Effect of high or low protamine dosing on postoperative bleeding following heparin anticoagulation in cardiac surgery a randomised clinical trial

Thrombosis and Haemostasis

Volumn 116, Issue 2, 2016, Pages 251-261

  Meesters, Michael I ^a   Veerhoek, Dennis ^a   De Lange, Fellery ^b   De Vries, Jacob Willem ^b   De Jong, Jan R ^a   Romijn, Johannes W A ^a   Kelchtermans, Hilde ^c   Huskens, Dana ^c   Van Der Steeg, Robin ^a   Thomas, Pepijn W A ^a   Burtman, David T M ^a   Van Barneveld, Laurentius J M ^a   Vonk, Alexander B A ^a   Boer, Christa ^a  

^a VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^b MEDICAL CENTER LEEUWARDEN   (Netherlands)

^c Synapse B V   (Netherlands)

Author keywords

Blood products; Coagulation factors; Heparins; Surgery; Thrombin

Indexed keywords

ACETYLSALICYLIC ACID; ANTITHROMBIN III; BLOOD CLOTTING FACTOR 10A; FRESH FROZEN PLASMA; HEMOGLOBIN; HEPARIN; PROTAMINE; THROMBOCYTE CONCENTRATE; THROMBOCYTE FACTOR 4; ANTICOAGULANT AGENT; HEPARIN ANTAGONIST;

AGED; ANTICOAGULATION; ARTICLE; BLOOD CLOTTING TEST; BLOOD CLOTTING TIME; CONTROLLED STUDY; CORONARY ARTERY BYPASS GRAFT; DRUG DOSE COMPARISON; DRUG MEGADOSE; ENZYME LINKED IMMUNOSORBENT ASSAY; ERYTHROCYTE TRANSFUSION; FEMALE; HEMOSTASIS; HUMAN; LOW DRUG DOSE; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; OPEN STUDY; POSTOPERATIVE HEMORRHAGE; PRIORITY JOURNAL; PROTHROMBIN TIME; RANDOMIZED CONTROLLED TRIAL; SINGLE BLIND PROCEDURE; THROMBIN TIME; THROMBOCYTE TRANSFUSION; THROMBOELASTOGRAPHY; TREATMENT OUTCOME; BLOOD CLOTTING; BLOOD TRANSFUSION; CARDIOPULMONARY BYPASS; CLINICAL TRIAL; DOSE RESPONSE; DRUG EFFECTS; MIDDLE AGED; OPERATIVE BLOOD LOSS; PROCEDURES;

AGED; ANTICOAGULANTS; BLOOD COAGULATION; BLOOD COAGULATION TESTS; BLOOD LOSS, SURGICAL; BLOOD TRANSFUSION; CARDIOPULMONARY BYPASS; CORONARY ARTERY BYPASS; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; HEMOSTASIS; HEPARIN; HEPARIN ANTAGONISTS; HUMANS; MALE; MIDDLE AGED; PROTAMINES; SINGLE-BLIND METHOD; THROMBELASTOGRAPHY;

EID: 84980360435     PISSN: 03406245     EISSN: None     Source Type: Journal    
DOI: 10.1160/TH16-02-0117     Document Type: Article

References (39)

1. Edmunds jr LH, Colman RW. Thrombin During Cardiopulmonary Bypass. Ann Thorac Surg 2006; 82: 2315-2322.
2. Despotis GJ, Avidan MS, Hogue CW Jr. Mechanisms of hemostatic activation during extracorporeal circulation. Ann Thorac Surg 2001; 72: 1821-1831.
3. Finley A, Greenberg C. Heparin sensitivity and resistance: management during cardiopulmonary bypass. Anesth Analg 2013; 116: 1210-22.
4. Khan NU, Wayne CK, Barker J, et al. The effects of protamine overdose on coagulation parameters as measured by the thrombelastograph. Eur J Anaesthesiol 2010; 27: 624-627.
5. Mittermayr M, Velik-Salchner C, Stalzer B, et al. Detection of protamine and he-parin after termination of cardiopulmonary bypass by thrombelastometry (rOTEM): results of a pilot study. Anesth Analg 2009; 108: 743-750.
6. Koster A, Borgermann J, Gummert J, et al. Protamine overdose and its impact on coagulation, bleeding, and transfusions after cardiopulmonary bypass: results of a randomised double-blind controlled pilot study. Clin Appl Thromb Hemost 2014; 20: 290-295.
7. Cobel-Geard RJ, Hassouna HI. Interaction of protamine sulphate with throm-bin. Am J Hematol 1983; 14: 227-233.
8. Ni Ainle F, Preston RJ, Jenkins PV, et al. Protamine sulfate down-regulates thrombin generation by inhibiting factor V activation. Blood 2009; 114: 1658-1665.
9. Nielsen VG. Protamine enhances fibrinolysis by decreasing clot strength: role of tissue factor-initiated thrombin generation. Ann Thorac Surg 2006; 81: 1720-1727.
10. Shigeta O, Kojima H, Hiramatsu Y, et al. Low-dose protamine based on heparin-protamine titration method reduces platelet dysfunction after cardiopulmonary bypass. J Thorac Cardiovasc Surg 1999; 118: 354-360.
11. Mochizuki T, Olson PJ, Szlam F, et al. Protamine reversal of heparin affects platelet aggregation and activated clotting time after cardiopulmonary bypass. An-esth Analg 1998; 87: 781-785.
12. Chu AJ, Wang ZG, Raicu M, et al. Protamine inhibits tissue factor-initiated extrinsic coagulation. Br J Haematol 2001; 115: 392-399.
13. Khan NU, Wayne CK, Barker J, et al. The effects of protamine overdose on coagulation parameters as measured by the thrombelastograph. Eur J Anaesthesiol 2010; 27: 624-627.
14. Berger RL, Ramaswamy K, Ryan TJ. Reduced protamine dosage for heparin neutralisation in open-heart operations. Circulation 1968; 37: II154-157.
15. Vonk AB, Veerhoek D, van den Brom CE, et al. Individualised heparin and pro-tamine management improves rotational thromboelastometric parameters and postoperative hemostasis in valve surgery. J Cardiothorac Vasc Anesth 2014; 28: 235-241.
16. Society of Thoracic Surgeons Blood Conservation Guideline Task Force, Ferraris VA, Brown JR, Despotis GJ, et al.; Society of Cardiovascular Anesthesiologists Special Task Force on Blood Transfusion, Shore-Lesserson LJ, Good-nough LT, Mazer CD, et al.; International Consortium for Evidence Based Per-fusion, Baker RA, Dickinson TA, FitzGerald DJ, et al. 2011 update to the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists blood conservation clinical practice guidelines. Ann Thorac Surg 2011; 91: 944-982.
17. Kozek-Langenecker SA, Afshari A, Albaladejo P, et al. Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiol-ogy. Eur J Anaesthesiol 2013; 30: 270-382.
18. Dunning J, Versteegh M, Fabbri A, et al.; EACTS Audit and Guidelines Committee. Guideline on antiplatelet and anticoagulation management in cardiac surgery. Eur J Cardiothorac Surg 2008; 34: 73-92.
19. Jobes DR, Aitken GL, Shaffer GW. Increased accuracy and precision of heparin and protamine dosing reduces blood loss and transfusion in patients undergoing primary cardiac operations. J Thorac Cardiovasc Surg 1995; 110: 36-45.
20. Meesters MI, Lance MD, van der Steeg R, et al. The value of the thromboelasto-metry heparinase assay (HEPTEM) in cardiac surgery. Thromb Haemost 2015; 114: 1058-1063.
21. Hemker HC, Giesen P, Al Dieri R, et al. Calibrated automated thrombin generation measurement in clotting plasma. Pathophysiol Haemost Thromb 2003; 33: 4-15.
22. Hemker HC, Beguin S. Phenotyping the clotting system. Thromb Haemost 2000; 84: 747-751.
23. Thompson WH. Die physiologische Wirkung der Protamine und ihrer Spal-tungsprodukte. Hoppe-Seyler Z Physiol Chem 1900; 29: 1.
24. Waldschmidt-Leitz E, Stadler P, Steigerwaldt F. Uber Blutgerinnung, Hemmung und Beschleunigung. Z physik Chem 1929; 183: 39.
25. Chargaff E, Olson KB. Studies on the chemistry of blood coagulation: VII. Studies on the action of heparin and other anticoagulants: The influence of pro-tamine on the anticoagulant effect in vivo. J Biol Chem 1937; 122: 153-167.
26. Balhorn R. The protamine family of sperm nuclear proteins. Genome Biol 2007; 8: 227.
27. Parkin TW, Kvale WF. Neutralisation of the anticoagulant effects of heparin with protamine (salmine). Am Heart J 1949; 37: 333-342.
28. Svenarud P, Ovrum E. Clinical effects of different protamine doses after cardio-pulmonary bypass. Asian Cardiovasc Thorac Ann 2002; 10: 119-123.
29. Guo Y, Tang J, Du L, et al. Protamine dosage based on two titrations reduces blood loss after valve replacement surgery: a prospective, double-blinded, randomised study. Can J Cardiol 2012; 28: 547-552.
30. Wang J, Ma HP, Zheng H. Blood loss after cardiopulmonary bypass, standard vs titrated protamine: a meta-analysis. Neth J Med 2013; 71: 123-127.
31. Koster A, Fischer T, Praus M, et al. Hemostatic activation and inflammatory response during cardiopulmonary bypass: impact of heparin management. Anes-thesiology 2002; 97: 837-841.
32. Despotis GJ, Joist JH, Hogue CW Jr, et al. The impact of heparin concentration and activated clotting time monitoring on blood conservation. A prospective, randomised evaluation in patients undergoing cardiac operation. J Thorac Car-diovasc Surg 1995; 110: 46-54.
33. Ohata T, Sawa Y, Ohtake S, et al. Clinical role of blood heparin level monitoring during open heart surgery. Jpn J Thorac Cardiovasc Surg 1999; 47: 600-606.
34. Keeler JF, Shah MV, Hansbro SD. Protamine--the need to determine the dose. Comparison of a simple protamine titration method with an empirical dose regimen for reversal of heparinisation following cardiopulmonary bypass. Anaesthesia 1991; 46: 925-928.
35. Butterworth J, Lin YA, Prielipp RC, et al. Rapid disappearance of protamine in adults undergoing cardiac operation with cardiopulmonary bypass. Ann Thorac Surg 2002; 74: 1589-1595.
36. Murray DJ, Brosnahan WJ, Pennell B, et al. Heparin detection by the activated coagulation time: a comparison of the sensitivity of coagulation tests and hepa-rin assays. J Cardiothorac Vasc Anesth 1997; 11: 24-28.
37. Ichikawa J, Kodaka M, Nishiyama K, et al. Reappearance of circulating heparin in whole blood heparin concentration-based management does not correlate with postoperative bleeding after cardiac surgery. J Cardiothorac Vasc Anesth 2014; 28: 1003-1007.
38. Schols SE, Lance MD, Feijge MA, et al. Impaired thrombin generation and fibrin clot formation in patients with dilutional coagulopathy during major surgery. Thromb Haemost 2010; 103: 318-328.
39. Portmann AF, Holden WD. Protamine sulphate, heparin, and blood coagulation. J Clin Invest 1949; 28: 1451-8145.