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Anesth Analg 2000;91:1124-1130
© 2000 International Anesthesia Research Society

CARDIOVASCULAR ANESTHESIA

Tranexamic Acid Reduces Blood Loss in Total Hip Replacement Surgery

Gustav Ekbäck, MD*, Kjell Axelsson, MD, PhD*, Lars Ryttberg, MD{dagger}, Bror Edlund, MD, PhD{ddagger}, Jill Kjellberg, Chief CRNA*, Johan Weckström, MD{dagger}, Olle Carlsson, PhD§, and Ulf Schött, MD, PhD*

Departments of *Anesthesiology and Intensive Care, {dagger}Orthopedic Surgery, {ddagger}Clinical Chemistry, Örebro Medical Center Hospital; and §Department of Statistics, University of Örebro, Örebro, Sweden

Address correspondence and reprint requests to Gustav Ekbäck, MD, Department of Anesthesiology and Intensive Care, Örebro Medical Center Hospital, S-701 85 Örebro, Sweden.


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
Intraoperatively administered, tranexamic acid (TA) does not reduce bleeding in total hip replacement (THR). Therefore, its prophylactic use was attempted in the present study because this has been shown to be more effective in cardiac surgery. We investigated 40 patients undergoing THR in a prospective, randomized, double-blinded study. Twenty patients received TA given in two bolus doses of 10 mg/kg each, the first just before surgical incision and the second 3 h later. In addition, a continuous infusion of TA, 1.0 mg · kg-1 · h-1 for 10 h, was given after the first bolus dose. The remaining 20 patients formed a control group. Both groups used preoperative autologous blood donation and intraoperative autotransfusion. Intraoperative bleeding was significantly less (P = 0.001) in the TA group compared with the control group (630 ± 220 mL vs 850 ± 260 mL). Postoperative drainage bleeding was correspondingly less (P = 0.001) (520 ± 280 vs 920 ± 410 mL). Up to 10 h postoperatively, plasma D-dimer concentration was halved in the TA group compared with the control group. One patient in each group had an ultrasound-verified late deep vein thrombosis. In conclusion, we found TA, administrated before surgical incision, to be efficient in reducing bleeding during THR.

Implications: In a prospective, double-blinded study of 40 patients undergoing total hip replacement, the preoperative administration of tranexamic acid reduced bleeding by 35%, probably by decreasing induced fibrinolysis. Whether tranexamic acid therapy can replace predonation of autologous blood or intraoperative autotransfusion requires further study.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
The prophylactic, i.e., preincisional, administrationof aprotinin and tranexamic acid (TA) can reduce bleeding and allogeneic blood use in cardiopulmonary bypass surgery (1). Both drugs have also been tried in orthopedic surgery, with mixed results. TA administered shortly before release of the pneumatic tourniquet nearly halved the perioperative bleeding in knee arthroplasty (2,3) The intraoperative administration of TA after cement injection of the femur in total hip replacement (THR) failed to reduce bleeding, leading to the need for blood transfusions (4). Aprotinin may reduce bleeding and blood transfusions in THR (5,6), but contrary results have been reported (7).

The mechanism by which these drugs decrease surgical bleeding is controversial (8) and probably varies with different types of surgery. Perhaps the antiprotease effects of aprotinin preserve platelet membrane receptors better than TA (1,9,10). Aprotinin is an expensive drug and can induce anaphylaxis. Therefore, TA could be a better alternative as it is inexpensive and apparently does not induce anaphylaxis.

In cardiac surgery, cardiopulmonary bypass induces fibrinolysis (1,9). In knee surgery, inflation of the pneumatic tourniquet is the powerful initiator of fibrinolysis (2,3), whereas in THR, fibrinolysis is induced by the surgical trauma (11). In THR, antifibrinolytic therapy should be started before the surgical incision, but there has been concern about an increased risk for pulmonary embolism during cement injection (12).

However, aprotinin given before cement injection had no such adverse effects (5,6). Also, in a recently published abstract with 70 patients undergoing THR (13), a preoperative single bolus of TA (15 mg/kg) significantly reduced postoperative bleeding with no reported increase in echo-Doppler verified thromboembolic complications compared with control patients without TA therapy. In an experimental animal study, 48 rabbits undergoing severe arterial trauma were evaluated with different antithrombotic regimes. With dextran 70 combined with TA, there were no vascular occlusions, indicating a profound antithrombotic effect (100%) of dextran 70 even when combined with TA (14). These values were significantly higher (P < 0.05) compared with those for the control group. At our center, the use of low molecular weight heparin as thromboprophylaxis, and dextran and intraoperative autotransfusion (IAT) as substitution for perioperative plasma and erythrocyte loss, are routine (15).

The aim of the present study was to evaluate the following: 1. If TA started before surgical incision will reduce intra- and postoperative bleeding as well as the need for allogeneic blood transfusion, and 2. Alterations in coagulation and fibrinolysis patterns with laboratory tests for coagulation and fibrinolysis.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
Forty patients undergoing THR were investigated in a prospective, randomized, double-blinded study. Invasive arterial pressure, the hourly measurement of diuresis, a three-lead electrocardiogram, and pulse oximetry were routine. Twenty patients received a first bolus dose of 10 mg/kg of TA before surgical incision. A continuous infusion of 1.0 mg · kg-1 · h-1 during 10 h was then started immediately after the first bolus dose. A second bolus dose of 10 mg/kg body weight was given 3 h later to counteract potential dilutive effects of IAT on TA concentrations in blood (16). The other 20 patients served as a control group and got the same treatment but with a placebo drug (physiological saline).

Before surgery, two units of packed red blood cells (PRBCs) and two units of plasma were drawn from all patients on two occasions within 4 wk. The exceptions were one patient in the control group from whom three units of blood and plasma were drawn, and one patient in the TA group from whom only one unit of blood and plasma was drawn. These patients were omitted when the blood hemoglobin (B-Hb) concentrations and hematocrit (Hct) values of the two groups were compared. Preoperative oral iron therapy (100–200 mg) was given daily. The erythrocytes were suspended in Sagman® (Baxter, Round Lake, IL) solution (containing natr. chloride 877 mg, dextrose monohydrate 900 mg, adenine 16.9 mg, and mannitol 525 mg per 100 mL solution) and contained in units of 225 mL (SAGM-PRBCs) in which the Hct was adjusted to 55%. The plasma was anticoagulated with citrate-phosphate-dextrose, and reinfused in units of 250 mL immediately after the operation was ended. IAT was performed with an AT 1000 autotransfusion device (Medtronic Electromedics, Englewood, CO) up to 2 h postoperatively in both groups with a 125-mL bowl. Blood losses were estimated by measuring the processed volumes in the autotransfusion device and in the swabs. Postoperative blood loss was recorded from the drainage bottles. Blood volume loss was estimated from these blood measurements and a preoperatively calculated blood volume (15). Plasma lost was replaced with 3% dextran 60 (Plasmodex®, Pharma-Link, Sweden), which is routine at our hospital. Allogeneic SAGM-PRBCs was transfused if Hct <27% after transfusion of the autologous PRBCs.

Platelet-inhibiting drugs had been withdrawn 10 days preoperatively. Thromboprophylaxis with low molecular weight heparin (Dalteparin; Pharmacia-Upjohn, Stockholm, Sweden) was administered subcutaneously from the evening before surgery up to Day 10 postoperatively. A combined lumbar spinal-epidural anesthesia (needle-through-needle technique) was administered with 4 mL of 0.5% bupivacaine. Postoperatively, 0.25% bupivacaine 6–10 mL/h was administered to Day 1 after surgery.

The patients were operated on in a horizontal lateral position. After lavage with saline, a polyethylene plug was inserted in the bottom of the drilled cavity. Vacuum-mixed cement was injected with a syringe in a retrograde direction. The proximal femur was sealed, and additional cement was injected under pressure. The femoral prosthesis was inserted during the viscous phase of the cement.

Venous blood samples were drawn for analytical tests approximately 6 wk before operation and on Days 3 and 7 after surgery. Arterial blood was drawn for the same purpose before spinal anesthesia and peroperatively and postoperatively up to Day 1.

B-Hb, Hct, and platelet whole count were determined in K3EDTA blood by using a Cell-Dyn 3500 cell counter (Abbot Scandinavia AB, Stockholm, Sweden). Serum creatinine and urea were determined by using a Vitros 950 analyzer (Johnson & Johnson, Rochester, NY).

As a result of restrictive laboratory facilities and costs of the analyses, the coagulation, fibrinolysis, and functional coagulation tests were randomly analyzed for only 10 patients in each group. Analysis failed in 1 patient in the TA group. Another 3 patients were randomly chosen from the remaining 20 patients; all, however, belonging to the control group. In all, these tests were performed for 9 patients in the TA group and 13 patients in the control group.

Activated partial thromboplastin time was determined in plasma by using the Cephotest reagent (Nycomed AB, Oslo, Norway). Prothrombin time (PT) was determined as PT% by using a combined reagent Nycotest PT (Nycomed AB). P-Fibrinogen was determined by using Fibromat (Biomereiux, Lyon, France). D-dimers and tPA (tissue-plasminogen activator), plasminogen-activator inhibitor, TAT (thrombin-antithrombin complex), and PAP (plasmin-antiplasmin complex) were determined by using enzyme-linked immunosorbent assay methods (Tint Elize D-Dimer, and Tint Elize tPA; Biopool AB, Umea, Sweden; Coaliza-PAI; Chromogenix, Molndal, Sweden; Enzygnost TATmicro; Dade-Behring, Marburg, Germany; Enzygnost PAPmicro; Dade-Behring, respectively).

Two viscoelastic coagulation analyzers, Sonoclot (Sienco, Denver, CO) and Thrombelastograph® (TEG®) (Haemoscope Corp, Skokie, IL), were used to evaluate interactions of red blood cells, platelets, and coagulation factors. The Sonoclot coagulation analyzer was used to analyze activated coagulation time, dynamic fibrin-platelet interaction variables rate 1 (R1), and time to peak in arterial whole blood (15). Two machines analyzed direct-sampled native blood with standard celite Sono-cyvettes to minimize the effect of test variance (17).

The TEG® was used to analyze variables {alpha}, R, K, and maximum amplitude (MA) in arterial whole blood (celite-activated) (18). The analyses were terminated after MA, as our time scheme did not allow for further analysis. Two channels were used to minimize the effect of test variance.

Ultrasonic screening for deep vein thrombosis (DVT) in both legs was blinded and was performed on Day 3 and Day 21 postoperatively by an experienced radiologist with real-time B-mode ultrasonography by using an Acuson 128XP (Acuson, Mountain View, CA). Dynamic venous compressibility of the femoralis communis—popliteal veins was performed with a 5-MHz linear transducer (15).

Statistical analyses with t-tests were performed to determine whether there were differences between the groups with respect to demographic and bleeding data. Individual changes from the starting values for B-Hb, Hct, creatinine, urea, and coagulation data (the coagulation data balanced by random exclusion) were analyzed by using analysis of variance, with the factors time, treatment, and patient within treatment. The first two factors were considered fixed factors and the last (patient within treatment) a random factor. Further, an approximate analysis of variance was done for the unbalanced coagulation data. Group means of interest were tested by using Tukey’s test. Residuals were examined and transformations were made if necessary. The study was approved by the local hospital ethics committee. Informed consent was obtained from each patient.


   Results
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 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
No significant differences between the groups were found in the demographic data (Table 1). There was a slight decrease (P < 0.05) in oxygen saturation (maximum value, 6%; mean decrease, 0.7%) during cement injection of the femur with no significant differences between the groups. No cardiovascular-related complications were found in any of the patients. No neurologic or epidural catheter complications were noted with the CSE technique.


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  		Table 1. Demographic Data and Blood Loss-Substitution Data
 
All autologous PRBCs and plasma were retransfused during the day of operation with no signs of volume overload. Intraoperative bleeding was decreased from 850 to 605 mL (P = 0.001) and postoperative bleeding from 925 to 525 mL (P = 0.001) when TA was added to treatment (Table 1). The volume of blood returned with the autotransfusion device was decreased from 276 mL in the control group to 119 mL (P < 0.001) in the TA group (Table 1). Five patients in the TA group did not receive IAT because of a very small blood loss versus none in the control group. Allogeneic blood use did not differ between the groups (Table 1).

Data for B-Hb, Hct, plasma creatinine, and urea are presented in Table 2. All three showed significant (P < 0.001) variation with time. The two groups did not differ significantly in any of these variables.


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  		Table 2. Laboratory Analyses
 
During the perioperative period up to Day 1 postoperatively (Table 3 and Figure 1), a coagulative screening was done. PT, activated partial thromboplastin time, fibrinogen, and plasminogen-activator inhibitor did not show any significant differences between the groups. PT and fibrinogen showed significant changes in time with an initial hypocoagulation and postoperative normalization (data not shown). Time effects for TAT, tPA, platelets, D-dimer, and PAP are described in Table 3. TAT and tPA did not show any significant differences between the groups. Platelets showed a significant difference between the groups (P < 0.05), but Tukey’s test failed to differentiate the time at which this occurred. D-dimer had a significant interaction effect between time and group (P < 0.001); the control group had a higher D-dimer plasma level at 4 h and 10 h, but then decreased faster at Day 1. PAP showed a significantly higher value at the 10 h (P < 0.01) analysis for the TA group, and there was also an interaction effect (P = 0.028) with a higher PAP plasma level for the TA group at 4 h and 10 h, and then a faster decrease at Day 1.


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  		Table 3. Laboratory Analyses
 


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  		Figure 1. Mean values of key fibrinolysis variables. For ± SD, see Table 3. Significant differences in time and between the groups are described in Table 3 and in the text. PAP = plasmin-antiplasmin complex; TAT = thrombin-antithrombin complex; tPA = tissue-plasminogen activator; Pre-op = before spinal anesthesia and surgery; 1h, 4h, etc. = 1 h, 4 h after pre-op measurement, etc.

 
The Sonoclot variables R1 and time to peak showed significant time effects (Figure 2). Preoperatively and on Day 1, R1 was higher (P < 0.01). Time to peak progressively increased and was longer (P < 0.05) at 6 to 9 h postoperatively, then decreased at 10 h and Day 1. There was a significant interaction effect between time and group (P < 0.05) with a longer time to peak at 4 h and 5 h in the TA group and a more rapid decrease at 10 h and Day 1. R1 showed no differences between the groups.



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  		Figure 2. Sonoclot (Sienco, Denver, CO) mean values during operation and the first postoperative day. ACT = activated coagulation time, R1 = rate 1, and Peak = time to peak. Significant differences in time and between the groups are described in the text. Pre-op = before spinal anesthesia and surgery; 1h, 4h, etc. = 1 h, 4 h after pre-op measurement, etc.

 
The TEG® variables all showed significant time effects (Figure 3) but no group differences. The preoperative R value was higher (P < 0.01) than the other values. At Day 1, R was significantly higher (P < 0.01) than at 2, 3, 5, 6, and 7 h postoperatively. K showed an increasing trend, and the Day 1 K value was higher (P < 0.01) than the preoperative, 1, 2, 3, and 5 h (P < 0.05) values. Preoperatively, MA showed the highest value obtained (P < 0.01) in comparison to all the other measurements, and it was higher at 1 h (P < 0.01) than at 4, 9, and 10 h. {alpha} progressively decreased, and the measurements preoperatively and at 2 and 3 h were higher (P < 0.05) than the 8 h to Day 1 measurements.



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  		Figure 3. Thrombelastograph {alpha}, R, K, and maximum amplitude (MA) mean values during operation and the first postoperative day. Significant differences in time and between the groups are described in the text. Pre-op = before spinal anesthesia and surgery; 1h, 4h, etc. = 1 h, 4 h after pre-op measurement, etc.

 
Two patients developed DVT. One patient in the TA group had DVT verified with ultrasonography and one patient in the control group had clinically suspected DVT that was verified with phlebography.


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
In contrast to the study by Benoni et al. (4), who used late intraoperative TA administration, we estimated less bleeding with preincisional TA in our THR patients. However, the concept of using IAT and preoperative autologous blood donation (PAD) in both groups was very effective in preventing allogeneic blood use. Despite a mean blood loss of nearly 1800 mL in the control group, there was only one patient who needed allogeneic blood transfusion. As both IAT and PAD are costly and time-consuming procedures, it seems reasonable to refrain from using one or both of them if TA is to be used, although this was not examined in the present study. Further, in patients with contraindications or no preparation time or access to IAT or PAD, TA could be an alternative to allogeneic blood. Other aspects not addressed in this study of primary THR are dryness in the surgical wound, less operating room time (1), and better conditions for cement injection (19).

There is concern that TA may promote a hypercoagulable state, and cerebral, pulmonary, mesenteric, and retinal thromboses have been reported (20). Christie et al. (12) have shown that cardiopulmonary embolism occurs during cement injection of the femoral component in THR. Therefore, it may be harmful to decrease the fibrinolytic capacity of the lungs during this period.

There was only a slight decrease in pulse oximetry saturation during cement injection in both groups, corroborating results of others (21) by using up-to-date cement injection techniques and monitoring with blood gas analysis and transesophageal echocardiography for embolic event detection. No increase in the frequency of peripheral venous thromboses was seen between the TA group and the control group or compared to results from an earlier study from our center (15). However, with an incidence of postoperative DVT of approximately 5%, being able to detect a 25% increase would demand a total study population of 7200 patients. We have therefore not made any safety assessment of the method based on our study population of only 40 patients.

Epsilon-aminocaproic acid, another fibrinolytic drug that is of less potency than TA but that is still a lysine analog, can cause obstructive uropathy, thrombosis in the glomerular capillaries, rhabdomyolysis, and myoglobinuria (22). There were no effect on creatinine and urea in the present study when TA was used, but these laboratory tests are not sensitive enough to detect the transient renal dysfunction that occurs with aprotinin (23). Whether a similar relationship exists when TA is administered has yet to be proven.

Both procoagulative factors and fibrinolysis are activated by surgical trauma (11). In major surgical proceedings, large amounts of tissues will be exposed to injury. These tissues will release enzymes, primarily tPA, activating the fibrinolytic system (24). The fibrinolytic response is most pronounced intraoperatively and early postoperatively. Also, dextran–used in this study as a plasma substitute–can enhance fibrinolysis through an increase in tPA and a change in fibrin structure (25).

Postoperatively, this response rapidly shifts to a fibrinolytic inhibition (11). Drug-induced inhibition of fibrinolysis could potentate the fibrinolytic shutdown often seen at day one after THR. The increasing D-dimer and decreasing tPA could indicate an early postoperative hyperfibrinolytic response in both groups. The increase in tPA on day 1 and the decrease in D-dimer hint at a sustained profibrinolytic potential after the previous fibrinolytic activity, leaving little fibrin left to degrade. The tPA levels were similar in both groups on day one, both significantly increased, indicating that the plasminogen levels were not impaired by the treatment. However, there was significantly less fibrinolytic activity in the TA group early postoperatively as shown by the D-dimer response. The mechanism of this antifibrinolytic effect is probably competitive antagonism of the TA molecule to the plasmin molecule at the fibrin site (1). The plasmin molecule will therefore be more easily repulsed to plasma where it will form a complex with antiplasmin, forming PAP. PAP was also significantly higher in the TA group at ten hours after start of operation.

An increased concentration of the short-lived TAT is an indicator of coagulation activation (11). The control and TA groups showed different patterns. In the control group, TAT rapidly increased to a high level early in the postoperative phase and was nearly normalized on Day 1. In the TA group, TAT peaked on Day 1. Whether this difference in TAT represents a higher risk for postoperative thromboembolism in either group needs to be addressed.

The viscoelastic tests, TEG, and Sonoclot coagulation data showed no early signs of hypercoagulation. Until nine hours after start of the operation, the Sonoclot and TEG® tests indicated a hypocoagulative response, probably reflecting dextran effects (15). The recordings from Sonoclot then indicated a more active coagulation response with normalization of time to peak and a slight hyperactive trend with (nonsignificant) higher R1 and lower activated coagulation time on the morning of the first postoperative day as compared with preoperative values. In the thromboelastogram from the TEG®, only {alpha} in TA patients remained unchanged as compared with preoperative values, whereas in both groups on day one the other measured variables indicated an overall hypoactive response.

In conclusion, the IV administration of TA started before THR decreased the perioperative bleeding to 65% of the control group value, probably by reducing induced fibrinolysis as shown by a decreased D-dimer and increased PAP in the TA group. No difference in allogeneic blood use was noted, but it was very small in both groups with the use of IAT + PAD. As the most obvious gain from a reduction in bleeding is a reduction in allogeneic blood usage, further studies with TA versus IAT or PAD are needed.


   Acknowledgments
 
Supported, in part, by grants from Örebro Medical Center Hospital, Örebro, Sweden, and Pharmacia-Upjohn, Sweden.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

  1. Shore-Lesserson L, Reich DL, Vela-Cantos F, et al. Tranexamic acid reduces transfusions and mediastinal drainage in repeat cardiac surgery. Anesth Analg 1996; 83: 18–26.[Abstract]
  2. Hiippala S, Strid L, Wennerstrand M, et al. Tranexamic acid (Cyklokapron) reduces perioperative blood loss associated with total knee arthroplasty. Br J Anaesth 1995; 74: 534–7.[Abstract/Free Full Text]
  3. Benoni G, Fredin H. Fibrinolytic inhibition with tranexamic acid reduces blood loss and blood transfusion after knee arthroplasty: a prospective, randomised, double-blind study of 86 patients. J Bone Joint Surg Br 1996; 78: 434–40.
  4. Benoni G, Lethagen S, Nilsson P, Fredin H. Fibrinolysis, tranexamic acid, blood loss and haematomas in hip arthroplasty. In: Benoni G. Fibrinolysis and blood loss in major arthroplasty: the effect of tranexamic acid. Lund: Lund University; 1997:105–26.
  5. Murkin JM, Shannon NA, Bourne RB, et al. Aprotinin decreases blood loss in patients undergoing revision or bilateral total hip arthroplasty. Anesth Analg 1995; 80: 343–8.[Abstract]
  6. Janssens M, Joris J, David JL, et al. High-dose aprotinin reduces blood loss in patients undergoing total hip replacement surgery. Anesthesiology 1994; 80: 23–9.[ISI][Medline]
  7. Landown A, Field J. The role of trasylol in primary THR [abstract]. J Bone Joint Surg Br 1999; 81 (Suppl II abstr 489): 233–4.
  8. Brown RS, Thwaites BK, Mongan PD. Tranexamic acid is effective in decreasing postoperative bleeding and transfusions in primary coronary artery bypass operations: a double-blind, randomized, placebo-controlled trial. Anesth Analg 1997; 85: 963–70.[Abstract]
  9. Mongan PD, Brown RS, Thwaites BK. Tranexamic acid and aprotinin reduce postoperative bleeding and transfusions during primary coronary revascularization. Anesth Analg 1998; 87: 258–65.[Abstract/Free Full Text]
  10. Fitch J, Elefteriades J. Editorial comment [on Jamieson WR et al. Beneficial effect of both tranexamic acid. Circulation 1997;96(9 Suppl II):96–100]. Circulation 1997;96(9 Suppl II):100–1.
  11. Dahl OE. The role of the pulmonary circulation in the regulation of coagulation and fibrinolysis in relation to major surgery. J Cardiothorac Vasc Anesth 1997; 11: 322–8.[ISI][Medline]
  12. Christie J, Robinson CM, Pell AC, et al. Transcardiac echocardiography during invasive intramedullary procedures. J Bone Joint Surg Br 1995; 77: 450–5.
  13. Duquenne P, Lhoest L, Henkes W, De Sart F. Tranexamic acid reduces postoperative blood losses associated with elective total hip replacement [abstract]. J Bone Joint Surg Br 1999;81(Suppl II abstr. 489):233–4.
  14. Zhang B, Wieslander JB. Dextran’s antithrombotic properties in small arteries are not altered by low-molecular-weight heparin or the fibrinolytic inhibitor tranexamic acid: an experimental study. Microsurgery 1993; 14: 289–95.[ISI][Medline]
  15. Ekbäck G, Ryttberg L, Axelsson K, et al. Preoperative platelet-rich plasmapheresis and hemodilution with an autotransfusion device in total hip replacement surgery. J Clin Apheresis. In press.
  16. Benoni G, Björkman S, Fredin H. Application of pharmacokinetic data from healthy volunteers for the prediction of plasma concentrations of tranexamic acid in surgical patients. Clin Drug Invest 1995; 10: 280–7.
  17. Ekbäck G, Carlsson O, Schött U. Sonoclot coagulation analysis: a study of test variability. J Cardiothorac Vasc Anesth 1999; 13: 393–7.[ISI][Medline]
  18. Yamakage M, Tsujiguchi N, Kohro S, et al. The usefulness of celite-activated thromboelastography for evaluation of fibrinolysis. Can J Anaesth 1998; 45: 993–6.[Abstract/Free Full Text]
  19. Ranawat CS, Beaver WB, Sharrock NE, et al. Effect of hypotensive epidural anaesthesia on acetabular cement-bone fixation in total hip arthroplasty. J Bone Joint Surg Br 1991; 73: 779–82.
  20. Reid RW, Zimmerman AA, Laussen PC, et al. The efficacy of tranexamic acid versus placebo in decreasing blood loss in pediatric patients undergoing repeat cardiac surgery. Anesth Analg 1997; 84: 990–6.[Abstract]
  21. Pitto RP, Koessler M, Kuehle JW. Comparison of fixation of the femoral component without cement and fixation with use of a bone-vacuum cementing technique for the prevention of fat embolism during total hip arthroplasty. A prospective, randomized clinical trial. J Bone Joint Surg Am 1999; 81: 831–43.[Abstract/Free Full Text]
  22. Eaton MP, Deeb GM. Aprotinin versus epsilon-aminocaproic acid for aortic surgery using deep hypothermic circulatory arrest. J Cardiothorac Vasc Anesth 1998; 12: 548–52.[ISI][Medline]
  23. O’Connor CJ, Brown DV, Avramov M, et al. The impact of renal dysfunction on aprotinin pharmacokinetics during cardiopulmonary bypass. Anesth Analg 1999; 89: 1101–7.[Abstract/Free Full Text]
  24. Kluft C, Verheijen JH, Jie AF, et al. The postoperative fibrinolytic shutdown: a rapidly reverting acute phase pattern for the fast-acting inhibitor of tissue-type plasminogen activator after trauma. Scand J Clin Lab Invest 1985; 45: 605–10.[ISI][Medline]
  25. Schött U, Sollen C, Axelsson K, et al. Desmopressin acetate does not reduce blood loss during total hip replacement in patients receiving dextran. Acta Anaesthesiol Scand 1995; 39: 592–98.[ISI][Medline]
Accepted for publication July 20, 2000.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press