They induced thrombosis in mice using FeCl3, which results in the formation free radicals followed by vascular endothelium injury

They induced thrombosis in mice using FeCl3, which results in the formation free radicals followed by vascular endothelium injury. initiated by contact activation of factor XII (FXII), which consequently activates plasma factor XI (FXI). Activated FXI (FXIa) then triggers factor IX activation and eventually leads to thrombin-mediated fibrin formation. Although FXIIa is an indispensable component for assessment of coagulation, congenital FXII deficiency is not associated with abnormally excessive bleeding, which may give the impression that FXII is not involved in the physiologic pathway of coagulation (4,5). However, blood contact with surfaces like extracorporeal membrane oxygenation (ECMO) system, hemodialysis membrane and catheters potentially leads to the activation of FXII and a subsequent high risk of thrombus formation (6). Since the use of conventional anticoagulants including heparin is associated with bleeding, new strategies seem to be necessary in this setting to avoid excessive bleeding after surgical operation. Considering these facts, one could imagine that FXII targeting is one of the promising strategies to fulfill this aim. Recently, in a study by Larsson in journal entitled A factor XIIa inhibitory antibody provides thromboprotection in extracorporeal circulation without increasing bleeding risk, it was attempted to evaluate this strategy (7). They developed a recombinant antibody against FXII by phage study. This antibody, also known as Ro 61-8048 3F7, specifically binds to the triggered FXII and not to the zymogen form, and therefore inhibits its proteolytic activity (7). Even though mentioned study was not the 1st attempt in this respect, it resulted in important findings by using both human being and animal plasma. There is also a earlier series of experiments primarily on animal models assessing different inhibitors of FXII or FXIIa. According to a valuable review by Kenne is the most recent experiment introducing a new anti-FXIIa neutralizing antibody. In the described study, analysis of clotting activity using rabbit and human being blood showed that Ro 61-8048 3F7 prolongs triggered partial thromboplastin time (aPTT) in both varieties with more effectiveness in rabbit but was not effective upon prothrombin time (PT) (7). The authors then investigated function of 3F7 action. They induced thrombosis in mice using FeCl3, which results in the formation free radicals followed by vascular endothelium injury. 3F7 safeguarded mice from thrombosis, and the blood collected from mice showed long term aPTT with no effect on PT. This result was similar with FXII?/? mice, which were all safeguarded from vessel-occlusive thrombus formation. Subsequently, 3F7 effect was assessed in larger animals, which provides more predictive ideals on anticoagulant connected bleedings in humans. For this purpose, the rabbits were treated with microglass chamber comprising shunt to assess thrombus formation. Chamber occlusion was inhibited in the animal treated with 3F7 and heparin, but not in saline-treated control group. However, 3F7 and heparin both provide similar thromboprotection but the effect of heparin on hemostasis was associated with long term bleeding time and improved bleeding from pores and skin and kidney wounds compared with 3F7. These data are consistent with long term PT induced by heparin but not by 3F7 (7). Finally, the authors offered a model of cardiopulmonary bypass using an ECMO system in rabbits to analyze the clinical software of 3F7. Circulation of blood in this system is definitely subject to thrombotic events without the use of anticoagulants. Administration of heparin in the same dose used for individual helps prevent thrombotic occlusion, whereas a single dose of 3F7 introduces a similar thromboprotection. As individuals undergo heparin therapy, administration of heparin to rabbits is definitely associated with impaired hemostasis and improved blood loss at wound sites, which was not observed in animals treated with 3F7 (7). Relating to Ro 61-8048 these findings, inhibition of FXIIa seems to be a new approach of anticoagulation, as 3F7 showed the same effectiveness of heparin but did not lead to excessive hemorrhage during invasive procedures. However, further experimental studies especially on human being models are necessary for better investigation of the effectiveness and probable risks of FXII inhibition methods for avoiding thrombosis. Acknowledgements The authors declare no discord of interest..There is also a previous series of experiments mainly on animal models assessing different inhibitors of FXII or FXIIa. deficiency is not associated with abnormally excessive bleeding, which may give the impression that FXII is not involved in the physiologic pathway of coagulation (4,5). However, blood contact with surfaces like extracorporeal membrane oxygenation (ECMO) system, hemodialysis membrane and catheters potentially leads to the activation of FXII and a subsequent high risk of thrombus formation (6). Since the use of standard anticoagulants including heparin is definitely associated with bleeding, fresh strategies seem to be necessary in this establishing to avoid excessive bleeding after medical operation. Considering these facts, one could imagine that FXII targeting is one of the promising strategies to fulfill this goal. Recently, in a study by Larsson in journal entitled A factor XIIa inhibitory antibody provides thromboprotection in extracorporeal blood circulation without increasing bleeding risk, it was attempted to evaluate this strategy (7). They developed a recombinant antibody against FXII by phage study. This antibody, also known as 3F7, specifically binds to the triggered FXII and not to the zymogen form, and therefore inhibits its proteolytic activity (7). Even though mentioned study was not the 1st attempt in this respect, it resulted in valuable findings by using both human being and animal plasma. There is also a previous series of experiments mainly on animal models assessing different inhibitors of FXII or FXIIa. Relating to a valuable review by Kenne is the most recent experiment introducing a new anti-FXIIa neutralizing antibody. In the described study, analysis of clotting activity using rabbit and human being blood showed that 3F7 prolongs triggered partial thromboplastin time (aPTT) in both varieties with more effectiveness in rabbit but was not effective upon prothrombin time (PT) (7). The authors then investigated function of 3F7 action. They induced thrombosis in mice using FeCl3, which results in the formation free radicals followed by vascular endothelium injury. 3F7 safeguarded mice from thrombosis, and the blood collected from mice showed long term aPTT with no effect on PT. This result was similar with FXII?/? mice, which were all safeguarded from vessel-occlusive thrombus formation. Subsequently, 3F7 effect was assessed in larger animals, which provides more predictive ideals on anticoagulant connected bleedings in humans. For this purpose, the rabbits were treated with microglass chamber comprising shunt to assess thrombus formation. Chamber occlusion was inhibited in the animal treated with 3F7 and heparin, but not in saline-treated control group. However, 3F7 and heparin both provide similar thromboprotection but the effect of heparin on hemostasis was associated with long term bleeding time and improved bleeding from pores and skin and kidney wounds compared with 3F7. These data are consistent with long term PT induced by heparin but not by 3F7 (7). Finally, the authors offered a model of cardiopulmonary bypass using an ECMO system in rabbits to analyze the clinical software of 3F7. Circulation of blood in this system is subject to thrombotic events without the use of anticoagulants. Administration of heparin in the same dose used for individual helps prevent thrombotic occlusion, whereas a single dose of 3F7 introduces a similar thromboprotection. As individuals undergo heparin therapy, administration of heparin to rabbits is definitely associated with impaired hemostasis and improved blood loss at wound sites, which was not observed in animals treated with 3F7 (7). Relating to these findings, inhibition of FXIIa seems to be a new approach of anticoagulation, as 3F7 showed the same effectiveness of heparin but did not lead to excessive hemorrhage during invasive procedures. However, further experimental studies especially.However, 3F7 and heparin both provide related thromboprotection but the effect of heparin about hemostasis was associated with long term bleeding time and improved bleeding from pores and skin and kidney wounds compared with 3F7. by contact activation of element XII (FXII), which as a result activates plasma element XI (FXI). Activated FXI (FXIa) then triggers element IX activation and eventually prospects to thrombin-mediated fibrin formation. Although FXIIa is an indispensable component for assessment of coagulation, congenital FXII deficiency is not associated with abnormally excessive bleeding, which may give the impression that FXII is not involved in the physiologic pathway of coagulation (4,5). However, blood contact with surfaces like extracorporeal membrane oxygenation (ECMO) system, hemodialysis membrane and catheters potentially leads to the activation of FXII and a subsequent high risk of thrombus formation (6). Since the use of standard anticoagulants including heparin is usually associated with bleeding, new strategies seem to be necessary in this establishing to avoid excessive bleeding after surgical operation. Considering these facts, one could imagine that FXII targeting is one of the promising strategies to fulfill this aim. Recently, in a study by Larsson in journal entitled A factor XIIa inhibitory antibody provides thromboprotection in extracorporeal blood circulation without increasing bleeding risk, it was attempted to evaluate this strategy (7). They developed a recombinant CD271 antibody against FXII by phage study. This antibody, also known as 3F7, specifically binds to the activated FXII and not to the zymogen form, and thereby inhibits its proteolytic activity (7). Even though mentioned study was not the first attempt in this respect, it resulted in valuable findings by using both human and animal plasma. There is also a previous series of experiments mainly on animal models assessing different inhibitors of FXII or FXIIa. According to a valuable review by Kenne is the most recent experiment introducing a new anti-FXIIa neutralizing antibody. In the pointed out study, analysis of clotting activity using rabbit and human blood showed that 3F7 prolongs activated partial thromboplastin time (aPTT) in both species with more efficiency in rabbit but was not effective upon prothrombin time (PT) (7). The authors then investigated function of 3F7 action. They induced thrombosis in mice using FeCl3, which results in the formation free radicals followed by vascular endothelium injury. 3F7 guarded mice from thrombosis, and the blood collected from mice showed prolonged aPTT with no effect on PT. This result was comparable with FXII?/? mice, which were all guarded from vessel-occlusive thrombus formation. Subsequently, 3F7 effect was assessed in larger animals, which provides more predictive values on anticoagulant associated bleedings in humans. For this purpose, the rabbits were treated with microglass chamber made up of shunt to assess thrombus formation. Chamber occlusion was inhibited in the animal treated with 3F7 and heparin, but not in saline-treated control group. However, 3F7 and heparin both provide similar thromboprotection but the effect of heparin on hemostasis was associated with prolonged bleeding time and increased bleeding from skin and kidney wounds compared with 3F7. These data are consistent with prolonged PT induced by heparin but not by 3F7 (7). Finally, the authors offered a model of cardiopulmonary bypass using an ECMO system in rabbits to analyze the clinical application of 3F7. Circulation of blood in this system is subject to thrombotic events without the use of anticoagulants. Administration of heparin in the same dose used for individual prevents thrombotic occlusion, whereas a single dose of 3F7 introduces a similar thromboprotection. As patients undergo heparin therapy, administration of heparin to rabbits is usually associated with impaired hemostasis and increased blood loss at wound sites, which was not observed in animals treated with 3F7 (7). According to these findings, inhibition of FXIIa seems to be a new approach of anticoagulation, as 3F7 showed the same efficacy of heparin but did.