The
n e w e ng l a n d j o u r na l
the best antithrombotic treatment for subclinical atrial fibrillation. In the meantime, however, clinicians who treat patients with stroke need to comprehensively address these patients’ vascular risk factors. In the face of uncertainty about whether or not subclinical atrial fibrillation is directly involved in the pathogenesis of stroke, a prudent evaluation of cryptogenic stroke includes thoroughly ascertaining the presence of atrial fibrillation and, at the very least, following it closely for progression, because subclinical atrial fibrillation frequently progresses to clinically apparent atrial fibrillation,1 which is associated with a high risk of stroke recurrence.3 The CRYSTAL AF and EMBRACE trials, which sought to determine the best strategy for ascertaining
of
m e dic i n e
atrial fibrillation after stroke, showed that several weeks or more of continuous heart-rhythm monitoring detects atrial fibrillation more reliably than routine follow-up. Hooman Kamel, M.D. Weill Cornell Medical College New York, NY Since publication of his article, the author reports no further potential conflict of interest. 1. Healey JS, Connolly SJ, Gold MR, et al. Subclinical atrial fi-
brillation and the risk of stroke. N Engl J Med 2012;366:120-9. 2. Brambatti M, Connolly SJ, Gold MR, et al. Temporal relationship between subclinical atrial fibrillation and embolic events. Circulation 2014;129:2094-9. 3. Kamel H, Johnson DR, Hegde M, et al. Detection of atrial fibrillation after stroke and the risk of recurrent stroke. J Stroke Cerebrovasc Dis 2012;21:726-31. DOI: 10.1056/NEJMc1409495
Prophylaxis against Venous Thromboembolism in Patients with Cancer To the Editor: Connors (June 26 issue)1 focuses on prophylaxis against venous thromboembolism in ambulatory patients with cancer who are receiving chemotherapy.2,3 We proposed a modified Khorana risk-assessment model (the Protecht score), in which we added platinum-based chemotherapy, gemcitabine-based chemotherapy, or both to the predictive variables already taken into account in the Khorana model.4 We compared the Khorana and Protecht models with respect to their ability to identify high-risk patients with cancer among the patients in the control group in the Prophylaxis of Thromboembolism during Chemotherapy (PROTECHT) study. The Protecht score, as compared with the Khorana score, identified more patients at high risk for venous thromboembolism (124 of 378 patients [32.8%] vs. 45 of 378 patients [11.9%]). Among patients at high risk, as defined according to the Protecht score, the rate of venous thromboembolism was 4% (3 of 70 patients) in the prophylaxis group and 11% (5 of 45 patients) in the placebo group, with a number needed to treat of 17. We believe that including chemotherapy as a variable in the Khorana model will improve risk stratification to identify ambulatory patients with cancer who are at risk for venous thromboembolism. Further investigations are needed to
1262
evaluate the clinical benefit of antithrombotic prophylaxis in high-risk patients who are identified with the use of this approach. Melina Verso, M.D. Giancarlo Agnelli, M.D. University of Perugia Perugia, Italy [email protected] No potential conflict of interest relevant to this letter was reported. 1. Connors JM. Prophylaxis against venous thromboembolism in
ambulatory patients with cancer. N Engl J Med 2014;370:2515-9.
2. Agnelli G, Gussoni G, Bianchini C, et al. Nadroparin for the
prevention of thromboembolic events in outpatients with metastatic or locally advanced solid cancer receiving chemotherapy: a randomised, placebo-controlled, double-blind study. Lancet Oncol 2009;10:943-9. 3. Agnelli G, George DJ, Kakkar AK, et al. Semuloparin for thromboprophylaxis in patients receiving chemotherapy for cancer. N Engl J Med 2012;366:601-9. 4. Verso M, Agnelli G, Barni S, Gasparini G, LaBianca R. A modified Khorana risk assessment score for venous thromboembolism in cancer patients receiving chemotherapy: the Protecht score. Intern Emerg Med 2012;7:291-2. DOI: 10.1056/NEJMc1408866
To the Editor: Although she places particular emphasis on discussing other controversial issues, Connors pays less attention to the debate concerning patients with primary or secondary
n engl j med 371;13 nejm.org september 25, 2014
The New England Journal of Medicine Downloaded from nejm.org at University of Arizona on August 10, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
correspondence
brain tumors. These patients have a high risk of venous thromboembolism (>20% per year).1 Notwithstanding, many physicians do not administer thromboprophylaxis because of a concern regarding intracranial hemorrhage. Small studies appear to show both good efficacy and the uncertain safety of pharmacologic thromboprophylaxis in these patients.2-4 Other data suggest that the benefit-to-risk ratio of heparin may be improved with consideration of the size, histologic type, and location of the tumor and the patient’s age and mobility.5 In everyday practice, should we consider the use of heparin in some (or none) of these very high-risk patients while we await the results of appropriately designed clinical trials? The heparin issue cannot be avoided because some of these patients might require full anticoagulation for deep-vein thrombosis. The author’s views regarding this controversy would be welcome. Angelo Porfidia, M.D. Tiziana Morretti, M.D. Raffaele Landolfi, M.D. Catholic University of the Sacred Heart School of Medicine Rome, Italy [email protected] No potential conflict of interest relevant to this letter was reported. 1. Brandes AA, Scelzi E, Salmistraro G, et al. Incidence of risk
of thromboembolism during treatment high-grade gliomas: a prospective study. Eur J Cancer 1997;33:1592-6. 2. Perry JR, Julian JA, Laperriere NJ, et al. PRODIGE: a randomized placebo-controlled trial of dalteparin low-molecular-weight heparin thromboprophylaxis in patients with newly diagnosed malignant glioma. J Thromb Haemost 2010;8:1959-65. 3. Robins HI, O’Neill A, Gilbert M, et al. Effect of dalteparin and radiation on survival and thromboembolic events in glioblastoma multiforme: a phase II ECOG trial. Cancer Chemother Pharmacol 2008;62:227-33. 4. Perry SL, Bohlin C, Reardon DA, et al. Tinzaparin prophylaxis against venous thromboembolic complications in brain tumor patients. J Neurooncol 2009;95:129-34. 5. Gerber DE, Grossman SA, Streiff MB. Management of venous thromboembolism in patients with primary and metastatic brain tumors. J Clin Oncol 2006;24:1310-8. [Erratum, J Clin Oncol 2006;24:2133.] DOI: 10.1056/NEJMc1408866
The Author Replies: Verso and colleagues1 developed a risk-assessment model to enhance risk stratification by including the risk associated with strongly thrombogenic chemotherapy, and they applied it to the population in the PROTECHT
study. Although the predictive value of their scoring system appears to be better than that of the Khorana risk-assessment model, this retrospective assessment requires prospective validation in a large cohort of patients. Platinum-based and gemcitabine-based regimens are used for highrisk cancers; whether these regimens are independent risk factors for venous thromboembolism as compared with the underlying type of cancer is difficult to analyze.2 The Khorana model, which is an easily calculated assessment of clinical and laboratory variables, was derived and validated in roughly 5000 patients with cancer.3 It was designed to assess patients before the initiation of chemotherapy and can be used regardless of treatment plans. Prophylaxis against venous thromboembolism in patients with primary or metastatic brain tumors was not included in my review, since insufficient data are available. Although the risk of venous thromboembolism among patients with central nervous system (CNS) tumors is high, the risk of bleeding is also high. The consequences of bleeding into the brain can be severe, permanent, and fatal. Prophylaxis against venous thromboembolism, and even treatment for acute venous thromboembolism, in this population requires an individualized approach. Assessment of bleeding risk is required. Factors that affect bleeding risk include the type and size of tumor or metastases and the occurrence of a recent major bleeding episode and thrombocytopenia. Melanoma, choriocarcinoma, and renal-cell cancers are associated with a high risk of spontaneous hemorrhage into intracranial metastases.4 Three small studies have involved the use of low-molecular-weight heparin for prophylaxis against venous thromboembolism in patients with primary brain tumors. PRODIGE (A Randomized Placebo-Controlled Trial of Dal teparin Low-Molecular-Weight Heparin Thromboprophylaxis in Patients with Newly Diagnosed Malignant Glioma) was the largest and the only randomized, placebo-controlled study.5 It enrolled 186 patients but was closed early because of low accrual and logistical problems. Although thromboembolic events were decreased in the treatment group, an increase in major bleeding episodes was also seen in this group. All the episodes involved intracranial bleeding. At this time, the use of prophylaxis against
n engl j med 371;13 nejm.org september 25, 2014
The New England Journal of Medicine Downloaded from nejm.org at University of Arizona on August 10, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
1263
The
n e w e ng l a n d j o u r na l
of
m e dic i n e
Since publication of her article, the author reports no further potential conflict of interest.
A modified Khorana risk assessment score for venous thromboembolism in cancer patients receiving chemotherapy: the PROTECHT score. Intern Emerg Med 2012;7:291-2. 2. Moore RA, Adel N, Riedel E, et al. High incidence of thromboembolic events in patients treated with cisplatin-based chemotherapy: a large retrospective analysis. J Clin Oncol 2011;29: 3466-73. 3. Ay C, Dunkler D, Marosi C, et al. Prediction of venous thromboembolism in cancer patients. Blood 2010;116:5377-82. 4. Mandybur TI. Intracranial hemorrhage caused by metastatic tumors. Neurology 1977;27:650-5. 5. Perry JR, Julian JA, Laperriere NJ, et al. PRODIGE: a randomized placebo-controlled trial of dalteparin low-molecular-weight heparin thromboprophylaxis in patients with newly diagnosed malignant glioma. J Thromb Haemost 2010;8:1959-65.
1. Verso M, Agnelli G, Barni S, Gasparini G, LaBianca R.
DOI: 10.1056/NEJMc1408866
venous thromboembolism cannot be endorsed for all patients with primary CNS tumors or untreated CNS metastases. After a frank discussion of the risks and benefits, it can be considered for an individual patient with additional high-risk factors, as described in my review. Jean M. Connors, M.D. Brigham and Women’s Hospital Boston, MA [email protected]
More on Platelet-Rich Plasma Injections in Acute Muscle Injury To the Editor: Reurink et al. (June 26 issue)1 report no benefit of intramuscular platelet-rich plasma (PRP) injections in patients with acute hamstring injuries. The delayed administration and low dosage of PRP injections in their trial may well have rendered PRP injections ineffective. Growth factors in PRP exert an antiapoptotic, chemotactic, antiinflammatory, and proliferative effect on fibroblasts, neurons, and myoblasts; some of these effects are dose-dependent and strongly influence myogenesis, angiogenesis, and fibrogenesis.2 These events occur a few hours after muscle damage. By the time PRP injections are administered (within 5 days after the injury), many of the injured microenvironmental biologic targets of PRP have either disappeared or undergone a phenotypic shift. Three in vivo studies in which PRP treatment was initiated either a few hours or 2 days after injury showed histologic or functional improvement in the group of patients who received treatment.3-5 The dosages in these studies3 were at least 2.5 times as high as the dosages conveyed for each injection in the trial by Reurink et al. (insulin-like growth factor 1 [IGF-1], 225,000 pg vs. 90,000 pg, and dosage of platelet-derived growth factor [PDGF], 50,000 pg vs. 20,000 pg). Eduardo Anitua, M.D., Ph.D. Eduardo Anitua Foundation Vitoria, Spain
Mikel Sánchez, M.D. Hospital Vithas San José Vitoria, Spain
1264
Sabino Padilla, M.D., Ph.D. Eduardo Anitua Foundation Vitoria, Spain Drs. Anitua and Padilla report being employed as researchers at BTI Biotechnology Institute, the developer of plasma rich in growth factors. No other potential conflict of interest relevant to this letter was reported. 1. Reurink G, Goudswaard GJ, Moen MH, et al. Platelet-rich
plasma injections in acute muscle injury. N Engl J Med 2014;370: 2546-7. 2. Borselli C, Storrie H, Benesch-Lee F, et al. Functional muscle regeneration with combined delivery of angiogenesis and myogenesis factors. Proc Natl Acad Sci U S A 2010;107:3287-92. 3. Wright-Carpenter T, Klein P, Schäferhoff P, Appell HJ, Mir LM, Wehling P. Treatment of muscle injuries by local administration of autologous conditioned serum: a pilot study on sportsmen with muscle strains. Int J Sports Med 2004;25:588-93. 4. Hammond JW, Hinton RY, Curl LA, Muriel JM, Lovering RM. Use of autologous platelet-rich plasma to treat muscle strain injuries. Am J Sports Med 2009;37:1135-42. 5. Wright-Carpenter T, Opolon P, Appell HJ, Meijer H, Wehling P, Mir LM. Treatment of muscle injuries by local administration of autologous conditioned serum: animal experiments using a muscle contusion model. Int J Sports Med 2004;25:582-7. DOI: 10.1056/NEJMc1409204
The Authors Reply: The timing of PRP injections is subject to debate, since the environmental milieu and the effect of growth factors change over time during healing.1 In vivo studies do not show that the optimal time window for injections is within 2 days after injury, since this has not been compared with a delayed period before administration of injections.2 In previous clinical studies involving athletes with acute muscle injuries, the PRP was injected 2 or 3 days after inju-
n engl j med 371;13 nejm.org september 25, 2014
The New England Journal of Medicine Downloaded from nejm.org at University of Arizona on August 10, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
n e w e ng l a n d j o u r na l
the best antithrombotic treatment for subclinical atrial fibrillation. In the meantime, however, clinicians who treat patients with stroke need to comprehensively address these patients’ vascular risk factors. In the face of uncertainty about whether or not subclinical atrial fibrillation is directly involved in the pathogenesis of stroke, a prudent evaluation of cryptogenic stroke includes thoroughly ascertaining the presence of atrial fibrillation and, at the very least, following it closely for progression, because subclinical atrial fibrillation frequently progresses to clinically apparent atrial fibrillation,1 which is associated with a high risk of stroke recurrence.3 The CRYSTAL AF and EMBRACE trials, which sought to determine the best strategy for ascertaining
of
m e dic i n e
atrial fibrillation after stroke, showed that several weeks or more of continuous heart-rhythm monitoring detects atrial fibrillation more reliably than routine follow-up. Hooman Kamel, M.D. Weill Cornell Medical College New York, NY Since publication of his article, the author reports no further potential conflict of interest. 1. Healey JS, Connolly SJ, Gold MR, et al. Subclinical atrial fi-
brillation and the risk of stroke. N Engl J Med 2012;366:120-9. 2. Brambatti M, Connolly SJ, Gold MR, et al. Temporal relationship between subclinical atrial fibrillation and embolic events. Circulation 2014;129:2094-9. 3. Kamel H, Johnson DR, Hegde M, et al. Detection of atrial fibrillation after stroke and the risk of recurrent stroke. J Stroke Cerebrovasc Dis 2012;21:726-31. DOI: 10.1056/NEJMc1409495
Prophylaxis against Venous Thromboembolism in Patients with Cancer To the Editor: Connors (June 26 issue)1 focuses on prophylaxis against venous thromboembolism in ambulatory patients with cancer who are receiving chemotherapy.2,3 We proposed a modified Khorana risk-assessment model (the Protecht score), in which we added platinum-based chemotherapy, gemcitabine-based chemotherapy, or both to the predictive variables already taken into account in the Khorana model.4 We compared the Khorana and Protecht models with respect to their ability to identify high-risk patients with cancer among the patients in the control group in the Prophylaxis of Thromboembolism during Chemotherapy (PROTECHT) study. The Protecht score, as compared with the Khorana score, identified more patients at high risk for venous thromboembolism (124 of 378 patients [32.8%] vs. 45 of 378 patients [11.9%]). Among patients at high risk, as defined according to the Protecht score, the rate of venous thromboembolism was 4% (3 of 70 patients) in the prophylaxis group and 11% (5 of 45 patients) in the placebo group, with a number needed to treat of 17. We believe that including chemotherapy as a variable in the Khorana model will improve risk stratification to identify ambulatory patients with cancer who are at risk for venous thromboembolism. Further investigations are needed to
1262
evaluate the clinical benefit of antithrombotic prophylaxis in high-risk patients who are identified with the use of this approach. Melina Verso, M.D. Giancarlo Agnelli, M.D. University of Perugia Perugia, Italy [email protected] No potential conflict of interest relevant to this letter was reported. 1. Connors JM. Prophylaxis against venous thromboembolism in
ambulatory patients with cancer. N Engl J Med 2014;370:2515-9.
2. Agnelli G, Gussoni G, Bianchini C, et al. Nadroparin for the
prevention of thromboembolic events in outpatients with metastatic or locally advanced solid cancer receiving chemotherapy: a randomised, placebo-controlled, double-blind study. Lancet Oncol 2009;10:943-9. 3. Agnelli G, George DJ, Kakkar AK, et al. Semuloparin for thromboprophylaxis in patients receiving chemotherapy for cancer. N Engl J Med 2012;366:601-9. 4. Verso M, Agnelli G, Barni S, Gasparini G, LaBianca R. A modified Khorana risk assessment score for venous thromboembolism in cancer patients receiving chemotherapy: the Protecht score. Intern Emerg Med 2012;7:291-2. DOI: 10.1056/NEJMc1408866
To the Editor: Although she places particular emphasis on discussing other controversial issues, Connors pays less attention to the debate concerning patients with primary or secondary
n engl j med 371;13 nejm.org september 25, 2014
The New England Journal of Medicine Downloaded from nejm.org at University of Arizona on August 10, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
correspondence
brain tumors. These patients have a high risk of venous thromboembolism (>20% per year).1 Notwithstanding, many physicians do not administer thromboprophylaxis because of a concern regarding intracranial hemorrhage. Small studies appear to show both good efficacy and the uncertain safety of pharmacologic thromboprophylaxis in these patients.2-4 Other data suggest that the benefit-to-risk ratio of heparin may be improved with consideration of the size, histologic type, and location of the tumor and the patient’s age and mobility.5 In everyday practice, should we consider the use of heparin in some (or none) of these very high-risk patients while we await the results of appropriately designed clinical trials? The heparin issue cannot be avoided because some of these patients might require full anticoagulation for deep-vein thrombosis. The author’s views regarding this controversy would be welcome. Angelo Porfidia, M.D. Tiziana Morretti, M.D. Raffaele Landolfi, M.D. Catholic University of the Sacred Heart School of Medicine Rome, Italy [email protected] No potential conflict of interest relevant to this letter was reported. 1. Brandes AA, Scelzi E, Salmistraro G, et al. Incidence of risk
of thromboembolism during treatment high-grade gliomas: a prospective study. Eur J Cancer 1997;33:1592-6. 2. Perry JR, Julian JA, Laperriere NJ, et al. PRODIGE: a randomized placebo-controlled trial of dalteparin low-molecular-weight heparin thromboprophylaxis in patients with newly diagnosed malignant glioma. J Thromb Haemost 2010;8:1959-65. 3. Robins HI, O’Neill A, Gilbert M, et al. Effect of dalteparin and radiation on survival and thromboembolic events in glioblastoma multiforme: a phase II ECOG trial. Cancer Chemother Pharmacol 2008;62:227-33. 4. Perry SL, Bohlin C, Reardon DA, et al. Tinzaparin prophylaxis against venous thromboembolic complications in brain tumor patients. J Neurooncol 2009;95:129-34. 5. Gerber DE, Grossman SA, Streiff MB. Management of venous thromboembolism in patients with primary and metastatic brain tumors. J Clin Oncol 2006;24:1310-8. [Erratum, J Clin Oncol 2006;24:2133.] DOI: 10.1056/NEJMc1408866
The Author Replies: Verso and colleagues1 developed a risk-assessment model to enhance risk stratification by including the risk associated with strongly thrombogenic chemotherapy, and they applied it to the population in the PROTECHT
study. Although the predictive value of their scoring system appears to be better than that of the Khorana risk-assessment model, this retrospective assessment requires prospective validation in a large cohort of patients. Platinum-based and gemcitabine-based regimens are used for highrisk cancers; whether these regimens are independent risk factors for venous thromboembolism as compared with the underlying type of cancer is difficult to analyze.2 The Khorana model, which is an easily calculated assessment of clinical and laboratory variables, was derived and validated in roughly 5000 patients with cancer.3 It was designed to assess patients before the initiation of chemotherapy and can be used regardless of treatment plans. Prophylaxis against venous thromboembolism in patients with primary or metastatic brain tumors was not included in my review, since insufficient data are available. Although the risk of venous thromboembolism among patients with central nervous system (CNS) tumors is high, the risk of bleeding is also high. The consequences of bleeding into the brain can be severe, permanent, and fatal. Prophylaxis against venous thromboembolism, and even treatment for acute venous thromboembolism, in this population requires an individualized approach. Assessment of bleeding risk is required. Factors that affect bleeding risk include the type and size of tumor or metastases and the occurrence of a recent major bleeding episode and thrombocytopenia. Melanoma, choriocarcinoma, and renal-cell cancers are associated with a high risk of spontaneous hemorrhage into intracranial metastases.4 Three small studies have involved the use of low-molecular-weight heparin for prophylaxis against venous thromboembolism in patients with primary brain tumors. PRODIGE (A Randomized Placebo-Controlled Trial of Dal teparin Low-Molecular-Weight Heparin Thromboprophylaxis in Patients with Newly Diagnosed Malignant Glioma) was the largest and the only randomized, placebo-controlled study.5 It enrolled 186 patients but was closed early because of low accrual and logistical problems. Although thromboembolic events were decreased in the treatment group, an increase in major bleeding episodes was also seen in this group. All the episodes involved intracranial bleeding. At this time, the use of prophylaxis against
n engl j med 371;13 nejm.org september 25, 2014
The New England Journal of Medicine Downloaded from nejm.org at University of Arizona on August 10, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
1263
The
n e w e ng l a n d j o u r na l
of
m e dic i n e
Since publication of her article, the author reports no further potential conflict of interest.
A modified Khorana risk assessment score for venous thromboembolism in cancer patients receiving chemotherapy: the PROTECHT score. Intern Emerg Med 2012;7:291-2. 2. Moore RA, Adel N, Riedel E, et al. High incidence of thromboembolic events in patients treated with cisplatin-based chemotherapy: a large retrospective analysis. J Clin Oncol 2011;29: 3466-73. 3. Ay C, Dunkler D, Marosi C, et al. Prediction of venous thromboembolism in cancer patients. Blood 2010;116:5377-82. 4. Mandybur TI. Intracranial hemorrhage caused by metastatic tumors. Neurology 1977;27:650-5. 5. Perry JR, Julian JA, Laperriere NJ, et al. PRODIGE: a randomized placebo-controlled trial of dalteparin low-molecular-weight heparin thromboprophylaxis in patients with newly diagnosed malignant glioma. J Thromb Haemost 2010;8:1959-65.
1. Verso M, Agnelli G, Barni S, Gasparini G, LaBianca R.
DOI: 10.1056/NEJMc1408866
venous thromboembolism cannot be endorsed for all patients with primary CNS tumors or untreated CNS metastases. After a frank discussion of the risks and benefits, it can be considered for an individual patient with additional high-risk factors, as described in my review. Jean M. Connors, M.D. Brigham and Women’s Hospital Boston, MA [email protected]
More on Platelet-Rich Plasma Injections in Acute Muscle Injury To the Editor: Reurink et al. (June 26 issue)1 report no benefit of intramuscular platelet-rich plasma (PRP) injections in patients with acute hamstring injuries. The delayed administration and low dosage of PRP injections in their trial may well have rendered PRP injections ineffective. Growth factors in PRP exert an antiapoptotic, chemotactic, antiinflammatory, and proliferative effect on fibroblasts, neurons, and myoblasts; some of these effects are dose-dependent and strongly influence myogenesis, angiogenesis, and fibrogenesis.2 These events occur a few hours after muscle damage. By the time PRP injections are administered (within 5 days after the injury), many of the injured microenvironmental biologic targets of PRP have either disappeared or undergone a phenotypic shift. Three in vivo studies in which PRP treatment was initiated either a few hours or 2 days after injury showed histologic or functional improvement in the group of patients who received treatment.3-5 The dosages in these studies3 were at least 2.5 times as high as the dosages conveyed for each injection in the trial by Reurink et al. (insulin-like growth factor 1 [IGF-1], 225,000 pg vs. 90,000 pg, and dosage of platelet-derived growth factor [PDGF], 50,000 pg vs. 20,000 pg). Eduardo Anitua, M.D., Ph.D. Eduardo Anitua Foundation Vitoria, Spain
Mikel Sánchez, M.D. Hospital Vithas San José Vitoria, Spain
1264
Sabino Padilla, M.D., Ph.D. Eduardo Anitua Foundation Vitoria, Spain Drs. Anitua and Padilla report being employed as researchers at BTI Biotechnology Institute, the developer of plasma rich in growth factors. No other potential conflict of interest relevant to this letter was reported. 1. Reurink G, Goudswaard GJ, Moen MH, et al. Platelet-rich
plasma injections in acute muscle injury. N Engl J Med 2014;370: 2546-7. 2. Borselli C, Storrie H, Benesch-Lee F, et al. Functional muscle regeneration with combined delivery of angiogenesis and myogenesis factors. Proc Natl Acad Sci U S A 2010;107:3287-92. 3. Wright-Carpenter T, Klein P, Schäferhoff P, Appell HJ, Mir LM, Wehling P. Treatment of muscle injuries by local administration of autologous conditioned serum: a pilot study on sportsmen with muscle strains. Int J Sports Med 2004;25:588-93. 4. Hammond JW, Hinton RY, Curl LA, Muriel JM, Lovering RM. Use of autologous platelet-rich plasma to treat muscle strain injuries. Am J Sports Med 2009;37:1135-42. 5. Wright-Carpenter T, Opolon P, Appell HJ, Meijer H, Wehling P, Mir LM. Treatment of muscle injuries by local administration of autologous conditioned serum: animal experiments using a muscle contusion model. Int J Sports Med 2004;25:582-7. DOI: 10.1056/NEJMc1409204
The Authors Reply: The timing of PRP injections is subject to debate, since the environmental milieu and the effect of growth factors change over time during healing.1 In vivo studies do not show that the optimal time window for injections is within 2 days after injury, since this has not been compared with a delayed period before administration of injections.2 In previous clinical studies involving athletes with acute muscle injuries, the PRP was injected 2 or 3 days after inju-
n engl j med 371;13 nejm.org september 25, 2014
The New England Journal of Medicine Downloaded from nejm.org at University of Arizona on August 10, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
