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Thrombin
Antonio Arauz,Aurelio Jara,Jorge Guerrero,Miguel A. Barboza,Nayelli Argüelles
- , 2018, DOI: 10.1177/1076029618766267
Abstract: Thrombin-activatable fibrinolysis inhibitor (TAFI) gene polymorphisms have been proposed as a predisposing factor for cerebral venous thrombosis (CVT). We analyzed the association between CVT and TAFI single-nucleotide polymorphisms (rs3742264, rs2146881, and rs1926447) compared to healthy controls. Mexico Mestizo confirmed cases with CVT and age- and sex-matched controls with no history of venous thrombotic events were recruited from July 2006 to July 2015. Demographic, clinical, and imaging information was included in the analysis. Genotyping single-nucleotide polymorphisms were performed by allele-specific polymerase chain reaction. Allelic univariate analysis, haplotype association, and Hardy-Weinberg equilibrium were assessed. A total of 113 CVT cases (94 females [83.2%]; median age 35 years [interquartile range 27-43 years]) and 134 age- and sex-matched controls were included. The main risk factors for CVT were pregnancy/puerperium (30.9%), oral contraceptive use (19.5%), and hereditary thrombophilia (7.1%). We found no significant association for heterozygous and homozygous models for rs3742264 (P = .30 and P = .69, respectively), rs2146881 (P = .90 and P = .17, respectively), or rs1926447 (P = .40 and P = .52, respectively) compared to controls; these findings were consistent in subgroup and haplotype analyses. In conclusion, TAFI rs3742264, rs2146881, and rs1926447 polymorphisms do not increase the risk of CVT in comparison to healthy controls
Valor pronóstico de la concentración del inhibidor de la fibrinolisis activable por trombina y del polimorfismo C1040T en el infarto agudo de miocardio tratado con fibrinolisis
González,F.J.; Caturla,J.M.; Fernández,M.; Carrasco,R.; Marco,P.; Sánchez,J.; Benlloch,S.;
Medicina Intensiva , 2010,
Abstract: objective: to analyze the prognostic value of thrombin activatable fibrinolysis inhibitor (tafi) and c1040t polymorphism in acute myocardial infarction treated with fibrinolysis. to analyze c1040t polymorphism influence on its plasma level. design: an observational, prospective study performed from november 2003 to november 2005 and with a 3 month follow-up. setting: intensive medicine service from a university-affiliated teaching hospital. patients: a total of 53 patients with acute myocardial infarction with persistent st segment elevation treated with the same fibrinolytic therapy. a control group of 53 biologically similar subjects was included. interventions: none. main measurements: baseline characteristics; frequency of wild-type genotype (thr325thr) and of those corresponding to the mutation (thr325lle and lle325lle), tafi levels at 6h, 34h and 3 months post-fibrinolysis; ejection fraction; killip-kimball; reperfusion; ischemic recurrence; death. results: no relationship was found between biological features and tafi concentration. the latter was significantly higher in infarct patients (p<0.01) and in the mutation group (p<0.01). the homozygotic mutation (ile325ile) was significantly higher in infarct patients (p<0.01). reperfusion was significantly associated with lower body mass index (p=0.02. or 0.22. 95% ci), ejection fraction (p=0.004. or 0.91. 95% ci), triglyceride level (p=0.01. or 1.02. 95% ci) and cholesterol levels (p=0.001. or=0.84. 95% ci). mutation was associated to a significant fall in post-fibrinolysis concentration tafi antigen and functional tafi (p=0.01) and (p=0.02), and lower frequency of reperfusion. reperfusion was associated with a significant post-fibrinolysis reduction in the level of tafi antigen (p=0.02). recurrence was associated to a significantly higher post-fibrinolysis level (p=0.05. or=0.84. 95% ci). this was more frequent in mutation. post-fibrinolysis tafi antigen concentration was significantly lower in non-recurrence pa
Activated protein C plays no major roles in the inhibition of coagulation or increased fibrinolysis in acute coagulopathy of trauma-shock: a systematic review
Satoshi Gando,Tomohiko Ukai,Toshihiko Mayumi
- , 2018, DOI: 10.1186/s12959-018-0167-3
Abstract: The online version of this article (10.1186/s12959-018-0167-3) contains supplementary material, which is available to authorized users
Acute fibrinolysis shutdown occurs early in septic shock and is associated with increased morbidity and mortality: results of an observational pilot study
Felix Carl Fabian Schmitt,Florian Uhle,Herbert Sch？chl,Jakob Morgenstern,Markus Alexander Weigand,Mohammed Al-Saeedi,Stefan Heitmeier,Stefan Hofer,Thilo Hackert,Thomas Bruckner,Thomas Fleming,Vasil Manolov
- , 2019, DOI: 10.1186/s13613-019-0499-6
Abstract: The online version of this article (10.1186/s13613-019-0499-6) contains supplementary material, which is available to authorized users
Partial Characterization of Thrombin Inhibitor(s) Derived from Salivary Glands of the Tick, Hyalomma dromedarii, and Related Anti-Cancer Potential  [PDF]
Wessam S. Ibrahim, Fatma S. A. Mohamed, Walaa A. Moselhy, Emtithal M. Abdel Samie, Aly Fahmy Mohamed
Advances in Entomology (AE) , 2021, DOI: 10.4236/ae.2021.91001
Abstract: A long-term blood feeder, like the Hyalomma？dromedarii？tick, requires extended control over all hemostatic defense mechanisms generated by the host during feeding, including blood coagulation. To overcome this, ticks have evolved numerous molecules that target proteases in the blood coagulation cascade. New insights into the role of clotting factors in the development and progression of cancer have identified anticoagulant treatment as a potential therapeutic approach. In this context, the present work assessed the anticoagulation activities of crude and fractionated salivary gland extract (SGE) prepared from semi-fed H. dromedarii？females. Additionally, the antitumor effects of the potent anti-thrombin fractions were determined against colon cancer (Caco-2) and normal skin (HFB4) cells. Crude SGE significantly prolonged clotting time in prothrombin time (PT), activated partial thromboplastin time (aPTT) and thrombin time (TT) assays and inhibited thrombin in FII-activity assay. Using anion-exchange chromatography, the fractions that strongly inhibited thrombin (3.A4 and 3.A5) were eluted. Both fractions prolonged the aPTT and TT clotting times and reduced the activity of FII significantly. The protein profiles of both fractions indicated the presence of a single polypeptide band of about 99 kDa. Regarding anti-cancer potential of the tested fractions, Caco-2 cells showed reduced viability with obvious morphological changes, induced apoptosis and a reduced level of vascular endothelial growth factor (VEGF). G2/M cell cycle arrest was observed only in 3.A5-treated？cells. No cytotoxic effects were observed in HFB4 cells. These results demonstrated the potential of tick-derived anticoagulants, specifically thrombin inhibitors, as effective tools in colorectal cancer treatment. Further purification of the effector molecule(s) is required to fully characterize their structures and mechanisms of action.
Clinical and pharmacological properties of new oral anticoagulants for the prevention of cerebral thromboembolism: Factor Xa and thrombin inhibitors  [PDF]
Yaroslav Winter, Richard Dodel, Alexei Korchounov, Martin Grond, Wolfgang H. Oertel, Tobias Back
World Journal of Neuroscience (WJNS) , 2012, DOI: 10.4236/wjns.2012.21002
Abstract: Vitamin K antagonists, such as warfarin and phen-procoumon, are the first-line oral anticoagulants for primary and secondary prevention of cerebral embo-lism in patients with atrial fibrillation. Although vitamin K antagonists can significantly decrease the risk of stroke, their use is limited by several important drawbacks, such as a narrow therapeutic window, the risk of intracranial and gastrointestinal bleeding, interactions with a number of drugs and nutrients, and the need for regular laboratory tests for therapy adjustment. Currently, new oral anticoagulants, such as direct thrombin inhibitors (e.g., dabigatran) and direct factor Xa inhibitors (e.g., apixaban, rivaroxaban), are being developed and tested in clinical trials. Dabigatran and rivaroxaban were recently approved for prevention of cerebral embolism in patients with atrial fibrillation. The ad-vantages of dabigatran in comparison to warfarin are a lower rate of major bleedings with dabigatran 110mg bid, a better efficacy with dabigatran 150mg bid, no clinically relevant interactions with other drugs and no need for routine coagulation monitoring. The disadvantages are the absence of antidote and the absence of routine laboratory tests for precise mea-surements of anticoagulant effect of direct thrombin/ factor Xa inhibitors. This review will focus on throm-bin and factor Xa inhibitors, which are new and promising oral anticoagulants for the prevention of cerebral embolism. We will discuss their pharmacol-ogical and clinical properties and provide the most recent updates on their clinical trials.
Efecto de los anticuerpos antifosfolipídicos en la formación y degradación de la malla de fibrina en pacientes con aborto recurrente
Marchi,Rita; Maya,Imelda; Garmendia,Jenny;
Investigación Clínica , 2011,
Abstract: the present work was intended to study the process of fibrin formation and lysis and plasmin generation in a group of patients with recurrent miscarriage (rm), due to the presence of antiphospholipid antibodies (n= 10); as well as in women with rm without the antiphospholipid syndrome (aps) (n= 6), compared with those of a group of healthy women (n= 8). in the group of patients with aps, nine were positive for antibodies against cardiolipin (acl), five for anti-b2-glycoprotein i (anti-b2gpi), four for both antibodies, and one for antibodies against prothrombin (apt) and lupus anticoagulant (la). fibrin formation and lysis was followed by turbidity and plasmin generation using chromogenic substrate s2251. the polymerization curves from rm patients without aps and the la patient showed an increased slope and maximum turbidity compared to those of the control group. the speed of lysis was higher in the la patient (21 ± 0) 10-4 dod/seg and the rm patients without aps (19.6 ± 5.7) 10-4 ddo/seg, compared to that of the control group (14.5 ± 2.8) 10-4 ddo/seg. plasmin generation increased only in rm patients without aps (85 ± 24%) against the control group (52 ± 3%), p= 0.005. the changes observed in the fibrin polymerization and lysis process of women with rm without aps and la seem to be related to their higher fibrinogen levels, while the increased plasmin generation was related to the patients′ morbidity
Acute coagulation disorder in a critically ill patient – A case report
Agnes Oberhuber,Benedikt Treml,Dietmar Fries,Friesenecker Barbara,Griesmacher Andrea,Ingo H Lorenz
- , 2019, DOI: 10.1177/1751143718761847
Abstract: A 79-year-old critically ill woman presented with remarkable prolongation of activated partial thromboplastin time and thrombin time combined with high levels of anti-factor IIa activity 26 days after coronary artery bypass grafting. Coagulation disorder was associated with severe bleeding. Cause of coagulopathy was accidental administration of argatroban in an unknown dosage. Clearance of argatroban was significantly prolonged because of a liver function disorder related to septic multiorgan failure. Argatroban reversal was performed with prothrombin complex concentrate
Peculiarities of homeostatic system in highland conditions using llizarov distraction transosseous osteosynthesis method
Yerokhin A.N.,Isakov B.D.,Jumabekov S.A.
Saratov Journal of Medical Scientific Research , 2012,
Abstract: Purpose. The purpose is to study the reaction of homeostasis system in stable and in distraction llizarov transosseous ostesysnthesis of the limbs bones at experimental animals (dogs) in highland conditions. Material and Methods. 63 adult mongrels aged from 1 to 3 years with 10-20 kg body weight and 15 cm minimal length of tibia were included in the experiment. Open osteosotmy of tibial mid-shaft followed by Kirschner wires insertion through tibial bone and llizarov frame assembly comprising 3 or 4 rings was performed under IV anaesthesia at 3200 m altitude above sea level. In experimental group including 33 mongrels the distraction was performed on the 5th day after osteotomy by 1 mm rate divided into 4 times within 10 days but in control group comprising 30 dogs the distraction was not provided. Every 10 days after distraction blood samples were taken in both groups to examine coagulation; the samples were taken from subcutaneous lateral tibial vein, ex tempora mixing with 3,8% solution of sodium citrate at 9:1 ratio. Then the plasma was separated and examined biochemically according to the accepted standards. Results. We obtained the data witnessing activation of coagulation component of homeostatic system in stable osteosynthesis of the limb bones using llizarov fixator with simultaneous inhibition of fibrinolytic component. In distraction osteosynthesis hyper-coagulation trend in homeostasis system with simultaneous suppression of fibrinolytic blood activity is vividly defined within the entire experiment period. Conclusion. Transosseous distraction osteosynthesis in highland condition causes considerable shifts in the system of homeostasis with definite domination of coagulation component which promotes formation of pre-thrombotic condition. Limb segment lengthening on the background of pre-thrombotic condition increases the risk of thromboembolic complications in highland conditions and requires appropriate measures of prophylaxis
PAI-1 and t-PA/PAI-1 complex potential markers of fibrinolytic bleeding after cardiac surgery employing cardiopulmonary bypass
Ozolina Agnese,Strike Eva,Jaunalksne Inta,Krumina Angelika
BMC Anesthesiology , 2012, DOI: 10.1186/1471-2253-12-27
Abstract: Background Enhanced bleeding remains a serious problem after cardiac surgery, and fibrinolysis is often involved. We speculate that lower plasma concentrations of plasminogen activator inhibitor – 1 (PAI-1) preoperatively and tissue plasminogen activator/PAI-1 (t-PA/PAI-1) complex postoperatively might predispose for enhanced fibrinolysis and increased postoperative bleeding. Methods Totally 88 adult patients (mean age 66 ± 10 years) scheduled for cardiac surgery, were enrolled into a prospective study. Blood samples were collected pre-operatively, on admission to the recovery and at 6 and 24 hours postoperatively. Patients with a surgical bleeding that was diagnosed during reoperation were discarded from the study. The patients were allocated to two groups depending on the 24-hour postoperative chest tube drainage (CTD): Group I > 500ml, Group II ≤ 500ml. Associations between CTD, PAI-1, t-PA/PAI-1 complex and D-dimer were analyzed with SPSS. Results Nine patients were excluded because of surgical bleeding. Of the 79 remaining patients, 38 were allocated to Group I and 41 to Group II. The CTD volumes correlated with the preoperative plasma levels of PAI-1 (r = 0.3, P = 0.009). Plasma concentrations of preoperative PAI-1 and postoperative t-PA/PAI-1 complex differed significantly between the groups (P < 0.001 and P = 0.012, respectively). Group I displayed significantly lower plasma concentrations of fibrinogen and higher levels of D-dimer from immediately after the operation and throughout the first 24 hours postoperatively. Conclusions Lower plasma concentrations of PAI-1 preoperatively and t-PA/PAI-1 complex postoperatively leads to higher plasma levels of D-dimer in association with more postoperative bleeding after cardiac surgery.
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