Aprotinin Prolongs Whole Blood Activated Partial Thromboplastin Time but Not Whole Blood Prothrombin Time in Patients Undergoing Cardiac Surgery

Aprotinin is being used increasingly to limit cardiopulmonary bypass (CPB)-induced coagulation derangements. Since whole blood prothrombin time (PT) and activated partial thromboplastin time (APTT) assays are beneficial in the treatment of bleeding after CPB, we studied the potential effect of aprotinin on these whole blood assays. Blood specimens from 151 cardiac surgical patients were obtained in two phases: prior to heparin administration, before CPB, and subsequent to heparin neutralization after CPB. After collection, blood specimens were divided into two aliquots and mixed with either normal saline (NS) or aprotinin (A, 200 or 400 Kallikrein inhibiting units (KIU)/mL). Whole blood specimens were used to measure whole blood PT and APTT using CoaguChek Registered Trademark Plus instruments. Whole blood PT results were similar between normal saline (NS)- and aprotinin-spiked specimens before CPB (A, 12.9 +/- 1.5 s; NS, 12.8 +/- 1.5 s; P = 0.76) and after CPB (A, 17.5 +/- 2.4 s; NS, 17.7 +/- 2.4 s; P = 0.58). In contrast, whole blood APTT results were prolonged in aprotininspiked specimens prior to CPB (A, 63.3 +/- 32.2 s; NS, 38.6 +/- 16.3 s; P < 0.0001) and after CPB (A, 65.9 +/- 23.7 s; NS, 45.7 +/- 14.4 s; P < 0.0001). A dose-dependent prolongation of whole blood APTT by aprotinin was demonstrated by a greater mean difference in APTT (P = 0.0001) between specimens spiked with NS or 200 KIU (17.5 +/- 12.2 s) vs 400 KIU (27.8 +/- 21.5 s) of aprotinin. A greater mean difference in APTT values (P < 0.0001) between NS- and aprotinin-spiked specimens was demonstrated when comparing APTT measurements between specimens obtained from patients receiving (H) or not receiving (NH) heparin preoperatively (H, 36.5 +/- 18 s; NH, 18.1 +/- 21.9 s). Our data demonstrate that aprotinin-mediated prolongation of whole blood APTT is dose-dependent and enhanced by heparin. We conclude that when the whole blood APTT assay is used to assess heparin anticoagulant effect or coagulation factor levels after CPB, results should be interpreted with caution in the setting of concurrent aprotinin administration. (Anesth Analg 1995;81:919-24)

[1]  C. Hogue,et al.  Effect of heparin on whole blood activated partial thromboplastin time using a portable, whole blood coagulation monitor. , 1995, Critical care medicine.

[2]  E. Spitznagel,et al.  The impact of heparin concentration and activated clotting time monitoring on blood conservation. A prospective, randomized evaluation in patients undergoing cardiac operation. , 1995, The Journal of thoracic and cardiovascular surgery.

[3]  D. Royston.  Intraoperative coronary thrombosis: can aprotinin be incriminated? , 1994, Journal of cardiothoracic and vascular anesthesia.

[4]  W. van Oeveren,et al.  Alternative perioperative anticoagulation monitoring during cardiopulmonary bypass in aprotinin-treated patients. , 1994, Journal of cardiothoracic and vascular anesthesia.

[5]  E. Spitznagel,et al.  On‐site Prothrombin Time, Activated Partial Thromboplastin Time, and Platelet Count A Comparison between Whole Blood and Laboratory Assays with Coagulation Factor Analysis in Patients Presenting for Cardiac Surgery , 1994, Anesthesiology.

[6]  E. Spitznagel,et al.  Prospective evaluation and clinical utility of on-site monitoring of coagulation in patients undergoing cardiac operation. , 1994, The Journal of thoracic and cardiovascular surgery.

[7]  T. Treasure,et al.  Aprotinin inhibits fibrinolysis, improves platelet adhesion and reduces blood loss. Results of a double-blind randomized clinical trial. , 1994, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[8]  R. Weisel,et al.  Prevention of postbypass bleeding with tranexamic acid and ϵ-aminocaproic acid , 1993 .

[9]  J. Chabbat,et al.  Aprotinin is a competitive inhibitor of the factor VIIa-tissue factor complex. , 1993, Thrombosis research.

[10]  T. Treasure,et al.  Aprotinin therapy in cardiac operations: a report on use in 41 cardiac centers in the United Kingdom. , 1993, The Annals of thoracic surgery.

[11]  H. Wendel,et al.  The prolonged activated clotting time (ACT) with aprotinin depends on the type of activator used for measurement , 1993, Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.

[12]  J. Francis,et al.  The effect of aprotinin on the response of the activated partial thromboplastin time (APTT) to heparin , 1993, Blood Coagulation and Fibrinolysis.

[13]  R. Karp,et al.  Monitoring of heparin-induced anticoagulation with kaolin-activated clotting time in cardiac surgical patients treated with aprotinin. , 1992, Anesthesiology.

[14]  W. Dietrich,et al.  APROTININ INHIBITS COAGULATION DURING CARDIOPULMONARY BYPASS IN MAN , 1992 .

[15]  W. Vanoeveren,et al.  Anticoagulation policy during use of aprotinin in cardiopulmonary bypass. , 1992 .

[16]  D. Royston.  High-dose aprotinin therapy: a review of the first five years' experience. , 1992, Journal of cardiothoracic and vascular anesthesia.

[17]  R. Thisted,et al.  In vitro effects of aprotinin on activated clotting time measured with different activators. , 1992, The Journal of thoracic and cardiovascular surgery.

[18]  W. van Oeveren,et al.  Anticoagulation policy during use of aprotinin in cardiopulmonary bypass. , 1992, Journal of Thoracic and Cardiovascular Surgery.

[19]  D. V. Van Riper,et al.  Hemostatic Effects of Tranexamic Acid and Desmopressin During Cardiac Surgery , 1991, Circulation.

[20]  D. Adler,et al.  Measurement of the activated partial thromboplastin time from a capillary (fingerstick) sample of whole blood. A new method for monitoring heparin therapy. , 1991, American journal of clinical pathology.

[21]  M. Jochum,et al.  Influence of high-dose aprotinin treatment on blood loss and coagulation patterns in patients undergoing myocardial revascularization. , 1990, Anesthesiology.

[22]  W. van Oeveren,et al.  Aprotinin protects platelets against the initial effect of cardiopulmonary bypass. , 1990, The Journal of thoracic and cardiovascular surgery.

[23]  G. Lemole,et al.  Prophylactic treatment of postperfusion bleeding using EACA. , 1989, Chest.

[24]  D. Mungall,et al.  A novel whole blood capillary technic for measuring the prothrombin time. , 1987, American journal of clinical pathology.

[25]  H. Fritz,et al.  Biochemistry and applications of aprotinin, the kallikrein inhibitor from bovine organs. , 1983, Arzneimittel-Forschung.