- |||||||||| desogestrel / Generic mfg.
Review, Journal: Combined Oral Contraceptives and Venous Thromboembolism: Review and Perspective to Mitigate the Risk. (Pubmed Central) - Feb 19, 2022
New progestins were also synthetized (e.g., desogestrel or gestodene) but their weak androgenic activity did not permit to counterbalance the effect of EE as did the initial progestins such as levonorgestrel...One rationale and affordable perspective which has already been considered in the past could be the implementation of a baseline screening of the prothrombotic state to provide health care professionals with objective data to support the prescription of the more appropriate contraceptive method. While this strategy was judged too expensive due to limited laboratory solutions, the endogenous thrombin potential-based APC resistance assay could now represent an interesting alternative.
- |||||||||| Coagulopathy in multiple myeloma (hall 1; hall 2; hall 3; hall 4; hall 5) - Feb 16, 2022 - Abstract #GTH2022GTH_251;
Targeting cellular senescence and UPR (with aPC) may be a useful therapy of atherosclerosis in diabetic patients. In newly diagnosed patients with MM, we recommend increased attention to the level of D-Dim and vWF, especially in patients with higher disease activity in order to estimate possible bleeding or thrombotic complications, for which long term observation is needed.
- |||||||||| The induction of Tregs by aPC depends on metabolic reprogramming and reduced αKG levels (hall 1; hall 2; hall 3; hall 4; hall 5) - Feb 16, 2022 - Abstract #GTH2022GTH_248;
In newly diagnosed patients with MM, we recommend increased attention to the level of D-Dim and vWF, especially in patients with higher disease activity in order to estimate possible bleeding or thrombotic complications, for which long term observation is needed. These data demonstrate that aPC metabolically re-programs T-cells and induces epigenetic changes, favoring a Treg phenotype.
- |||||||||| SEVERE HAEMOPHILIA A AND FACTOR V LEIDEN: A CASE REPORT ([VIRTUAL]) - Jan 28, 2022 - Abstract #EAHAD2022EAHAD_312;
The definitive effect of coexistence of factor V Leiden mutation on the phenotypical expression in heamophilic patients is not clear yet. However, in this case the mutation apparently had resulted in attenuation of the clinical presentation: delayed diagnosis, reduced frequency and severity of bleeding episodes, delayed hemartrosis onset with reduced intra-articular damage and factor concentrate consumption.
- |||||||||| Hemlibra (emicizumab-kxwh) / Roche, SerpinPC (APC-specific serpin) / Centessa, fitusiran (ALN-AT3) / Sanofi, Alnylam
CURRENT AND FUTURE PRODUCTS ([VIRTUAL]) - Jan 28, 2022 - Abstract #EAHAD2022EAHAD_98;
The only licenced non-replacement therapy is the bi-specific antibody Emicizumab which can be used to provide prophylaxis for people with haemophilia A. Studies and real world experience have shown Emicizumab to have good efficacy in preventing bleeding in adults and children with severe haemophilia A and encouraging results are emerging from studies in people with mild and moderate disease...Fitusiran is a small inhibitory RNA molecule, administered subcutaneously once a month, that reduces antithrombin levels with the aim of rebalancing the coagulation system and enhancing thrombin generation in people with factor VIII and IX deficiencies...SerpinPC, based on a variant of α1antitrypsin, inhibits activated protein C with the aim of enhancing thrombin generation...It is important to recognised that there have been no randomised trials that compare non-replacement therapy and coagulation factor concentrates. The options for treating haemophilia are expanding rapidly and studies that compare novel and standard treatment options will be required.
- |||||||||| warfarin / Generic mfg.
VASCULAR ACCESS FAILURE IN A PATIENT WITH FACTOR V LEIDEN HOMOZYGOUS MUTATION (Poster Area (Virtual)) - Jan 21, 2022 - Abstract #ISNWCN2022ISN_WCN_1072;
The options for treating haemophilia are expanding rapidly and studies that compare novel and standard treatment options will be required. Factor V Leiden mutation is a controversial cause for vascular access thrombosis in leturature.It is a wise idea to shift patients who have no viable hemodialysis access to peritoneal dialysis for renal replacement.Inheritance of the factor V Leiden (FVL), prothrombin G20210A mutation, or the presence of antiphospholipid antibodies (APA) may increase the risk of renal allograft thrombosis approximately 3-fold in selected patients.
- |||||||||| 3K3A-APC / ZZ Biotech
Journal: Cerebroprotection for Acute Ischemic Stroke: Looking Ahead. (Pubmed Central) - Jan 11, 2022
Examples of pleiotropic treatments include therapeutic hypothermia and 3K3A-APC (activated protein C)...Before clinical trials, preclinical assessment could include subjects that are aged, of both sexes, and harbor comorbid conditions such as diabetes or hypertension. With these new definitions, novel approaches, and renewed attention to rigor, the prospect for successful cerebroprotective therapy should improve.
- |||||||||| Journal: Extracellular histones, a new class of inhibitory molecules of CNS axonal regeneration. (Pubmed Central) - Jan 8, 2022
Histone-mediated inhibition can be reversed by the addition of activated protein C in vitro, and activated protein C treatment promotes axonal regeneration in the crushed optic nerve in vivo. These findings identify extracellular histones as a new class of nerve regeneration-inhibiting molecules within the injured CNS.
- |||||||||| 3K3A-APC / ZZ Biotech
Preclinical, Journal: Protection of ischemic white matter and oligodendrocytes in mice by 3K3A-activated protein C. (Pubmed Central) - Jan 4, 2022
We show that PAR1 and PAR3 were also required for 3K3A-APC's suppression of post-WM stroke microglia and astrocyte responses and overall improvement in neuropathologic and functional outcomes. Our data provide new insights into the neuroprotective APC pathway in the WM and illustrate 3K3A-APC's potential for treating WM stroke in humans, possibly including multiple WM strokes that result in vascular dementia.
- |||||||||| Journal: Activated Protein C has a Regulatory Role in Factor VIII Function. (Pubmed Central) - Dec 16, 2021
FVIII-QQ again demonstrated enhanced hemostatic function in HA/FV-Leiden mice; however, FVIII-QQ and FVIII-WT performed analogously in the presence of the PC/APC inhibitory antibody, supporting the increased hemostatic effect of FVIII-QQ was APC specific. Our data demonstrate APC contributes to the in vivo regulation of FVIIIa, which has the potential to be exploited to develop novel HA therapeutics.
- |||||||||| Journal: Cryo-EM structures of human coagulation factors V and Va. (Pubmed Central) - Dec 16, 2021
Ordering of this region and full exposure of the factor Xa epitope emerge as a necessary step for the assembly of the prothrombin-prothrombinase complex. These structures offer molecular context for the function of factors V and Va and pioneer the analysis of coagulation factors by cryo-EM.
- |||||||||| Journal: Genome-wide CRISPR screen identifies RACK1 as a critical host factor for flavivirus replication. (Pubmed Central) - Dec 16, 2021
Using an innovative flavivirus protein expression system, we demonstrate for the first time the impact of the loss of RACK1 on the formation of viral replication factories known as 'vesicle packets' (VPs). In addition, we show that RACK1 can interact with numerous flavivirus NS1 proteins as a potential mechanism by which VP formation can be induced by the former.
- |||||||||| Preclinical, Journal: A reactive center loop-based prediction platform to enhance the design of therapeutic SERPINs. (Pubmed Central) - Dec 16, 2021
This variant attenuates blood loss in an in vivo hemophilia A model at a lower dosage than the previously developed variant AIKR/KIPP because of improved potency and specificity. We propose that this SERPIN-based RCL mutagenesis approach improves our understanding of SERPIN behavior and will facilitate the design of therapeutic SERPINs.
- |||||||||| Journal: Revising Host Phenotypes of Sepsis Using Microbiology. (Pubmed Central) - Nov 24, 2021
The treatment effect of rhAPC obviously changed in gamma type when microbiology data were added (P-values of log rank test changed from 0.047 to 0.780). Sepsis host phenotype assignment was significantly modified when microbiology data were added to clinical variables, increasing cluster cohesiveness and homogeneity.
- |||||||||| Journal: Relationship between serum soluble endothelial protein C receptor level and COVID-19 findings. (Pubmed Central) - Nov 21, 2021
Patients with ground-glass opacity and bilateral involvement on thorax CT have higher serum sEPCR levels (P = 0.012 and 0.043, respectively). This study has shown for the first time that serum sEPCR levels, which is a member of coagulation cascade and has also been reported to be associated with inflammation, is higher in patients with positive RT-qPCR test and patients with GGO or bilateral involvement on thorax CT regardless of the PCR result.
- |||||||||| Journal: Activated Protein C Ameliorates Diabetic Cardiomyopathy via Modulating OTUB1/YB-1/MEF2B Axis. (Pubmed Central) - Nov 17, 2021
As a former FDA approved anti-sepsis drug, aPC along with its derivatives can be applied from bench to bed and can be explored as a new strategy for personalized treatment for DCM. Mechanistically, OTUB1/YB-1/MEF2B axis plays a critical role in the occurrence and development of DCM and offers a potential avenue for therapeutic targeting of DCM.
- |||||||||| epinephrine / Generic mfg.
Prothrombotic Phenotype of a Protein S Mutant Lacking Anticoagulant Activity (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_3705;
Taken together with the embryonic phenotype of Pros1 D136A homozygous mice, these data support the notion that protein S can function to augment platelet responsiveness. Further studies on this and other ligands for the TAM family of receptor tyrosine kinases should provide additional insights into their roles in physiological platelet activation.
- |||||||||| Ordering Patterns of Thrombophilia Testing and Its Appropriateness (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_3484;
Given the large number of services ordering thrombophilia testing at our training hospital and this testing being sent for a variety of reasons, it is unlikely that physician education alone will lead to a substantial or sustained decrease in the number of inappropriate tests. Rather, it may be necessary to restrict at least some thrombophilia testing to certain services.
- |||||||||| ProCase (AB002) / Aronora
A Phase 2 Trial of the Protein C Activator AB002 in End-Stage Renal Disease Patients on Chronic Hemodialysis (GWCC - B401-B402, Level 4) - Nov 5, 2021 - Abstract #ASH2021ASH_2152;
P2
In ESRD patients undergoing heparin-free hemodialysis, AB002 was well-tolerated and reduced thrombus accumulation in the hemodialysis circuit without observable hemostasis impairment. The results of this study support further clinical evaluation of AB002 as a novel drug candidate to limit thrombus development or device-initiated clotting in patients with elevated bleeding risk, including ESRD patients on chronic heparin-free hemodialysis.
- |||||||||| Review, Journal: Thrombin generation and activity in multiple sclerosis. (Pubmed Central) - Oct 29, 2021
Thrombin is a serine protease capable of cleaving multiple substrates, including protease activated receptors (PARs), fibrinogen, and protein C. Cleavage of all three of these substrates represent pathways through which thrombin activity may exert immuno-regulatory effects and regulate permeability of the BBB during MS and EAE. In this review, we summarize evidence that thrombin activity directly, through PARs, and indirectly, through fibrin formation and activation of protein C influences neuro-immune responses associated with MS and EAE pathology.
- |||||||||| enoxaparin sodium / Generic mfg.
[VIRTUAL] THROMBOPHILIA: AN UNUSUAL PRESENTATION () - Oct 27, 2021 - Abstract #HEMO2021HEMO_1633;
It presented a total of 15 episodes of deep vein thrombosis (DVT) in the lower limbs. She had her second stroke in 2013. She had arterial hypertension, dyslipidemia and grade III obesity. It has research for other hereditary thrombophilias and negative Antiphospholipid Antibody Syndrome. Positive family history (maternal grandfather had multiple thrombotic events). She started anticoagulation in 2007 with Warfarin, but the INR was difficult to manage, requiring high doses of medication with persistent thrombosis. She presented with upper gastrointestinal bleeding in 2013, and warfarin was suspended and rivaroxaban was started, but the patient progressed to oligoanuric renal failure. Currently, she is anticoagulated with enoxaparin 200 mg/day, 1 mg/kg/day twice a day, but even with regular use of this medication, she presented thrombotic episodes, the last being a PTE in 2019.Discussion The prevalence of DPS in the general population is unknown, but it is known that the relative risk of a first episode of VTE is five times higher when compared to the general population. In patients with a previous episode of VTE, the incidence of DPS is 1%. The annual incidence of VTE described in patients already diagnosed with DPS ranges from 1.65% to 3.5%. Most clinically, DPS presents itself as a VTE, but when it is not accompanied by a family history, it is not considered such an important risk factor for thrombotic events. Some individuals with DPS and VTE also have a second thrombophilic defect. Regarding arterial thrombosis, studies have not convincingly demonstrated that DPS is a risk factor for such an event.Conclusion In order of prevalence, DPS is the 4th most common hereditary thrombophilia, among the five currently researched thrombophilias. And the recurrence of a new thrombotic episode every year does not have high values either, that is, it is not a mutation that leads to a high thrombotic risk. The patient in the clinical case mentioned above has a protein S deficiency proven by laboratory tests and also a positive family history for thrombotic events, but with an unusual presentation of the disease. She presented 20 episodes of VTE's and 02 arterial thrombotic events, even when using anticoagulation, which shows that their relative risk of developing thrombosis was higher than that studied and defined for DPS.
- |||||||||| [VIRTUAL] A SYSTEMATIC LITERATURE REVIEW OF BUDD-CHIARI SYNDROME IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS () - Oct 27, 2021 - Abstract #HEMO2021HEMO_11;
Discussion Studies suggest that lupus anticoagulant can be sought in patients with idiopathic hepatic venous thrombosis. Possible mechanisms by which antiphospholipid antibodies induce thrombotic events in patients with SLE have been suggested: it can bind to platelet membrane phospholipids and accentuate their adhesion and aggregation ability, it can interfere in the interaction of proteins C and S and impair the formation of the coagulation control complex (activated protein C, protein S and factor V). Conclusion Budd-Chiari syndrome can be a rare complication in patients with SLE. A methodical search for hepatic vein occlusion in patients with SLE who develop unexplained hepatomegaly should be performed. In addition, screening for lupus anticoagulant and anticardiolipin antibodies should take place to reduce the percentage of apparently idiopathic BCS cases.
- |||||||||| Journal: Selective Modulation of the Protease Activated Protein C Using Exosite Inhibiting Aptamers. (Pubmed Central) - Oct 22, 2021
In addition, G-NB3 prolongs the plasma half-life of APC through inhibition of APC-serine protease inhibitor complex formation. These physicochemical and functional characteristics qualify G-NB3 as a promising therapeutic agent usable to enhance the cytoprotective functions of APC without increasing the risk of APC-related hemorrhage.
|
