Delving into the Latest Updates on Danaparoid Sodium with Synapse

Overview

Basic Info

Drug Type

Chemical drugs

Synonyms

Danaparoid sodium (JAN/USAN), 达那肝素钠

+ [4]

Target

factor Xa

Mechanism

factor Xa inhibitors(Factor Xa inhibitors)

Therapeutic Areas

Cardiovascular DiseasesHemic and Lymphatic DiseasesOther Diseases

Active Indication

Disseminated Intravascular CoagulationVenous ThrombosisThromboembolism+ [3]

Inactive Indication

Stroke

Originator Organization

Merck Sharp & Dohme Corp.

Active Organization

MSD Oss BV

Lupin Ltd

Organon & Co.

+ [2]

Inactive Organization

Aspen Global, Inc.

Drug Highest PhaseApproved

First Approval Date

NL (01 Jan 1991),

ThrombocytopeniaVenous Thromboembolism

Regulation-

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AbstractCurrent guidelines for treating vaccine-induced immune thrombotic thrombocytopenia (VITT) recommend nonheparin anticoagulants and IV immunoglobulin (IVIg). However, the efficacy of these treatments remains uncertain due to case studies involving small patient numbers, confounding factors (eg, concurrent treatments), and a lack of animal studies. A recent study proposed danaparoid and heparin as potential VITT therapies because of their ability to disrupt VITT IgG-platelet factor 4 (PF4) binding. Here, we examined the effects of various anticoagulants (including unfractionated [UF] heparin, danaparoid, bivalirudin, fondaparinux, and argatroban), IVIg, and the FcγRIIa receptor-blocking antibody, IV.3. Our investigation focused on VITT IgG-PF4 binding, platelet activation, thrombocytopenia, and thrombosis. Danaparoid, at therapeutic doses, was the sole anticoagulant that reduced VITT IgG-PF4 binding, verified by affinity-purified anti-PF4 VITT IgG. Although danaparoid and high-dose UF heparin (10 U/mL) inhibited platelet activation, none of the anticoagulants significantly affected thrombocytopenia in our VITT animal model and all prolonged bleeding time. IVIg and all anticoagulants except UF heparin protected the VITT mice from thrombosis. Direct FcγRIIa receptor inhibition with IV.3 antibody is an effective approach for managing both thrombosis and thrombocytopenia in the VITT mouse model. Our results underscore the necessity of animal model investigations to inform and better guide clinicians on treatment choices. This study provides compelling evidence for the development of FcγRIIa receptor blockers to prevent thrombosis in VITT and other FcγRIIa-related inflammatory disorders.

01 Oct 2024·Journal of the College of Physicians and Surgeons Pakistan

Short-Term Prognostic Risk Factors and Nomogram Predictive Model Construction for Acute Ischaemic Stroke after Endovascular Treatment

Article

Author: Lei, Sanxi ; Jin, Guilin ; Chen, Yifei ; Chen, Boyu ; Ma, Xiang ; Deng, Ruoyu

OBJECTIVETo investigate the factors influencing the severity of acute ischaemic stroke (AIS) and short-term prognosis after endovascular treatment.STUDY DESIGNObservational study. Place and Duration of the Study: Department of Cerebrovascular Diseases, The First People's Hospital of Qujing City, Yunnan Province, China, from June 2020 to December 2022.METHODOLOGYAn analysis was conducted on 160 AIS patients undergoing endovascular treatment, classified into atherosclerosis subtype (AS) and cardioembolic subtype (CE) based on the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification, each comprising 80 cases. The association among baseline and endovascular treatment parameters, clinical characteristics, postoperative complications, and short-term outcomes (risks of mortality and poor prognosis) was tested.RESULTSUnivariate analysis revealed significant positive correlations between increased fasting glucose, diastolic pressure, and the number of thrombectomy procedures with the frequency of cerebral haemorrhage in CE-type stroke. The time from femoral artery puncture to vessel opening was positively associated with the degree of brain oedema. In the AS subtype, univariate regression analysis demonstrated a significant association between heart rate, fasting glucose, cholesterol, time from femoral artery puncture to vessel opening, and degree of brain oedema with short-term prognosis. Fasting glucose and the number of thrombectomy procedures were significantly linked to short-term prognosis in CE-type AIS. A predictive model using line charts was developed for factors associated with postoperative complications and short-term prognosis, achieving predictive accuracies of 95.5% for the risk of death and 92.7% for poor prognosis (mRS >2), notably surpassing traditional prediction methods.CONCLUSIONClinical characteristics and endovascular treatment-related factors are important for the short-term prognosis of AIS patients. Development of predictive models can efficiently identify high-risk patients at an early stage.KEY WORDSAcute ischaemic stroke, Atherosclerosis, Cardioembolic, Severity, Prognosis.

01 Oct 2024·Stroke

Sex-Stratified Genome-Wide Association Study in the Spanish Population Identifies a Novel Locus for Lacunar Stroke

Article

Author: Segura, Tomás ; Castillo, José ; Campos, Francisco ; Lopez-Cancio, Elena ; Krupinski, Jerzy ; Guasch, Marina ; Montaner, Joan ; Jiménez-Conde, Jordi ; Gallego-Fabrega, Cristina ; Freijo, Marimar ; Cruchaga, Carlos ; Martín-Campos, Jesús M. ; Muñoz-Narbona, Lucia ; Heitsch, Laura ; Lledós, Miquel ; Blay, Natalia ; Martí-Fàbregas, Joan ; Lee, Jin-Moo ; Molina, Carlos A. ; Ezcurra, Garbiñe ; Muiño, Elena ; Ibañez, Laura ; Millán, Mònica ; Llucià-Carol, Laia ; Cárcel-Márquez, Jara ; Diaz-Navarro, Rosa ; Serrano-Heras, Gemma ; Sobrino, Tomás ; Sumoy, Lauro ; Arenillas, Juan Francisco ; Dhar, Rajat ; Roquer, Jaume ; Camps-Renom, Pol ; Ribó, Marc ; Obach, Victor ; Delgado, Pilar ; Cullell, Natalia ; Férnandez-Cadenas, Israel ; de Cid, Rafael ; Vives-Bauza, Cristòfol ; Álvarez-Sabín, José ; Prats-Sánchez, Luis

BACKGROUND:Ischemic stroke (IS) represents a significant health burden globally, necessitating a better understanding of its genetic underpinnings to improve prevention and treatment strategies. Despite advances in IS genetics, studies focusing on the Spanish population and sex-stratified analyses are lacking.METHODS:A case-control genome-wide association study was conducted with 9081 individuals (3493 IS cases and 5588 healthy controls). IS subtypes using Trial of ORG 10172 in Acute Stroke Treatment criteria were explored in a sex-stratified approach. Replication efforts involved the MEGASTROKE, GIGASTROKE, and the UK Biobank international cohorts. Post-genome-wide association study analysis included: in silico proteomic analysis, gene-based analysis, quantitative trait loci annotation, transcriptome-wide association analysis, and bioinformatic analysis using chromatin accessibility data.RESULTS: Identified as associated with IS and its subtypes were 4 significant and independent loci. Replication confirmed 5p15.2 as a new locus associated with small-vessel occlusion stroke, with rs59970332-T as the lead variant (beta [SE], 0.13 [0.02]; P =4.34×10 −8 ). Functional analyses revealed CTNND2 given proximity and its implication in pathways involved in vascular integrity and angiogenesis. Integration of Hi-C data identified additional potentially modulated genes, and in silico proteomic analysis suggested a distinctive blood proteome profile associated with the lead variant. Gene-set enrichment analyses highlighted pathways consistent with small-vessel disease pathogenesis. Gene-based associations with known stroke-related genes such as F2 and FGG were also observed, reinforcing the relevance of our findings. CONCLUSIONS: We found CTNND2 as a potential key molecule in small-vessel occlusion stroke risk, and predominantly in males. This study sheds light on the genetic architecture of IS in the Spanish population, providing novel insights into sex-specific associations and potential molecular mechanisms. Further research, including replication in larger cohorts, is essential for a comprehensive understanding of these findings and for their translation to clinical practice.

100 Deals associated with Danaparoid Sodium

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External Link

KEGG	Wiki	ATC	Drug Bank
D03644	Danaparoid Sodium	B01AB09	DBSALT001136

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Disseminated Intravascular Coagulation	JP	Kyowa Criticare Co. Ltd.	20 Apr 2001
Venous Thrombosis	US	MSD Oss BV	06 Jul 1999
Thromboembolism	NL	Organon & Co.	10 Jun 1991
Thrombocytopenia	NL	-	01 Jan 1991
Venous Thromboembolism	NL	-	01 Jan 1991

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Heparin-induced thrombocytopenia	Phase 2	PL	Aspen Global, Inc.	16 May 2019
Heparin-induced thrombocytopenia	Phase 2	BA	Aspen Global, Inc.	16 May 2019
Heparin-induced thrombocytopenia	Phase 2	IT	Aspen Global, Inc.	16 May 2019
Heparin-induced thrombocytopenia	Phase 2	RS	Aspen Global, Inc.	16 May 2019
Heparin-induced thrombocytopenia	Phase 2	DE	Aspen Global, Inc.	16 May 2019
Heparin-induced thrombocytopenia	Phase 2	CA	Aspen Global, Inc.	16 May 2019
Heparin-induced thrombocytopenia	Phase 2	RU	Aspen Global, Inc.	16 May 2019
Heparin-induced thrombocytopenia	Phase 2	US	Aspen Global, Inc.	16 May 2019

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


GlobeNewswire Manual	Not Applicable	CD19 positive Acute Lymphoblastic Leukemia	233	ORG-101 (adults patients)	(phlezmtino) = wbifdkyqru vroqjycnoe (uypxcyiodj ) View more	Positive	29 Aug 2024
				ORG-101 (pediatric patients)	(phlezmtino) = dnexanfffg vroqjycnoe (uypxcyiodj ) View more