Role of the Contact System in Fibrinolysis

Kluft, C.; Dooijewaard, G.; Emeis, J.J.

doi:10.1055/s-2007-1003475

Cited by 154 publications

(87 citation statements)

References 128 publications

(172 reference statements)

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“…In addition to cell cycle related genes such as cyclin D1 and p27, one group of KLF5-induced genes, including RAIG1, 36 EMP1, 37 and Dri42, 38 has been implicated in cellular differentiation. Another group of KLF5-responsive genes, including PDGFA, TGFA, B94, and HBP17, has been implicated in angiogenesis [39][40][41] (Table 1). More studies are needed to determine whether and how these specific target genes mediate different functions of KLF5 in different biological processes.…”

Section: Discussionmentioning

confidence: 99%

KLF5 promotes cell proliferation and tumorigenesis through gene regulationin the TSU-Pr1 human bladder cancer cell line

et al. 2005

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KLF5 is a transcription factor that plays important roles in multiple physical and pathological processes, including cell growth, cell cycle regulation, and angiogenesis. To better characterize KLF5 function in bladder carcinogenesis, we established stable TSU-Pr1 cell clones expressing different levels of KLF5. These clones were then characterized for cell growth, cell cycle progression, tumorigenesis, and alteration in gene expression. Overexpression of KLF5 promoted tumorigenesis of the TSU-Pr1 cancer cells in mice. Consistently, KLF5 increased G1 to S phase transition, which was accompanied by the upregulation of cyclin D1, phosphorylation of MAPK and Akt, and reduced protein levels for CDK inhibitors p27 and p15. Microarray analysis combined with expression verification in different cell systems identified a number of additional genes that are potentially regulated by KLF5, including HBP17, ITGA6, and RAIG1. These findings suggest that the KLF5 transcription factor plays an oncogenic role in the TSU-Pr1 bladder cancer cell line through the regulation of a subset of genes. ' 2005 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

KLF5 promotes cell proliferation and tumorigenesis through gene regulationin the TSU-Pr1 human bladder cancer cell line

et al. 2005

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“…17 Activation of kallikrein results in the formation of bradykinin, a potent stimulator of tPA release from endothelial cells. 18 In vitro studies have indicated that aprotinin concentrations greater than 200 KIU/mL are required for adequate inhibition of kallikrein. 19 We previously showed that plasma concentrations of approximately 100 KIU/mL were obtained with the regular-dose regimen, and concentrations of 200 to 300 KIU/mL, with the high-dose regimen.…”

Section: Discussionmentioning

confidence: 99%

Aprotinin in orthotopic liver transplantation: Evidence for a prohemostatic, but not a prothrombotic, effect

Molenaar

2001

Liver Transplantation

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Aprotinin reduces blood transfusion requirements in orthotopic liver transplantation (OLT). Concern has been voiced about the potential risk for thrombotic complications when aprotinin is used. The aim of this study is to evaluate the effects of aprotinin on the two components of the hemostatic system (coagulation and fibrinolysis) in patients undergoing OLT. As part of a larger, randomized, double-blind, placebo-controlled study, we compared coagulation ( H emostasis is the overall result of a balance between two proteolytic cascades: the coagulation and fibrinolytic systems. In end-stage liver disease, the delicate balance between coagulation and fibrinolysis is often disturbed. 1,2 One problem encountered in orthotopic liver transplantation (OLT) is the occurrence of hyperfibrinolysis, mainly caused by increased levels of tissue-type plasminogen activator (tPA). 3,4 Especially during the anhepatic and postreperfusion periods, tPA plasma levels are significantly increased, resulting in consumption of its naturally occurring inhibitor, plasminogen activator inhibitor (PAI-1). 5,6 High tPA activity during OLT stimulates the conversion of plasminogen into plasmin, which causes premature degradation of fibrin clots and subsequent increased blood loss and transfusion requirements. 6 Aprotinin is a serine protease inhibitor derived from bovine lung. 7 It has the ability to inhibit a wide range of proteases that have serine residues at their active site, such as plasmin, kallikrein, and trypsin, by forming reversible stoichiometric enzyme-inhibitor complexes. Inhibition of plasmin and kallikrein results in a strong reduction in fibrinolysis. Neuhaus et al 8 first reported on the blood-sparing effect of aprotinin in OLT. Recently, we completed the European Multicenter Study on the Use of Aprotinin in Liver Transplantation (EMSALT). Results of this randomized, double-blind, placebo-controlled study showed significant reductions in blood loss and transfusion requirements of 50% and 30%, respectively. 9 A potential adverse effect of a prohemostatic drug, such as aprotinin, could be an increased rate of thrombotic complications. Concern has been voiced about the potential risk for this type of complication when aprotinin is administered during OLT. 10 Although the antifibrinolytic activity of aprotinin in OLT has been studied before, data on the specific effects of aprotinin on coagulation and fibrinolysis separately, as well as their interaction in the same

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“…20,31) FXII functions as an activator in at least four important biochemical pathways: intrinsic coagulation system, kinin-kallikrein system, complement system, and fibrinolysis dependent on plasminogen. 3,16,17,23) Fibrinolytic activity can be generated via the extrinsic and intrinsic coagulation pathways. Fifty percent of the intrinsic activity is contributed by urokinase-type plasminogen activator; 35% from contact activation dependent plasminogen proactivator; and the remaining 15% from direct activation of plasminogen by activated FXII and kallikrein.…”

Section: Discussionmentioning

confidence: 99%

“…Fifty percent of the intrinsic activity is contributed by urokinase-type plasminogen activator; 35% from contact activation dependent plasminogen proactivator; and the remaining 15% from direct activation of plasminogen by activated FXII and kallikrein. 16,17) Reduced activity of the FXII-dependent fibrinolytic activity is supposed to be responsible for thromboembolic events in FXII deficient patients. 21,23) Subdural hematoma is a typical complication of a head trauma.…”

Section: Discussionmentioning

confidence: 99%

“…FXII is also involved in the activation of plasminogen-dependent fibrinolysis, the complement system, and kinin generations. 3,16,17,23) Congenital coagulation factor deficiencies of the contact system are extremely rare. 7,8) Such deficiencies manifest as significantly prolonged activated partial thromboplastin time (APTT) and normal prothrombin time in screening tests for coagulation.…”

Section: Introductionmentioning

confidence: 99%

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Subdural Hematoma in a Patient With Hageman Trait-Case Report-

Kaspera

Rothkegel²,

Stadnicki

2005

Neurol. Med. Chir.(Tokyo)

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A 61-year-old man with severe factor XII deficiency presented with a subdural hematoma appearing as mixed but mainly high density by computed tomography in the left frontotemporoparietal region. No cranial injury was reported in the medical history of the patient. Clotting system study showed less than 1% functional activity of factor XII, whereas the levels of the other clotting factors were within the normal ranges. Partially clotted and hemolyzed subdural hematoma was removed through a craniotomy. The postoperative course was uneventful. The patient later died of severe circulatoryrespiratory failure. We believe that the subdural hematoma may have developed as a result of a minor head trauma sustained in the past. We suggest that impairment of fibrinolytic activation related to severe factor XII deficiency might have contributed to the delay of dissolution of the subdural hematoma which, under ordinary circumstances, would have formed chronic subdural hematoma.

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Role of the Contact System in Fibrinolysis

Cited by 154 publications

References 128 publications

KLF5 promotes cell proliferation and tumorigenesis through gene regulationin the TSU-Pr1 human bladder cancer cell line

KLF5 promotes cell proliferation and tumorigenesis through gene regulationin the TSU-Pr1 human bladder cancer cell line

Aprotinin in orthotopic liver transplantation: Evidence for a prohemostatic, but not a prothrombotic, effect

Subdural Hematoma in a Patient With Hageman Trait-Case Report-

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