis (San Diego Convention Center, Area E (Hall A-B2, Ground Level)) - Feb 20, 2024 - Abstract #ATS2024ATS_2068;
It reveals novel pathways that promote EV generation, the potential role of EVs in angiogenesis and the mesenchymal transition of diverse cell types. These new insights may offer future therapeutic applications.
- | 3K3A-APC / ZZ Biotech
Preclinical, Journal: Endothelial Protein C Receptor and 3K3A-Activated Protein C Protect Mice from Allergic Contact Dermatitis in a Contact Hypersensitivity Model. (Pubmed Central) - Jan 31, 2024
3K3A-aPC reduced CHS severity in wild-type and EPCRKO mice by suppressing immune cell infiltration/activation and inflammatory cytokines. In summary, EPCRKO exacerbated CHS, whereas 3K3A-aPC could reduce the severity of CHS in both EPCRKO and wild-type mice.
- | Journal: Neuroprotective Effects of Noncanonical PAR1 Agonists on Cultured Neurons in Excitotoxicity. (Pubmed Central) - Jan 31, 2024
In summary, EPCRKO exacerbated CHS, whereas 3K3A-aPC could reduce the severity of CHS in both EPCRKO and wild-type mice. Both APC and AP9 reduced the dysregulation of intracellular calcium homeostasis in cultured neurons induced by excitotoxic Glu (100
- | 3K3A-APC / ZZ Biotech
Preclinical, Journal: A recombinant signalling-selective activated protein C that lacks anticoagulant activity is efficacious and safe in cutaneous wound preclinical models. (Pubmed Central) - Jan 29, 2024
However the female pigs exhibited transient and mild local reactions after treatments in week three, which did not impact healing. Overall these preclinical studies support the hypothesis that 3K3A-APC merits future human wound studies.
- || Review, Journal: Neuroprotection during Thrombectomy for Acute Ischemic Stroke: A Review of Future Therapies. (Pubmed Central) - Jan 27, 2024
Sedation and blood pressure management in endovascular thrombectomy also play crucial roles in improved stroke outcomes. A hand-in-hand approach with both endovascular therapy and neuroprotection may be the key to targeting disability due to stroke.
- | PD98059 / Wayne State University
Journal: A novel Trichinella spiralis serine proteinase disrupted gut epithelial barrier and mediated larval invasion through binding to RACK1 and activating MAPK/ERK1/2 pathway. (Pubmed Central) - Jan 22, 2024
rTsSPc bound to RACK1 receptor in gut epithelium, activated MAPK/ERK1/2 pathway, decreased the expression of gut epithelial TJs proteins and disrupted the epithelial integrity, consequently mediated T. spiralis larval invasion of gut epithelium. The results are valuable to understand T. spiralis invasion mechanism, and TsSPc might be regarded as a vaccine target against T. spiralis invasion and infection.
- | Journal: Involvement of PAR-2 in the Induction of Cell-Specific Matrix Metalloproteinase-2 by Activated Protein C in Cutaneous Wound Healing. (Pubmed Central) - Jan 15, 2024
This study shows for the first time that PAR-2 is essential for APC-induced MMP-2 production. Considering the important role of MMP-2 in wound healing, this work helps explain the underlying mechanisms of action of APC to promote wound healing through PAR-2.
- | Journal: Association between Factor-V Leiden and occurrence of acute myocardial infarction using a large NIS database. (Pubmed Central) - Jan 15, 2024
Considering the important role of MMP-2 in wound healing, this work helps explain the underlying mechanisms of action of APC to promote wound healing through PAR-2. In a population over 18, Factor V Leiden did not correlate with an increased risk of acute myocardial infarction in our studied population.
- | Journal: Thrombomodulin Switches Signaling and Protease-Activated Receptor 1 Cleavage Specificity of Thrombin. (Pubmed Central) - Jan 4, 2024
APC in the absence of EPCR cleaved Arg41 to initiate disruptive signaling responses like thrombin. These results suggest that coreceptor signaling by thrombomodulin and EPCR determines the PAR1 cleavage and signaling specificity of thrombin and APC, respectively.
- | Journal: Activated Protein C Prevents Neuronal Apoptosis via Protease Activated Receptors 1 and 3. (Pubmed Central) - Dec 27, 2023
These results suggest that coreceptor signaling by thrombomodulin and EPCR determines the PAR1 cleavage and signaling specificity of thrombin and APC, respectively. No abstract available
- | Journal: Determining Thrombogenicity: Using a Modified Thrombin Generation Assay to Detect the Level of Thrombotic Event Risk in Lupus Anticoagulant-Positive Patients. (Pubmed Central) - Dec 23, 2023
These data suggest that the determination of LA thrombogenicity with the TGA assay leads to an increased prediction of the manifestation of a thromboembolic event. Our findings appear to be particularly relevant for the prediction of thrombotic events in patients with laboratory-expressed APS and no clinical manifestations.
- || spironolactone / Generic mfg.
Clinical, Journal: Effectiveness and Safety of Different Estradiol Regimens in Transgender Women (TREAT Study): Protocol for a Randomized Controlled Trial. (Pubmed Central) - Dec 22, 2023
P2
The Transgender Estradiol Affirming Therapy (TREAT) study offers a rigorous and reproducible approach to answer important questions regarding GAHT in transgender women, specifically, the most effective 17-? estradiol regimen to suppress testosterone levels to 50 ng/dL, as currently recommended.
- | Preclinical, Journal: Expression of human thrombomodulin by GalTKO.hCD46 pigs modulates coagulation cascade activation by endothelial cells and during ex vivo lung perfusion with human blood. (Pubmed Central) - Dec 21, 2023
Decreased platelet activation was observed during ex vivo perfusion of GalTKO.hCD46 lungs expressing hTBM and, in conjunction with transgenic hTBM, blockade of the platelet GPIb receptor further inhibited platelets and increased survival time. Altogether, our data indicate that expression of transgenic hTBM partially addresses coagulation pathway dysregulation associated with pig lung xenograft injury and, in combination with vWF-GP1b-directed strategies, is a promising approach to improve the outcomes of lung xenotransplantation.
- | NXT007 / Roche
Journal: NXT007-mediated hemostatic potential is suppressed by activated protein C-catalyzed inactivation of activated factor V. (Pubmed Central) - Dec 20, 2023
The NXT007-driven thrombin generation in FVIII-depleted FV plasma was suppressed by APC, similar to the reaction in native FV plasma. NXT007 did not impair APC-mediated downregulation of FVa in FVIIIdef-plasmas, regardless of the presence of FV mutation with APC resistance.
- | 3K3A-APC / ZZ Biotech
Journal: Mitigation of Trauma Induced Endotheliopathy by Activated Protein C: A Potential Therapeutic for Post-Injury Thromboinflammation. (Pubmed Central) - Dec 17, 2023
Pretreatment with 3K3A-aPC, which retains its cytoprotective function but has only ~5% of its anticoagulant function, abrogates the effects of trauma-induced endotheliopathy. This represents a potential therapeutic treatment for dysregulated thromboinflammation for injured patients by minimizing aPC's role in trauma-induced coagulopathy while concurrently amplifying its essential cytoprotective function.
- | Journal: Impact of Increased Activated Protein-C Resistance, Decreased Antithrombin III Activity and Hypocomplementemia on the Gestational Outcomes of Pregnancies with MTHFR Polymorphisms. (Pubmed Central) - Nov 30, 2023
This represents a potential therapeutic treatment for dysregulated thromboinflammation for injured patients by minimizing aPC's role in trauma-induced coagulopathy while concurrently amplifying its essential cytoprotective function. Hypocomplementemia is a risk factor for poor gestational outcome in pregnancies with MTHFR polymorphisms.
- || sirolimus / Generic mfg.
Review, Journal: Nutrition- and hormone-controlled developmental plasticity in Blattodea. (Pubmed Central) - Nov 27, 2023
Insulin/insulin-like growth factor signaling (IIS), target of rapamycin complex 1 (TORC1), and adenosine monophosphate-activated protein complex are the three primary nutrition-responsive signals...We also highlight several perspectives that should be further emphasized in the studies of developmental plasticity in Blattodea. This review provides a general landscape in the field of nutrition- and hormone-controlled developmental plasticity in insects.
- | Journal: Design and characterization of novel activated protein C (APC) variants for the proteolysis of cytotoxic extracellular histone H3. (Pubmed Central) - Nov 27, 2023
This review provides a general landscape in the field of nutrition- and hormone-controlled developmental plasticity in insects. Our data show that it is possible to rationally design APC variants that may be further developed into therapeutic biologicals to treat histone-mediated disease, by proteolytic reduction of histone-associated cytotoxic properties that do not induce an increased bleeding risk.
- The Anticoagulant Systems Cooperate Synergistically on Phospholipid Vesicle and Endothelial Cell Membranes, but Not on Platelets (Halls G-H - Blood Journals Studio (San Diego Convention Center); In-Person) - Nov 27, 2023 - Abstract #ASH2023ASH_6997;
On PL or EC membranes in the plasma environment, APC, TFPI?, and PS cooperate synergistically to inhibit prothrombinase activity, preventing excessive clot propagation. Conversely, platelets protect prothrombinase from inhibition, supporting a procoagulant environment within the clot.
- || Review, Journal: Lactoferrin and Activated Protein C: Potential Role in Prevention of Cancer Progression and Recurrence. (Pubmed Central) - Nov 9, 2023
Hence, in this review, the anticancer potential and mechanism of APC and LF along with their potential to mitigate inflammation and NETs-mediated cancer progression and recurrence has been discussed. Additionally, possible future strategies to develop effective and safe anticancer treatment using LF and APC have also been discussed in this review.
- | Biomarker, Journal: Longitudinal profile of estrogen-related thrombotic biomarkers after cessation of combined hormonal contraceptives. (Pubmed Central) - Nov 8, 2023
In conclusion, CHC cessation is followed by a rapid decrease in estrogen-related thrombotic biomarkers. Two to four weeks of cessation prior to planned major surgery, or withdrawal of anticoagulants in VTE patients, appears sufficient for the majority of women.
- 3K3A-APC / ZZ Biotech
Multi-omic signature of therapeutic activated protein C analog on APOE4 neurovascular dysregulation (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_10105;
Together these data provide a multi-omic signature of the restorative therapeutic effects of 3K3A-APC. 3K3A-APC may be a promising therapeutic to counteract the effects of APOE4 mediated transcriptomic, proteomic, and functional BBB disruption.
- 3K3A-APC / ZZ Biotech
Activated protein C analog protects ischemic brain injury in mice via ?-arrestin-2-dependent signaling (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_7460;
The effects of 3K3A-APC on neuroprotection and blood-brain barrier protection were lost in ?-arrestin-2 null mice. Thus, our data supports that 3K3A-APC reduces ischemic brain injury via ?-arrestin-2-dependent signaling pathways.
- aspirin / Generic mfg.
External Validation of PRISM Score in Multiple Myeloma Patients in a Community Setting: A Retrospective Cohort Study (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_6173;
Abnormal metaphase cytogenetics was a significant predictor of VTE in the validation cohort. Abnormal cytogenetics has been well established to be an indicator of aggressive tumor biology and proliferation in stroma-independent MM.