Antithrombin

Subclinical bioprosthetic valve thrombosis (BPVT) is a relatively common finding in asymptomatic patients during follow-up imaging. However, its clinical significance is unclear. Data from registries associate BPVT with elevated valve gradients, thromboembolic complications, recurrence, and valve degeneration. Given the dynamic nature of the disease process, management is challenging. The duration of anticoagulation is unpredictable, and the need for frequent monitoring of BPVT, even in subclinical scenarios, is unclear...

To investigate the effect of reduced early-pregnancy activated partial thrombin time (APTT), prothrombin time (PT), and international standardized ratio (INR) on the risk of preeclampsia. A total of 8549 pregnant women with singleton births were included. Early pregnancy APTT, PT, and INR levels, with age, birth, prepregnancy body mass index, fibrinogen (FBG), thrombin time (TT), D-dimer (DD2), antithrombin III (ATIII), fibrin degradation products (FDP) as confounders, generalized linear model of APTT, the relative risk of PT and INR when INR reduction...

Nonocclusive mesenteric ischemia (NOMI) is a life-threatening disorder. Early diagnosis is challenging because NOMI lacks specific symptoms. A 52-year-old man who received extended cholecystectomy with Roux-en-Y hepaticojejunostomy for gallbladder cancer (GBC) presented to our hospital with nausea and vomiting. Neither tender nor peritoneal irritation sign was present on abdominal examination. Blood test exhibited marked leukocytosis (WBC:19,800/mm3). A contrast-enhanced abdominal computed tomography (CT) scan revealed remarkable wall thickening and lower contrast enhancement effect localized to Roux limb...

BACKGROUND AND AIMS: Uncertainty of the causality determinations for ambient ozone (O3 ) on cardiovascular events is heightened by the limited understanding of the mechanisms involved in humans. We aimed to examine the pro-atherothrombotic impacts of O3 exposure and to explore the potential mediating roles of dysfunctional neutrophils, focusing on neutrophil extracellular traps (NETs). METHODS: A longitudinal panel study of 152 healthy adults was conducted in the cool to cold months with relatively low levels of O3 between September 2019 and January 2020 in Beijing, China...

Protein C inhibitor (PCI) maintains hemostasis by inhibiting both procoagulant and anticoagulant serine proteases, and plays important roles in coagulation, fibrinolysis, reproduction, and anti-angiogenesis. The reactive site loop of PCI traps and irreversibly inhibits the proteases like APC (activating protein C), thrombin (FIIa) and factor Xa (FXa). Previous studies on antithrombin (ATIII) had identified Tyr253 and Glu255 as functional exosites that interact and aid in the inhibition of factor IXa and FXa...

Insufficient data exist regarding the investigation of the impact of novel oral anticoagulants (NOACs) on coagulation activation biomarkers in the context of left atrial appendage closure (LAAC) and device-related thrombosis (DRT). The study was designed to investigate the changes and presence of coagulation activation biomarkers between different antithrombotic strategies following LAAC. A total of 120 nonvalvular atrial fibrillation patients intolerant of long-term anticoagulants, who underwent successful WATCHMAN closure implantation, were enrolled (rivaroxaban, n = 82; dabigatran, n = 38)...

BACKGROUND: Venous thromboembolism(VTE)is a common multifactorial disease. Anticoagulant protein deficiency is the most usual hereditary thrombophilia in the Chinese people, which includes protein C(PC), protein S and antithrombin deficiencies. CASE PRESENTATION: A retrospective analysis was conducted on clinical manifestations, laboratory tests, genetic information, and other relevant data of siblings diagnosed with VTE in 2020 at the Department of Pediatrics of Shenzhen Second People's Hospital...

Deep vein thrombosis (DVT) is caused by a clot (thrombus) formed in the deep veins, usually the legs. The incidence of DVT is notably less prevalent in children than in adults. Here, we present a rare case of DVT in an eight-year-old female child with a significant family history involving the untimely death of the maternal aunt. The child presented with pain and edema in the left lower limb causing immobilization without any obvious cause. The clinical features suggested the possibility of DVT. On further evaluation and radiological investigations, the diagnosis of DVT was confirmed...

While direct oral anticoagulants (DOACs) are frequently used to treat venous thromboembolism (VTE), the outcomes of patients with inherited thrombophilia (IT) receiving DOACs for VTE remain understudied. We used data from the international RIETE registry to compare the rates of VTE recurrences, major bleeding, and mortality during anticoagulant treatment in VTE patients with and without IT, grouped by the use of DOACs or standard anticoagulant therapy. Among 103,818 enrolled patients, 21,089 (20.3%) were tested for IT, of whom 8422 (39...

OBJECTIVE: Breastfeeding is associated with a reduced maternal risk for cardiovascular diseases. Since the underlying mechanisms are still poorly understood, we here examined the impact of breastfeeding on the plasmatic coagulation system in women with and without history of gestational diabetes mellitus (GDM). METHODS: 76 participants of the German Gestational Diabetes Study (PREG; NCT04270578) were examined 14 [interquartile range: 12-26] months after delivery with a 5-point oral glucose tolerance test...

BACKGROUND: Recently, we have shown alterations in the anticoagulant response to recombinant activated factor VII (rFVIIa)-induced coagulation activation in patients with thrombophilia. OBJECTIVES: This study aimed to extend this in vivo model to fibrinolysis biomarkers. METHODS: This interventional in vivo study included 56 patients with thrombophilia and previous venous thromboembolism (VTE+), 38 without VTE (VTE-), and 35 healthy controls...

Antithrombin (AT) is the major plasma inhibitor of thrombin (FIIa) and activated factor X (FXa), and antithrombin deficiency (ATD) is one of the most severe thrombophilic disorders. In this study, we identified nine novel AT mutations and investigated their genotype-phenotype correlations. Clinical and laboratory data from patients were collected, and the nine mutant AT proteins (p.Arg14Lys, p.Cys32Tyr, p.Arg78Gly, p.Met121Arg, p.Leu245Pro, p.Leu270Argfs*14, p.Asn450Ile, p.Gly456delins_Ala_Thr and p.Pro461Thr) were expressed in HEK293 cells; then, Western blotting, N-Glycosidase F digestion, and ELISA were used to detect wild-type and mutant AT...

BACKGROUND: Thrombophilia is a coagulation disorder closely associated with venous thromboembolism. Hereditary antithrombin III (AT III) deficiency is a type of genetic thrombophilia. In China, genetic thrombophilia patients mainly suffer from deficiencies in AT III, protein S, and protein C. Multiple mutations in the serpin family C member 1 (SERPINC1) can affect AT III activity, resulting in thrombosis. CASE PRESENTATION: This case presented a 17-year-old adolescent female who developed lower extremity venous thrombosis and subsequently pulmonary embolism (PE) following a right leg injury...

INTRODUCTION: Despite older adults being more vulnerable to sepsis, most preclinical research on sepsis has been conducted using young animals. This results in decreased scientific validity since age is an independent predictor of poor outcome. In this study, we explored the impact of aging on the host response to sepsis using the fecal-induced peritonitis (FIP) model developed by the National Preclinical Sepsis Platform (NPSP). METHODS: C57BL/6 mice (3 or 12 months old) were injected intraperitoneally with rat fecal slurry (0...

Anticoagulation is an essential component of optimal extracorporeal membrane oxygenation (ECMO) management. Unfractionated heparin is still the anticoagulant of choice in most centers due to longstanding familiarity with the agent. Disadvantages include alterations in drug responses due to its capability to bind multiple heparin-binding proteins that compete with antithrombin and the potential for heparin-induced thrombocytopenia. In such cases, direct thrombin inhibitors are the treatment of choice but pose difficulties in monitoring due to the limited experience and target ranges for non-aPTT-guided management (aPTT: activated partial thromboplastin time)...

BACKGROUND: Coagulopathy is a major cause of morbidity and mortality in COVID-19 patients. Hypercoagulability in COVID-19 results in deep vein thrombosis, thromboembolic complications, and diffuse intravascular coagulation. Microbiome dysbiosis influences the clinical course of COVID-19. However, the role of dysbiosis in COVID-19-associated coagulopathy is not fully understood. OBJECTIVES: The present study tested the hypothesis that the microbiota-derived proapoptotic corisin is involved in the coagulation system activation during SARS-CoV-2 infection...

Fitusiran, a subcutaneous (SC) investigational siRNA therapeutic, targets antithrombin to rebalance hemostasis in people with hemophilia A or B (PwHA/B), irrespective of inhibitor status. This Phase 3, open-label study (NCT03549871) evaluated the efficacy and safety of fitusiran prophylaxis in males aged ≥ 12 years with hemophilia A or B, with or without inhibitors, who received prior bypassing agent (BPA)/clotting factor concentrate (CFC) prophylaxis. Participants continued their prior BPA/CFC prophylaxis for 6 months before switching to once-monthly 80 mg fitusiran prophylaxis for 7 months (onset and efficacy periods)...

OBJECTIVE: To analyze the clinical phenotype and genetic characteristics of a Chinese pedigree affected with Hereditary antithrombin deficiency. METHODS: A pedigree diagnosed at the the Second Affiliated Hospital of Wenzhou Medical University, Yuying Children's Hospital in June, 2020 was selected as the study subject. Plasma prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), and thrombin time (TT) of the probands and their pedigree members were determined using a STA-R automatic coagulation analyzer...

BACKGROUND: Antithrombin (AT) is a natural anticoagulant and potent inhibitor of several coagulation proteins, including activated factor X (FXa) and FIIa. The therapeutic activity of heparin depends on the presence of AT. Levels of plasma AT are low in neonates and young infants compared to those in adults. Exogenous AT supplementation is postulated to enhance the activity of heparin and facilitate attainment of therapeutic anticoagulation in infants. OBJECTIVES: To describe the efficacy and safety of AT administration in infants on a continuous heparin infusion...

BACKGROUND: Factor (F)IXa activity has been detected in human plasma and may impact thrombotic risk. Current FIXa activity assays are complex and cumbersome. OBJECTIVES: To develop a reproducible enzyme-linked immunosorbent assay (ELISA) using a novel monoclonal antibody that detects total FIXa in human plasma. METHODS: A monoclonal antibody was raised against the new N-terminus exposed upon activation of FIX to FIXa by cleavage after R226...