Ain-Shams Journal of Anaesthesiology

ORIGINAL ARTICLE
Year
: 2017  |  Volume : 10  |  Issue : 1  |  Page : 131--139

Efficacy of preoperative autologous blood donation and tranexamic acid in revision total hip arthroplasty: a randomized controlled trial


Dina Y Kassim1, Ibrahim M Esmat2, Mohammed A Elgendy2,  
1 Department of Anesthesia and Intensive Care Medicine, Beni Sweif University Hospitals, Beni Suef, Egypt
2 Department of Anesthesia and Intensive Care Medicine, Ain Shams University Hospitals, Cairo, Egypt

Correspondence Address:
Ibrahim M Esmat
Associate Professor of Anesthesia and Intensive Care Medicine, Ain-Shams University, 29-Ahmed Fuad St., Saint Fatima Square, Heliopolis, Cairo, Egypt; Department of Anesthesia, Intensive Care and Pain Management, Faculty of Medicine, Ain Shams University, Cairo, 11361
Egypt

Abstract

Background Revision total hip arthroplasty (RTHA) is known to entail some risk of hemorrhage during the intraoperative period. Preoperative autologous blood donation (PAD) is one of the most popular alternatives to allogeneic blood transfusion (ABT) in elderly patients undergoing major orthopedic procedures in which a substantial blood loss is expected. The aim of this study was to evaluate the effectiveness of a combination of PAD and intravenous tranexamic acid (TXA) in reducing the need for ABT following RTHA. Patients and methods A total of 60 patients were included in this randomized study that were divided into a study group of 30 patients, who had been transfused autologous blood and a control group of 30 patients who had been transfused only allogeneic blood. Parenteral iron preparation was given to all patients of the study group after each donation. Intraoperatively all patients of the study group received 2 g of intravenous TXA. This study was conducted through laboratory analysis of hemoglobin and hematocrit values during blood donation and for both groups in the preoperative and the postoperative period and the assessment of the amount of transfused blood units in both groups. Results The average values of hemoglobin and hematocrit in the first and the second donation were 11.9±1.2 g/dl, 36.1±3.8%, and 11.9±1.0 g/dl, 35.6±3.5%, respectively. During operative and postoperative periods, the statistical data processing showed that there was a nonsignificant difference between the study and control groups regarding the number of transfused blood units (both autologous and allogeneic) (P=0.578 and 0.089), respectively, and only 10% of patients in the study group needed allogeneic blood. Conclusion PAD combined with intraoperative intravenous TXA administration reduced the number of ABTs in patients who underwent RTHA.



How to cite this article:
Kassim DY, Esmat IM, Elgendy MA. Efficacy of preoperative autologous blood donation and tranexamic acid in revision total hip arthroplasty: a randomized controlled trial.Ain-Shams J Anaesthesiol 2017;10:131-139


How to cite this URL:
Kassim DY, Esmat IM, Elgendy MA. Efficacy of preoperative autologous blood donation and tranexamic acid in revision total hip arthroplasty: a randomized controlled trial. Ain-Shams J Anaesthesiol [serial online] 2017 [cited 2020 Mar 29 ];10:131-139
Available from: http://www.asja.eg.net/text.asp?2017/10/1/131/238439


Full Text



 Introduction



The American Academy of Orthopedic Surgeons has estimated that the number of revision total hip arthroplasties (RTHAs) will continue to rise at a rate of 20–30% per year over the next 3 decades due to factors related to implant longevity and an increase in the number of procedures performed in younger and more active patients in the USA over the past decade [1].

Total lower limb arthroplasty is associated with significant perioperative blood loss and even if a transfusion protocol is applied, up to 20–30% of patients receive allogeneic blood transfusion (ABT) with mean transfusion index of 2 units of packed red cell per patient [2].

As the risks of ABT-transmitted viruses were reduced to exceedingly low levels in the USA, transfusion-related acute lung injury, hemolytic transfusion reactions, and transfusion-associated sepsis emerged as the leading causes of ABT-related deaths [3]. These limitations of ABT have prompted a review of transfusion practices and led to recommendation to use restrictive transfusion criteria and implementation of alternatives to ABT such as the use of autologous blood transfusion [4].

Preoperative autologous donation is a technique for collection and reinfusion of a patient’s own blood. Preoperative autologous donation is applicable to patients scheduled for elective surgery who are judged likely to have blood losses that require blood transfusion. Its aim is to meet the patient’s need for blood products without allogeneic transfusion [5]. Thus by means of using autologous transfusion, the risk of alloimmunization against erythrocyte antigens, leukocytes, thrombocytes, and plasma proteins, as well as the risk of immunosuppression and the risk of transmitting the causes of infectious diseases are eliminated. Hematopoietic system of the autologous blood ‘donor’ is boosted for endogenous cytopoiesis through autologous blood transfusion. For all of the above stated reasons, autologous blood transfusion is considered the safest of all treatments with blood products [6].

Allogeneic transfusion has been shown to increase the length of hospitalization. Autologous blood transfusion is actually believed to diminish the need for allogeneic blood and shortens the patient recovery period [7].

Intravenous iron is used to boost the production of erythrocytes and is extremely used in predonation. It is a relatively safe and cheap medication though patients should be admitted to hospital for the intravenous application. The adverse reactions of Intravenous iron include nausea, vomiting, abdominal pain, backache, muscle pain, fast heartbeats, hypotension, chest pain, chills, dizziness, fainting, fever with increased sweating, flushing, headache, metallic taste, numbness, pain, tingling of hands or feet, pain or redness of skin at injection site, skin rash or swelling of mouth or throat. The adverse reactions were commonly associated with iron dextran and less with iron sucrose or sodium ferric gluconate (50, 36, 35%, respectively) [8],[9].

The use of antifibrinolytic drugs, such as tranexamic acid (TXA) is useful to decrease blood loss perioperatively. TXA is a popular adjunct drug used to decrease intraoperative blood loss. TXA is a lysine analog that inhibits competitively the activation of plasminogen to plasmin (slowing the rate of fibrinolysis) [10]. It is applied intravenously or topically to the surgical field [11]. The optimal effect of TXA is reached by starting with a bolus of 10–15 mg/kg. There is less effect in every dose given on top of the initial dose [12]. The analog has been documented as efficacious in orthognathic procedures because of its relatively low cost and successful use [13]. No serious adverse effects were found while using TXA [14].

In this study, our primary outcome measure was to assess the efficacy of preoperative autologous blood donation (PAD) combined with intraoperative intravenous TXA administration in reducing the need for ABT in elective RTHA. And our secondary outcome measure was to assess the drop in hemoglobin (Hb) after surgery and in postoperative hospital stay.

 Patients and methods



The study was conducted in from August 2010 to October 2013. The study protocol was approved from the institutional ethics committee of Heliopolis Hospital (Cairo, Egypt) and a written informed consent was obtained from all the patients. Randomization was done using computer-generated random numbers in a 1 : 1 ratio and conducted using sequentially numbered, opaque, and sealed envelope (SNOSE). Intraoperative and postoperative data collection were achieved by anesthesia residents and they were not involved in any other parts of the study (ClinicalTrials.gov Identifier: NCT02747615).

Revision total hip replacement (THR) surgery was performed in 60 patients aged 60–75 years. The study population was divided into two groups: the study group that included 30 patients who were transfused preoperatively donated autologous blood, either during surgery or after it; and the control group that consisted of 30 patients who were transfused only allogeneic blood.

Indications for autologous blood donation were all elective surgical procedures for patients (American Society of Anesthesiologists I, II), weighing from 60 to 90 kg with a Hb level greater than 11 g/dl and a hematocrit (Hct) level of greater than 34%. Patients were referred to the blood bank of the hospital from the department of orthopedic surgery for blood collection.

This study excluded cases of RTHA for infection or fractures as well as early revisions for dislocations secondary to implant malposition, patients with cardiac decompensation, severe hemodynamic problems, respiratory insufficiency, severe defect of central nervous system, active infection, blood disease, coagulopathies, and operative time that exceeded 3 h.

All patients of the study group donated 2 units, provided the laboratory analysis showed an Hb level of 11 g/dl or more, and an Hct level of 34% or more. The first blood collecting step was planned 2 or 3 weeks before the patient was admitted to hospital and the next blood collecting step was repeated in 7 days time. Prior to each blood donation, the Hb concentration and Hct level were evaluated. Iron supplementation was administered parenterally after each donation in order not to get the patient into the anemic condition before surgery. Parenteral iron was calculated according to the patient’s body weight and total iron deficits.[INLINE:1][INLINE:2][INLINE:3]

Intravenous iron infusion [Ferosac iron saccharate solution by Saudi Pharmaceutical Industries & Medical Appliances Corporation (SPIMACO), (Saudi Arabia) must be diluted in sterile 0.9% sodium chloride solution (NS): intravenous infusion for a 100 mg (ampoule 5 ml Ferosac) dilute to a 100 ml, and for 200 mg (10 ml Ferosac) dilute to 200 ml in NS and infuse for more than 30 min (using flow regulator, ULTRAMED, Ultra for Medical Products Ind., Abnob, Asciout, Egypt). The first 25 ml should be observed for adverse reaction(s).

The second donation took place at least 48–72 h before surgery to allow for re-equilibration of the blood volume. On each occasion, about half a liter of the patient’s own blood was taken into sterile plastic bags (JMS CPDA-1-70 ml for collection of 500 ml blood), and the blood was stored in the refrigerator at 4°C at a hospital blood bank until the time of surgery.

The control group consisted of patients who did not donate autologous blood and who received only allogenic blood and also included the patients who had contraindications for autologous blood donation.

The surgery was preceded by a 6 h fasting period. Upon arrival of patients to the operating room, a wide bore cannula was inserted and loading the patients with 1 l of crystalloids. Routine monitoring of the patient was placed including pulse oximetry, five-lead ECG, and noninvasive blood pressure (Dräger Fabius plus with Drager infinity Kappa monitor; Dräger, Technology for Life, United States). Anesthesia was obtained by combined spinal epidural technique (epidural kit; MINI-PERISAFE PLUS, Weiss epidural needle 17 G 3.1’ 15/10e mm×80 mm with closed-end round catheter 19 G 36’ 11/10e mm×914 mm) (spinal anesthesia needle, LANCET 25 G; Uniever; Unisis Corp., Japan). Urinary catheter was inserted before the patient turned to lateral position to be operated upon.

All the operations were done by the same group of surgeons who used the same operative technique and methods of hemostasis. Five patients in the study group and three patients in the control group were operated on, using non-cemented acetabular components.

All patients of the study group received two doses of intravenous TXA in the perioperative period: 1 g prior to skin incision and another 1 g during wound closure. TXA solution is mixed with 100 ml NS and administered slowly by intravenous infusion (manufactured as Kapron ampoules, each ampoule contains 5 ml of 500 mg, 100 mg/ml, for intravenous use only; Sunny Pharmaceutical for Amoun Pharmaceutical Co., Cairo, Egypt).

The intraoperative blood loss was assessed by measuring the estimated amount of blood in the sponges, operation drapes, and the blood collected in the suction container. Postoperatively, blood loss was assessed by measuring the amount of blood collected in the drainage system.

During the perioperative period, the number of transfused units of blood (autologous and allogeneic blood), Hb and Hct values, value of blood loss intraoperatively and postoperatively through a medical drain, post-transfusion reactions occurrence, and the length of hospitalization were observed and recorded.

Analysis of data

It was estimated that a sample of 30 patients in either group would achieve a power of 87 and 86% to detect effect sizes of w=0.4 and d=0.8 for both outcomes, respectively. This calculation assumed a two-sided type-I error of 0.05 using the χ2-test and unpaired t-test for the primary and secondary outcome measures, respectively.

The collected data were coded, tabulated, and statistically analyzed using IBM SPSS statistics (Statistical Package for the Social Sciences) software version 22.0, 2013 (IBM Corp., Chicago, Illinois, USA).

Descriptive statistics were done for quantitative data as minimum and maximum of the range as well as mean±SD for quantitative parametric data, median and first and third interquartile range (IQR) for quantitative nonparametric data, whereas it was done for qualitative data as number and percentage.

Inferential analyses were done for quantitative variables using independent t-test in cases of two independent groups with parametric data and Mann–Whitney U-test in cases of two independent groups with nonparametric data, repeated measure analysis of variance test for more than two dependent groups with parametric data. In qualitative data, inferential analyses for independent variables were done using χ2-test for differences between proportions and Fisher’s exact test for variables with small expected numbers. The level of significance taken at a P value of less than 0.050 is significant, otherwise is nonsignificant.

 Results



A total of 73 patients were assessed for eligibility from August 2010 to October 2013 in the hospital. Out of these, 69 were randomized, 34 patients included in the study group (four patients of which denied blood donation and only 30 patients completed in the study group) and 35 patients were scheduled in the control group of which five patients were not included (three patients exceeded 3 h of operation time and two patients were referred to other hospitals) and only 30 patients completed in the control group. Sixty patients completed the study (30 patients for each group) and their data were included in the final analysis ([Figure 1]).{Figure 1}

Results of the current study did not show significant differences in the demographic data of the two groups of patients regarding age, sex, body weight, height, American Society of Anesthesiologists physical status, and operative time ([Table 1]).{Table 1}

There were statistically significant elevations in Hb and Hct values in the study group after each intravenous Ferosac following blood donation ([Table 2]).{Table 2}

No significant difference between the two groups regarding Hb and Hct at preoperative, postoperative, and discharge ([Table 3] and [Figure 2] and [Figure 3]).{Table 3}{Figure 2}{Figure 3}

No significant differences were found between the study and control groups in either intraoperative or postoperative blood loss. The total hospital stay was significantly shorter in the study group compared with the control group as presented in [Table 4].{Table 4}

The total number of transfused blood units both autologous and allogeneic (operative and postoperative) in both groups was nonsignificant (P=0.089) ([Table 5]).{Table 5}

The amounts of transfused allogeneic blood units were significantly reduced in the study group in comparison to the control group as presented in [Table 6].{Table 6}

 Discussion



Revision THR surgeries have transfusion rates of 2.9±2.3 units have been documented. These blood transfusions save lives, but they also put patients at risk for serious complications [5]. In spite of advances in surgical and anesthetic techniques, blood loss during total joint arthroplasty can be significant [15].

In the study group, we found that 90% of the patients who donated 2 blood units before surgery did not need allogeneic blood after their own blood units were reinfused. The remaining 10% of patients received 3 units of allogeneic blood, that is, 1 unit per patient in addition to their own blood. The results of our study showed that the amounts of transfused allogeneic blood units were significantly reduced due to PAD. Anemia may be diagnosed with confidence when the Hb concentration is lower than the level considered normal for the person’s age/sex group [16]. According to the WHO criteria, anemia is defined as Hb concentration lower than 13 g/dl or Hct lower than 39% in adult men and Hb concentration lower than 12 g/dl or Hct lower than 37% in adult nonpregnant women [17]. In this study, in order not to bring the patient into the anemic condition before surgery, the value of 13 g/dl or less for Hb was taken as the border value when parenteral iron preparation was introduced.

Our results were in agreement with the findings of Awad et al. [18], who conducted a prospective randomized study of the efficacy and effects of autologous blood transfusion in revision hip arthroplasty and found that the combination of preoperative blood donation and intraoperative blood salvage reduced blood loss and homologous blood transfusion in revision hip arthroplasty [18].

These results were supported by the study of Lisander et al. [19], who found that the administration of autologous blood diminished the usage of allogeneic blood by 35–40% during the perioperative period in THR surgery.

Similarly, Kubota et al. [20] studied a series of 161 consecutive THA patients to find that the need for ABT was avoided with the use of PAD (2–3 units per patient).

Our results were partially consistent with the study of Bierbaum et al. [21] who confirmed in their study that allogeneic blood was transfused despite extensive use of predonated autologous blood. Twenty percent (n=796) of the 3920 patients who had procedure on the hip joint had a transfusion of allogeneic blood. The rates of transfusion of allogeneic blood were highest for the patients who had a revision procedure and for those who had a baseline Hb level of 13 g/dl or less [21].

Recommended official guidelines is restricted transfusion strategies involving Hb threshold between 7 g/dl in healthy participants and 8–9 g/dl in patients with cardiovascular history and no clinical or electrocardiographic signs of anemia [22]. In this study, blood was transfused when Hb values were less than or equal to 9 g/dl because the patients were elderly and had chronic diseases.

Based on the obtained results, preoperative Hb correction by administering intravenous iron preparations along with PAD significantly reduced the need for ABT.

Kajikawa et al. [23] evaluated the benefit of autologous blood transfusion and the effect of recombinant human erythropoietin (rh-EPO) on PAD for hepatectomy in patients with cirrhosis and treated those participants who donated autologous blood with 80 mg of iron sulfate and 500 ml of Ringer’s lactate solution intravenously on the day of blood collection, followed by 100 mg of iron sulfate given orally once daily until the operation. They reported that autologous blood transfusion yields clinically superior results for hepatectomy in patients with cirrhosis when compared with homologous transfusion and preoperative rh-EPO administration minimizes presurgical decreases in Hct caused by autologous blood donation [23].

Christopoulou et al. [24] also determined the impact of autologous blood transfusion with or without rh-EPO in patients who underwent elective maxillofacial operations and all patients received 150 mg ferrous sulfate daily by mouth, preoperatively until 1 week postoperatively and their results showed that improvement of blood parameters of the patients preoperatively underwent autologous blood predonation with intravenous injection of erythropoietin 600 IU/kg after each blood predonation and autologous blood transfusion intraoperatively.

In contrast to our results, Billote et al. [25] prospectively analyzed the effectiveness of preoperative autologous donation as a method for decreasing allogeneic transfusion among patients undergoing unilateral primary THR and all patients received 325 mg of oral ferrous sulfate twice daily after the first donation in the PAD group and 10 days prior to surgery in the control group. They reported that preoperative autologous donation provided no benefit for nonanemic patients undergoing primary THR surgery and preoperative autologous donation increased the likelihood of autologous transfusion, wastage of predonated units and costs [25].

Bezwada et al. [26] also evaluated the efficacy of erythropoietin in combination with, and compared with, preoperative autologous donation for reducing allogeneic blood requirements for total joint arthroplasty and the PAD groups received oral supplementation of 325 iron sulfate three times a day. They reported that the preoperative use of erythropoietin in conjunction with preoperative autologous donation reduces the need for ABT associated with total joint arthroplasty more effectively than does either erythropoietin or preoperative autologous donation alone [26].

Our results were in agreement with the findings of Bouchard et al. [27], who assessed the efficacy of PAD in reducing patient exposure to allogeneic blood products following elective cardiac surgery and patients in the PAD group received 300 mg ferrous sulfate orally three times daily throughout the period between donation and surgery. They found that preoperative blood donation was completed in 92% of the targeted low-risk population and the procedure significantly reduced exposure to perioperative allogeneic blood products [27].

Our results were in agreement with the findings of Serrano-Trenas et al. [28], who compared iron sucrose supplementation in surgeries of hip fracture patients with no iron supplementation and found that preoperative iron infusion can be administered successfully and reduced transfusion requirements in patients given 600 mg iron intravenously.

Our results were in agreement with the findings of Tesić et al. [6], who evaluated autologous blood transfusion in patients undergoing THR surgery. Oral iron preparation had been given to 12 patients for 2 weeks before the first donation and to six more patients after the second donation. The patients had been using the iron preparation before they were admitted to hospital. The average value of Hb had been 127.4 g/l in 12 patients before the oral iron preparation was introduced, and after 2 weeks, that is, before the first donation it was 136.9 g/l, that being a statistically significant difference (t=3.06, te=3.305, P<0.01) [6].

The prospective study of Borghi and Casati [29] highlighted the clinical relevance of applying an extensive and integrated autotransfusion regimen in order to reduce allogenic blood transfusion and associated complications in patients undergoing major joint replacement.

Preoperative autologous donation provides a safe supply of blood to the patient [30], but physiological compensation after donation may be inadequate [31] and sometimes the amount of donated blood is not used [28],[31]. As such TXA would be useful as an adjuvant strategy for patients with preoperative anemia to limit the rate of blood loss and ABT.

Our study had shown that PAD combined with the intraoperative intravenous TXA administration reduced significantly the number of ABTs in patients who underwent RTHA.

Our results were in agreement with the findings of Ortega-Andreu et al. [32], compared a group of patients undergoing total knee arthroplasty who received intravenous TXA infusion in two doses of 10–15 mg/kg, 15 min before tourniquet release and 3 h later to a control group. They found that there were no transfusion requirements in the TXA group (0%), with 23/61 (37.7%) transfusions in the control group and a 24 h significant decrease in visible bleeding in the TXA group [32].

Our results were consistent with the study of Sukeik et al. [33], who reported a systematic review and meta-analysis of published randomized controlled trials evaluating the efficacy of TXA in reducing blood loss and transfusion in THR. They found that TXA led to a significant reduction in the proportion of patients requiring ABT and there were no significant differences in deep-vein thrombosis, pulmonary embolism, or infection rates among the study groups [33].

Ho and Ismail [34] also reported the efficacy of the intravenous TXA to reduce the allogenic blood transfusion and the blood loss without complications related to the drug in total hip arthroplasty and total knee arthroplasty.

Rajesparan et al. [35] and Husted et al. [36] similarly evaluated the use of intravenous TXA in reducing blood loss and transfusion requirements in total hip arthroplasty [35],[36].

Our results were in agreement with the findings of Kagoma et al. [37], who reported that antifibrinolytic agents reduce the risk of transfusion by almost 50%, reduce bleeding, and do not appear to increase the risk of venous thromboembolism in a randomized trial among patients undergoing elective THR or total knee arthroplasty.

A study by Good et al. [38], also found a reduction in total blood loss when using TXA in total knee replacement. However, the concealed blood loss was not influenced when TXA was used [38].

Our results have shown that the average length of hospitalization in the study group was 3.2 days, and in the control group was 5.27 days (P<0.001), which is highly statistically significant.

Consistent with our study, Weber et al. [39], described an increase of hospital admission time of 2.7 days (±0.5 days) per transfused unit of red blood cells in total hip arthroplasty patient. Van Erve et al. [40] also found increasing hospital admission time by 1.78 days per unit packed red blood cells (P<0.000) in a study performed in 1422 patients who underwent total hip arthroplasty.

Our results were in agreement with the findings of Tesić et al. [6], who evaluated autologous blood transfusion in patients undergoing THR surgery and observing the length of hospitalization. They found that the average length of hospitalization in the study group was 20.3 days and in the control group it was 21.5 days, that being statistically significant (t=2.00, te=2.45, P<0.05) [6].

Strengths and limitations

In the study group, there is a risk of postponing the surgery in some patients due to various reasons, and in such cases the units of collected blood have to be disposed of due to expiry date. In order to avoid this situation, we collected 2 blood units from each of our patients, because the period between the first donation and surgery was shorter (∼2 weeks). Such protocol made it possible to postpone surgery for the period of 2 weeks maximum.

 Conclusion



This study concluded that the administration of PAD with TXA intraoperatively reduced the number of units transfused to the patients receiving only allogeneic blood. Autologous blood is a justifiable and safe alternative. Preoperative administration of parenteral iron preparations following each donation significantly increased the Hb values, thus enabling us to take 2 blood units from the patient.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Kurtz S, Ong K, Lau E, Mowat F, Halpern M. Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J Bone Joint Surg Am 2007; 89:780–785.
2Spahn DR. Anemia and patient blood management in hip and knee surgery: a systematic review of the literature. Anesthesiology 2010; 113:482–495.
3Vamvakas EC, Blajchman MA. Transfusion-related mortality: the ongoing risks of allogeneic blood transfusion and the available strategies for their prevention. Blood 2009; 113:3406–3417.
4Muñoz Mand Leal SR. Restrictive transfusion triggers in major orthopedic surgery: effective and safe? Blood Transfus 2013; 11:169–171.
5Henry DA, Carless PA, Moxey AJ, O’Connell D, Forgie MA, Wells PS, Fergusson D. Pre-operative autologous donation for minimizing perioperative allogeneic blood transfusion. Cochrane Database Syst Rev 2002; CD003602.
6Tesić I, Sekulić J, Arbutinov V, Popov D, Velisavljev D. Autologous blood transfusion in patients undergoing hip replacement surgery. Med Pregl 2014; LXVII:101–107.
7Osaro E, Njemanze C. Challenges of meeting the future blood transfusion requirement in England and Wales. Autologous blood transfusion could become an adjunct to the UK blood transfusion program in the future. Transfus Altern Transfus Med 2010; 11:72–81.
8Johnson-Wimbley TD, Graham DY. Diagnosis and management of iron deficiency anemia in the 21st century. Therap Adv Gastroenterol 2011; 4:177–184.
9Chertow GM, Mason PD, Vaage-Nilsen O, Ahlmén J. Update on adverse drug events associated with parenteral iron Nephrol Dial Transplant 2006; 21:378–382.
10McCormack PL. Tranexamicacid: a review in its use in the treatment of hyperfibrinolysis. Drugs 2012; 72:585–617.
11Patel JN, Spanyer JM, Smith LS, Huang J, Yakkanti MR, Malkani AL. Comparison of intravenous versus topical tranexamic acid in total knee arthroplasty: a prospective randomized study. J Arthroplasty 2014; 29:1528–1531.
12Nilsen RE, Husted H. Tranexamic acid reduces blood loss and the need of blood transfusion after knee arthroplasty. Ugeskr Laeger 2002; 164:326–329.
13Sankar D, Krishnan R, Veerabahu M, Vikraman B. Evaluation of the efficacy of tranexamic acid on blood loss in orthognathic surgery. A prospective, randomized clinical study. Int J Oral Maxillofac Surg 2012; 41:713–717.
14Henry DA, Carless PA, Moxey AJ, O’Connell D, Stokes BJ, Fergusson DA, Ker K. Antifibrinolytic use for minimizing perioperative allogeneic blood transfusion. Cochrane Database Syst Rev 2011; 16;3:CD001886.
15Parvizi J, Chaudhry S, Rasouli MR, Pulido L, Joshi A, Herman JH, Rothman RH. Who needs autologous blood donation in joint replacement? J Knee Surg 2011; 24:25–31.
16Baker SJ, DeMaeyer EM. Nutritional anemia: its understanding and control with special reference to the work of the World Health Organization. Am J Clin Nutr 1979; 32:368–417.
17Natvig K. (1966) Acta Med Scand, 180, 613; Tibblin, G., unpublished observations; Kilpatrick, G. S. and Hardisty, R. M. (1961) Brit Med 1, 778; De Leeuw, N. K. M., Lowenstein, L. and Hsiek, Y. S. (1966) Medicine (Baltimore), 45, 291; Sturgeon, P. (1959) Brit J Hemat, 5, 31.
18Awad AL, Ohlin AK, Berntorp E, Nilsson IM, Fredin H. Autologous blood transfusion in revision hip arthroplastycta. Ortop Scand 1992; 63:373.
19Lisander B, Ivarsson I, Jacobsson SA. Intraoperativeautotransfusionis associated with modest reduction of allogeneic transfusion in prosthetic hip surgery. Acta Anaesthesiol Scand 1998; 42:707–712.
20Kubota R, Nozawa M, Matsuda K, Maezawa K, Kim SG, Maeda K et al. Combined preoperative autologous blood donation and intraoperative cell salvage for hip surgery. J Orthop Surg (Hong Kong) 2009; 17:288–290.
21Bierbaum BE, Callaghan JJ, Galante JO, Rubash HE, Tooms RE et al. An analysis of blood management in patients having a total hip or knee arthroplasty. J Bone Joint Surg Am 1999; 81:2–10.
22Giral T, Tesniere A, Bellamy L, Ozier Y, Samama CM et al. Bleeding kinetic after total hip or knee replacement: a prospective observational study. J Anesth Clin Res 2013; 4:9.
23Kajikawa M, Nonami T, Kurokawa T, Hashimoto S, Harada A et al. Autologous blood transfusion for hepatectomy in patients with cirrhosis and hepatocellular carcinoma:use of recombinant human erythropoietin. Surgery 1994; 115:727–734.
24Christopoulou M, Derartinian H, Hatzidimitriou G, Iatrou L. Autologous blood transfusion in oral and maxillofacial surgery patients with the use of erythropoietin. J Craniomaxillofac Surg 2001; 29:118–125.
25Billote DB, Glisson SN, Green D, Wixson RL. A prospective, randomized study of preoperative autologous donation for hip replacement surgery. J Bone Joint Surg Am 2002; 84-A:1299–1304.
26Bezwada HP, Nazarian DG, Henry DH, Booth RE. Preoperative use of recombinant human erythropoietin before total joint arthroplasty. J Bone Joint Surg Am 2003; 85-A:1795–1800.
27Bouchard D, Marcheix B, Al-Shamary S, Vanden Eynden F, Demers P, Robitaille D et al. Preoperative autologous blood donation reduces the need for allogeneic blood products: a prospective randomized study. Can J Surg 2008; 51:422–427.
28Serrano-Trenas JA, Ugalde PF, Cabello LM, Chofles LC, Lázaro PS, Benítez PC. Role of perioperative intravenous iron therapy in elderly hip fracture patients: a single center randomized controlled trial. Transfusion 2011; 51:97–104.
29Borghi B, Casati A on behalf of the Rizzoli Study Group on Orthopedic Anesthesia. Incidence and risk factors for allogeneic blood transfusion duringmajor joint replacement using an integrated autotransfusion regimen. Eur J Anesthesiol 2002; 17:411–417.
30Monsef JB, Figgie MP, Mayman D. Targeted preoperative autologous blood donation; a prospective study of two thousand and three hundred and fifty total hip arthroplasties. Int Orthop 2014; 38:1591–1595.
31Hatzidakis AM, Mendlick RM, McKillip T, Reddy RL, Garvin KL. Preoperative autologous donation for total joint arthroplasty. An analysis of risk factors for allogenic transfusion. J Bone Joint Surg Am 2000; 82:89–100.
32Ortega-Andreu M, Perez-Chrzanowska H, Figueredo R, Gómez-Barrena E. Blood loss control with two doses of tranexamic acid in a multimodal protocol for total knee arthroplasty. Open Orthop J 2011; 5:44–48.
33Sukeik M, Alsharyda S, Hadad FS, Mason JM. Systematic review and meta-analysis of the use of tranexamic acid in total hip replacement. J Bone Joint Surg Br 2011; 93:39–46.
34Ho KM, Ismail H. Use of intravenous tranexamic acid to reduce allogenic blood transfusion in total hip and knee arthroplasty: a meta-analysis. Anesth Intensive Care 2003; 31:529–537.
35Rajesparan K, Biant LC, Ahmad M, Field RE. The effect of intravenous bolus of tranexamic acid on blood loss in total hip replacement. J Bone Joint Surg Br 2009; 91:776–783.
36Husted H, Blønd L, Sonne-Holm S, Holm G, Jacobsen TW, Gebuhr P. Tranexamic acid reduces blood loss and blood transfusion in primary total hip arthroplasty: a prospective randomized double-blind study in 40 patients. Acta Orthop Scand 2003; 74:665–669.
37Kagoma YK, Crowther MA, Douketis J, Bhandari M, Eikelboom J, Lim W. Use of antifibrinolytictherapy to reduce transfusion in patients undergoing orthopedic surgery: a systemic review of randomized trials. Tromb Res 2009; 123:687–696.
38Good L, Peterson E, Lisander B. Tranexamic acid decreases external blood loss but not hidden blood loss in total knee replacement. Br J Anaesth 2003; 90:596–599.
39Weber EW, Slappendel R, Prins MH, Van der Schaaf DB, Durieux ME, Strümper D. Perioperative blood transfusions and delayed wound healing after hip replacement surgery: effects on duration of hospitalization. Anesth Analg 2005; 100:1416–1421.
40Van Erve RHGP, Wippert I, Six Dijkstra WMC, Oosterveld FGJ. Is ASA class a predictor for longer hospital stay in short track programs for elective total hip arthroplasties? [Is de ASA classificatie een voorspellende factor voor een verlenging van de ligduur in een short track programma voor electieve totale heup arthroplastieken?] (Dutch). Presentation for the annual congress of the Dutch Orthopedic Society; 22 Jan 2010 Abstract in NTvO 2010; 17:55–56.