Thrombin

Optimal management of cardiovascular disease (CVD) in people with haemophilia (PWH) is a growing issue, given the continuing improvement in life expectancy among PWH. The evolving treatment paradigms targeting higher trough levels and the advent of non-factor replacement therapies (NFRT) means much of the 'protection' PWH were thought to have against CVD may be lost. There is a paucity of evidence regarding the safety of using anticoagulants in PWH. We designed a study assessing the thrombin generation (TG) of PWH of different severities and treatments, compared to non-haemophilia patients receiving a Factor Xa (FXa) inhibitor (apixaban or rivaroxaban), healthy controls, and assessing TG parameters of adding FXa inhibitor to the plasma of PWH receiving emicizumab prophylaxis...

Platelet aggregation is a complicated process mediated by different signaling pathways. As the process is highly complex and apparently redundant, the relationships between these pathways are not yet fully known. The aim of this project was to study the interconnections among seven different aggregation pathways in a group of 53 generally healthy volunteers aged 20 to 66 years. Platelet aggregation was induced with thrombin receptor activating peptide 6 (TRAP), arachidonic acid (AA), platelet activating factor 16 (PAF), ADP, collagen, thromboxane A2 analogue U46619 or ristocetin (platelet agglutination) ex vivo in fasting blood samples according to standardized timetable protocol...

DNA origami, a method for constructing nanostructures from DNA, offers potential for diverse scientific and technological applications due to its ability to integrate various molecular functionalities in a programmable manner. In this study, we examined the impact of internal crossover distribution and the compositional uniformity of staple strands on the structure of multilayer DNA origami using cryogenic electron microscopy (cryo-EM) single-particle analysis. A refined DNA object was utilized as an alignment framework in a host-guest model, where we successfully resolved an 8 kDa thrombin binding aptamer (TBA) linked to the host object...

Macrocycles offer an attractive format for drug development due to their good binding properties and potential to cross cell membranes. To efficiently identify macrocyclic ligands for new targets, methods for the synthesis and screening of large combinatorial libraries of small cyclic peptides were developed, many of them using thiol groups for efficient peptide macrocyclization. However, a weakness of these libraries is that invariant thiol-containing building blocks such as cysteine are used, resulting in a region that does not contribute to library diversity but increases molecule size...

BACKGROUND: Despite systematic thromboprophylaxis, 30% of the COVID-19 patients in intensive care units develop thrombosis. This occurrence is associated with a hypofibrinolytic state measured by thromboelastometry when adding tissue plasminogen activator (tPA) to citrated whole blood for a further run for EXTEM (ROTEM). OBJECTIVES: Because hydroxyethyl starches (HESs) affect fibrin polymerization, we have assessed its potential effect on in vitro tPA-induced fibrinolysis...

The microvascular network plays an important role in providing nutrients to the injured tissue and exchanging various metabolites. However, how to achieve efficient penetration of the injured tissue is an important bottleneck restricting the reconstruction of microvascular network. Herein, the hydrogel precursor solution can efficiently penetrate the damaged tissue area, and ultrasound triggers the release of thrombin from liposomes in the solution to hydrolyze fibrinogen, forming a fibrin solid hydrogel network in situ with calcium ions and transglutaminase as catalysts, effectively solving the penetration impedance bottleneck of damaged tissues and ultimately significantly promoting the formation of microvascular networks within tissues...

BACKGROUND: Andexanet alfa is a Gla-domainless mutant (S195A) factor Xa (GDXa) approved for acute reversal of oral factor Xa inhibitors. Cardiac surgery patients exposed to andexanet before cardiopulmonary bypass often exhibit severe heparin resistance. There is a paucity of data on the effectiveness and optimal dosage of antithrombin use in this setting. The objective of this study was to evaluate the in vitro effect of increased heparin with antithrombin levels on attenuating heparin resistance induced by GDXa...

Plasma kallikrein (PKa) is an important activator of factor (F)XII of the contact pathway of coagulation. Several studies have shown that PKa also possesses procoagulant activity independent of FXII, likely through its ability to directly activate FIX. We evaluated the procoagulant activity of PKa using a mouse whole blood (WB) thrombin generation (TG) assay. TG was measured in WB from PKa-deficient mice using contact pathway or extrinsic pathway triggers. PKa-deficient WB had significantly reduced contact pathway-initiated TG compared to wild-type controls and was comparable to that observed in FXII-deficient WB...

The paper presents the investigation of the biological properties of Poly(Lactide)-Copper composite material obtained by sputter deposition of copper onto Poly(lactide) melt-blown nonwoven fabrics. The functionalized composite material was subjected to microbial activity tests against colonies of Gram-positive ( Staphylococcus aureus ), Gram-negative ( Escherichia coli , Pseudomonas aeruginosa ) bacteria, Chaetomium globosum and Candida albicans fungal mold species and biochemical-hematological tests including the evaluation of the Activated Partial Thromboplastin Time, Prothrombin Time, Thrombin Time and electron microscopy fibrin network imaging...

Colon adenocarcinoma (COAD) is a common cause of cancer-related death. Due to the difficulty in early diagnosis and drug resistance, conventional treatments are difficult to be effective. Some studies have found that the functional recovery of T cells in the tumor microenvironment, especially regulatory T cells (Tregs), plays an important role in the progression of cancer. This study used the TCGA data set, clinical information and RNA-seq data of COAD patients to construct a Tregs-related risk score (TRS) through methods such as WGCNA, single-factor Cox, multi-factor Cox and random survival forest (RSF)...

Thyrocervical trunk pseudoaneurysms are a rare entity among pseudoaneurysms, mostly caused by trauma. We present the case of a 74-year-old male who suffered a traumatic pseudoaneurysm of the supra-scapular artery after a rib and scapular fracture. The patient was treated with various interventions along the treatment algorithm, including ultrasound-guided thrombin injection, coil embolization, and surgical excision. In our patient, the pseudoaneurysm was successfully treated with coil embolization, but a persistent thrombosed pseudoaneurysm caused the patient discomfort, prompting the eventual surgical removal...

Pseudoaneurysm development is a well-recognized consequence of arterial injury, frequently observed in procedures involving arterial groin access. Breast emergencies are infrequent but need prompt attention. We present a notable case of breast pseudoaneurysm postcore needle biopsy, incidentally, identified through subsequent magnetic resonance imaging. Remarkably, the patient's lactating status emerged as a unique risk factor. Our report thoroughly explores the pathogenesis, etiology, preventive measures, and treatment strategies specific to breast pseudoaneurysms...

INTRODUCTION: Refrigeration of platelets is considered to provide advantages in therapy of acute hemorrhage due to increased platelet responsiveness. The alleviation of inhibitory signaling caused by cold temperature (CT) has been identified as an important mechanism contributing to enhanced platelet reactivity, detectable in freshly prepared platelets within 1 h of cold storage. The aim of this study was to confirm the effects of short-term refrigeration in platelets from apheresis-derived platelet concentrates (APC)...

BACKGROUND: Emicizumab has been approved for the prophylaxis of patients with hemophilia A with or without inhibitors. However, spontaneous and trauma-induced breakthrough bleeds have been reported in patients on emicizumab prophylaxis and no laboratory assay is validated to evaluate the hemostatic activity of emicizumab . OBJECTIVES: The thrombin generation assay (TGA) could be a surrogate marker of the hemostatic efficacy of emicizumab. The correlation between TGA and the methods used to measure emicizumab blood concentration was evaluated in this study...

BACKGROUND: Thrombin, a coagulation system protease, is a key enzyme involved in the coagulation cascade and has been developed as a marker for coagulation disorders. However, the methods developed in recent years have the disadvantages of complex operation, long reaction time, low specificity and sensitivity. Meanwhile, thrombin is at a lower level in the pre-disease period. Therefore, to accurately diagnose the disease, it is necessary to develop a fast, simple, highly sensitive and specific method using signal amplification technology...

Despite rapid technological advancement in factor and nonfactor products in the prevention and treatment of bleeding in haemophilia patients, it is imperative that we acknowledge gaps in our understanding of how hemostasis is achieved. The authors will briefly review three unresolved issues in persons with haemophilia (PwH) focusing on the forgotten function that red blood cells play in hemostasis, the critical role of extravascular (outside circulation) FIX in hemostasis in the context of unmodified and extended half-life FIX products and finally on the role that skeletal muscle myosin plays in prothrombinase assembly and subsequent thrombin generation that could mitigate breakthrough muscle hematomas...

OBJECTIVE: To demonstrate the non-inferiority of the novel hemostatic agent, Hemofence® (BMI Korea Co. Ltd., Jeju Korea, thrombin cross-linked sodium hyaluronate gel matrix) compared to the established agent, Floseal Hemostatic Matrix (Baxter, thrombin-gelatin matrix) in achieving hemostasis for spinal surgeries, with secondary objectives to assess additional efficacy and safety. METHODS: This clinical trial was a multicenter, randomized, subject-blinded, active-controlled, parallel-group, phase 3 study...

PURPOSE: Radiation therapy (RT) plays an important role in the treatment of glioblastoma multiforme (GBM). However, inherent intrinsic resistance of tumors to radiation, coupled with the need to consider the tolerance of normal tissues and the potential effects on neurocognitive function, impose constraints on the amount of RT that can be safely delivered. A strategy for augmenting the effectiveness of RT involves the utilization of radiation sensitizers (RS). Directly implanting RS-loaded fibrin glue (FG) into the tumor resection cavity would by-pass the blood brain barrier, potentially enhancing the impact of RT on tumor recurrence...

Despite the prognostic effect of physical activity, acute bouts of high-volume endurance exercise can induce cardiac stress and post-exercise hypercoagulation associated with increased thrombotic risk. The aim of this study was to explore the effect of high-volume endurance exercise on coagulation and thrombotic activity in recreational cyclists. Thirty-four recreational cyclists completed 4.8 ± 0.3 hours cycling at 45 ± 5% of maximal power output on a bicycle ergometer. Intravenous blood samples were collected pre-exercise, immediately post-exercise, 24 and 48 hours post-exercise and analysed for brain natriuretic peptide (BNP), cardiac troponin (cTn), C-reactive protein (CRP), D-dimer, thrombin-antithrombin (TAT) complex, tissue factor (TF), tissue factor pathway inhibitor (TFPI) and TF to TFPI ratio (TF:TFPI)...

Brachial artery pseudoaneurysms are a rare entity, which can occur secondary to infectious, traumatic, or iatrogenic causes. We present a 78-year-old female with end-stage renal disease on hemodialysis via a right brachio-basilic arteriovenous fistula. She had previously undergone numerous fistulograms and endovascular interventions for right upper extremity swelling due to prolonged bleeding following dialysis. After a recent fistulogram she developed recurrent arm swelling. Duplex showed a large hematoma without any evidence of vascular flow...