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thrombin (ThrombiRAAS)

✓ Approved

Shanghai RAAS Blood Products Co., Ltd. · F2 · 细胞治疗

什么是 thrombin？

thrombin 是一种细胞治疗，由Shanghai RAAS Blood Products Co., Ltd.研发。该药已获批，用于治疗相关适应症，给药途径：Oral (PO)。

药物档案

商品名ThrombiRAAS
公司Shanghai RAAS Blood Products Co., Ltd.
药物类别细胞治疗
分子靶点F2
给药途径Oral (PO)
状态Approved
来源： ClinicalTrials.gov, Shanghai RAAS Blood Products Co., Ltd.

作用机制

分子靶点

thrombin 作用于 1 个分子靶点：

F2coagulation factor II, thrombin (THPH1, PT)
需要更深入的分析？Noah AI 可解释复杂机制并与同类药物比较。

治疗适应症

thrombin 针对 2 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Vascular disordersExtravasation blood✓ Approved
Vascular disordersHaemorrhage✓ Approved

相关研究文献

PubMedBiochemical and biophysical research communications2026-06-13

Non-canonical Platelet activation by oral squamous cell carcinoma extracellular vesicles through cooperative thrombin formation.

Chen Rui R, Jin Ge G, McIntyre Thomas M TM

Coagulation contributes to cancer mortality, and tumor cells activate platelets to release growth factors. However, this activation is non-canonical, employs unknown agonists and, uniquely, is not immediate. Platelets are activated by human cell lines derived from Oral Squamous Cell Carcinomas (OSCC) with this atypical delay. The stimulatory activity was not a soluble factor, but rather was completely recovered in spontaneously shed extracellular vesicles (EV). EV did not contain established platelet agonists. Instead, chemical and pharmacologic inhibitors show OSCC EV interacted with quiescent platelets to assemble extrinsic and common coagulation complexes that generated thrombin after a significant delay. Newly generated thrombin then stimulated platelets through their PAR1 thrombin receptor. Translocation of intracellular phosphatidylserine to the platelet surface, enabled by its enzymatic oxidation, is essential for de novo formation of coagulation complexes. The delay in OSCC EV-induced platelet aggregation correlated to the delay in phosphatidylserine surface expression. Platelets express the oxidant-generating prorenin receptor (p)RR, while OSCC-EV contained its prorenin ligand. (p)RR non-proteolytically activates the prorenin zymogen and blockade of either this interaction by the decoy PRO20 peptide or inhibition of renin activity suppressed phosphatidylserine translocation and platelet activation. OSCC EV induced delayed peroxidation of platelet membrane lipids, while the intra-membranous radical trap Liproxstatin-1 suppressed phospholipid oxidation, phosphatidylserine display, and platelet activation. We conclude hysteresis characteristic of non-canonical, tumor cell-induced platelet activation reflects a novel time-dependent process of pro-thrombin activation. The rate-limiting step is membrane oxidation that enables phosphatidylserine translocation to the platelet surface and subsequent formation of the premier platelet agonist, thrombin.

PMID 42284996
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PubMedCarbohydrate polymers2026-06-13

Structural characterization, in vitro anticoagulant, and antiplatelet activities of a Distolasterias nipon dermatan sulfate-like polymer with a distinctive sulfation pattern.

Filshtein Alina P AP, Belova Vlada S VS, Taran Ilya V IV, Kokoulin Maxim S MS

A novel dermatan sulfate-like polysaccharide (DNP) was isolated from the body walls of the starfish Distolasterias nipon. Its structure was elucidated using chemical methods and 2D NMR spectroscopy, revealing a backbone of →4)-α-L-IdopA-(1→3)-β-D-GalpNAc-(1→, with the α-L-iduronic acid residues predominantly 2,3-di-O-sulfated, alongside 2-O- and 3-O-monosulfated variants, and the β-D-GalpNAc residues 4-O-sulfated. Functional assays showed that DNP prolongs thrombin time (TT) comparable to heparin and more potently than enoxaparin (Clexane®), whereas its effect on activated partial thromboplastin time (APTT) is less pronounced. The anticoagulant activity of DNP is characterized by antithrombin-dependent thrombin inhibition and moderate suppression of factor Xa. Furthermore, the polysaccharide does not induce platelet aggregation nor interfere with physiological ADP-mediated pathways, but it inhibits ristocetin-induced aggregation. These findings identify D. nipon as a source of a dermatan sulfate structurally distinct from those found in other starfishes and invertebrates, and characterized by an antithrombin-dependent anti-IIa/anti-Xa profile and additional antiplatelet properties.

PMID 42285676
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PubMedCancers2026-06-12

Enoxaparin, Tinzaparin, and Apixaban Modulate Cancer Cell Procoagulant Activity and Viability: Comparison with Quercetin.

Baghdadi Mohammed A MA, do Carmo Las Casas Pedro Henrique Fernandes PHF, Mbemba Elisabeth E, Rousseau Aurélie A et al.

Background/Objectives: Tissue factor (TF)-expressing cancer cells and their extracellular vesicles (CaCe-dEVs) are key drivers of cancer-associated hypercoagulability and vascular dysfunction. While low-molecular-weight heparins (LMWHs) and direct FXa inhibitors are standard therapies for cancer-associated thrombosis, their direct effects on cancer cell procoagulant potential and endothelial responses remain incompletely defined. This study compared the impact of LMWHs (enoxaparin, tinzaparin), apixaban, and quercetin on cancer cell viability, thrombin generation, and CaCe-dEVs-induced endothelial injury. Methods: Pancreatic (BXPC3) and breast (MCF7) cancer cells and their vesicles were analyzed for TF expression and thrombin generation. Human umbilical vein endothelial cells (HUVECs) were pretreated with each agent prior to vesicle exposure. Cell viability, thrombin generation, and endothelial morphology were assessed using standard assays and microscopy. Results: Tinzaparin and quercetin significantly reduced cancer cell viability, whereas enoxaparin and apixaban showed no cytotoxicity. None of the agents affected HUVEC viability. All suppressed TF-mediated thrombin generation induced by cancer cells, with tinzaparin being most effective in BXPC3 cells. Quercetin exhibited a partial and limited protective effect on endothelial cells against CaCe-dEVs-induced dysfunction, while LMWHs and apixaban did not prevent endothelial damage. Conclusions: These findings suggest that LMWHs, apixaban, and quercetin modulate cancer-cell-driven hypercoagulability beyond anticoagulation, with quercetin and tinzaparin showing additional cytotoxic potential. Such dual effects may reduce thrombosis risk while impacting tumor progression, meriting further investigation.

PMID 42279366
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PubMedJournal of thrombosis and haemostasis : JTH2026-06-12

Trp83 is vital to the interaction with phospholipids in Gla domain of protein C.

Yuan Junwei J, Zhou Shijie S, Wu Xi X, Liu Yu Y et al.

Activated protein C is an important physiological anticoagulant protein. It can downregulate thrombin generation by inactivating coagulation factors Va and VIIIa, thereby exerting an anticoagulant effect. We identified that several families presenting with thrombosis harbored heterozygous mutations at the identical Trp83 residue of PROC, c.247T>C, p.Trp83Arg (W83R) and c.248G>C, p.Trp83Ser (W83S). While the mutations were previously reported in a large-scale screening of the Chinese population, functional studies to elucidate the pathogenic mechanisms remain uninvestigated. This study aims to evaluate the contribution of PC-W83R and PC-W83S mutations to thrombosis risk and to elucidate the specific pathogenic mechanisms. We expressed the recombinant PC-W83R and PC-W83S in mammalian cells and characterized their properties in established coagulation and anti-inflammatory assay systems. Both PC-W83R and PC-W83S were expressed at levels comparable to that of PC-WT. The activation rate of PC-W83R by thrombin was higher than that of WT, whereas the activation rate of PC-W83S was comparable to WT. However, when activated by the thrombin and thrombomodulin (TM) complex, both PC-W83R and PC-W83S variants exhibited reduced activation rates compared to PC-WT. The catalytic efficiency toward the chromogenic substrate was comparable to that of the wild type. Both mutants exhibited reduced interaction with phospholipids and led to a dramatically attenuated capacity for FVa inhibition. Additionally, the anti-inflammatory activity of APC-W83R and APC-W83S was also impaired. The W83R and W83S mutations impair the binding of PC to phospholipids, consequently leading to a substantial reduction in its anticoagulant function, which increases the thrombosis risk in patients.

PMID 42276270
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PubMedTranslational research : the journal of laboratory and clinical medicine2026-06-12

Immunothrombosis promotes the interaction between neutrophils and synovial fibroblasts in rheumatoid arthritis.

Papadimitriou Evangelos E, Natsi Anastasia-Maria AM, Tsironidou Victoria V, Eftalitsidis Evgenios E et al.

Rheumatoid arthritis (RA) is a chronic autoimmune disease marked by persistent synovial inflammation, yet the processes driving disease progression are not completely understood. Here, we examined the role of fibroblast-like synoviocytes (FLS) and neutrophils in RA pathophysiology, using primary FLS, neutrophils, and synovial fluid (SF) from RA and osteoarthritis (OA) patients, as well as healthy controls. Our findings demonstrate that FLS and neutrophils drive an immunothrombotic state in RA SF by expressing tissue factor (TF), an effect mediated by JAK1/2 signaling. Furthermore, we showed that RA SF stimulates IL-8 (CXCL8) expression in control FLS through PAR-1 signaling, and this response was attenuated by DNase I treatment and CIT-013, a monoclonal antibody targeting anti-citrullinated histones H2A and H4 in neutrophil extracellular traps (NETs), supporting the hypothesis that the effect is mediated by NETs. Notably, FLS derived from RA patients exhibit enhanced CXCL8 expression, and elevated IL-8 levels were detected in RA SF, both contributing to neutrophil recruitment, a process that could be mitigated through blockade with an anti-CXCL-8 neutralizing antibody. These results suggest an amplification loop in which TF expression, thrombin activity, and NET formation converge to activate FLS, sustain IL-8 mediated neutrophil migration, and perpetuate synovial inflammation, revealing how stromal and immune cells interact to propagate RA pathophysiology.

PMID 42276163
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PubMedBlood advances2026-06-11

Effect of PCC on Thrombin Generation in Patients on FXaI with Bleeding or Needing Urgent Surgery (GAUGE).

Shaw Joseph R JR, Gray Hannah H, Xu Yan Y, Le Gal Grégoire G et al.

Prothrombin complex concentrates (PCC) are used off-label to treat direct factor Xa inhibitor (FXaI)-associated bleeding or before urgent surgery. GAUGE was a prospective observational cohort study of the effects of PCC on thrombin generation and hemostasis in FXaI-treated patients. FXaI-treated patients with major bleeding or needing urgent surgery received PCC (50 IU/kg). Platelet-poor plasma was collected pre-/post-PCC. TGA parameters (LT=lag time, TTP=time-to-peak, peak, ETP=endogenous thrombin potential, mVRI=mean velocity rate index) were measured using calibrated automated thrombography. Hemostatic efficacy, thromboembolism, and mortality were adjudicated in duplicate. Multivariable log-linear regression was used to evaluate PCC effects on FXaI levels. Unsupervised K-means clustering was used to identify patients with the largest ETP increment. GAUGE included 101 episodes of FXaI-associated PCC use (FXaI-associated bleeding = 71; urgent surgery = 30). Median PCC dosing was 48.0 IU/kg [42.0-50.0]. PCC did not affect FXaI levels (p>0.05). PCC increased ETP (Δ868.9±766.6 nM·min), peak (Δ85.7 nM±108.2), and the mVRI (Δ16.5 nM/min [4.4-45.0]). PCC did not affect the LT or TTP (p>0.05). Patients in Cluster 1 had significantly lower pre-PCC FXaI levels (79 ng/mL [55-93] vs 165 ng/mL [77-219]; p = 0.009) and a greater ΔETP increment (p < 0.0001) than patients in Cluster 2. Effective hemostasis occurred in 50.0% [95%CI 38.4-61.6] of major bleeds; procedural hemostasis was normal in 76.7% [95%CI 59.1-88.2]. The 30-day risks of thromboembolism and mortality were 6.9% [95%CI 3.4-13.6] and 12.9% [95%CI 7.7-20.8], respectively. PCC increased quantitative thrombin generation without shortening LT or TTP, supporting a prohemostatic effect rather than true FXaI reversal.

PMID 42275536
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