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J Thorac Cardiovasc Surg 1995;110:46-54
© 1995 Mosby, Inc.
CARDIOPULMONARY BYPASS, |
St. Louis, Mo.
Supported in part by a research grant from Medtronic Hemotec.
Received for publication August 2, 1994. Accepted for publication Nov. 15, 1994. Address for reprints: George Despotis, MD, Division of Cardiothoracic Anesthesiology, Department of Anesthesiology, Box 8054, Washington University School of Medicine, 660 South Euclid Ave., St. Louis, MO 63110
Abstract
A whole blood hemostasis system (Hepcon) provides both activated clotting time and accurate whole blood heparin concentration measurements via an automated protamine titration method. This study was designed to prospectively evaluate the impact of heparin and protamine administration using this system on the incidence and treatment of bleeding after cardiopulmonary bypass. Two hundred fifty-four patients requiring cardiopulmonary bypass were enrolled in this prospective study over a 7-month period. Patients treated with antifibrinolytic agents (aprotinin,
-aminocaproic or tranexamic acid) were excluded. Patients were randomly assigned to either a control (n = 127) or intervention (n = 127) group. For control patients, the anticoagulation protocol consisted of an initial fixed dose of 250 U/kg of heparin, and additional 5000 U heparin doses were administered if the activated clotting time was less than 480 seconds. Heparin was neutralized with an initial fixed dose of protamine (0.8 mg protamine per milligram total heparin). For the intervention group, an initial dose of heparin was based on an automated heparin dose-response assay. Additional heparin doses were administered if the heparin concentration was less than the reference concentration or for an activated clotting time less than 480 seconds. The protamine dose was based on the residual heparin concentration. Treatment of excessive bleeding after cardiopulmonary bypass was based on an algorithm using point-of-care testing with whole blood prothrombin time, activated partial thromboplastin time, heparinase activated clotting time, and platelet count. No differences between the two treatment groups were identified in reference to demographic factors, preoperative anticoagulant medications, preoperative coagulation data, number of reoperations, or combined procedures and duration of cardiopulmonary bypass. Indirect evidence for coagulation factor consumption was demonstrated in control patients by more prolonged whole blood prothrombin time and activated partial thromboplastin time values after cardiopulmonary bypass when compared with values obtained in the intervention group. Patients in the intervention cohort received greater doses of heparin (intervention: 612±147, control: 462±114 U/kg, p < 0.0001) and had lower protamine to heparin ratios (intervention: 0.70±0.64, control: 0.94±0.21, p = 0.0001) compared with control patients. Patients in the intervention cohort received significantly fewer platelet (intervention: 1.7±3.6 U, control: 3.7±6.7 U, p = 0.003), plasma (intervention: 0.4±1.3 U, control: 1.4±2.5 U, p = 0.0001), and cryoprecipitate units (intervention: 0.0±0.0 U, control: 0.2±1.2 U, p = 0.04) during the perioperative interval than control patients. A greater percentage of control patients required hemostatic transfusion (intervention: 17%, control: 33%, p = 0.005) during the perioperative period. Control patients also required longer operative times for closure (intervention: 92±32, control: 102±34, p = 0.02). Chest tube drainage in the first 24 postoperative hours was not different between treatment groups (intervention: 839±377, control: 924±520, p = 0.14). In summary, maintenance of patient-specific heparin concentrations, based on heparin activated clotting time response, during cardiopulmonary bypass led to greater heparin doses and lower doses of protamine relative to heparin dose. Higher porcine heparin doses were not associated with excessive postoperative bleeding. By facilitating maintenance of a therapeutic heparin concentration and determination of an appropriate protamine dose, point-of-care testing using the Hepcon system was associated with reduced blood product utilization. This difference may, in part, be due to better preservation of the coagulation system. (J THORACCARDIOVASCSURG1995;110:46-54)
The activated clotting time (ACT) is routinely used to assess adequacy of anticoagulation during cardiopulmonary bypass (CPB), to estimate protamine dose required to reverse heparin, and to evaluate heparin rebound after CPB. Monitoring coagulation in the perioperative period exclusively with the ACT, however, may be misleading inasmuch as previous studies have demonstrated that ACT values during CPB do not correlate well with plasma heparin level and are affected by many variables such as hemodilution and hypothermia.
1-5 As previously described, 6-11 a whole blood hemostasis system (Hepcon; Medtronic Hemotec, Englewood, Colo.) provides both ACT and accurate whole blood heparin concentration measurements via an automated protamine titration method. 12 Although data from a retrospective study indicate that use of this system can result in reduced use of blood products, 13 another evaluation failed to demonstrate a difference. 7 This prior, prospective evaluation was limited because it did not include an adequate number of high-risk patients with prolonged extracorporeal circulation times; in addition, a preset heparin level that was independent of each patient's heparin anticoagulant response was maintained in all patients.
Therefore this study was designed to prospectively evaluate the impact of heparin and protamine administration, as guided by on-site measurements of whole blood heparin concentration and ACT, on the incidence of bleeding and blood product use after CPB.
MATERIAL AND METHODS
Informed consent was obtained from all patients enrolled in this protocol approved by the Institutional Human Studies Committee. Exclusion criteria included patients requiring emergency procedures, patients treated with antifibrinolytic agents (aprotinin, -aminocaproic or tranexamic acid), and patients who had a surgical source of bleeding during subsequent exploration. All patients were anesthetized with an opioid-based technique; the anesthesia was supplemented with inhalational anesthetic agents, muscle relaxants, and benzodiazepines. Extracorporeal circulation was accomplished with a Bio-Medicus (Medtronics, Minneapolis, Minn.) centripetal pump and a Sorin (Sorin Inc., Irvine, Calif.) membrane oxygenator, and systemic hypothermia was maintained at 28º C during cardioplegia. The CPB system was routinely primed with 1.5 L of Plasma-Lyte solution, 50 mEq of sodium bicarbonate (NaHCO3), and 25 gm of mannitol.
Patients were randomly assigned to either a control (C; n = 127) or intervention (I; n = 127) group. For control patients, the anticoagulation and reversal protocol consisted of an initial fixed dose of 250 U/kg of porcine heparin, 5000 U added to the CPB circuit, and additional 5000 U heparin doses administered when the diatomaceous earth (Celite) ACT was less than 480 seconds. The initial protamine dose for control patients consisted of a fixed dose of 0.8 mg protamine per milligram total heparin administered. For control patients, adequacy of heparin neutralization was based on return of the ACT value to the pre-CPB baseline. For patients in the intervention group, a heparin dose-response (HDR) assay directed the initial dose of heparin and the dose of heparin added to the CPB circuit. Additional heparin doses were administered when the heparin concentration was less than the initially measured reference concentration or when the kaolin ACT was less than 480 seconds. The heparin concentration measured after administration of heparin and before initiation of CPB that was associated with a kaolin ACT value of approximately 480 seconds was designated as the reference heparin concentration. In the intervention group, the initial protamine dose was based on the most recent whole blood heparin concentration measurement before discontinuation of CPB (1.3 mg of protamine per milligram of residual heparin). For intervention-group patients, adequacy of heparin neutralization was based on a less than 10% difference between kaolin ACT and heparinase-treated kaolin ACT values. Intraoperative values for ACT or ACT/heparinase ACT were obtained 5 minutes after the initial protamine dose was given. An additional 50 mg of protamine was administered at the discretion of managing physicians with administration of blood salvaged in a cell salvage auto transfusion instrument (Medtronic Electromedics, Inc., Parker, Colo.) or if patients demonstrated evidence of excessive bleeding.
After the patient was rewarmed to 37º C, extracorporeal circulation was discontinued, heparin was neutralized with protamine, and patients were observed for excessive microvascular bleeding. Excessive microvascular bleeding was defined as diffuse bleeding without an identifiable surgical source and this diagnosis was made by our surgical staff who were unaware of the anticoagulation protocol. Treatment of excessive intraoperative bleeding after CPB was standardized by use of a previously described algorithm 14 based on whole blood prothrombin time (PT), activated partial thromboplastin time (aPTT), and platelet count, which identified quantitative deficiencies of platelets and coagulation factors. Mediastinal chest tube drainage during the first 24 postoperative hours was recorded hourly; the first recorded value included the drainage that occurred intraoperatively after chest closure and during the first postoperative hour. Mediastinal chest tube drainage designated as excessive by our surgical staff during the postoperative period prompted hemostatic therapy that was directed by either initially obtained laboratory PT, aPTT, and platelet count assays or by subsequently obtained whole blood assays. Administration of additional protamine in the postoperative period was based on whole blood kaolin ACT (heparinase correction) or laboratory-based thrombin time assays (protamine correction), or both methods, for both patient groups.
Coagulation assays
Preoperative and postoperative laboratory hematologic assays. Laboratory-based hematologic analysis obtained preoperatively included complete blood cell count (CBC) with platelet count, PT, and aPTT; bleeding times were done (Simplate technique) as described by Babson and Babson. 15 On patient arrival in the cardiac intensive care unit, laboratory-based hematologic analysis included CBC with platelet count, PT, aPTT, and thrombin time with protamine correction. In a subset (n = 31) of high-risk patients (reoperations or combined procedures) bleeding times were done after patient arrival in the intensive care unit. A laboratory diagnosis of heparin rebound in the post-CPB period was defined with the use of two diagnostic criteria: (1) an abnormal thrombin time (>18 seconds) that corrects (<18 seconds) with protamine and (2) patients who meet the first criterion and who also have an aPTT value greater than the normal range (>35 seconds).
On-site, whole blood hematologic assays. Single blood specimens obtained either from radial or femoral intraarterial catheters after removal of six dead space volumes or from the CPB arterial cannula were used for coagulation analysis by on-site, whole blood assays. For control patients, anticoagulation and reversal for extracorporeal circulation were monitored with diatomaceous earth ACT measurements with the Hemochron 801 instrument (International Technidyne, Edison, N.J.). For intervention-group patients, anticoagulation and reversal for extracorporeal circulation were monitored with whole blood heparin and kaolin ACT measurements with the Hepcon instrument (Medtronic Hemotec). Adequacy of heparin neutralization was assessed with the heparinase ACT assay using the ACT instrument (Medtronic Hemotec) for intervention-group patients intraoperatively and for all patients postoperatively. Whole blood PT, aPTT, and platelet count were done on specimens obtained from patients with excessive bleeding after CPB to guide specific therapy. Whole blood PT and aPTT were determined with use of a Biotrack 512 instrument (Boehringer-Mannheim, Indianapolis, Ind.), whereas whole blood CBC with platelet counts was measured with either the Coulter T540 instrument (Coulter Electronics, Hialeah, Fla.) during the intraoperative period or the MD series instrument (Coulter) during the postoperative period.
Statistical analysis
Student's unpaired t test was used to compare demographic, hematologic, operative interval, transfusion, and postoperative blood loss variables that were expressed as mean values between treatment groups. 
2 and Fisher's exact analyses were used to compare variables that were expressed as percentages between treatment groups.
RESULTS
Two hundred fifty-four adult patients scheduled for cardiac operation requiring CPB were enrolled in this study during a 7-month interval. There were no differences in demographic or operative variables between the two cohorts (Table I). An equal distribution (p = 0.68) of patients with a surgical source of bleeding at reexploration was evident between the control (n = 4) and intervention cohorts (n = 3). These seven patients were excluded from the analysis. Control patients had significantly greater prolongation in whole blood PT and aPTT values as compared with intervention-cohort patients (Table II). A trend toward prolonged bleeding times during the postoperative period was also evident in control patients (C: 8.4 ± 5.9 minutes, I: 5.9 ± 3.2 minutes, p = 0.12). Otherwise, similar values for laboratory-based hematologic assays in both the preoperative and postoperative intervals were obtained between treatment groups. Intervention-group patients received larger initial and final heparin doses per kilogram of weight than control patients (Table III). Although the protamine dose per kilogram of weight was similar between treatment groups, the protamine to heparin ratio was significantly less in the intervention cohort.
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Table IV). Moreover, a greater percentage (p = 0.005) of control patients (33%) received hemostatic blood product transfusion as compared with the intervention-cohort patients (17%). The operative period after heparin neutralization (closure time) was also greater in the control patients.
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Table III). Only one patient with a laboratory diagnosis (criterion 1) of heparin rebound had clinically significant bleeding that necessitated a follow-up dose of protamine. Control patients had greater mediastinal chest tube drainage in the initial postoperative interval (hours 1 through 4). Although control patients tended to have greater mediastinal chest tube drainage in the subsequent postoperative intervals, this was not statistically significant (Table IV). DISCUSSION
Administration of blood and blood products in patients undergoing cardiac operation is being reviewed with intense scrutiny as a consequence of increased awareness of the hazards of transfusion-related sequelae and cost-containment strategies. Consequently, strategies to optimize administration of heparin and protamine and the assessment of their effects on coagulation are undergoing reevaluation in these patients. The impact of heparin/protamine dosing guided by in vitro ACT 13, 16, 17 and heparin concentrationmeasurements 7, 13 on blood conservation has been previously investigated. Recent data suggest that patients in whom these values are monitored with in vitro testing receive more heparin, less protamine, and exhibit less postoperative blood loss. 18 The improved clinical outcome in this previous trial was ascribed to administration of an optimal heparin dose or optimal neutralization of heparin with protamine, both on the basis of predicted in vitro estimates. The present study also demonstrates that a coagulation monitoring protocol can minimize blood loss and reduce transfusion in patients undergoing cardiac operation. In addition to projecting optimal heparin and protamine doses, our protocol facilitated maintenance of therapeutic heparin concentrations during extracorporeal circulation. Patients in our intervention group also received more heparin, had a lower protamine dose relative to heparin dose, and required fewer blood products. Although Gravlee and colleagues 7 could not demonstrate a clinical advantage when heparin concentrations were maintained, our trial differed in that it included a significant number of patients at risk for bleeding (e.g., long CPB intervals), the type of heparin used (porcine), and maintainence of patient-specific heparin concentrations.
The ACT is routinely determined to assess the adequacy of anticoagulation before and during CPB, on the basis of numerous studies that described a reduction in postoperative bleeding when the ACT was used to monitor heparin therapy. 16, 19, 20 Maintenance of ACT values between 300 and 600 seconds 21 was initially recommended, because of a threefold to sixfold variation in heparin effect and a fourfold variation in heparin half-life. 22 Accordingly, neither total heparin dose nor total time of CPB can adequately predict anti-Xa heparin concentrations at the end of CPB. 12 Although there is controversy as to what the optimal ACT value for CPB is, 5, 23 values between 400 and 480 seconds are commonly maintained. The original recommendation to maintain a minimum ACT of 300 seconds was based on the absence of detectable clots in the CPB oxygenator circuit at values higher than this. 24 Although consumption of clotting factors may be minimal for up to 2 hours during CPB if the ACT exceeds 400 seconds, 25 ACT-based protocols do not suppress thrombin generation during CPB, because concentrations of prothrombin fragment 1.2, thrombin/antithrombin complexes, and fibrin monomers increase with time during CPB. 26 Recent evaluations indicate that duration of CPB is the best predictor of microvascular bleeding 14 and blood loss 27 after CPB. Patients with long CPB times have lower platelet and coagulation factor levels because of a greater degree of consumption. 28 Furthermore, judging the adequacy of anticoagulation on the basis of the ACT during CPB may be problematic inasmuch as numerous studies have illustrated that ACT values during CPB do not correlate with plasma heparin concentration. 1-5, 12, 29 This may be a result, at least in part, of the influence of CPB-related hypothermia and hemodilution on the ACT assay. 1, 3, 12 Other factors that may contribute to inconsistent ACT measurements include intrinsic variability of ACT measurements during anticoagulation, along with activation or depression of platelet function. 30 Therefore ACT-based anticoagulation protocols may contribute to a subclinical consumptive state particularly in patients who require prolonged use of CPB (>2 hours).
Instead, the use of heparin concentration assays to maintain a defined heparin level during CPB has been recommended by some authors. 6, 31 The Hepcon instrument provides both ACT and heparin concentration measurements via an automated protamine titration method. 6-11 In a recent evaluation, good correlations between whole blood heparin concentration and anti-Xa plasma heparin concentration were obtained, indicating that this method provides accurate determination of heparin concentration. 12 In this previous evaluation involving an ACT-based anticoagulation protocol in patients in whom CPB averaged approximately 2
hours, plasma equivalent heparin concentration fell below previously designated acceptable concentrations (2 U/ml) 6, 30 at the end of CPB. In patients with CPB times greater than 150 minutes, the decline in heparin concentration may reach a subtherapeutic level and, by facilitating the consumption of coagulation factors, may contribute to excessive bleeding in patients undergoing cardiac operation. Because generation of fibrinopeptide A 8, 32 and inhibition of clot-bound thrombin 33 are inversely related to heparin concentration, maintenance of therapeutic heparin levels may more effectively preserve coagulation factors by reducing activation of the coagulation system through antithrombin III or possibly heparin cofactor II-mediated inactivation of thrombin. 34 Accordingly, patients in the control cohort had greater prolongations in whole blood PT and aPTT assays after heparin neutralization and required more plasma administration.
In addition, maintenance of a stable heparin concentration during extracorporeal circulation may preserve platelet function. Although previous studies demonstrate that heparin may be a platelet agonist, 35, 36 recent evaluations have demonstrated a consistent dose-related inhibition of collagen-mediated platelet aggregation by heparin in both in vitro 37 and ex vivo 7 models. Higher heparin levels during extracorporeal circulation were associated with decreased platelet function in the ex vivo evaluation. In addition, platelet function is more commonly inhibited by heparin, 38 possibly through either factor VIII-associated platelet aggregation 39 or through von Willebrand factor-dependent mechanisms. 40 In our study, although control patients had similar platelet counts after heparin neutralization, they also had persistent bleeding that necessitated additional transfusion. The trend to more prolonged bleeding times in high-risk control patients indicates that these patients may have had a more pronounced qualitative platelet defect. Accordingly, patients who have increased heparin needs because of prolonged use of CPB or preoperative heparin infusion may benefit the most from a system that guides the maintenance of a therapeutic heparin concentration.
The ACT has been used to estimate protamine dose after CPB and to evaluate heparin rebound in the postoperative setting. Studies have illustrated that reduced doses of protamine for heparin neutralization after CPB can result in lower perioperative blood losses. 16-18 Lower perioperative blood losses may be a result of reduced complement levels 41, 42 or reduced protamine-induced platelet inhibition 43 associated with lower protamine doses. Because Hepcon-derived measurements more reliably reflect heparin concentration than ACT measurements, protamine dosing schedules based on whole blood heparin measurements facilitated administration of lower protamine doses relative to heparin doses. Therefore use of a hemostasis management system that evaluates both heparin concentration and heparin response (ACT) may result in the optimal administration of both heparin and protamine.
As previously described in patients who received higher heparin doses, postoperative bleeding is not increased if patients are monitored for heparin rebound in the postoperative period. 7 On the basis of this finding, we monitored all patients enrolled in this project for laboratory and clinical evidence of heparin rebound. No evidence of a higher incidence of heparin rebound was found in our intervention cohort with use of an extremely sensitive laboratory-based thrombin time assay (criterion 1) or when we evaluated heparin rebound with both thrombin time and aPTT assays (criterion 2). In addition, the incidence of clinically significant heparin rebound involving both laboratory (thrombin time) and clinical criteria (excessive chest tube drainage) was extremely low (1 patient of 250 or 0.4%). In contrast to recommendations by others, 7 our data do not support routine monitoring for heparin rebound in the postoperative period when porcine heparin is used. However, we would suggest assessment of heparin rebound in the setting of clinically significant bleeding before the administration of hemostatic blood products. Most important, administration of larger heparin doses in our intervention cohort was not accompanied by excessive perioperative bleeding. In fact, less chest tube drainage was observed in the intervention-group patients in the initial postoperative period (hours 1 through 4) and a lower percentage of these patients required hemostatic therapy for excessive postoperative bleeding.
In conclusion, our data demonstrate that maintenance of reference porcine heparin concentrations during CPB results in reduced perioperative use of blood products possibly because of preservation of the coagulation system. In addition, a lower percentage of intervention-group patients who were monitored with point-of-care heparin concentration testing required hemostatic transfusion. Through facilitated maintenance of a therapeutic heparin concentration and identification of an accurate protamine dose, use of this system can result in reduced use of blood products.
Acknowledgments
We express appreciation to Cindy Camillo and Amy Howe for their invaluable technical support during the study and to the cardiac anesthesia and cardiac surgical staff for their assistance during this project.
Footnotes
J THORAC CARDIOVASC SURG 1995;110:46-54. 
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M. Codispoti, C. A. Ludlam, D. Simpson, and P. S. Mankad Individualized heparin and protamine management in infants and children undergoing cardiac operations Ann. Thorac. Surg., March 1, 2001; 71(3): 922 - 927. [Abstract] [Full Text] [PDF]
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W. Dietrich, S. Braun, M. Spannagl, and J. A. Richter Low Preoperative Antithrombin Activity Causes Reduced Response to Heparin in Adult but not in Infant Cardiac-Surgical Patients Anesth. Analg., January 1, 2001; 92(1): 66 - 71. [Abstract] [Full Text] [PDF]
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G. J. Despotis and L. T. Goodnough Management approaches to platelet-related microvascular bleeding in cardiothoracic surgery Ann. Thorac. Surg., August 1, 2000; 70(2): S20 - 32. [Abstract] [Full Text] [PDF]
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J. H. Lemmer Jr Clinical experience in coronary bypass surgery for abciximab-treated patients Ann. Thorac. Surg., August 1, 2000; 70(2): S33 - 37. [Abstract] [Full Text] [PDF]
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E. W. Muriithi, P. R. Belcher, S. P. Day, V. C. Menys, and D. J. Wheatley Heparin-induced platelet dysfunction and cardiopulmonary bypass Ann. Thorac. Surg., June 1, 2000; 69(6): 1827 - 1832. [Abstract] [Full Text] [PDF]
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R. Saleem, M. Bigham, E. Spitznagel, and G. J. Despotis The Effect of Epsilon-Aminocaproic Acid on HemoSTATUS(R) and Kaolin-Activated Clotting Time Measurements Anesth. Analg., June 1, 2000; 90(6): 1281 - 1285. [Abstract] [Full Text] [PDF]
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M. Codispoti and P. S Mankad Management of anticoagulation and its reversal during paediatric cardiopulmonary bypass: a review of current UK practice Perfusion, May 1, 2000; 15(3): 191 - 201. [Abstract] [PDF]
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C. J. East, F. Clements, J. Mathew, and T. F. Slaughter Antiphospholipid Syndrome and Cardiac Surgery: Management of Anticoagulation in Two Patients Anesth. Analg., May 1, 2000; 90(5): 1098 - 1101. [Full Text] [PDF]
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J. H. Lemmer Jr, M. T. Metzdorff, A. H. Krause Jr, M. A. Martin, J. E. Okies, and J. G. Hill Emergency coronary artery bypass graft surgery in abciximab-treated patients Ann. Thorac. Surg., January 1, 2000; 69(1): 90 - 95. [Abstract] [Full Text] [PDF]
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R. Berryessa, R. Wiencek, J. Jacobson, D. Hollingshead, K. Farmer, and G. Cahill Practical techniques Vacuum-assisted venous return in pediatric cardiopulmonary bypass Perfusion, January 1, 2000; 15(1): 63 - 67. [Abstract] [PDF]
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O. Shigeta, H. Kojima, Y. Hiramatsu, T. Jikuya, Y. Terada, N. Atsumi, Y. Sakakibara, T. Nagasawa, and T. Mitsui LOW-DOSE PROTAMINE BASED ON HEPARIN-PROTAMINE TITRATION METHOD REDUCES PLATELET DYSFUNCTION AFTER CARDIOPULMONARY BYPASS J. Thorac. Cardiovasc. Surg., August 1, 1999; 118(2): 354 - 360. [Abstract] [Full Text] [PDF]
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F. M LaDuca, M. L Zucker, and C. E Walker Assessing heparin neutralization following cardiac surgery: sensitivity of thrombin time-based assays versus protamine titration methods Perfusion, May 1, 1999; 14(3): 181 - 187. [Abstract] [PDF]
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 N. Ramamurthy, N. Baliga, J. A. Wahr, U. Schaller, V. C. Yang, and M. E. Meyerhoff Improved protamine-sensitive membrane electrode for monitoring heparin concentrations in whole blood via protamine titration§ Clin. Chem., March 1, 1998; 44(3): 606 - 613. [Abstract] [Full Text] [PDF]
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G. J. Despotis, J. H. Joist, and L. T. Goodnough Monitoring of hemostasis in cardiac surgical patients: impact of point-of-care testing on blood loss and transfusion outcomes Clin. Chem., September 1, 1997; 43(9): 1684 - 1696. [Abstract] [Full Text] [PDF]
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G. J. Despotis, J. H. Joist, L. T. Goodnough, S. A. Santoro, and E. Spitznagel WHOLE BLOOD HEPARIN CONCENTRATION MEASUREMENTS BY AUTOMATED PROTAMINE TITRATION AGREE WITH PLASMA ANTI-XA MEASUREMENTS J. Thorac. Cardiovasc. Surg., March 1, 1997; 113(3): 611 - 613. [Full Text]
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G. S. Aldea, M. Doursounian, P. O'Gara, P. Treanor, O. M. Shapira, H. L. Lazar, and R. J. Shemin Heparin-Bonded Circuits With a Reduced Anticoagulation Protocol in Primary CABG: A Prospective, Randomized Study Ann. Thorac. Surg., August 1, 1996; 62(2): 410 - 418. [Abstract] [Full Text]
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J.-F. Hardy, S. Belisle, D. Robitaille, J. Perrault, M. Roy, and L. Gagnon MEASUREMENT OF HEPARIN CONCENTRATION IN WHOLE BLOOD WITH THE HEPCON/HMS DEVICE DOES NOT AGREE WITH LABORATORY DETERMINATION OF PLASMA HEPARIN CONCENTRATION USING A CHROMOGENIC SUBSTRATE FOR ACTIVATED FACTOR X J. Thorac. Cardiovasc. Surg., July 1, 1996; 112(1): 154 - 161. [Abstract] [Full Text]
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M. J. Moulton, L. L. Creswell, M. E. Mackey, J. L. Cox, and M. Rosenbloom REEXPLORATION FOR BLEEDING IS A RISK FACTOR FOR ADVERSE OUTCOMES AFTER CARDIAC OPERATIONS J. Thorac. Cardiovasc. Surg., May 1, 1996; 111(5): 1037 - 1046. [Abstract] [Full Text]
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G. J. Despotis, A. L. Alsoufiev, E. Spitznagel, L. T. Goodnough, and D. G. Lappas Response of Kaolin ACT to Heparin: Evaluation With an Automated Assay and Higher Heparin Doses Ann. Thorac. Surg., March 1, 1996; 61(3): 795 - 799. [Abstract] [Full Text]
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P. Martin, S. Bannan, and S. S. Ashraf Individualized patient heparinization and protamine reversal J. Thorac. Cardiovasc. Surg., February 1, 1996; 111(2): 493 - 493. [Full Text]
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