- |||||||||| Variegin, a Potent Direct Thrombin Inhibitor From Tick Saliva (Room:516) - Apr 5, 2023 - Abstract #ISTH2023ISTH_278;
Learning Objectives: the importance of high selectivity and affinity of thrombin inhibitorsstrategies to evaluate in vivo efficacy and bleeding side effects of thrombin inhibitors the role of endogenous thrombin potential in thrombosis and hemostasis
- |||||||||| Genetics of the Antithrombin-Prothrombin Axis (Room:516) - Apr 5, 2023 - Abstract #ISTH2023ISTH_118;
Learning Objectives: the importance of high selectivity and affinity of thrombin inhibitorsstrategies to evaluate in vivo efficacy and bleeding side effects of thrombin inhibitors the role of endogenous thrombin potential in thrombosis and hemostasis Learning Objectives: To establish the impact of genetic variants affecting the key hemostatic elements thrombin and its inhibitor antithrombinTo appraise the relevance and relationship of two opposite elements of a crucial systemTo discriminate between the bleeding or thrombotic consequences of gene defects affecting the same molecule
- |||||||||| Hemlibra (emicizumab-kxwh) / Roche, Roctavian (valoctocogene roxaparvovec) / BioMarin
Journal, IO biomarker: From a bispecific monoclonal antibody to gene therapy: A new era in the treatment of hemophilia A. (Pubmed Central) - Mar 20, 2023
Emicizumab, a bispecific-humanized monoclonal antibody, is able to improve coagulation by bridging activated factor IX and factor X. Emicizumab is administered subcutaneously and much less often compared to factor VIII products...Future objectives are: the development of an ideal viral vector, the possibility of its re-administration, the use of gene therapy in hemophiliac children, and determining whether it can be successfully used to induce immune tolerance to factor VIII ceteri paribus. The future will determine the place of each type of treatment and group of patients for which it is indicated.
- |||||||||| bivalirudin / Generic mfg.
ECMO: Time for a direct approach () - Mar 14, 2023 - Abstract #PAS2023PAS_1767;
Further research is warranted to address the optimal test to guide clinical decision-making for anticoagulation dosing in ECMO patients. However, the use of direct thrombin inhibitors such Bivalirudin (Bival) is growing in popularity due to its physiologic advantages specifically in the pediatric population.
- |||||||||| rivaroxaban / Generic mfg., fondaparinux / Generic mfg., argatroban / Generic mfg.
Journal, Tumor cell: Expression and Release of Tumor Cell Tissue Factor Triggers Recurrent Thromboembolism in a Patient with Endometrial Cancer. (Pubmed Central) - Mar 3, 2023
Multimodal antineoplastic treatment, including neoadjuvant chemotherapy followed by surgery and postoperative radiotherapy, resulted in clinical cancer remission, which was paralleled by normalization of tumor markers, CA125 and CA19-9, D-dimer levels, and TF-bearing microvesicles. In summary, continuous anticoagulation with argatroban and multimodal anticancer treatment may be necessary to control TF-driven coagulation activation with recurrent CAT in endometrial cancer.
- |||||||||| apixaban / Generic mfg.
Journal: Investigating thrombin-loaded fibrin in whole blood clot microfluidic assay via fluorogenic peptide. (Pubmed Central) - Feb 27, 2023
This thrombin activity was ablated by Phe-Pro-Arg-chloromethylketone (PPACK), apixaban, or Gly-Pro-Arg-Pro to inhibit fibrin...Similarly, introduction of plasma/AF647-fibrinogen generated substantial red fibrin masses that did not penetrate the original green clots, demonstrating that fibrin cannot be re-clotted with fibrinogen. Overall, thrombin within fibrin is non-elutable, easily accessed by peptides, slowly accessed by average-sized proteins (heparin/AT), and not accessible to fresh fibrinogen.
- |||||||||| Journal: Anticoagulant Property of a Sulfated Polysaccharide with Unique Structural Characteristics from the Green Alga Chaetomorpha aerea. (Pubmed Central) - Feb 24, 2023
PCA significantly inhibited the activities of the intrinsic coagulation factors XII, XI, IX and VIII, and exhibited weak inhibition effects on the common coagulation factors II and X. The anticoagulant mechanism of PCA was attributed to strong thrombin inhibition potentiated by heparin cofactor II or antithrombin III, and it also possessed an apparent inhibition effect on coagulation factor Xa mediated by antithrombin III. The investigation demonstrated that PCA could be a promising anticoagulant agent for health promotion and the treatment of thrombotic diseases.
- |||||||||| Review, Journal: Practical Guide for Anticoagulant and Antiplatelet Reversal in Clinical Practice. (Pubmed Central) - Feb 24, 2023
DOACs are associated with lower rates of fatal, life-threatening, and significant bleeding risks compared to those of warfarin...Andexanet alfa and idarucizumab are specific reversal agents for DOACs and DTIs, respectively...However, there are no specific reversal agents for antiplatelets. This article aims to provide a practical guide for clinicians regarding the reversal of anticoagulants and antiplatelets in clinical practice based on the most recent studies.
- |||||||||| Aggrastat (tirofiban) / Correvio, Medicure, Kengreal (cangrelor) / Chiesi
Review, Journal: How to Solve the Conundrum of Heparin-Induced Thrombocytopenia during Cardiopulmonary Bypass. (Pubmed Central) - Feb 12, 2023
Temporary reduction of anti-PF4 with intravenous immunoglobulins (IvIg) has recently been described as a complementary strategy. In this article, we briefly described the pathophysiology of HIT and focused on the various strategies that can be applied to safely manage CPB in these patients.
- |||||||||| Expression and release of tumor cell tissue factor triggers recurrent thromboembolism in a patient with endometrial cancer (#24) (foyer) - Feb 8, 2023 - Abstract #GTH2023GTH_333;
Results Despite therapeutic anticoagulation with various agents, including rivaroxaban, fondaparinux and low-molecular-weight heparin (LMWH), the patient experienced recurrent venous and arterial thromboembolism with at least seven distinct thromboembolic events within 3 months...Thus, anticoagulation was continued with the LMWH, enoxaparin...No further thrombotic events have occurred. Conclusion Continuous anticoagulation with argatroban and multimodal anticancer treatment may be necessary to control TF-driven paraneoplastic coagulation activation with recurrent CAT in endometrial cancer.
- |||||||||| Preclinical, Journal: Factor IXa variants resistant to plasma inhibitors enhance clot formation in vivo. (Pubmed Central) - Feb 2, 2023
Overall, the results demonstrate that regulation of factor IXa inhibition contributes in a major way to the spatial and temporal control of coagulation at the site of vascular injury. Our findings provide novel insights into the physiologic regulation of factor IXa, enhance our understanding of thrombus formation in vivo via the intrinsic pathway, and suggest that altering inhibition of factor IXa could have therapeutic benefit.
- |||||||||| Journal: Activation of Most Toll-Like Receptors in Whole Human Blood Attenuates Platelet Deposition on Collagen under Flow. (Pubmed Central) - Jan 28, 2023
Since TLR signaling can activate nuclear factor-kappaB (NF-κB), the IKK-inhibitor (IKK inhibitor VII) and NF-κB inhibitor (Bay 11-7082) were tested...Furthermore, addition of Pam3CSK4 (TLR1/2 ligand), MALP-2 (TLR2/6 ligand), and Imquimod (TLR7 ligand) reduced phosphotidylserine (PS) exposure. Activation of TLR1/2, TLR2/6, TLR3, TLR7, and TLR9 in whole blood reduced platelet deposition under flow on collagen; however, LPS (major Gram negative bacterial pathogenic component) activation of LTR4 was clearly prothrombotic.
- |||||||||| bivalirudin / Generic mfg.
BIVALIRUDIN VERSUS HEPARIN FOR ANTICOAGULATION IN EXTRACORPOREAL MEMBRANE OXYGENATION () - Jan 25, 2023 - Abstract #SCCM2023SCCM_1783;
Patients with COVID-19 experienced greater thrombotic and bleeding events, with longer ECMO duration and lengths of stay. In the propensity matched analysis comparing UFH vs. bivalirudin in VV-ECMO, non-COVID-19 patients, there were no significant differences between thrombotic or bleeding events, but significantly greater mortality in the UFH arm.
- |||||||||| EVALUATION OF A PHARMACY-MANAGED HEPARIN-INDUCED THROMBOCYTOPENIA STANDARD OPERATING PROCEDURE () - Jan 25, 2023 - Abstract #SCCM2023SCCM_1259;
In the propensity matched analysis comparing UFH vs. bivalirudin in VV-ECMO, non-COVID-19 patients, there were no significant differences between thrombotic or bleeding events, but significantly greater mortality in the UFH arm. The implementation of a pharmacist-driven heparin-induced thrombocytopenia standard operating procedure demonstrated a similar incidence of appropriate heparin allergy documentation in the medical record compared to a physician-driven approach.
- |||||||||| bivalirudin / Generic mfg.
PROGRAM-WIDE TRANSITION FROM HEPARIN TO BIVALIRUDIN ANTICOAGULATION IN ADULT ECMO: A COST ANALYSIS () - Jan 25, 2023 - Abstract #SCCM2023SCCM_1117;
Antithrombin assessment and supplementation comprised a majority of anticoagulant-related costs in heparin-based ECMO patients, which was significantly reduced following transition to bivalirudin-based anticoagulation. When considering laboratory and drug costs in aggregate, there is a favorable association between bivalirudin and heparin anticoagulation in adult ECMO patients.
- |||||||||| ANTI THE ANTICOAGULATION IN ECMO? A SURVEY OF PRACTICES IN ADULT ECMO PATIENTS () - Jan 25, 2023 - Abstract #SCCM2023SCCM_1056;
While UFH remains the anticoagulant of choice at most centers despite recent evidence, variability still exists with monitoring methods and anticoagulation practices for VV ECMO patients. Further research is necessary to standardize anticoagulation practices.
- |||||||||| Savaysa (edoxaban) / Daiichi Sankyo, Bevyxxa (betrixaban) / AstraZeneca
Review, Journal: Direct oral anticoagulants (DOACs): From the laboratory point of view. (Pubmed Central) - Jan 19, 2023
Therefore, specific quantitative methods (LC-MS/MS as a gold standard method for all DOACs, coagulometric and chromogenic assays for dabigatran, and chromogenic anti-Xa assays with drug-specific calibrators for inhibitors of FXa) should only be used for determination of DOACs concentration. The aim of this review is to present all aspects of laboratory assessment of DOACs, including pre-analytical, analytical and post-analytical factors in the overall testing process with a special accent on the available specific quantitative methods for measurement of DOACs in circulation.
- |||||||||| Journal: Mechanism and clinical treatment strategy of heparin resistance (Pubmed Central) - Jan 13, 2023
Common etiologies include heparin-induced thrombocytopenia, severe infections such as severe COVID-19, treatment with extracorporeal circulation or extracorporeal membrane oxygenation (ECMO), and use of factor Xa reversal agents; heparin resistance is now often identified by the concordance of activated partial thromboplastin time (APTT) ratio with anti-FXa. Common clinical management strategies include antithrombin supplementation and replacement of anticoagulant drugs (e.g., direct thrombin inhibitors), but their safety and efficacy still need to be further validated.
- |||||||||| Hypercoagulability Impairs Plaque Stability in Diabetes-Induced Atherosclerosis (#83) (Conclusion (C2)) - Jan 7, 2023 - Abstract #GTH2023GTH_117;
Congruently, more macrophages and fewer smooth muscle cells were observed within lesions of diabetic TMPro/Pro ApoE-/- mice. Conclusion Thus, it can be concluded that impaired TM function reduces plaque stability, a characteristic of hyperglycemia-associated plaques, thus suggesting the crucial role of impaired TM function in mediating diabetes-associated atherosclerosis.
- |||||||||| bivalirudin / Generic mfg.
Anticoagulation During Pediatric ECMO: Evaluation of Efficacy and Cost (Moscone Center South - 201) - Jan 4, 2023 - Abstract #SCCM2023SCCM_490;
However, drug cost for bivalirudin has been reported as potentially prohibitive for some centers...Survival to ECMO decannulation was 72%. CONCLUSIONS : DTI use in pediatric ECMO was efficacious for prolonged runs, directed by EAC, with rapid time to therapeutic range and decreased thrombotic complications, as well as being cost-effective While drug cost for UFH alone is inexpensive, laboratory cost for anti-Xa was more expensive than PTT and if antithrombin is administered the cost significantly increases, for drug and monitoring of activity.
- |||||||||| Besivance (besifloxacin ophthalmic suspension) / Bausch Health
Journal: Keratitis following leech therapy for periocular eczematous dermatitis: a case report. (Pubmed Central) - Jan 2, 2023
CONCLUSIONS : DTI use in pediatric ECMO was efficacious for prolonged runs, directed by EAC, with rapid time to therapeutic range and decreased thrombotic complications, as well as being cost-effective While drug cost for UFH alone is inexpensive, laboratory cost for anti-Xa was more expensive than PTT and if antithrombin is administered the cost significantly increases, for drug and monitoring of activity. MLT should be performed by certified physicians with sterile medicinal leeches and precautious antibiotics should be used before MLT for prevention against potential infections.
- |||||||||| bivalirudin / Generic mfg., argatroban / Generic mfg.
Review, Journal: Anticoagulation Management during Extracorporeal Membrane Oxygenation-A Mini-Review. (Pubmed Central) - Dec 24, 2022
The knowledge of the advantages and disadvantages of particular drugs, limitations of particular tests, and individualization are cornerstones of prevention against critical events, such as life-threatening bleeding or acute oxygenator failure followed by life-threatening hypoxemia and hemodynamic deterioration. This paper describes the effects of anticoagulant drugs used in ECMO and their monitoring, highlighting specific conditions and factors that might influence coagulation and anticoagulation measurements.
- |||||||||| Journal: What is known in pre-, peri-, and post-procedural anticoagulation in micro-axial flow pump protected percutaneous coronary intervention? (Pubmed Central) - Dec 16, 2022
This includes anticoagulant therapy with unfractionated heparin, direct thrombin inhibitors, DAPT, purge blockage prevention by bicarbonate-based purge solution, and monitoring by activated clotting time, partial thromboplastin time, as well as anti-factor Xa levels. Here, we provide a standardized approach to the management of peri-interventional anticoagulation in patients undergoing protected PCI.
- |||||||||| aspirin / Generic mfg.
Journal: Drug-Drug Interaction between Antiplatelet Therapy and Lipid-Lowering Agents (Statins and PCSK9 Inhibitors). (Pubmed Central) - Dec 16, 2022
Aspirin is the most frequently used antiplatelet drug, either alone or in combination with other antiplatelet agents (P2Y inhibitors), while statins are first-line treatment of hypercholesterolemia...Furthermore, statins upregulate endothelial NO-synthase and improve endothelial oxygen defense by inhibition of NADPH-oxidase. PCSK9 antibodies target a serine protease (PCSK9), which promotes the degradation of the LDL-C receptor impacting on LDL-C plasma levels and (ox)LDL-C-receptor-mediated signaling in platelets similar to but more potent than statins.These functionally synergistic actions are the basis for numerous interactions between antiplatelet and these lipid-lowering drugs, which may, in summary, reduce the incidence of atherothrombotic vascular events.
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