Role of perioperative intravenous iron therapy in ... - Wiley Online Library

TRANSFUSION PRACTICE Role of perioperative intravenous iron therapy in elderly hip fracture patients: a single-center randomized controlled trial

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97..104

José Antonio Serrano-Trenas, Pilar Font Ugalde, Laura Muñoz Cabello, Luis Castro Chofles, Pilar Serrano Lázaro, and Pedro Carpintero Benítez

BACKGROUND: The main objective of this study was to determine the efficacy of intravenous (IV) iron sucrose therapy reducing transfusion requirements in elderly patients undergoing hip fracture surgery. STUDY DESIGN AND METHODS: This study was a prospective randomized controlled trial involving 200 patients undergoing hip fracture surgery. Group A (100 patients) received standard treatment, while Group B (100 patients) received iron sucrose (600 mg IV). The primary endpoint was the number of patients that were transfused postoperatively. The secondary endpoints were the rate of red blood cell units used, hematimetric variables of blood tests, mortality, infection rates, length of hospital stay, and appearance of side effects. RESULTS: Differences in the percentage of patients requiring transfusion (Group A 41.3% vs. Group B 33.3%) and in the number of concentrates transfused (0.87 ⫾ 1.21 for Group A vs. 0.76 ⫾ 1.16 for Group B) were not significant for the patient group as a whole, but were significant for patients with intracapsular fractures (45.7% required transfusion in Group A vs. 14.3% in Group B; p < 0.005) and in patients with a baseline hemoglobin (Hb) level of 12 g/dL or more (35.2% required transfusions in Group A vs. 19% in Group B; p < 0.05). CONCLUSIONS: Transfusion requirements in patients with intracapsular fracture or baseline Hb level of 12 g/dL or more appear to be reduced by IV iron sucrose therapy, but there was no difference in morbidity, mortality, or length of hospital stay. The treatment is safe and hastens recovery from blood loss.

B

ecause osteoporotic hip fractures are both common and serious, they are not simply a medical or health problem, but also have social, family, and economic implications. The incidence of hip fracture is constantly increasing, and most current treatment techniques require early surgery to ensure that the patient’s prior functional status is restored as quickly as possible. The bleeding caused by the fracture itself, coupled with inevitable blood loss during surgery, often gives rise to anemia. As in any other major surgery, recovery from anemia is hindered by functional iron deficiency.1,2 The clinical status of elderly patients, often with multiple comorbidities, renders them especially vulnerable to the adverse consequences of anemia. Allogeneic blood transfusions are widely used to counter the adverse effects of anemic status in patients undergoing nonscheduled orthopedic surgery, but for

ABBREVIATION: ASA = American Society of Anesthesiology. From the Orthopedic and Trauma Surgery Unit, the Rheumatology Unit, and the Physiotherapy and Rehabilitation Unit, Hospital Universitario Reina Sofía, Córdoba, Spain. Address reprint requests to: José Antonio Serrano Trenas, Avenida de los Almogávares, 29. 1°-3. 14007 Córdoba, Spain; e-mail: [email protected]. This trial was funded by the Spanish Ministry of Health and Consumer Affairs, through the Instituto de Salud Carlos III, under Protocol Code EC07/90842, as part of the Biomedical and Health Science Research Promotion Programme for the implementation of noncommercial clinical research projects using drugs intended for human use, within the framework of the National Plan for Scientific Research, Development and Innovation (RI+D+I) for the period 2004-2007. Prior authorization was obtained from the Spanish Agency for Medicines and Health Products, under EudraCT Number 2007-007044-10. Received for publication March 24, 2010; revision received May 12, 2010, and accepted May 15, 2010. doi: 10.1111/j.1537-2995.2010.02769.x TRANSFUSION 2011;51:97-104. Volume 51, January 2011 TRANSFUSION 97

SERRANO-TRENAS ET AL.

some decades alternative treatments have been sought to transfusion, due to the shortage of donors; the high cost of collecting, processing, storing, and checking blood products; and above all, the potential adverse effects of allogeneic blood transfusion in patients undergoing surgery, in particular the increase in infectious complications due to an immunologic effect.3 Perioperative intravenous (IV) iron therapy is one such alternative. Countless reports in the literature testify to the value of IV iron therapy, either alone or in combination with erythropoietin (EPO), in scheduled digestive, gynecologic or obstetric, vascular, and heart surgery.4-7 Over the past 5 years, a number of studies have focused on the potential influence of IV iron therapy, either alone or combined with EPO, on transfusion requirements in patients undergoing surgery for hip fracture repair.8-15 The authors conclude that, while iron therapy appears to be useful in certain types of patient, randomized controlled trials are required to confirm these findings. To test the hypothesis that perioperative IV iron therapy reduces transfusion requirements in elderly patients undergoing hip fracture surgery, the present trial used a randomized controlled design to evaluate the efficacy of IV iron administration in osteoporotic hip fracture patients in reducing transfusion requirements. The secondary objectives were to determine whether hematimetric variables recover more quickly in treatment group and whether IV iron therapy reduced the rate of infectious complications, the length of hospital stay, and 30-day mortality in these patients. This article was drafted in accordance with the recommendations of the CONSORT (Consolidated Standards of Reporting Trials) declaration16 aimed at improving the quality of reports on randomized parallel-group trials.

PATIENTS AND METHODS A total of 200 patients aged over 65 undergoing hip fracture surgery at the Orthopedic and Trauma Surgery Unit of the Hospital Reina Sofia in Córdoba (Spain) between October 2006 and October 2008 were randomized to two groups each comprising 100 patients. Sample size was calculated bearing in mind that roughly 50% of patients undergoing hip fracture repair require transfusion and that—according to published studies—IV iron therapy prompts a decline of approximately 20% in the percentage of patients requiring transfusion. Therefore, we chose a sample of 100 patients per group to obtain an 80% statistical power to detect a difference of 20% in transfusion rates between the study arms. It was assumed that there would be no loss to follow-up; an alpha error of 0.05 and a beta error of 0.20 were accepted. The exclusion criteria were diseases diagnosed before the admission of patient (iron overload disorders, hypersensitivity to oral or parenteral iron preparations, asthma 98 TRANSFUSION

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or other severe atopic, active infection or neoplasm), treatment with clopidogrel or with acetylsalicylic acid at dose rates greater than 150 mg/24 hr, no surgical indication for the current fracture, disorders impaired coagulation (partial thromboplastin time > 2.5%, international normalized ratio > 1.5), liver disorders with elevated transaminases (aspartase aminotransferase [AST] > 70 U/L, alanine aminotransferase [ALT] > 55 U/L), and chronic kidney failure (creatinine > 2 mg/dL) or patients including in dialysis. No one of our patients refused the transfusion. Patients agreeing to take part in the trial were asked to sign an informed consent form (which, together with the trial protocol, was approved by the local hospital ethics committee), and the investigator then assigned them randomly to one or other of the two study groups. Randomization lists were generated in blocks of 10 to ensure equal group sizes, and allocation was made using sequentially numbered opaque sealed envelopes, so that neither the patient nor the investigator could know which group the subject was assigned to before his or her consent to participation. Blinding procedures were not used in the trial because they were considered too complex for daily clinical practice; this was compensated for by the rigorous nature of most of the study variables and by the blinded evaluation of trial data by an independent evaluator. Both groups underwent the treatment protocol drawn up at this center following the Guidelines on the Integrated Treatment of Hip Fractures in Elderly Patients.17 Criteria for transfusion were also protocolized in conjunction with the hematology and anesthesiology units at the same hospital and based on the guidelines published by the Spanish Blood Transfusion Society (preoperative hemoglobin [Hb] level of less than 10 g/dL, postoperative Hb level of less than 8 or less than 9 g/dL in patients with a history of cardiorespiratory conditions, or any Hb in patients with symptoms of untreated anemia).18 The red blood cell (RBC) units used in our hospital were leukoreduced, with anticoagulant citrate-phosphate-dextrose and preservative solution sagmanitol (100 mL), conserved between 2 and 6°C. Group A patients received only the standard protocolized treatment. Group B patients additionally received 600 mg of iron sucrose IV (Venofer, Vifor France Company, Levallois-Perret, France) in three doses of 200 mg at 48-hour intervals, starting on the day of admission; administration was by slow perfusion of two 100-mg ampoules diluted in 250 mL of 9% saline solution over a 90-minute period. The first dose was administered in the first 24 hours after admission, always before surgical intervention. The following doses were administered before or after surgery, depending on the time of surgery. Twenty patients (20.2%) received a single dose, 63 patients (63.6%) received two doses, and 16 patients (16.2%) received tree doses before surgery. No study patient received EPO.

IV IRON IN HIP FRACTURE SURGERY

The following variables were recorded for each patient: age, sex, medical history, type of fracture using the AO classification, associated fractures, anesthetic risk classification using the American Society of Anesthesiology (ASA) scale, and blood tests on admission. They included RBCs, Hb, hematocrit (Hct), white blood cells, platelets, partial thromboplastin time, international normalized ratio, glucose, urea, creatinine, sodium, potassium, chlorine, AST, ALT, ferritin, transferrin, iron levels, vitamin B12, RBC folate, thyroxine, and thyroidstimulating hormone. The hematimetric tests were repeated 24 hours and 7 days after surgery. Also were recorded type and duration of surgery, transfusion of RBC units requirement, and number of RBC units transfused pre- and postoperatively, appearance of respiratory; urinary or surgical-wound infections; preoperative stay and total hospital stay; mortality; and possible appearance of side effects of IV iron therapy. In the first clinical visit 30 days after discharge were recorded as postdischarge morbidity any health problems suffered by the patient, especially infectious problem or need for further transfusions. The primary endpoint was the number and rate of patient transfused postoperatively in each therapy arm. The secondary endpoints were mean of RBC units used by patient, hematimetric variables in blood tests, 30-day mortality, infection rates and length of hospital stay in each therapy arm, and appearance of side effects in the treated group. Depending on pretransfusional Hb levels, transfusions were classified as “protocol-compliant” (low Hb levels or uncontrolled anemic symptoms) or “protocolnoncompliant” (transfused patients without justification according to the protocol). Transfusion timing was classed as intraoperative (in the operating theater or recovery room), early (during the first 72 hr postsurgery), or late (from Postsurgery Day 4 onward). Records also allowed for potential undertransfusion (patients who should have received transfusion and did not).

Statistical analysis Absolute frequencies and percentages were calculated for qualitative variables and arithmetic means, standard deviation (SD), and range for quantitative variables. Qualitative variables were compared using Pearson’s chisquare test or Fisher’s test where any expected frequency was lower than 5 for 2 ¥ 2 comparisons; Pearson’s chisquare test was applied to h ¥ k comparisons. Quantitative variables were compared using that t test for independent variables. A one-way repeated-measures analysis of variance (ANOVA) was performed to compare subjects, later using Sidak’s adjustment to compare mean Hct values on admission, at 24 hours postsurgery, and on Day 7 postsurgery as a function of treatment group.

First, an overall comparison was made of all patients, and then patients were divided into two groups depending on whether the fracture was intra- or extracapsular and on whether Hb levels on admission were lower or higher than 12 g/dL; comparison of the main variables was then repeated for those groups. Data were analyzed on an intention-to-treat basis. All comparisons were bilateral and differences were considered significant at p values of less than 0.05. A statistical software package (SPSS Version 17.0, SPSS, Inc., Chicago, IL) was used for statistical analyses.

RESULTS The flow diagram for patients taking part in the trial is shown in Fig. 1. Main patient demographic data, baseline clinical characteristics, and admission blood tests variables are shown, by treatment group, in Table 1. No significant differences between the two groups were found for the remaining baseline variables. During the hospital stay, 29 patients (14.8%) displayed infections: most of these were superficial surgical wound infections (11 patients, 5.6%); eight patients (4.1%) developed respiratory infections, six (3.1%) developed urinary infections, and two patients developed deep surgical wound infections. An additional two patients (1%) developed “other” infections (diarrhea in one case and colorectal abscess in the other). Only three patients in the treatment group (3.03%) displayed side effects requiring treatment to be suspended; these comprised skin rash in one case and general discomfort in the other two. Postoperative transfusion was required in 74 patients (37.8%). No significant intergroup differences were found for the type of timing of transfusion or for protocol compliance (Table 2). Neither significant differences were found for the number of patients classed as “infratransfusions” (two patients, 2.1%, in Group A and four patients, 4%, in Group B). Differences in the percentage of patients receiving transfusions (41.3% in Group A vs. 33.3% in Group B) and in the number of concentrates required (0.87 ⫾ 1.21 in Group A vs. 0.76 ⫾ 1.16 in Group B) failed to attain significance for the trial as a whole. Intergroup differences were also nonsignificant for appearance of infections during hospitalization (13 infections in Group A vs. 16 in Group B), postdischarge morbidity (21 patients in Group A vs. 20 in Group B), total length of hospital stay (12.9 ⫾ 6.9 days in Group A vs. 13.5 ⫾ 7.1 days in Group B), and mortality (10 patients in Group A vs. 11 in Group B). The one-way repeated-measures ANOVA performed to compare mean Hct values on admission, at 24 hours postsurgery, and on Day 7 postsurgery revealed no significant differences between groups. In both groups, baseline values differed from those recorded at 24 hours and at 7 days postsurgery. In Group B patients, mean Hct values on Volume 51, January 2011 TRANSFUSION 99


Fig. 1. Patient flow diagram.

Day 7 postsurgery were significantly higher than those recorded 24 hours postsurgery. That did not happen in Group A (Table 3). Subsequent analysis was performed including only those patients with intracapsular fractures (70 patients, 35 in Group A and 35 in Group B). Prior analysis of baseline variables in the two groups revealed no significant difference for any variables except blood iron levels (38.9 mg/dL ⫾ 22.3 in Group A vs. 63.6 mg/dL ⫾ 57.7 in Group B; p = 0.021). Significantly fewer patients received transfusions in Group B than in Group A (Table 4) and those patients required on average fewer RBC units (0.86 units in Group A vs. 0.29 units in Group B; p < 0.05). No significant differences were found for infections during hospitalization, postdischarge morbidity, length of hospital stay, or mortality. Finally, analysis was performed only for those patients with Hb levels on admission equal to or greater than 12 g/dL (110 patients, 50 in Group A and 60 in Group B). Prior analysis of baseline variables in the two groups revealed no significant differences. Fewer patients received transfusions in Group B than in Group A (Table 4), but no significant differences were found for 100 TRANSFUSION


mean number of concentrates required, infections during hospitalization, postdischarge morbidity, length of hospital stay, or mortality.

DISCUSSION Over the past few years, alternatives have been sought to allogeneic blood transfusion in patients requiring surgery. Alternative treatments tend to prove more problematic where surgery is not scheduled but is relatively urgent. This is the case of elderly patients undergoing hip fracture repair, whose situation may additionally be complicated by their medical history and by their physiologic status, which renders them especially vulnerable to blood loss and less able to respond to anemia. One alternative to allogeneic blood transfusion is the IV administration of iron, which may contribute to the rapid and safe recovery of erythroid mass with few side effects. Numerous reports in the literature testify to the value of IV iron therapy, either alone or in combination with EPO, in scheduled orthopedic surgery.4-7 However, only over the past few years has research focused on evaluating the role of IV iron therapy in patients undergoing surgery


and Izuel-Rami in 200513 and 2007.14 TABLE 1. Demographic data and baseline clinical characteristics by These authors highlighted the need treatment groups* for prospective, randomized, controlled Characteristics Group A (n = 97) Group B (n = 99) p value† trials to confirm their preliminary Age (years) 82.53 ⫾ 6.37 83.46 ⫾ 7.11 NS findings; this was the primary purpose Female 77 (79.4) 79 (79.8) NS of this trial. In an article published in Hb admission (g/dL) 11.9 ⫾ 1.8 12.1 ⫾ 1.6 NS Ferritin (ng/mL) 134.3 ⫾ 122.4 161.5 ⫾ 144.3 NS 2006, Muñoz and colleagues21 presented Iron levels (mg/dL) 46.3 ⫾ 34.8 53.2 ⫾ 42.6 NS the results obtained with IV iron therapy Transferrin (mg/dL) 206.6 ⫾ 44.9 208.6 ⫾ 48.1 NS in orthopedic and trauma surgery. In Fracture type Extracapsular 62 (63.9) 64 (64.6) NS 2008, the findings of an expert panel Intracapsular 35 (36.1) 35 (35.4) NS convened by the Network for AdvanceASA II/III 24/70 (24.7/72.2) 22/73 (22.2/3.7) NS ment of Transfusion Alternatives to History Arterial hypertension 69 (71.1) 66 (66.7) NS review the evidence on the efficacy and Heart disease 19 (19.6) 27 (27.3) NS safety of IV iron administration to NIDDM 18 (18.6) 20 (20.2) NS increase Hb levels and reduce allogeSenile dementia 19 (19.6) 19 (19.2) NS Acetylsalicylic acid 22 (22.7) 18 (18.2) NS neic blood transfusions in patients Chronic respiratory disease 6 (6.2) 11 (11.1) NS undergoing surgery were published.22 Surgery The panel concluded that IV iron Partial hip replacement 24 (24.7) 22 (22.2) NS Short sliding nail 42 (43.3) 50 (50.5) NS administration either alone or in conSliding screw 17 (17.5) 13 (13.1) NS junction with EPO might be useful, but Preoperative stay (days) 4.3 ⫾ 2.2 3.9 ⫾ 1.6 NS that it was currently to be recomHospital stay (days) 13.1 ⫾ 6.9 13.5 ⫾ 7.1 NS Preoperative transfusion 13 (13.4) 11 (11.1) NS mended only in patients undergoing * Data are reported as mean ⫾ SD or number of patients (%). scheduled surgery; this recommenda† Significance based on Pearson’s chi-square test or t test. tion was based on what the panel NIDDM = Non Insulin Dependent Diabetes Mellitus; NS = nonsignificant difference. termed moderate and/or low-quality evidence. Similar conclusions were reached by two other reviews of the efficacy and safety of IV iron administraTABLE 2. Number and mean of patients transfused postoperatively, depending of compliance with the transfusion protocol and timing tion, also published in 2008.23,24 of transfusion* Between 30 and 70% of patients Type of transfusion Group A Group B p value undergoing hip fracture repair require Timing of transfusion allogeneic blood transfusion.25-28 The Intraoperatively 21 (21.6) 23 (23.2) Early 8 (8.2) 4 (4) NS† risk factor most directly related to transLate 12 (12.4) 6 (6.1) fusion requirement in these patients is Compliance with the protocol preoperative anemia.29,30 Extracapsular Protocol-compliant 39 (95.1) 32 (97) NS‡ Protocol-noncompliant 2 (2.1) 1 (1) fracture has also been identified as a risk factor for transfusion, especially in the * Data are reported as number (%). † Significance based on Pearson’s chi-square test. case of multifragmented and subtro‡ Significance based on Fisher’s exact test. chanteric fractures.31 Other studies NS = nonsignificant difference. report an increased likelihood of transfusion with increasing anesthetic risk and patient age.28 Cuenca and col9,10 leagues for hip fracture repair. In the first published study in 1996, noted that the percentage of pertrochanteric Goodnough and Merkel19 administered iron dextran plus fracture patients requiring transfusion decreased by approximately 20% after IV iron administration, although EPO intravenously to nine patients undergoing hip fracdifferences with respect to untreated patients were not ture surgery, measuring reticulocyte counts, and Hct significant. However, it was noted that in patients with before and after treatment. Seven patients did not require baseline Hb levels of more than 12 g/dL, the decrease in allogeneic blood transfusion. In the second of the two the percentage requiring transfusion after IV iron therapy studies, published in 1998, Schmidt and colleagues20 was significant. In a different study, the same authors reported on only four patients receiving combined IV iron found that the percentage requiring transfusion and EPO, observing an improvement in blood test values decreased by 59%, but again the difference was not signifiin these patients. cant. However, a significant difference was observed in the The first studies involving considerable patient number of transfusion units required.11 These findings numbers were published by Cuenca and coworkers in 9,10 11 12 2004 and 2005, García-Erce and coworkers in 2005, were confirmed in this study: patients with intracapsular Volume 51, January 2011

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TABLE 3. Hct level preoperation, 24 hours postoperation, and 7 days postoperation* Group A

B

p value‡

Admission Hct 36.4 ⫾ 0.5

24 hr postoperation Hct 30.1 ⫾ 0.4

7°days postoperation Hct 30.8 ⫾ 0.4

36.8 ⫾ 0.5

30.7 ⫾ 0.4

31.6 ⫾ 0.4

0.603

0.284

p value† (a) 0.000 (b) 0.000 (c) NS (a) 0.000 (b) 0.000 (c) 0.037

0.146

* Data are reported as mean ⫾ SD. † Within-subjects contrast. ‡ Between-groups contrast. (a) Admission Hct versus 24 hours postoperation. (b) Admission Hct versus 7°days postoperation. (c) 24 hours postoperation versus 7°days postoperation. NS = nonsignificant difference.

transfusion. Johnson and colleagues,35 TABLE 4. Number and mean of postoperative transfusions in a study of 3625 consecutive patients Group Group A* Group B* p value† undergoing hip fracture surgery, found All patients (n = 196) 41 (41.3) 33 (33.3) NS no significant differences between the Patients with intracapsular fracture (n = 70) 16 (45.7) 5 (14.3) 0.004 transfusion and the nontransfusion Patients with admission Hb ⱖ 12 g/dL (n = 110) 18 (36) 11 (18.3) 0.049 group with regard to mortality, morbid* Data are reported as number of patients (%). ity, or infection rates. Cuenca and † Significance based on Pearson’s chi-square test. NS = nonsignificant difference. coworkers,9,10 García-Erce and coworkers,12 and Izuel-Rami and coworkers14 report a significant decrease in infection rates in patients receiving IV iron therapy. These findings, fractures and patients with baseline Hb values of more however, were not confirmed either here or in more recent than 12 g/dL benefited from IV iron administration, with a studies by Cuenca and coworkers,11 Izuel-Rami and significant decrease in the percentage of patients requiring transfusion and in the mean number of concentrates coworkers,13 and García-Erce and coworkers,15 in which per patient. In subsequent studies by Izuel-Rami and colurinary, respiratory, and surgical wound infection rates leagues13,14 and García-Erce and colleagues,12,15 recombiwere similar in treated and untreated groups. Mortality among elderly hip fracture patients is three nant human EPO was administered to patients with times greater than expected mortality for a nonfracture baseline Hb levels of lower than 13 g/dL (a standard propopulation of similar age. Between 3 and 10% of hip fraccedure in patients undergoing orthopedic surgery in ture patients die before being discharged from hospital Europe); a significant reduction in transfusion requireand one in every four patients die within the first year ments was recorded in all patients. postfracture. These figures have not varied greatly over the However, our work has limitations when generalizing past 40 years, as a recent review shows.36 The risk factors the results. We should remember that reducing the transfusion rate is obtained in a subgroup analysis, with fewer for greater mortality include age over 85, male sex, history patients. We should also highlight the difference that, of cardiac or respiratory disease,37 anesthetic risk greater despite randomization, there is in the basal levels of iron than II on the ASA scale, and mental deterioration and when comparing the two treatment groups in the subfunctional dependency before fracture. While allogeneic group of intracapsular fractures. Patients in Group B have blood transfusion has also been identified as a risk factor higher baseline levels of iron, which could magnify the for mortality in these patients,38 only one published study effect of IV iron therapy. of IV iron therapy found that this therapy prompted a sigThis trial also confirmed that patients receiving IV nificant decrease in mortality.11 This study found no sigiron sucrose displayed a faster recovery of RBC indices nificant difference in mortality between the two treatment than nontreated patients. This finding is significant, since groups. The study by Cuenca and colleagues11 was also the 32 33 Lawrence and coworkers and Halm and coworkers only one to record a significant reduction in the length of hospital stay in patients receiving IV iron therapy. This have shown that higher Hb levels are associated with finding has not been confirmed by any other published better early functional recovery after hip fracture repair. study, including this trial. The relationship between allogeneic transfusion and Like all the articles published to date, this study coninfection in patients undergoing surgery is not clearly firmed that the side effects of IV iron therapy were few and established. Hill and colleagues34 in their meta-analysis minor; iron sucrose is considered safe and generally wellfound a five times higher risk of infection for patients tolerated. Because it also has low economic cost (one dose undergoing emergency trauma surgery that required 102 TRANSFUSION



of iron sucrose has a price similar to that of any of the commonly used analgesics in these patients), we believe that this could be an efficient treatment. To conclude, IV iron sucrose therapy in elderly hip fracture patients appears to reduce perioperative transfusion requirements when the fracture is intracapsular and when baseline Hb levels are at least 12 g/dL. These results of subgroup analysis should be considered as a working hypothesis for future studies. Treatment with IV iron sucrose accelerates the recovery of blood loss suffered by these patients. However, the results are not conclusive regarding to a decrease in postoperative infection rates, length of hospital stay, or 30-day mortality.

Parenteral iron useful in the management of trochanteric hip fracture. TATM 2003;5:63. 9. Cuenca J, García Erce JA, Martínez AA, Solano VM, Modrego FJ. Seguridad y eficacia del hierro intravenoso en la anemia aguda por fractura trocantérea de cadera en el anciano. Med Clin (Barc) 2004;123:281-5. 10. Cuenca J, García Erce JA, Muñoz M, Izuel M, Martínez AA, Herrera A. Patients with pertrochanteric hip fracture may benefit fron preoperative intravenous iron therapy: a pilot study. Transfusion 2004;44:1-6. 11. Cuenca J, García Erce JA, Martínez AA, Solano VM, Molina J, Muñoz M. Role of parenteral iron in the management of anaemia in the elderly patient undergoing displaced subcapital hip fracture repair: preliminary data. Arch Orthop

ACKNOWLEDGMENT The authors are grateful to Dr Paul Edson for revising the manuscript before publication.

CONFLICT OF INTEREST The authors declare that they have no conflicts of interest relevant to the manuscript submitted to TRANSFUSION.

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