CU-2010-A novel small molecule protease inhibitor with antifibrinolytic and anticoagulant properties

Anesthesiology

Volumn 110, Issue 1, 2009, Pages 123-130

  Dietrich, Wulf ^a,b   Nicklisch, Silke ^c   Koster, Andreas ^d   Spannagl, Michael ^b   Giersiefen, Helmut ^c   Van De Locht, Andreas ^c  

^a Institute for Research in Cardiac Anesthesia   (Germany)

^b UNIVERSITY OF MUNICH   (Germany)

^c Curacyte Discovery GmbH   (Germany)

^d DEUTSCHES HERZZENTRUM BERLIN   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

APROTININ; BLOOD CLOTTING FACTOR 10A; BLOOD CLOTTING FACTOR 11A; CU 2010; KALLIKREIN; PLASMIN; PROTEINASE INHIBITOR; TRANEXAMIC ACID; UNCLASSIFIED DRUG; ANTICOAGULANT AGENT; ANTIFIBRINOLYTIC AGENT; SERINE PROTEINASE INHIBITOR;

ANTICOAGULATION; ARTICLE; BLEEDING; BLOOD CLOTTING TIME; CARDIOPULMONARY BYPASS; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG EFFICACY; DRUG POTENCY; FIBRINOLYSIS; HEART SURGERY; HUMAN; HUMAN TISSUE; IN VITRO STUDY; PRIORITY JOURNAL; THROMBIN TIME; THROMBOCYTE ACTIVATION; THROMBOELASTOGRAPHY; TURBIDIMETRY; ANIMAL; BLOOD CLOTTING; CATTLE; COMPARATIVE STUDY; DOSE RESPONSE; DRUG EFFECT; PHYSIOLOGY; SYNTHESIS;

ANIMALS; ANTICOAGULANTS; ANTIFIBRINOLYTIC AGENTS; APROTININ; BLOOD COAGULATION; CATTLE; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; PROTEASE INHIBITORS; SERINE PROTEINASE INHIBITORS;

EID: 58749083266     PISSN: 00033022     EISSN: 15281175     Source Type: Journal    
DOI: 10.1097/ALN.0b013e318191408c     Document Type: Article

References (41)

1. Ferraris VA, Ferraris SP, Saha SP, Hessel EA 2nd, Haan CK, Royston BD, Bridges CR, Higgins RS, Despotis G, Brown JR, Spiess BD, Shore-Lesserson L, Stafford-Smith M, Mazer CD, Bennett-Guerrero E, Hill SE, Body S: Perioperative blood transfusion and blood conservation in cardiac surgery: The Society of Thoracic Surgeons and The Society of Cardiovascular Anesthesiologists clinical practice guideline. Ann Thorac Surg 2007; 83:S27-86
2. Boisclair MD, Lane DA, Philippou H, Esnouf MP, Sheikh S, Hunt B, Smith KJ: Mechanisms of thrombin generation during surgery and cardiopulmonary bypass. Blood 1993; 82:3350-7
3. Mannucci PM, Levi M: Prevention and treatment of major blood loss. N Engl J Med 2007; 356:2301-11
4. Brown JR, Birkmeyer NJ, O'Connor GT: Meta-analysis comparing the effectiveness and adverse outcomes of antifibrinolytic agents in cardiac surgery. Circulation 2007; 115:2801-13
5. Henry DA, Carless P, Moxey A, O'Connell D, Stokes B, McClelland B, Laupacis A, Fergusson D: Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev 2007:CD001886
6. Sedrakyan A, Treasure T, Elefteriades JA: Effect of aprotinin on clinical outcomes in coronary artery bypass graft surgery: A systematic review and meta-analysis of randomized clinical trials. J Thorac Cardiovasc Surg 2004; 128: 442-8
7. Zufferey P, Merquiol F, Laporte S, Decousus H, Mismetti P, Auboyer C, Samama CM, Molliex S: Do antifibrinolytics reduce allogeneic blood transfusion in orthopedic surgery? ANESTHESIOLOGY 2006; 105:1034-46
8. Landis RC, Asimakopoulos G, Poullis M, Haskard DO, Taylor KM: The antithrombotic and antiinflammatory mechanisms of action of aprotinin. Ann Thorac Surg 2001; 72:2169-75
9. Asimakopoulos G, Thompson R, Nourshargh S, Lidington EA, Mason JC, Ratnatunga CP, Haskard DO, Taylor KM, Landis RC: An anti-inflammatory property of aprotinin detected at the level of leukocyte extravasation. J Thorac Cardiovasc Surg 2000; 120:361-9
10. Sperzel M, Huetter J: Evaluation of aprotinin and tranexamic acid in different in vitro and in vivo models of fibrinolysis, coagulation and thrombus formation. J Thromb Haemost 2007; 5:2113-8
11. Hill GE, Robbins RA: Aprotinin but not tranexamic acid inhibits cytokineinduced inducible nitric oxide synthase expression. Anesth Analg 1997; 84:1198- 202
12. Dietrich W, Ebell A, Busley R, Boulesteix AL: Aprotinin and anaphylaxis: Analysis of 12,403 exposures to aprotinin in cardiac surgery. Ann Thorac Surg 2007; 84:1144-50
13. Fergusson DA, Hebert PC, Mazer CD, Fremes S, MacAdams C, Murkin JM, Teoh K, Duke PC, Arellano R, Blajchman MA, Bussieres JS, Cote D, Karski J, Martineau R, Robblee JA, Rodger M, Wells G, Clinch J, Pretorius R: The BI: A Comparison of aprotinin and lysine analogues in high-risk cardiac surgery. N Engl J Med 2008; 358:2319-31
14. Shaw AD, Stafford-Smith M, White WD, Phillips-Bute B, Swaminathan M, Milano C, Welsby IJ, Aronson S, Mathew JP, Peterson ED, Newman MF: The effect of aprotinin on outcome after coronary-artery bypass grafting. N Engl J Med 2008; 358:784-93
15. Mangano DT, Tudor IC, Dietzel C: The risk associated with aprotinin in cardiac surgery. N Engl J Med 2006; 354:353-65
16. Karkouti K, Beattie WS, Dattilo KM, McCluskey SA, Ghannam M, Hamdy A, Wijeysundera DN, Fedorko L, Yau TM: A propensity score case-control comparison of aprotinin and tranexamic acid in high-transfusion-risk cardiac surgery. Transfusion 2006; 46:327-38
17. Mouton R, Finch D, Davies I, Binks A, Zacharowski K: Effect of aprotinin on renal dysfunction in patients undergoing on-pump and off-pump cardiac surgery: A retrospective observational study. Lancet 2008; 371:475-82
18. Westaby S: Aprotinin: Twenty-five years of claim and counterclaim. J Thorac Cardiovasc Surg 2008; 135:487-91
19. Dietrich W, Busley R, Boulesteix AL: Effects of aprotinin dosage on renal function: An analysis of 8,548 cardiac surgical patients treated with different dosages of aprotinin. ANESTHESIOLOGY 2008; 108:189-98
20. Edmunds LH Jr, Colman RW: Thrombin during cardiopulmonary bypass. Ann Thorac Surg 2006; 82:2315-22
21. Katz BA, Sprengeler PA, Luong C, Verner E, Elrod K, Kirtley M, Janc J, Spencer JR, Breitenbucher JG, Hui H, McGee D, Allen D, Martelli A, Mackman RL: Engineering inhibitors highly selective for the S1 sites of Ser190 trypsin-like serine protease drug targets. Chem Biol 2001; 8:1107-21
22. Hemker HC, Giesen P, Al Dieri R, Regnault V, de Smedt E, Wagenvoord R, Lecompte T, Beguin S: Calibrated automated thrombin generation measurement in clotting plasma. Pathophysiol Haemost Thromb 2003; 33:4-15
23. Sturzebecher J, Prasa D, Hauptmann J, Vieweg H, Wikstrom P: Synthesis and structure-activity relationships of potent thrombin inhibitors: Piperazides of 3-amidinophenylalanine. J Med Chem 1997; 40:3091-9
24. Kim PY, Stewart RJ, Lipson SM, Nesheim ME: The relative kinetics of clotting and lysis provide a biochemical rationale for the correlation between elevated fibrinogen and cardiovascular disease. J Thromb Haemost 2007; 5:1250-6
25. Luddington RJ: Thrombelastography/thromboelastometry. Clin Lab Haematol 2005; 27:81-90
26. Ganter MT, Hofer CK: Coagulation monitoring: Current techniques and clinical use of viscoelastic point-of-care coagulation devices. Anesth Analg 2008; 106:1366-75
27. Nielsen VG, Cohen BM, Cohen E: Elastic modulus-based thrombelastographic quantification of plasma clot fibrinolysis with progressive plasminogen activation. Blood Coagul Fibrinolysis 2006; 17:75-81
28. Gerotziafas GT, Elalamy I, Depasse F, Perzborn E, Samama MM: In vitro inhibition of thrombin generation, after tissue factor pathway activation, by the oral, direct factor Xa inhibitor rivaroxaban. J Thromb Haemost 2007; 5:886-8
29. Avidan MS, Alcock EL, Da Fonseca J, Ponte J, Desai JB, Despotis GJ, Hunt BJ: Comparison of structured use of routine laboratory tests or near-patient assessment with clinical judgement in the management of bleeding after cardiac surgery. Br J Anaesth 2004; 92:178-86
30. Cammerer U, Dietrich W, Rampf T, Braun SL, Richter JA: The predictive value of modified computerized thromboelastography and platelet function analysis for postoperative blood loss in routine cardiac surgery. Anesth Analg 2003; 96:51-7
31. Wachtfogel YT, Kucich U, Hack CE, Gluszko P, Niewiarowski S, Colman RW, Edmunds LH Jr: Aprotinin inhibits the contact, neutrophil, and platelet activation systems during simulated extracorporeal perfusion. J Thorac Cardiovasc Surg 1993; 106:1-9
32. Bhoola KD, Figueroa CD, Worthy K: Bioregulation of kinins: Kallikreins, kininogens, and kininases. Pharmacol Rev 1992; 44:1-80
33. Laffey JG, Boylan JF, Cheng DC: The systemic inflammatory response to cardiac surgery: Implications for the anesthesiologist. ANESTHESIOLOGY 2002; 97: 215-52
34. Levy JH, Tanaka KA: Inflammatory response to cardiopulmonary bypass. Ann Thorac Surg 2003; 75:S715-20
35. Mojcik CF, Levy JH: Aprotinin and the systemic inflammatory response after cardiopulmonary bypass. Ann Thorac Surg 2001; 71:745-54
36. Kleinschnitz C, Stoll G, Bendszus M, Schuh K, Pauer HU, Burfeind P, Renne C, Gailani D, Nieswandt B, Renne T: Targeting coagulation factor XII provides protection from pathological thrombosis in cerebral ischemia without interfering with hemostasis. J Exp Med 2006; 203:513-8
37. Fritz H, Wunderer G: Biochemistry and applications of aprotinin, the kallikrein inhibitor from bovine organs. Arzneim Forsch/Drug Res 1983; 33: 479-94
38. Dietrich W, Busley R, Kriner M: High-dose aprotinin in cardiac surgery: is high-dose high enough? An analysis of 8281 cardiac surgical patients treated with aprotinin. Anesth Analg 2006; 103:1074-81
39. Weitz JI: Activation of blood coagulation by plaque rupture: Mechanisms and prevention. Am J Cardiol 1995; 75:B18-B22
40. Augoustides JG: Vascular thrombosis associated with aprotinin and deep hypothermic circulatory arrest: Where are we in 2006? ANESTHESIOLOGY 2007; 106:873
41. Madjdpour C, Thyes C, Buclin T, Frascarolo P, von Roten I, Fisch A, Burmeister M, Bombeli T, Spahn DR: Novel starches: Single-dose pharmacokinetics and effects on blood coagulation. ANESTHESIOLOGY 2007; 106:132-43