- Email: [email protected]
Treatment of perioperative anemia in hip fracture
554
Letters to the Editor / Med Clin (Barc). 2015;145(12):551–555
Neutropenia can accompany various immunodeficiencies with immunoglobulin deficiency or disorder.3 The combined immunodeficiencies (Wiskott-Aldrich syndrome, ataxiatelangiectasia, X-linked hyper-IgM syndrome, severe combined immunodeficiency4 ) and X-linked agammaglobulinemia5 begin in childhood with severe hypogammaglobulinemias and neutropenia of diverse etiologies (autoimmune, infectious, bone marrow deficiency). The common variable, as most common immunodeficiency in the adult population, occurs along with neutropenia, being usually autoinmune.6 IgG3 congenital deficiency is the rarest IgG subtype.7 It is most frequently detected in adults, who may have recurrent respiratory infections typically by Moraxella sp., and recurrent skin infections such as erysipelas by Streptococcus pyogenes. Patients with IgG3 congenital deficiency would not have higher prevalence of neutropenia according to the few cases reported to date.8 However, studies evaluating populations with chronic neutropenia in adults, of any etiology, have reported IgG3 deficiency was frequently associated. Karlström et al.8 analyzed 30 patients with chronic neutropenia in adults (with 8 cases of autoimmune cause) and almost half of them with IgG3 deficiency associated (47% patients), a phenomenon that remained over a long period of years of follow up. The infection rate was similar in those with or without IgG3 deficiency. Another study with 83 patients with chronic neutropenia in adults,9 all of idiopathic etiology, showed significant decreased levels of IgG3 (p < 0.001) compared to the control group, in addition to increased IgA in those with more severe neutropenia. Regarding the possible explanation for this association, 2 studies9,10 showed how in idiopathic forms of chronic neutropenia, considered a myelodysplastic syndrome of the granulocyte progenitors, patients had elevated levels of serum TGFB1. In addition, mesenchymal stem cells of bone marrow produced excessive TGFB1; we know that this cytokine may decrease IgG3 production and increase isotype switching to IgA in B cells. No similar pathophysiological studies are available on autoimmune forms of chronic neutropenia. In conclusion, we have verified through the description of a case and literature review that: (a) chronic neutropenia in adults of any etiology, in our case, autoimmune, may be accompanied by an isolated IgG3 deficiency; (b) it will not change the clinical course of these patients who remain generally indolent, with low prevalence
Treatment of perioperative anemia in hip fracture夽 Tratamiento de la anemia perioperatoria de la fractura de cadera Dear Editor, We have carefully read the review article by Pareja and Sierra Rodriguez Solis on perioperative medical treatment in elderly patients with hip fracture, recently published in Clinical Medicine.1 On Table 6 of this review, the authors provide transfusion criteria and guidelines on treatment with intravenous iron (FeIV) and recombinant erythropoietin (rHuEPO) depending on the levels of hemoglobin (Hb) at admission, referencing some of our papers and reviews. Therefore, we would like to clarify some of the authors’ statements and provide, from our experience and
夽 Please cite this article as: García Erce JA, Gómez Ramírez S, Cuenca Espiérrez J, ˜ Gómez M. Tratamiento de la anemia perioperatoria de la fractura de cadera. Munoz Med Clin (Barc). 2015;145:554–555.
of recurrent infections, and; (c) it will probably be secondary to changes in the immune profile of cytokine secretion (increased TGFB1) which may accompany chronic neutropenia, although this pathophysiological explanation based on idiopathic forms has not been corroborated in chronic autoimmune neutropenia. References 1. Lalezari P, Jiang AF, Yegen L, Santorineou M. Chronic autoimmune neutropenia due to anti-NA2 antibody. N Engl J Med. 1975;293:744–7. 2. Capsoni F, Sarzi-Puttini P, Zanella A. Primary and secondary autoimmune neutropenia. Arthritis Res Ther. 2005;7:208–14. 3. Rezaei N, Farhoudi A, Pourpak Z, Aghamohammadi A, Moin M, Gharagozlou M, et al. Neutropenia in patients with primary antibody deficiency disorders. Iran J Allergy Asthma Immunol. 2004;3:77–81. 4. Stephan JL, Vlekova V, Le Deist F, Blanche S, Donadieu J, de Saint-Basile G, et al. Severe combined immunodeficiency: a retrospective single-center study of clinical presentation and outcome in 117 patients. J Pediatr. 1993;123:564–72. 5. Plo Rodríguez F, García Rodríguez MC, Ferreira Cerdán A, Fontán Casariego G. Neutropenia como manifestación precoz de una agammaglobulinemia ligada al cromosoma X. Descripcion de cuatro pacientes. An Esp Pediatr. 1999;51:235–40. 6. Conley ME, Park CL, Douglas SD. Childhood common variable immunodeficiency with autoimmune disease. J Pediatr. 1986;108:915–22. 7. Oxelius VA, Hanson LA, Björkander J, Hammarström L, Sjöholm A. IgG3 deficiency: common in obstructive lung disease. Hereditary in families with immunodeficiency and autoimmune disease. Monogr Allergy. 1986;20:106–15. 8. Karlström R, Gustafson R, Palmblad J. Chronic mild neutropenia in adults: relation to IgG3 deficiency and infection susceptibility. J Intern Med. 2001;250:342–7. 9. Papadaki HA, Palmblad J, Kapsimali V, Anagnou NP, Eliopoulos GD. Increased serum IgA and decreased IgG3 strongly correlate with increased serum TGFbeta1 levels in patients with nonimmune chronic idiopathic neutropenia of adults. Eur J Haematol. 2000;65:237–44. 10. Stavroulaki E, Kastrinaki MC, Pontikoglou C, Eliopoulos D, Damianaki A, Mavroudi I, et al. Mesenchymal stem cells contribute to the abnormal bone marrow microenvironment in patients with chronic idiopathic neutropenia by overproduction of transforming growth factor-1. Stem Cells Dev. 2011;20:1309–18. b , Antonio Sanjose a ˜ José Pardos-Gea a,∗ , Gonzalo Artaza Minano a
Servicio de Medicina Interna, Hospital Universitario Vall d’Hebron, Barcelona, Spain b Servicio de Hematología, Hospital Universitario Vall d’Hebron, Barcelona, Spain ∗ Corresponding
author. E-mail address: [email protected] (J. Pardos-Gea).
current scientific evidence, some treatment recommendations that we consider more correct and effective. Approximately 45–60% patients with hip fracture have preoperative anemia, prevalence up to 90% in the postoperative period. Depending on the type of fracture or surgical procedure, 95% of fractures have perioperative bleeding, ranging from 500 to 1500 ml, in addition to bleeding the days before the surgery, which results in an average decreased Hb by 4 gdl.2 Assuming about 200 mg iron are required to increase Hb by 1 g/dl, then 600–1000 mg iron would be required to compensate for the red cells lost. Therefore, the Libro azul (Blue Book) of the Spanish Society of Osteoporotic Fracture recommends prophylactic FeIV administration, from admission, plus administration of rHuEPO sc if Hb levels are below 13 g/dl, along with the application of “restrictive” transfusional treatment.2 This recommendation has been shown to decrease transfusion rate in patients with Hb <13 g/dl before fracture.3–6 We also recommend indicating blood transfusion based on clinical criteria, adjusted for cardiovascular risk factors and with the administration of the lowest effective dose: one unit of red blood cell concentrate can be sufficient.7 Our group has recently published8 an analysis of pooled data from over 1300 patients with pertrochanteric or subcapital hip
Letters to the Editor / Med Clin (Barc). 2015;145(12):551–555
fracture treated with FeIV (200–600 mg) from admission with or without rHuEPO (40,000 IU). In this analysis, there is a significant reduction in blood transfusion, in the incidence of postoperative infection, in mortality at 30 days and in the length of hospital stay, without increased risk of thrombosis or strokes. The major benefit was reported in patients with pertrochanteric fracture, with Hb <13 g/dl treated with FeIV and rHuEPO.5 Therefore, it is surprising that the Hb cutoff values selected for the various treatments are < 11 g/dl for FeIV administration and <10 g/dl for rHuEPO.1 Particularly, because the literature reviewed states that the inflection points for transfusional risk and effectiveness of FeIV, without erythropoietin coadjuvant treatment, are consistent with Hb levels of 13 and 12 g/dl, respectively.3–6,9 Based on the data previously shown, we believe that if no contraindications, all patients with hip fracture should receive FeIV from admission (at least 600 mg), and those with Hb levels < 13 g/dl during hospital admission, should also receive preoperative administration of at least one rHuEPO dose of 40,000 IU. Finally, the authors state that “due to the increasing transfusional restriction recommendation and the proven relationship with postoperative infection resulting from transfusion immunomodulation, alternative therapies will be promoted for anemia treatment.” We believe that the implementation of these therapies, such as treatment of perioperative anemia, reducing bleeding and/or the application of restrictive transfusion criteria should not be focused merely on “transfusional savings” or even economical savings.10 On the contrary, they should be included within the concept of patient blood management (PBM), recently recognized by WHO and whose approach accounts for a paradigm shift. The PBM approach is multidisciplinary and multimodal, and is focused on identifying and providing for the necessary care for continuity of patient care, where communication and coordination among the various disciplines might reduce not only the likelihood of requiring transfusion, but improve clinical outcome and reduce therapy costs.7 Acknowledgement Dr. Ana Isabel Peral García, Anesthesiology and Resuscitation Department, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid. References 1. Pareja Sierra T, Rodriguez Solis J. Perioperative medical treatment of old patients admitted with hip fracture. Med Clin (Barc). 2014;143:455–60.
555
2. García-Erce JA, Cassinello Ogea C, Díaz Curiel M. Tratamiento con precursores hematínicos. In: Gomar Sancho F, González Macías J, Cassinello Ogea C, Carpintero Benítez P, Díez Pérez A, coordinadores. Libro azul de la fractura osteo˜ Madrid: Medical & Marketing Communications, S. L.; 2012. porótica en Espana. p. 51–55. ˜ M, Izuel M, Martínez AA, Herrera A. Patients 3. Cuenca J, García-Erce JA, Munoz with pertrochanteric hip fracture may benefit of preoperative intravenous iron therapy: a pilot study. Transfusion (Paris). 2004;44:1447–52. ˜ 4. Cuenca J, García-Erce JA, Martínez AA, Solano VM, Molina J, Munoz M. Role of parenteral iron in the management of anaemia in the elderly patient undergoing displaced subcapital hip fracture repair. Preliminary data. Arch Orthop Trauma Surg. 2005;125:342–7. ˜ 5. García-Erce JA, Cuenca J, Haman-Alcober S, Martínez AA, Herrera A, Munoz M. Efficacy of preoperative recombinant human erythropoietin administration for reducing transfusion requirements in patients undergoing surgery for hip fracture repair. An observational cohort study. Vox Sang. 2009;97: 260–7. ˜ ˜ 6. Munoz M, Iglesias D, Garcia-Erce JA, Cuenca J, Herrera A, Martin-Montanez E, et al. Utility and cost of low-vacuum reinfusion drains in patients undergoing surgery for subcapital hip fracture repair. A before and after cohort study. Vox Sang. 2014;106:83–91. 7. Canillas F, Gómez-Ramírez S, García-Erce JA, Pavía-Molina J, Gómez-Luque A, ˜ M. Patient blood management in orthopaedic surgery. Rev Esp Cir Ortop Munoz Traumatol. 2015, http://dx.doi.org/10.1016/j.recot.2014.11.005. ˜ M, Gómez-Ramírez S, Cuenca J, García-Erce JA, Iglesias-Aparicio D, 8. Munoz Haman-Alcober S, et al. Very-short-term perioperative intravenous iron administration and postoperative outcome in major orthopedic surgery: a pooled analysis of observational data from 2547 patients. Transfusion. 2014;54: 289–99. 9. Serrano-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 (Paris). 2011;51: 97–104. 10. Izuel Rami M, Gómez Barrera M, Villar Fernández I, Rabanaque Hernández MJ, Cuenca Espiérrez J, García-Erce JA. Budget impact analysis of a blood saving program for urgent traumatological surgery. Med Clin (Barc). 2007;128:7–11 [in Spanish].
José Antonio García Erce a,e,∗ , Susana Gómez Ramírez b , ˜ Gómez d,e Jorge Cuenca Espiérrez c,e , Manuel Munoz a
Servicio de Hematología y Hemoterapia, Hospital General San Jorge, Huesca, Spain b Servicio de Medicina Interna, Hospital Internacional Xanit, Benalmádena, Málaga, Spain c Cirugía Ortopédica y Traumatología, Clínica Quirón, Zaragoza, Spain d Medicina Transfusional Perioperatoria, Facultad de Medicina, Málaga, Spain e GIEMSA, Medicina Transfusional Perioperatoria, Facultad de Medicina, Málaga, Spain ∗ Corresponding
author. E-mail address: [email protected] (J.A. García Erce).
Letters to the Editor / Med Clin (Barc). 2015;145(12):551–555
Neutropenia can accompany various immunodeficiencies with immunoglobulin deficiency or disorder.3 The combined immunodeficiencies (Wiskott-Aldrich syndrome, ataxiatelangiectasia, X-linked hyper-IgM syndrome, severe combined immunodeficiency4 ) and X-linked agammaglobulinemia5 begin in childhood with severe hypogammaglobulinemias and neutropenia of diverse etiologies (autoimmune, infectious, bone marrow deficiency). The common variable, as most common immunodeficiency in the adult population, occurs along with neutropenia, being usually autoinmune.6 IgG3 congenital deficiency is the rarest IgG subtype.7 It is most frequently detected in adults, who may have recurrent respiratory infections typically by Moraxella sp., and recurrent skin infections such as erysipelas by Streptococcus pyogenes. Patients with IgG3 congenital deficiency would not have higher prevalence of neutropenia according to the few cases reported to date.8 However, studies evaluating populations with chronic neutropenia in adults, of any etiology, have reported IgG3 deficiency was frequently associated. Karlström et al.8 analyzed 30 patients with chronic neutropenia in adults (with 8 cases of autoimmune cause) and almost half of them with IgG3 deficiency associated (47% patients), a phenomenon that remained over a long period of years of follow up. The infection rate was similar in those with or without IgG3 deficiency. Another study with 83 patients with chronic neutropenia in adults,9 all of idiopathic etiology, showed significant decreased levels of IgG3 (p < 0.001) compared to the control group, in addition to increased IgA in those with more severe neutropenia. Regarding the possible explanation for this association, 2 studies9,10 showed how in idiopathic forms of chronic neutropenia, considered a myelodysplastic syndrome of the granulocyte progenitors, patients had elevated levels of serum TGFB1. In addition, mesenchymal stem cells of bone marrow produced excessive TGFB1; we know that this cytokine may decrease IgG3 production and increase isotype switching to IgA in B cells. No similar pathophysiological studies are available on autoimmune forms of chronic neutropenia. In conclusion, we have verified through the description of a case and literature review that: (a) chronic neutropenia in adults of any etiology, in our case, autoimmune, may be accompanied by an isolated IgG3 deficiency; (b) it will not change the clinical course of these patients who remain generally indolent, with low prevalence
Treatment of perioperative anemia in hip fracture夽 Tratamiento de la anemia perioperatoria de la fractura de cadera Dear Editor, We have carefully read the review article by Pareja and Sierra Rodriguez Solis on perioperative medical treatment in elderly patients with hip fracture, recently published in Clinical Medicine.1 On Table 6 of this review, the authors provide transfusion criteria and guidelines on treatment with intravenous iron (FeIV) and recombinant erythropoietin (rHuEPO) depending on the levels of hemoglobin (Hb) at admission, referencing some of our papers and reviews. Therefore, we would like to clarify some of the authors’ statements and provide, from our experience and
夽 Please cite this article as: García Erce JA, Gómez Ramírez S, Cuenca Espiérrez J, ˜ Gómez M. Tratamiento de la anemia perioperatoria de la fractura de cadera. Munoz Med Clin (Barc). 2015;145:554–555.
of recurrent infections, and; (c) it will probably be secondary to changes in the immune profile of cytokine secretion (increased TGFB1) which may accompany chronic neutropenia, although this pathophysiological explanation based on idiopathic forms has not been corroborated in chronic autoimmune neutropenia. References 1. Lalezari P, Jiang AF, Yegen L, Santorineou M. Chronic autoimmune neutropenia due to anti-NA2 antibody. N Engl J Med. 1975;293:744–7. 2. Capsoni F, Sarzi-Puttini P, Zanella A. Primary and secondary autoimmune neutropenia. Arthritis Res Ther. 2005;7:208–14. 3. Rezaei N, Farhoudi A, Pourpak Z, Aghamohammadi A, Moin M, Gharagozlou M, et al. Neutropenia in patients with primary antibody deficiency disorders. Iran J Allergy Asthma Immunol. 2004;3:77–81. 4. Stephan JL, Vlekova V, Le Deist F, Blanche S, Donadieu J, de Saint-Basile G, et al. Severe combined immunodeficiency: a retrospective single-center study of clinical presentation and outcome in 117 patients. J Pediatr. 1993;123:564–72. 5. Plo Rodríguez F, García Rodríguez MC, Ferreira Cerdán A, Fontán Casariego G. Neutropenia como manifestación precoz de una agammaglobulinemia ligada al cromosoma X. Descripcion de cuatro pacientes. An Esp Pediatr. 1999;51:235–40. 6. Conley ME, Park CL, Douglas SD. Childhood common variable immunodeficiency with autoimmune disease. J Pediatr. 1986;108:915–22. 7. Oxelius VA, Hanson LA, Björkander J, Hammarström L, Sjöholm A. IgG3 deficiency: common in obstructive lung disease. Hereditary in families with immunodeficiency and autoimmune disease. Monogr Allergy. 1986;20:106–15. 8. Karlström R, Gustafson R, Palmblad J. Chronic mild neutropenia in adults: relation to IgG3 deficiency and infection susceptibility. J Intern Med. 2001;250:342–7. 9. Papadaki HA, Palmblad J, Kapsimali V, Anagnou NP, Eliopoulos GD. Increased serum IgA and decreased IgG3 strongly correlate with increased serum TGFbeta1 levels in patients with nonimmune chronic idiopathic neutropenia of adults. Eur J Haematol. 2000;65:237–44. 10. Stavroulaki E, Kastrinaki MC, Pontikoglou C, Eliopoulos D, Damianaki A, Mavroudi I, et al. Mesenchymal stem cells contribute to the abnormal bone marrow microenvironment in patients with chronic idiopathic neutropenia by overproduction of transforming growth factor-1. Stem Cells Dev. 2011;20:1309–18. b , Antonio Sanjose a ˜ José Pardos-Gea a,∗ , Gonzalo Artaza Minano a
Servicio de Medicina Interna, Hospital Universitario Vall d’Hebron, Barcelona, Spain b Servicio de Hematología, Hospital Universitario Vall d’Hebron, Barcelona, Spain ∗ Corresponding
author. E-mail address: [email protected] (J. Pardos-Gea).
current scientific evidence, some treatment recommendations that we consider more correct and effective. Approximately 45–60% patients with hip fracture have preoperative anemia, prevalence up to 90% in the postoperative period. Depending on the type of fracture or surgical procedure, 95% of fractures have perioperative bleeding, ranging from 500 to 1500 ml, in addition to bleeding the days before the surgery, which results in an average decreased Hb by 4 gdl.2 Assuming about 200 mg iron are required to increase Hb by 1 g/dl, then 600–1000 mg iron would be required to compensate for the red cells lost. Therefore, the Libro azul (Blue Book) of the Spanish Society of Osteoporotic Fracture recommends prophylactic FeIV administration, from admission, plus administration of rHuEPO sc if Hb levels are below 13 g/dl, along with the application of “restrictive” transfusional treatment.2 This recommendation has been shown to decrease transfusion rate in patients with Hb <13 g/dl before fracture.3–6 We also recommend indicating blood transfusion based on clinical criteria, adjusted for cardiovascular risk factors and with the administration of the lowest effective dose: one unit of red blood cell concentrate can be sufficient.7 Our group has recently published8 an analysis of pooled data from over 1300 patients with pertrochanteric or subcapital hip
Letters to the Editor / Med Clin (Barc). 2015;145(12):551–555
fracture treated with FeIV (200–600 mg) from admission with or without rHuEPO (40,000 IU). In this analysis, there is a significant reduction in blood transfusion, in the incidence of postoperative infection, in mortality at 30 days and in the length of hospital stay, without increased risk of thrombosis or strokes. The major benefit was reported in patients with pertrochanteric fracture, with Hb <13 g/dl treated with FeIV and rHuEPO.5 Therefore, it is surprising that the Hb cutoff values selected for the various treatments are < 11 g/dl for FeIV administration and <10 g/dl for rHuEPO.1 Particularly, because the literature reviewed states that the inflection points for transfusional risk and effectiveness of FeIV, without erythropoietin coadjuvant treatment, are consistent with Hb levels of 13 and 12 g/dl, respectively.3–6,9 Based on the data previously shown, we believe that if no contraindications, all patients with hip fracture should receive FeIV from admission (at least 600 mg), and those with Hb levels < 13 g/dl during hospital admission, should also receive preoperative administration of at least one rHuEPO dose of 40,000 IU. Finally, the authors state that “due to the increasing transfusional restriction recommendation and the proven relationship with postoperative infection resulting from transfusion immunomodulation, alternative therapies will be promoted for anemia treatment.” We believe that the implementation of these therapies, such as treatment of perioperative anemia, reducing bleeding and/or the application of restrictive transfusion criteria should not be focused merely on “transfusional savings” or even economical savings.10 On the contrary, they should be included within the concept of patient blood management (PBM), recently recognized by WHO and whose approach accounts for a paradigm shift. The PBM approach is multidisciplinary and multimodal, and is focused on identifying and providing for the necessary care for continuity of patient care, where communication and coordination among the various disciplines might reduce not only the likelihood of requiring transfusion, but improve clinical outcome and reduce therapy costs.7 Acknowledgement Dr. Ana Isabel Peral García, Anesthesiology and Resuscitation Department, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid. References 1. Pareja Sierra T, Rodriguez Solis J. Perioperative medical treatment of old patients admitted with hip fracture. Med Clin (Barc). 2014;143:455–60.
555
2. García-Erce JA, Cassinello Ogea C, Díaz Curiel M. Tratamiento con precursores hematínicos. In: Gomar Sancho F, González Macías J, Cassinello Ogea C, Carpintero Benítez P, Díez Pérez A, coordinadores. Libro azul de la fractura osteo˜ Madrid: Medical & Marketing Communications, S. L.; 2012. porótica en Espana. p. 51–55. ˜ M, Izuel M, Martínez AA, Herrera A. Patients 3. Cuenca J, García-Erce JA, Munoz with pertrochanteric hip fracture may benefit of preoperative intravenous iron therapy: a pilot study. Transfusion (Paris). 2004;44:1447–52. ˜ 4. Cuenca J, García-Erce JA, Martínez AA, Solano VM, Molina J, Munoz M. Role of parenteral iron in the management of anaemia in the elderly patient undergoing displaced subcapital hip fracture repair. Preliminary data. Arch Orthop Trauma Surg. 2005;125:342–7. ˜ 5. García-Erce JA, Cuenca J, Haman-Alcober S, Martínez AA, Herrera A, Munoz M. Efficacy of preoperative recombinant human erythropoietin administration for reducing transfusion requirements in patients undergoing surgery for hip fracture repair. An observational cohort study. Vox Sang. 2009;97: 260–7. ˜ ˜ 6. Munoz M, Iglesias D, Garcia-Erce JA, Cuenca J, Herrera A, Martin-Montanez E, et al. Utility and cost of low-vacuum reinfusion drains in patients undergoing surgery for subcapital hip fracture repair. A before and after cohort study. Vox Sang. 2014;106:83–91. 7. Canillas F, Gómez-Ramírez S, García-Erce JA, Pavía-Molina J, Gómez-Luque A, ˜ M. Patient blood management in orthopaedic surgery. Rev Esp Cir Ortop Munoz Traumatol. 2015, http://dx.doi.org/10.1016/j.recot.2014.11.005. ˜ M, Gómez-Ramírez S, Cuenca J, García-Erce JA, Iglesias-Aparicio D, 8. Munoz Haman-Alcober S, et al. Very-short-term perioperative intravenous iron administration and postoperative outcome in major orthopedic surgery: a pooled analysis of observational data from 2547 patients. Transfusion. 2014;54: 289–99. 9. Serrano-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 (Paris). 2011;51: 97–104. 10. Izuel Rami M, Gómez Barrera M, Villar Fernández I, Rabanaque Hernández MJ, Cuenca Espiérrez J, García-Erce JA. Budget impact analysis of a blood saving program for urgent traumatological surgery. Med Clin (Barc). 2007;128:7–11 [in Spanish].
José Antonio García Erce a,e,∗ , Susana Gómez Ramírez b , ˜ Gómez d,e Jorge Cuenca Espiérrez c,e , Manuel Munoz a
Servicio de Hematología y Hemoterapia, Hospital General San Jorge, Huesca, Spain b Servicio de Medicina Interna, Hospital Internacional Xanit, Benalmádena, Málaga, Spain c Cirugía Ortopédica y Traumatología, Clínica Quirón, Zaragoza, Spain d Medicina Transfusional Perioperatoria, Facultad de Medicina, Málaga, Spain e GIEMSA, Medicina Transfusional Perioperatoria, Facultad de Medicina, Málaga, Spain ∗ Corresponding
author. E-mail address: [email protected] (J.A. García Erce).