輸血・細胞治療学会：輸血副反応ガイドver1.0，2014．.
M J Kuehnert, V R Roth, N R Haley, K R Gregory, K V Elder, G B Schreiber, M J Arduino, S C Holt, L A Carson, S N Banerjee, W R Jarvis
Transfusion-transmitted bacterial infection in the United States, 1998 through 2000.
Transfusion. 2001 Dec;41(12):1493-9.
Abstract/Text
BACKGROUND: Bacterial contamination of blood components can result in transfusion-transmitted infection, but the risk is not established.
STUDY DESIGN AND METHODS: Suspected cases of transfusion-transmitted bacteremia were reported to the CDC by participating blood collection facilities and transfusion services affiliated with the American Red Cross, AABB, or Department of Defense blood programs from 1998 through 2000. A case was defined as any transfusion reaction meeting clinical criteria in which the same organism species was cultured from a blood component and from recipient blood, with the organism pair confirmed as identical by molecular typing.
RESULTS: There were 34 cases and 9 deaths. The rate of transfusion-transmitted bacteremia (in events/million units) was 9.98 for single-donor platelets, 10.64 for pooled platelets, and 0.21 for RBC units; for fatal reactions, the rates were 1.94, 2.22, and 0.13, respectively. Patients at greatest risk for death received components containing gram-negative organisms (OR, 7.5; 95% CI, 1.3-64.2; p = 0.009).
CONCLUSION: Bacterial contamination of blood is an important cause of transfusion-transmitted infection; infection risk from platelet transfusion is higher compared with that from RBCs, and, overall, the risk of infection from bacterial contamination now may exceed that from viral agents. Recipients of components containing gram-negative organisms are at highest risk for transfusion-related death. The results of this study may help direct efforts to improve transfusion-related patient safety.
C P McDonald, A Roy, P Mahajan, R Smith, A Charlett, J A J Barbara
Relative values of the interventions of diversion and improved donor-arm disinfection to reduce the bacterial risk from blood transfusion.
Vox Sang. 2004 Apr;86(3):178-82. doi: 10.1111/j.0042-9007.2004.00404.x.
Abstract/Text
BACKGROUND AND OBJECTIVES: The aim of this study was to demonstrate the efficiency of diverting the initial 20-ml donation from the collection bag and of an improved donor-arm disinfection procedure in reducing bacterial contamination in blood.
MATERIALS AND METHODS: Donations were collected in bags specially manufactured for the study. These bags incorporated two satellite pouches into each of which 20 ml of blood was collected. Blood initially flowed into sample pouch P1, representing a diversion pouch. Pouch P2 was then filled with 20 ml of blood, which allowed us to sample the collection bag after diversion was complete. Blood then flowed into the standard collection bag. The contents of the pouches were aerobically and anaerobically cultured on the BacT/ALERT automated culture system for 7 days. Two procedures were investigated in the study (each involving 1409 blood donations): one analysed the current disinfection procedure; and the other analysed an improved donor-arm disinfection procedure.
RESULTS: The use of diversion alone resulted in a 47% reduction in contamination, and improved donor-arm disinfection alone resulted in a 57% reduction in contamination. Diversion plus improved donor-arm disinfection produced a predicted 77% reduction in contamination.
CONCLUSIONS: The study validates diversion and an improved donor-arm disinfection procedure. In combination, these two interventions produced a substantial reduction in contamination. These procedures are to be introduced by the English National Blood Service to enhance the safety of the blood supply.
Beth H Shaz, Sean R Stowell, Christopher D Hillyer
Transfusion-related acute lung injury: from bedside to bench and back.
Blood. 2011 Feb 3;117(5):1463-71. doi: 10.1182/blood-2010-04-278135. Epub 2010 Oct 13.
Abstract/Text
Over the past 60 years, the transfusion medicine community has attained significant knowledge regarding transfusion-related acute lung injury (TRALI) through the bedside to bench and back to the bedside model. First, at the bedside, TRALI causes hypoxia and noncardiogenic pulmonary edema, typically within 6 hours of transfusion. Second, bedside studies showed a higher incidence in plasma and platelet products than in red blood cell products (the fatal TRALI incidence for plasma is 1:2-300 000 products; platelet, 1:3-400 000; red blood cells, 1:25 002 000), as well as an association with donor leukocyte antibodies (∼ 80% of cases). Third, at the bench, antibody-dependent and antibody-independent mechanisms have been described, requiring neutrophil and pulmonary endothelial cell activation. Antibodies, as well as alternate substances in blood products, result in neutrophil activation, which, in a susceptible patient, result in TRALI (2-hit hypothesis). Fourth, back to the bedside, policy changes based on results of these studies, such as minimizing use of plasma and platelet products from donors with leukocyte antibodies, have decreased the incidence of TRALI. Thus, steps to mitigate TRALI are in place, but a complete mechanistic understanding of the pathogenesis of TRALI and of which patients are at highest risk remains to be elucidated.
Robert C Skeate, Ted Eastlund
Distinguishing between transfusion related acute lung injury and transfusion associated circulatory overload.
Curr Opin Hematol. 2007 Nov;14(6):682-7. doi: 10.1097/MOH.0b013e3282ef195a.
Abstract/Text
PURPOSE OF REVIEW: The purpose of this review is to provide an overview of concepts recently presented in the literature that impact our understanding of transfusion related acute lung injury (TRALI) and transfusion associated circulatory overload (TACO), and how to distinguish between the two disorders.
RECENT FINDINGS: An exceptionally clear review article by Brux and Sachs clarified the two-hit model of TRALI pathogenesis. The TRALI definition developed at the 2004 consensus conference helped demonstrate that TRALI is likely underreported. Brain natriuretic peptide can be useful in distinguishing cardiogenic from noncardiogenic pulmonary edema. Blood centers are implementing male predominant plasma programs to limit TRALI, and preliminary evidence suggests that this is a useful intervention.
SUMMARY: TACO and TRALI have emerged as important causes of posttransfusion morbidity and mortality. As understanding of their pathogenesis improves, incidence, risk factors, differences, and possible preventive interventions are becoming clearer. There is no sentinel feature that distinguishes TRALI from TACO. Developing a thorough clinical profile including presenting signs and symptoms, fluid status, cardiac status including measurement of brain natriuretic peptide, and leukocyte antibody testing is the best strategy currently available to distinguish the two disorders.
K Takahashi, T Juji, M Miyamoto, S Uchida, T Akaza, K Tadokoro, Y Shibata, T Ino, A Hidano
Analysis of risk factors for post-transfusion graft-versus-host disease in Japan. Japanese Red Cross PT-GVHD Study Group.
Lancet. 1994 Mar 19;343(8899):700-2.
Abstract/Text
We distributed a questionnaire to highlight the effects of post transfusion graft-versus-host disease (PT-GVHD) and to elucidate the risk factors that would predispose people to the disease. The questionnaire described the pathogenesis and the clinical profiles of PT-GVHD and was distributed to doctors in Japan whose hospital conducted more than 1000 units of blood transfusions a year. Doctors were asked about their awareness and experience of PT-GVHD cases. Those who had seen cases of PT-GVHD were then asked to detail clinical course and laboratory data. Of the 14,083 doctors who replied to the first question, 47.4% did not realise that PT-GVHD could occur in immunocompetent hosts. From 304 cases where detailed information was supplied, 171 were considered clinically compatible with PT-GVHD. From these it seems that the risk factors linked to PT-GVHD are cardiovascular surgery, cancer, fresh and consanguineous blood transfusion, and being male. Patients with any of these factors should have some prophylactic therapy such as irradiation of blood before transfusion.
Masaaki Takatoku, Takashi Uchiyama, Shinichiro Okamoto, Yuzuru Kanakura, Kenichi Sawada, Masao Tomonaga, Shinji Nakao, Tatsutoshi Nakahata, Mine Harada, Takashi Murate, Keiya Ozawa, Japanese National Research Group on Idiopathic Bone Marrow Failure Syndromes
Retrospective nationwide survey of Japanese patients with transfusion-dependent MDS and aplastic anemia highlights the negative impact of iron overload on morbidity/mortality.
Eur J Haematol. 2007 Jun;78(6):487-94. doi: 10.1111/j.1600-0609.2007.00842.x. Epub 2007 Mar 28.
Abstract/Text
OBJECTIVE: Myelodysplastic syndromes (MDS) and aplastic anemia (AA) are the most common anemias that require transfusion therapy in Japan. This retrospective survey investigated relationships between iron overload, chelation practices, and morbidity/mortality in patients with these diseases.
METHOD: Medical histories of transfusion-dependent patients were assessed at transfusion onset, chelation onset, and study end.
RESULTS: Data were collected from 292 patients with MDS, AA, pure red cell aplasia, myelofibrosis, and other conditions. Patients received a mean of 61.5 red blood cell units during the previous year. Fewer than half (43%) of patients had previously received deferoxamine (DFO) therapy. Only 8.6% received daily/continuous DFO. In all, 75 deaths were reported, with cardiac and liver failure noted in 24.0 and 6.7% of cases. Of these, 97% had ferritin levels >1000 ng/mL. Abnormal cardiac and liver function was observed in 21.9% (14/64) and 84.6% (11/13) of all patients assessed. Effective chelation with DFO resulted in improved serum ferritin, liver enzymes, and fasting blood sugar.
CONCLUSIONS: Mortality is higher in heavily iron-overloaded patients, with liver and cardiac dysfunction being the primary cause. Daily/continuous chelation therapy was effective at reducing iron burden and improving organ function. Chelation therapy should be initiated once serum ferritin levels exceed 1000 ng/mL.
Kim A Janatpour, Norman D Kalmin, Hanne M Jensen, Paul V Holland
Clinical outcomes of ABO-incompatible RBC transfusions.
Am J Clin Pathol. 2008 Feb;129(2):276-81. doi: 10.1309/VXY1ULAFUY6E6JT3.
Abstract/Text
Factors that predict outcome after ABO-incompatible RBC transfusions are not well defined. We studied whether the volume of incompatible blood transfused would determine the signs and symptoms and survival outcome for ABO-incompatible RBC transfusions. We reviewed ABO-incompatible RBC transfusions from our institutions and our consultations for 35 years and from a survey of America's Blood Centers' members regarding causes, volume, signs, symptoms, and outcomes of ABO-incompatible RBC transfusions in their service areas from 1995 through 2005. All ABO-incompatible transfusions were due to error; 26 (62%) of 42 occurred at the patient's bedside. Of 36 patients who received more than 50 mL of incompatible blood, 23 (64%) manifested signs or symptoms related to the incompatible transfusion, and 6 (17)% died. Only 3 (25%) of 12 patients who received 50 mL or less of incompatible blood had associated signs or symptoms, and none died. Hypotension, hemoglobinuria, and/or hemoglobinemia were the most frequent findings in survivors and patients who died.ABO-incompatible RBC transfusion does not inevitably mean death or even occurrence of symptoms. Prompt recognition and discontinuation of the transfusion are critical because transfusing less ABO-incompatible blood may minimize signs and symptoms and may prevent death.
藤井康彦，松崎道男，宮田茂樹，東谷孝徳，稲葉頌一，浅井隆善，星順隆，稲田英一，河原和夫，高松純樹，高橋孝喜，佐川公矯： ABO型不適合輸血の発生原因による解析．日本輸血細胞治療学会誌2007;53:374-382.
Taira Maekawa
[Delayed hemolytic transfusion reaction (DHTR)--unrecognized and underestimated clinico-pathological conditions].
Rinsho Ketsueki. 2008 Oct;49(10):1306-14.
Abstract/Text
Mark H Yazer, Linda Podlosky, Gwen Clarke, Susan M Nahirniak
The effect of prestorage WBC reduction on the rates of febrile nonhemolytic transfusion reactions to platelet concentrates and RBC.
Transfusion. 2004 Jan;44(1):10-5.
Abstract/Text
BACKGROUND: Febrile non-hemolytic transfusion reactions (FNHTRs) are a common complication of platelet concentrate (PC) and RBC transfusions, usually ascribed to cytokines released by WBCs and perhaps the platelets themselves during storage. Prestorage WBC reduction should abrogate the accumulation of these cytokines reducing the number of FNHTRs.
STUDY DESIGN AND METHODS: A retrospective analysis of FNHTR to PCs and RBCs before universal WBC reduction (PrUR) (July 1997-January 1998 for PCs, July 1997-July 1999 for RBCs) and after its introduction (PoUR) (February 1998-August 2001 for PC, August 1999-August 2001 for RBCs) was undertaken. All transfusion reactions were stratified based on component and date of reaction. Other adverse transfusion reactions were grouped into three periods: July 1997-January 1998, February 1998-July 1999, and August 1999-August 2001. A chi-square test was performed to determine the significance of the differences between groups.
RESULTS: In the PRUR group, there were: 231 FNHTRs in 70,396 RBC units transfused (0.33%) and 29 FNHTRs in 6502 PC units transfused (0.45% percent). In the PoUR group, there were 136 FNHTRs in 72,949 RBC units transfused (0.19%, p < 0.001) and 56 FNHTRs in 50,555 PC units transfused (0.11%, p < 0.001). Of the other adverse events, only TRALI reactions were significantly reduced.
CONCLUSION: Prestorage WBC reduction significantly reduced the rate of FNHTRs to PCs and RBCs.
B J Patterson, J Freedman, V Blanchette, G Sher, P Pinkerton, B Hannach, J Meharchand, W Lau, N Boyce, E Pinchefsky, T Tasev, J Pinchefsky, S Poon, L Shulman, P MacK, K Thomas, N Blanchette, D Greenspan, T Panzarella
Effect of premedication guidelines and leukoreduction on the rate of febrile nonhaemolytic platelet transfusion reactions.
Transfus Med. 2000 Sep;10(3):199-206.
Abstract/Text
Platelet transfusion reactions were prospectively studied in haematology/oncology patients at five university teaching hospitals over three consecutive summers. The initial summer study provided baseline information on the use of premedications and the rate of platelet transfusion reactions (fever, chills, rigors and hives). Most (73%) platelet recipients were premedicated and 30% (95% CI 28-33%) of transfusions were complicated by reactions. The second study followed implementation of guidelines for premedicating platelet transfusions. Despite a marked reduction in premedication (50%), there was little change in the platelet transfusion reaction rate, 26% (95% CI 24-29%), or the type of reactions. The third study followed implementation of prestorage platelet leukoreduction while maintaining the premedication guidelines. The reaction rate decreased to 19% (95% CI 17-22%). For nonleukoreduced platelets, there was a statistically significant association between the platelet age and reaction rate (P = 0.04). For leukoreduced platelets, there was no statistically significant association between platelet age and reaction rate (P = 0.5). Plasma reduction of nonleukoreduced platelet products also reduced the reaction rate. These prospective studies document a high rate of platelet transfusion reactions in haematology/oncology patients and indicate premedication use can be reduced without increasing the reaction rate. Prestorage leukoreduction and/or plasma reduction of platelet products reduces but does not eliminate febrile nonhemolytic platelet transfusion reactions.
Robert P Sanders, Sunil D Maddirala, Terrence L Geiger, Stanley Pounds, John T Sandlund, Raul C Ribeiro, Ching-Hon Pui, Scott C Howard
Premedication with acetaminophen or diphenhydramine for transfusion with leucoreduced blood products in children.
Br J Haematol. 2005 Sep;130(5):781-7. doi: 10.1111/j.1365-2141.2005.05670.x.
Abstract/Text
Febrile non-haemolytic or allergic reactions occur in 0.1-30% of transfusions; physicians often premedicate patients with acetaminophen or diphenhydramine to prevent these reactions. The effectiveness of this practice has not been demonstrated. In this retrospective review of all transfusions at our institution during 2002, 385 patients received 7900 evaluable leucoreduced, irradiated blood products (4280 single-donor apheresis platelets and 3620 packed red blood cells). Febrile reactions occurred in 0.95% of 4108 transfusions with, and 0.53% of 3792 transfusions without, acetaminophen premedication. Allergic reactions occurred in 0.90% of 4315 transfusions with, and 0.56% of 3585 transfusions without, diphenhydramine premedication. In a multivariate analysis that adjusted for age, patient category, transfusion location, product, transfusion history, and reaction history, premedication with acetaminophen was associated with a statistically non-significant increase in the odds of a febrile reaction (odds ratio 1.74; 95% confidence interval 0.71-4.23; P = 0.22), and diphenhydramine with a non-significant increase in allergic reactions (odds ratio 1.74; 95% confidence interval 0.99-3.06; P = 0.054). Reactions occurred in only 1.3% of the 518 transfusions to patients with a history of two or more prior reactions. Febrile and allergic transfusion reactions were rare in paediatric patients transfused with leucoreduced, irradiated blood products, whether premedication was used or not.
Hazel Tinegate, Janet Birchall, Alexandra Gray, Richard Haggas, Edwin Massey, Derek Norfolk, Deborah Pinchon, Carrock Sewell, Angus Wells, Shubha Allard, BCSH Blood Transfusion Task Force
Guideline on the investigation and management of acute transfusion reactions. Prepared by the BCSH Blood Transfusion Task Force.
Br J Haematol. 2012 Oct;159(2):143-53. doi: 10.1111/bjh.12017. Epub 2012 Aug 29.
Abstract/Text
Although acute non-haemolytic febrile or allergic reactions (ATRs) are a common complication of transfusion and often result in little or no morbidity, prompt recognition and management are essential. The serious hazards of transfusion haemovigilance organisation (SHOT) receives 30-40 reports of anaphylactic reactions each year. Other serious complications of transfusion, such as acute haemolysis, bacterial contamination, transfusion-related acute lung injury (TRALI) or transfusion-associated circulatory overload (TACO) may present with similar clinical features to ATR. This guideline describes the approach to a patient developing adverse symptoms and signs related to transfusion, including initial recognition, establishing a likely cause, treatment, investigations, planning future transfusion and reporting within the hospital and to haemovigilance organisations. Key recommendations are that adrenaline should be used as first line treatment of anaphylaxis, and that transfusions should only be carried out where patients can be directly observed and where staff are trained in manging complications of transfusion, particularly anaphylaxis. Management of ATRs is not dependent on classification but should be guided by symptoms and signs. Patients who have experienced an anaphylactic reaction should be discussed with an allergist or immunologist, in keeping with UK resuscitation council guidelines.
© 2012 Blackwell Publishing Ltd.
Francesco Bennardello, Carmelo Fidone, Vincenzo Spadola, Sergio Cabibbo, Simone Travali, Giovanni Garozzo, Agostino Antolino, Giuseppe Tavolino, Cadigia Falla, Pietro Bonomo
The prevention of adverse reactions to transfusions in patients with haemoglobinopathies: a proposed algorithm.
Blood Transfus. 2013 Jul;11(3):377-84. doi: 10.2450/2013.0017-12. Epub 2013 May 21.
Abstract/Text
BACKGROUND: Transfusion therapy remains the main treatment for patients with severe haemoglobinopathies, but can cause adverse reactions which may be classified as immediate or delayed. The use of targeted prevention with drugs and treatments of blood components in selected patients can contribute to reducing the development of some reactions.The aim of our study was to develop an algorithm capable of guiding behaviours to adopt in order to reduce the incidence of immediate transfusion reactions.
MATERIALS AND METHODS: Immediate transfusion reactions occurring over a 7-year period in 81 patients with transfusion-dependent haemoglobinopathies were recorded. The patients received transfusions with red cell concentrates that had been filtered prestorage. Various measures were undertaken to prevent transfusion reactions: leucoreduction, washing the red blood cells, prophylactic administration of an antihistamine (loratidine 10 mg tablet) or an antipyretic (paracetamol 500 mg tablet).
RESULTS: Over the study period 20,668 red cell concentrates were transfused and 64 adverse transfusion reactions were recorded in 36 patients. The mean incidence of reactions in the 7 years of observation was 3.1‰. Over the years the incidence gradually decreased from 6.8‰ in 2004 to 0.9‰ in 2010.
DISCUSSION: Preventive measures are not required for patients who have an occasional reaction, because the probability that such a type of reaction recurs is very low. In contrast, the targeted use of drugs such as loratidine or paracetamol, sometimes combined with washing and/or double filtration of red blood cells, can reduce the rate of recurrent (allergic) reactions to about 0.9‰. The system for detecting adverse reactions and training staff involved in transfusion therapy are critical points for reliable collection of data and standardisation of the detection system is recommended for those wanting to monitor the incidence of all adverse reactions, including minor ones.
Lawrence B Schwartz
Diagnostic value of tryptase in anaphylaxis and mastocytosis.
Immunol Allergy Clin North Am. 2006 Aug;26(3):451-63. doi: 10.1016/j.iac.2006.05.010.
Abstract/Text
Serum (or plasma) levels of total and mature tryptase measurements are recommended in the diagnostic evaluation of systemic anaphylaxis and systemic mastocytosis, but their interpretation must be considered in the context of a complete workup of each patient. Total tryptase levels generally reflect the increased burden of mast cells in patients with all forms of systemic mastocytosis (indolent systemic mastocytosis, smoldering systemic mastocytosis, systemic mastocytosis associated with a hematologic clonal non-mast cell disorder, aggressive systemic mastocytosis, and mast cell leukemia) and the decreased burden of mast cells associated with cytoreductive therapies in these disorders. Causes of an elevated total tryptase level other than systemic mastocytosis must be considered, however, and include systemic anaphylaxis, acute myelocytic leukemia, various myelodysplastic syndromes, hypereosinophilic syndrome associated with the FLP1L1-PDGFRA mutation, end-stage renal failure, and treatment of onchocerciasis. Mature (beta) tryptase levels generally reflect the magnitude of mast cell activation and are elevated during most cases of systemic anaphylaxis, particularly with parenteral exposure to the inciting agent.
Meghan Delaney, Silvano Wendel, Rachel S Bercovitz, Joan Cid, Claudia Cohn, Nancy M Dunbar, Torunn O Apelseth, Mark Popovsky, Simon J Stanworth, Alan Tinmouth, Leo Van De Watering, Jonathan H Waters, Mark Yazer, Alyssa Ziman, Biomedical Excellence for Safer Transfusion (BEST) Collaborative
Transfusion reactions: prevention, diagnosis, and treatment.
Lancet. 2016 Dec 3;388(10061):2825-2836. doi: 10.1016/S0140-6736(15)01313-6. Epub 2016 Apr 12.
Abstract/Text
Blood transfusion is one of the most common procedures in patients in hospital so it is imperative that clinicians are knowledgeable about appropriate blood product administration, as well as the signs, symptoms, and management of transfusion reactions. In this Review, we, an international panel, provide a synopsis of the pathophysiology, treatment, and management of each diagnostic category of transfusion reaction using evidence-based recommendations whenever available.
Copyright © 2016 Elsevier Ltd. All rights reserved.
S F Kemp, R F Lockey, F E R Simons, World Allergy Organization ad hoc Committee on Epinephrine in Anaphylaxis
Epinephrine: the drug of choice for anaphylaxis. A statement of the World Allergy Organization.
Allergy. 2008 Aug;63(8):1061-70. doi: 10.1111/j.1398-9995.2008.01733.x.
Abstract/Text
Anaphylaxis is an acute and potentially lethal multi-system allergic reaction. Most consensus guidelines for the past 30 years have held that epinephrine is the drug of choice and the first drug that should be administered in acute anaphylaxis. Some state that properly administered epinephrine has no absolute contraindication in this clinical setting. A committee of anaphylaxis experts assembled by the World Allergy Organization has examined the evidence from the medical literature concerning the appropriate use of epinephrine for anaphylaxis. The Committee strongly believes that epinephrine is currently underutilized and often dosed suboptimally to treat anaphylaxis, is under-prescribed for potential future self-administration, that most of the reasons proposed to withhold its clinical use are flawed, and that the therapeutic benefits of epinephrine exceed the risk when given in appropriate i.m. doses.
LeAnne D Kennedy, L Douglas Case, David D Hurd, Julia M Cruz, Gregory J Pomper
A prospective, randomized, double-blind controlled trial of acetaminophen and diphenhydramine pretransfusion medication versus placebo for the prevention of transfusion reactions.
Transfusion. 2008 Nov;48(11):2285-91. doi: 10.1111/j.1537-2995.2008.01858.x. Epub 2008 Jul 30.
Abstract/Text
BACKGROUND: Acetaminophen and diphenhydramine are commonly used as pretransfusion medications to prevent transfusion reactions. The purpose of this study was to prospectively compare the risk of transfusion reactions in hematology/oncology patients who receive acetaminophen with diphenhydramine or placebo before transfusion.
STUDY DESIGN AND METHODS: A randomized, double-blind, placebo-controlled transfusion reaction study of 315 eligible patients was performed. Inclusion criteria were patients aged 18 to 65 years admitted to the leukemia or bone marrow transplant (BMT) services. Patients were excluded if they had a known allergy to either acetaminophen or diphenhydramine or had a documented history of a febrile or allergic transfusion reaction. All blood products were administered using a leukofilter. Study medications were given 30 minutes before transfusions and no other acetaminophen or diphenhydramine was given within 4 hours of administration of the study medications. Patients were monitored for the development of reaction symptoms within 4 hours after the transfusion.
RESULTS: A total of 154 active drug patients were compared to 161 placebo patients. There was no significant difference in the overall risk of transfusion reactions between the two groups. However, analysis of specific reaction types revealed a significant decrease in the risk of febrile reactions when pretransfusion medication is used in addition to bedside leukoreduction.
CONCLUSIONS: Pretransfusion medication of leukemia or BMT patients without a history of transfusion reaction does not decrease the overall risk of transfusion reactions. However, pretransfusion medication may decrease the risk of febrile nonhemolytic transfusion reactions to leukoreduced blood products.
Stephen E Wang, Primo N Lara, Angie Lee-Ow, Jeanne Reed, Lori R Wang, Patti Palmer, Joseph M Tuscano, Carol M Richman, Laurel Beckett, Ted Wun
Acetaminophen and diphenhydramine as premedication for platelet transfusions: a prospective randomized double-blind placebo-controlled trial.
Am J Hematol. 2002 Jul;70(3):191-4. doi: 10.1002/ajh.10119.
Abstract/Text
Non-hemolytic transfusion reactions (NHTR) occur in up to 30% of patients receiving platelet transfusions. Premedication with acetaminophen and diphenhydramine is a common strategy to prevent NHTR, but its efficacy has not been studied. In this prospective trial, transfusions in patients receiving pre-storage leukocyte-reduced single-donor apheresis platelets (SDP) were randomized to premedication with either acetaminophen 650 mg PO and diphenhydramine 25 mg IV, or placebo. Fifty-one patients received 98 transfusions. Thirteen patients had 15 NHTR: 15.4% (8/52) in the treatment arm and 15.2% (7/46) in the placebo arm. Premedication prior to transfusion of pre-storage leukocyte reduced SDP does not significantly lower the incidence of NHTR as compared to placebo.
Copyright 2002 Wiley-Liss, Inc.
Ida Wong-Sefdan, Amine Ale-Ali, Patricia A DeMoor, Samuel Martinez, Peter Curtin, Thomas Lane, Eric Roeland
Implementing inpatient, evidence-based, antihistamine-transfusion premedication guidelines at a single academic US hospital.
J Community Support Oncol. 2014 Feb;12(2):56-64.
Abstract/Text
Allergic transfusion reactions (ATRs) are a common complication of blood transfusions. Advances in transfusion medicine have significantly decreased the incidence of ATRs; however, ATRs continue to be burdensome for patients and problematic for providers who regularly order packed red blood cells and platelet transfusions. To further decrease the frequency of ATRs, routine premedication with diphenhydramine is common practice and is part of "transfusion culture" in a majority of institutions. In this article, we review the history, practice, and literature of transfusion premedication, specifically antihistamines given the adverse-effect profile. We discuss the rationale and original academic studies, which have supported the use of premedication for transfusions for decades. However, despite the common use of premedication to prevent ATRs, recent literature has not conclusively validated its use. In addition, the existing premedication that is routinely prescribed often causes a number of adverse effects. These findings have motivated the Moores Cancer Center (University of California, San Diego) to change its current transfusion premedication practices, particularly with regard to ATRs and first-generation antihistamines. We outline the preliminary development of an evidence-based and patient-specific approach to transfusion premedication, including the challenges and steps taken to revise inpatient premedication protocols. We plan to expand this protocol to the outpatient setting at a later date. Future efforts require a prospective validation of our presented transfusion premedication guidelines.
P M Mertes, A Bazin, F Alla, J Bienvenu, C Caldani, B Lamy, D Laroche, M F Leconte des Floris, J-Y Py, D Rebibo, B Willaert, P Demoly, French Medicines and Healthcare Products Regulatory Agency
Hypersensitivity reactions to blood components: document issued by the allergy committee of the French medicines and healthcare products regulatory agency.
J Investig Allergol Clin Immunol. 2011;21(3):171-8.
Abstract/Text
These guidelines represent a consensus among experts on hypersensitivity reactions occurring after transfusion of blood components. They cover recognition, investigation, treatment, and prevention of such reactions. Implemented in France under the auspices of the French Medicines and Healthcare Products Regulatory Agency (AFSSAPS) and based on current knowledge, research, and experience, they aim to provide effective and easily teachable means of further improving the quality of hemovigilance databases, promote interest in this field, and help identify possible mechanisms and at-risk patient groups.
J de Wildt-Eggen, S Nauta, J G Schrijver, M van Marwijk Kooy, M Bins, H C van Prooijen
Reactions and platelet increments after transfusion of platelet concentrates in plasma or an additive solution: a prospective, randomized study.
Transfusion. 2000 Apr;40(4):398-403.
Abstract/Text
BACKGROUND: Reactions after platelet transfusions are rather common and frequently are caused by plasma constituents. In recent developments, the preparation and storage of platelet concentrates (PCs) in a platelet additive solution (PAS-2) have been shown to result in acceptable storage conditions. A major drawback of the use of these PCs is the progressive increase of P-selectin-positive platelets during storage. The clinical benefit of transfusions of PCs in PAS-2 was studied.
STUDY DESIGN AND METHODS: PCs prepared from buffy coats were suspended in either plasma or PAS-2 and stored for up to 5 days. Clinical responses were evaluated in a prospective study in 21 patients treated with intensive chemotherapy for hematologic malignancies. Eligible patients were randomly assigned to receive prophylactic transfusions of PCs prepared in either plasma or PAS-2. Reactions and CCIs were recorded after each transfusion.
RESULTS: The incidence of reactions in 12 patients given PCs in plasma (n = 192) was 12 percent. Transfusions to 9 patients of PCs in PAS-2 (n = 132) showed a reduction in the incidence of reactions to 5.3 percent (p<0.05). The average 1-hour and 20-hour CCIs after transfusion of PCs in plasma were 20.7 +/- 8. 5 and 11.5 +/- 8.0, respectively. CCIs after transfusion of PCs in PAS-2 were significantly lower: the average 1-hour CCI was 17.1 +/- 6.6 (p<0.001) and the average 20-hour CCI was 9.5 +/- 7.0 (p<0.05). Storage conditions of PCs were optimal: in each group, average 1-hour CCIs of both fresh and stored PCs were similar. The 20-hour CCIs after the transfusion of fresh and stored PCs in PAS-2 also were similar.
CONCLUSION: Transfusion of PCs in PAS-2 significantly reduces the incidence of reactions. The 1-hour and 20-hour CCIs after transfusion of PCs in PAS-2 were significantly lower than the CCIs after transfusion of PCs in plasma. Because storage conditions of both PCs were found to be optimal, the decrease in CCIs after transfusion of PCs prepared in PAS-2 may be caused by rapid elimination of a subpopulation of P-selectin-positive platelets from the circulation.
Jean-Louis H Kerkhoffs, Jeroen C Eikenboom, Martin S Schipperus, Rinie J van Wordragen-Vlaswinkel, Ronald Brand, Mark S Harvey, Rene R de Vries, Renee Barge, Dick J van Rhenen, Anneke Brand
A multicenter randomized study of the efficacy of transfusions with platelets stored in platelet additive solution II versus plasma.
Blood. 2006 Nov 1;108(9):3210-5. doi: 10.1182/blood-2006-04-020131. Epub 2006 Jul 6.
Abstract/Text
Randomized studies testing the clinical efficacy of platelet additive solutions (PASs) for storage of platelets are scarce and often biased by patient selection. We conducted a multicenter, randomized study to investigate clinical efficacy of platelets stored in PAS II versus plasma, also including patients with clinical complications associated with increased platelet consumption. A total of 168 evaluable patients received pooled buffy coat-derived platelet concentrates (PCs) suspended in either plasma (n = 354) or PAS II (n = 411) stored up to 5 days. Both univariate as well as multivariate analysis showed a significant effect of used storage medium in regard to 1- and 24-hour count increments and corrected count increments, in favor of plasma PCs. However, there were no significant differences between the groups regarding bleeding complications and transfusion interval. Adverse transfusion reactions occurred significantly less after transfusions with PAS II PCs (P = .04). Multivariate analysis showed no significant effect of the used storage medium on the incidence of 1- and 24-hour transfusion failure. We showed safety and efficacy of PAS II PCs in intensively treated patients; however, plasma PCs show superior increments.
Hiroshi Azuma, Junichi Hirayama, Mitsuaki Akino, Reiko Miura, Yoshio Kiyama, Kiyotoshi Imai, Masaharu Kasai, Kazuki Koizumi, Yasutaka Kakinoki, Yusuke Makiguchi, Koji Kubo, Yoshiko Atsuta, Mitsuhiro Fujihara, Chihiro Homma, Sadamitsu Yamamoto, Toshiaki Kato, Hisami Ikeda
Reduction in adverse reactions to platelets by the removal of plasma supernatant and resuspension in a new additive solution (M-sol).
Transfusion. 2009 Feb;49(2):214-8. doi: 10.1111/j.1537-2995.2008.01918.x. Epub 2008 Sep 16.
Abstract/Text
BACKGROUND: Leukodepletion reduces but does not eliminate adverse reactions to platelet concentrate (PC). As an alternative strategy, plasma reduction or washing of platelets should be considered. However, the efficacy of this strategy is still unclear.
STUDY DESIGN AND METHODS: A total of 12 patients who experienced adverse reactions at a 29 to 100 percent reaction rate for plasma-PC were enrolled. The reactions were allergic reactions and nonhemolytic transfusion reactions, such as chills. Plasma-removed PC (W/R-PC), which was suspended in a recently developed additive solution (M-sol) containing less than 20 mL plasma, was prepared. W/R-PCs in M-sol were then transfused into patients after an overnight storage period; the occurrence of adverse reactions was monitored and 1- and 24-hour corrected count increment (CCI) values were evaluated.
RESULTS: Although plasma-PC caused reaction in 12 patients, W/R-PC prevented reactions in 11 of 12 patients, with 1 patient having one minor allergic reaction of 15 transfusions. There was a significant difference in the incidence of reaction (p < 0.0001, Fisher's exact test). On a per-transfusion basis, the reaction rate for W/R-PC (1/156, 0.64%; 95% confidence interval [CI], 0.02%-3.5%) was reduced significantly compared to that for plasma-PC (117/276, 42%; 95% CI, 36%-48%; p < 0.0001). W/R-PC gave findings of satisfactory CCI at 1 hour (22,400 +/- 8,000/microL) and 24 hours (15,400 +/- 8,000/microL). No clinically evident bleeding episodes were recorded.
CONCLUSIONS: W/R-PC suspended in M-sol in the presence of less than 20 mL plasma can be transfused safely and eliminate a wide range of adverse reactions to plasma-PC.
Aaron A R Tobian, William J Savage, Daniel J Tisch, Sandra Thoman, Karen E King, Paul M Ness
Prevention of allergic transfusion reactions to platelets and red blood cells through plasma reduction.
Transfusion. 2011 Aug;51(8):1676-83. doi: 10.1111/j.1537-2995.2010.03008.x. Epub 2011 Jan 7.
Abstract/Text
BACKGROUND: The incidence of allergic transfusion reactions (ATRs) ranges from 1% to 3% of all transfusions, and they are difficult to prevent. This study evaluated whether removing plasma from apheresis platelets (APs) or red blood cells (RBCs) by concentrating or washing transfusion products can decrease the incidence of ATRs.
STUDY DESIGN AND METHODS: A retrospective cohort study of 179 individuals who received unmanipulated and subsequently concentrated and/or washed APs was conducted. Poisson regression with generalized estimating equations was used to estimate the incident rate ratios and 95% confidence intervals (CIs) of ATRs.
RESULTS: The incidence of ATRs to unmanipulated APs was 5.5% (306 ATRs/5575 AP units). The incidence decreased to 1.7% (135 ATRs/4327 AP units) when individuals received concentrated APs (73% reduction; 95% CI, 65%-79%) and 0.5% (21 ATRs/4082 AP units) when individuals received washed APs (95% reduction; 95% CI, 91%-97%). Of the 39 individuals who received unmanipulated RBCs and subsequently washed RBCs, the incidence of ATRs decreased from 2.7% (33 ATRs/1236 RBC units) to 0.3% (2 ATRs/733 RBC units; 89.4% reduction; 95% CI, 55.5%-97.5%). The median number of AP transfusions to first ATR was six (interquartile range [IQR], 2-19) for unmanipulated APs and increased to 13 (IQR, 4-32) for concentrated APs and 40 (IQR, 29-73.5) for washed APs.
CONCLUSIONS: Concentrating APs and washing APs and RBCs substantially reduces ATRs, suggesting that the plasma component of APs and RBCs has an essential role in the etiology of ATRs.
© 2010 American Association of Blood Banks.
T D Vo, J Cowles, J M Heal, N Blumberg
Platelet washing to prevent recurrent febrile reactions to leucocyte-reduced transfusions.
Transfus Med. 2001 Feb;11(1):45-7.
Abstract/Text
Symptoms of fever and/or rigours after transfusion continue to occur commonly in patients receiving platelets leucocyte-reduced after storage. A cohort of 24 consecutive patients who had experienced severe or repeated febrile nonhaemolytic reactions to post-storage leucocyte-reduced platelet transfusions were treated with saline-washed, post-storage leucocyte-reduced platelets. The frequency of reactions declined from 20% of transfusions (n = 191) to 0.6% (n = 331) after instituting saline-washed, post-storage leucocyte-reduced platelet transfusions. These results support the hypothesis that substances present in the supernatant of stored platelet concentrates mediate febrile nonhaemolytic transfusion reactions, and provide one strategy for preventing their occurrence.
J Kobayashi, R Yanagisawa, T Ono, Y Tatsuzawa, Y Tokutake, N Kubota, E Hidaka, K Sakashita, S Kojima, S Shimodaira, T Nakamura
Administration of platelet concentrates suspended in bicarbonated Ringer's solution in children who had platelet transfusion reactions.
Vox Sang. 2018 Feb;113(2):128-135. doi: 10.1111/vox.12608. Epub 2017 Oct 25.
Abstract/Text
BACKGROUND AND OBJECTIVES: Adverse reactions to platelet transfusions are a problem. Children with primary haematological and malignant diseases may experience allergic transfusion reactions (ATRs) to platelet concentrates (PCs), which can be prevented by giving washed PCs. A new platelet additive solution, using bicarbonated Ringer's solution and acid-citrate-dextrose formula A (BRS-A), may be better for platelet washing and storage, but clinical data are scarce.
MATERIALS AND METHODS: A retrospective cohort study for consecutive cases was performed between 2013 and 2017. For 24 months, we transfused washed PCs containing BRS-A to children with primary haematological and malignant diseases and previous adverse reactions. Patients transfused with conventional PCs (containing residual plasma) were assigned as controls, and results were compared in terms of frequency of ATRs, corrected count increment (CCI) and occurrence of bleeding. We also studied children transfused with PCs washed by a different system as historical controls.
RESULTS: Thirty-two patients received 377 conventional PC transfusions. ATRs occurred in 12 (37·5%) patients from transfused with 18 (4·8%) bags. Thirteen patients, who experienced reactions to regular PCs in plasma, then received 119 transfusion bags of washed PCs containing BRS-A, and none had ATRs to washed PCs containing BRS-A. Before study period, six patients transfused 137 classical washed PCs with different platelet additive solution, under same indication, ATRs occurred in one (16·7%) patient from transfused with one (0·7%) bags. CCIs (24 h) in were lower with classical washed PCs (1·26 ± 0·54) compared to regular PCs in plasma (2·07 ± 0·76) (P < 0·001), but there was no difference between washed PCs containing BRS-A (2·14 ± 0·77) and regular PCs (2·21 ± 0·79) (P = 0·769), and we saw no post-transfusion bleeding.
CONCLUSION: Washed PCs containing BRS-A appear to prevent ATRs without loss of transfusion efficacy in children with primary haematological and malignant diseases. Their efficacy should be further evaluated through larger prospective clinical trials.
© 2017 International Society of Blood Transfusion.
Pearl Toy, Ognjen Gajic, Peter Bacchetti, Mark R Looney, Michael A Gropper, Rolf Hubmayr, Clifford A Lowell, Philip J Norris, Edward L Murphy, Richard B Weiskopf, Gregory Wilson, Monique Koenigsberg, Deanna Lee, Randy Schuller, Ping Wu, Barbara Grimes, Manish J Gandhi, Jeffrey L Winters, David Mair, Nora Hirschler, Rosa Sanchez Rosen, Michael A Matthay, TRALI Study Group
Transfusion-related acute lung injury: incidence and risk factors.
Blood. 2012 Feb 16;119(7):1757-67. doi: 10.1182/blood-2011-08-370932. Epub 2011 Nov 23.
Abstract/Text
Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality. To determine TRALI incidence by prospective, active surveillance and to identify risk factors by a case-control study, 2 academic medical centers enrolled 89 cases and 164 transfused controls. Recipient risk factors identified by multivariate analysis were higher IL-8 levels, liver surgery, chronic alcohol abuse, shock, higher peak airway pressure while being mechanically ventilated, current smoking, and positive fluid balance. Transfusion risk factors were receipt of plasma or whole blood from female donors (odds ratio = 4.5, 95% confidence interval [CI], 1.85-11.2, P = .001), volume of HLA class II antibody with normalized background ratio more than 27.5 (OR = 1.92/100 mL, 95% CI, 1.08-3.4, P = .03), and volume of anti-human neutrophil antigen positive by granulocyte immunofluoresence test (OR = 1.71/100 mL, 95% CI, 1.18-2.5, P = .004). Little or no risk was associated with older red blood cell units, noncognate or weak cognate class II antibody, or class I antibody. Reduced transfusion of plasma from female donors was concurrent with reduced TRALI incidence: 2.57 (95% CI, 1.72-3.86) in 2006 versus 0.81 (95% CI, 0.44-1.49) in 2009 per 10 000 transfused units (P = .002). The identified risk factors provide potential targets for reducing residual TRALI.
Alexander P J Vlaar, Pearl Toy, Mark Fung, Mark R Looney, Nicole P Juffermans, Juergen Bux, Paula Bolton-Maggs, Anna L Peters, Christopher C Silliman, Daryl J Kor, Steve Kleinman
A consensus redefinition of transfusion-related acute lung injury.
Transfusion. 2019 Jul;59(7):2465-2476. doi: 10.1111/trf.15311. Epub 2019 Apr 16.
Abstract/Text
BACKGROUND: Transfusion-related acute lung injury (TRALI) is a serious complication of blood transfusion and is among the leading causes of transfusion-related morbidity and mortality in most developed countries. In the past decade, the pathophysiology of this potentially life-threatening syndrome has been increasingly elucidated, large cohort studies have identified associated patient conditions and transfusion risk factors, and preventive strategies have been successfully implemented. These new insights provide a rationale for updating the 2004 consensus definition of TRALI.
STUDY DESIGN AND METHODS: An international expert panel used the Delphi methodology to develop a redefinition of TRALI by modifying and updating the 2004 definition. Additionally, the panel reviewed issues related to TRALI nomenclature, patient conditions associated with acute respiratory distress syndrome (ARDS) and TRALI, TRALI pathophysiology, and standardization of reporting of TRALI cases.
RESULTS: In the redefinition, the term "possible TRALI" has been dropped. The terminology of TRALI Type I (without an ARDS risk factor) and TRALI Type II (with an ARDS risk factor or with mild existing ARDS) is proposed. Cases with an ARDS risk factor that meet ARDS diagnostic criteria and where respiratory deterioration over the 12 hours before transfusion implicates the risk factor as causative should be classified as ARDS. TRALI remains a clinical diagnosis and does not require detection of cognate white blood cell antibodies.
CONCLUSIONS: Clinicians should report all cases of posttransfusion pulmonary edema to the transfusion service so that further investigation can allow for classification of such cases as TRALI (Type I or Type II), ARDS, transfusion-associated circulatory overload (TACO), or TRALI or TACO cannot distinguish or an alternate diagnosis.
© 2019 The Authors. Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.
Steven Kleinman, Tim Caulfield, Penny Chan, Robertson Davenport, Janice McFarland, Susan McPhedran, Maureen Meade, Douglas Morrison, Thomas Pinsent, Pierre Robillard, Peter Slinger
Toward an understanding of transfusion-related acute lung injury: statement of a consensus panel.
Transfusion. 2004 Dec;44(12):1774-89. doi: 10.1111/j.0041-1132.2004.04347.x.
Abstract/Text
Ognjen Gajic, Michael A Gropper, Rolf D Hubmayr
Pulmonary edema after transfusion: how to differentiate transfusion-associated circulatory overload from transfusion-related acute lung injury.
Crit Care Med. 2006 May;34(5 Suppl):S109-13. doi: 10.1097/01.CCM.0000214311.56231.23.
Abstract/Text
OBJECTIVE: Pulmonary edema is an under-recognized and potentially serious complication of blood transfusion. Distinct mechanisms include adverse immune reactions and circulatory overload. The former is associated with increased pulmonary vascular permeability and is commonly referred to as transfusion-related acute lung injury (TRALI). The latter causes hydrostatic pulmonary edema and is commonly referred to as transfusion-associated circulatory overload (TACO). In this review article we searched the National Library of Medicine PubMed database as well as references of retrieved articles and summarized the methods for differentiating between hydrostatic and permeability pulmonary edema.
RESULTS: The clinical and radiologic manifestations of TACO and TRALI are similar. Although echocardiography and B-type natriuretic peptide measurements may aid in the differential diagnosis between hydrostatic and permeability pulmonary edema, invasive techniques such as right heart catheterization and the sampling of alveolar fluid protein are sometimes necessary. The diagnostic differentiation is especially difficult in critically ill patients will multiple comorbidities so that the cause of edema may only be determined post hoc based on the clinical course and response to therapy. Guided by available evidence, we present an algorithm for establishing the pretest probability of TRALI as opposed to TACO. The decision to test donor and recipient blood for immunocompatibility may be made on this basis.
CONCLUSIONS: The distinction between hydrostatic (TACO) and permeability (TRALI) pulmonary edema after transfusion is difficult, in part because the two conditions may coexist. Knowledge of strengths and limitations of different diagnostic techniques is necessary before initiation of complex TRALI workup.
田崎哲典ほか. TRALI, TACO鑑別診断のためのガイドライン．日本輸血細胞治療学会誌 61:474-479, 2015.
Ramesh Kumar, Mohammed Jaber Sedky, Sunny Joseph Varghese, Osama Ebrahim Sharawy
Transfusion Related Acute Lung Injury (TRALI): A Single Institution Experience of 15 Years.
Indian J Hematol Blood Transfus. 2016 Sep;32(3):320-7. doi: 10.1007/s12288-015-0604-4. Epub 2015 Sep 29.
Abstract/Text
Transfusion related acute Lung injury (TRALI) though a serious blood transfusion reaction with a fatality rate of 5-25 % presents with acute respiratory distress with hypoxaemia and noncardiac pulmonary oedema within 6 h of transfusion. In non fatal cases, it may resolve within 72 h or earlier. Although reported with an incidence of 1:5000, its true occurrence is rather unknown. Pathogenesis is believed to be related to sequestration and adhesion of neutrophils to the pulmonary capillary endothelium and its activation leading to its destruction and leaks. The patient's underlying condition, anti-neutrophil antibody in the transfused donor plasma and certain lipids that accumulate in routinely stores blood and components are important in its aetiopathogenesis. Patient's predisposing conditions include haematological malignancy, major surgery (especially cardiac), trauma and infections. The more commonly incriminated products include fresh frozen plasma (FFP), platelets (whole blood derived and apheresis), whole blood and Packed RBC. Occasional cases involving cryoprecipitate and Intravenous immunoglobulin (IVig) have also been reported. We present a 15 year single institution experience of TRALI, during which we observed 9 cases among 170,871 transfusions, giving an incidence of 1:19,000. We did not encounter cases of haematological malignancy or cardiac surgery in our TRALI patients. Among the blood products, that could be related to TRALI in our patients included solitary cases receiving cryoprecipitate, IVIg, and recombinant Factor VII apart from platelets and FFP. All patients were treated with oxygen support. Six patients required mechanical ventilation. Off label hydrocortisone was given to all patients. There were no cases of fatality among our patients.
3 学会合同 ARDS 診療ガイドライン 2016 作成委員会,一般社団法人日本呼吸器学会,一般社団法人日本呼吸療法学会,一般社団法人日本集中治療医学会. ARDS 診療ガイドライン 2016, 一般社団法人日本呼吸器学会，東京，2016.
Sat Sharma
Acute respiratory distress syndrome.
BMJ Clin Evid. 2010 Nov 30;2010. Epub 2010 Nov 30.
Abstract/Text
INTRODUCTION: Acute respiratory distress syndrome (ARDS) is characterised by a profound deterioration in systemic oxygenation or ventilation, or both, despite supportive respiratory therapy. ARDS is an acute and progressive respiratory disease of a non-cardiac cause that is associated with progressively diffuse bilateral pulmonary infiltrates, reduced pulmonary compliance, and hypoxaemia. The main causes of ARDS include direct lung injury (e.g., pneumonia, gastric acid aspiration) or indirect lung injury (e.g., sepsis, pancreatitis, massive blood transfusion, non-thoracic trauma). Sepsis and pneumonia account for about 60% of cases. Between one third and one half of people with ARDS die from the disease, but mortality depends on the underlying cause. Some survivors have long-term respiratory or cognitive problems.
METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of interventions in adults with acute respiratory distress syndrome? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS: We found 20 systematic reviews, RCTs, or observational studies that met our inclusion criteria.
CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: corticosteroids, low tidal-volume mechanical ventilation, nitric oxide, prone position, and protective ventilation.
Rimki Rana, Evans R Fernández-Pérez, S Anjum Khan, Sameer Rana, Jeffrey L Winters, Timothy G Lesnick, S Breanndan Moore, Ognjen Gajic
Transfusion-related acute lung injury and pulmonary edema in critically ill patients: a retrospective study.
Transfusion. 2006 Sep;46(9):1478-83. doi: 10.1111/j.1537-2995.2006.00930.x.
Abstract/Text
BACKGROUND: Using the recent Consensus Panel recommendations, we sought to describe the incidence of transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) in critically ill patients.
STUDY DESIGN AND METHODS: Consecutive patients at four intensive care units (ICUs) who did not require respiratory support at the time of transfusion were identified with custom electronic surveillance system that prospectively tracks the time of transfusion and onset of respiratory support. Respiratory failure was defined as the onset of noninvasive or invasive ventilator support within 6 hours of transfusion. Experts blinded to specific transfusion factors categorized the cases of pulmonary edema as permeability edema (suspected or possible TRALI) or hydrostatic edema (TACO) according to predefined algorithm. In a nested case-control design, transfusion variables and lung injury risk factors were compared between the TRALI cases and controls matched by age, sex, and admission diagnosis.
RESULTS: There were 8902 units transfused in 1351 patients of whom 94 required new respiratory support within 6 hours of transfusion. Among 49 patients with confirmed acute pulmonary edema, experts identified 7 cases with suspected TRALI, 17 patients with possible TRALI, and 25 cases with TACO. The incidence of suspected TRALI was 1 in 1271 units transfused; possible TRALI, 1 in 534 per unit transfused; and TACO, 1 in 356 per unit transfused. When adjusted for sepsis and fluid balance in a stepwise conditional logistic regression analysis, patients who developed acute lung injury (suspected or possible TRALI) received larger amount of plasma (odds ratio 3.4, 95% confidence interval 1.2-10.2, for each liter infused; p = 0.023).
CONCLUSION: In the ICU, pulmonary edema frequently occurs after blood transfusion. The association between infusion of plasma and the development of suspected or possible TRALI may have important implications with regards to etiology and prevention of this syndrome.
Andrea Piccin, Marina Cronin, Róisín Brady, Jackie Sweeney, Luigi Marcheselli, Emer Lawlor
Transfusion-associated circulatory overload in Ireland: a review of cases reported to the National Haemovigilance Office 2000 to 2010.
Transfusion. 2015 Jun;55(6):1223-30. doi: 10.1111/trf.12965. Epub 2014 Dec 18.
Abstract/Text
BACKGROUND: Transfusion-associated circulatory overload (TACO) is an increasingly reported condition but symptoms and signs are still unrecognized. We present a review of the incidence and clinical features of TACO reported to the National Haemovigilance Office at the Irish Blood Transfusion Service.
STUDY DESIGN AND METHODS: Between 2000 and 2010, a total of 1071 cases of serious transfusion-related reactions were reported, of which 221 (21%) cases were TACO.
RESULTS: A total of 2,000,684 blood components were issued, with a TACO incidence of one in 9177. The TACO incidence per red blood cells, plasma, and platelet components issued was one in 8000, one in 16,000, and one in 57,884, respectively. The majority of cases (68%, n = 151) were elderly patients, while no sex difference was seen. Twenty-eight (13%) patients experienced severe morbidity; 31 (14%) deaths were reported, of which five (2%) were considered due to TACO and the other deaths considered due to and underlying conditions, which in most cases were cardiovascular (76%). An increased risk of mortality was found in patients on diuretics either before transfusion as part of their routine therapy or given as pretransfusion medication (odds ratio, 2.49; 95% confidence interval, 1.06-6.01). In 19 (21%) cases, TACO reaction was due to human error.
CONCLUSIONS: The strong association between TACO and human errors supports the role of hemovigilance and of adequate transfusion medicine teaching for preventing morbidity and mortality associated with TACO.
© 2014 AABB.
Lani Lieberman, Carolyn Maskens, Christine Cserti-Gazdewich, Mark Hansen, Yulia Lin, Jacob Pendergrast, Qi Long Yi, Jeannie Callum
A retrospective review of patient factors, transfusion practices, and outcomes in patients with transfusion-associated circulatory overload.
Transfus Med Rev. 2013 Oct;27(4):206-12. doi: 10.1016/j.tmrv.2013.07.002. Epub 2013 Sep 26.
Abstract/Text
Transfusion-associated circulatory overload (TACO) is a common yet underrecognized and underreported complication of transfusion associated with significant morbidity and mortality. The objective of this study was to examine patient and transfusion characteristics in a cohort of TACO cases. A retrospective medical record review of 100 consecutive TACO episodes reported at 2 academic centers was performed. Information related to demographics, medical history, radiologic and echocardiographic investigations, infusion practices, reaction features, management, and outcome were collected. Ninety-eight cases were accessible for review. A history of congestive heart failure (41%), renal dysfunction (44%), and age more than 70 years (56%) were common in TACO patients. Suboptimal fluid status management and inappropriate infusion practices were often seen (eg, verbal orders, double red cell transfusions, rapid infusion rates, lack or improper timing of preemptive diuretics). The median volume of blood ordered was 500 mL, and the median volume of crystalloid or colloid (preceding 24 hours) was 2200 mL. A physician order specifying the infusion rate was documented in 50% of transfusion orders. Preemptive diuretics were ordered in only 29% of cases, most commonly introduced midway or after the transfusion at a dose of furosemide 20 mg intravenously. After TACO, 18% of patients required transfer to the intensive care unit, 8% suffered a major complication, and 2% died. Suboptimal ordering and infusion practices may be contributing to the high incidence and severity of TACO. Research in TACO prevention strategies, such as slow rates of infusion and preemptive diuretics, is warranted.
© 2013.
Fanny Gosmann, Astrid Nørgaard, Maj-Britt Rasmussen, Charlotte Rahbek, Jens Seeberg, Tom Møller
Transfusion-associated circulatory overload in adult, medical emergency patients with perspectives on early warning practice: a single-centre, clinical study.
Blood Transfus. 2018 Feb;16(2):137-144. doi: 10.2450/2017.0228-16. Epub 2017 Jan 26.
Abstract/Text
BACKGROUND: Transfusion-associated circulatory overload is characterised by acute respiratory distress, tachycardia, increased blood pressure, acute pulmonary oedema and/or evidence of positive fluid balance occurring within 6 hours after transfusion. Transfusion-associated circulatory overload is a serious, underreported reaction, which makes this iatrogenic condition difficult to prevent. We present an audit of patients admitted to a medical emergency unit, aiming to investigate: (i) the incidence of transfusion-associated circulatory overload; and (ii) whether cases were reported to the haemovigilance system. The clinical implications are discussed within the frame of the Early Warning Score.
METHODS: We conducted a retrospective audit of electronic hospital medical records of patients receiving blood transfusion in a single medical emergency unit. Patients were admitted during a 6-month period and data on symptoms and vital signs were extracted from the records.
RESULTS: Of 4,353 consecutively admitted patients, 156 patients were transfused with a total of 411 blood components. The audit identified five cases of transfusion-associated circulatory overload (incidence 3.2%) and four cases of transfusion-associated dyspnoea. Vital signs and changes in dyspnoea and blood pressure were registered within the frame of the Early Warning Score, and one case was documented as being transfusion-related in the medical record. No cases were reported to the haemovigilance system.
DISCUSSION: The incidence of transfusion-associated circulatory overload in acute emergency patients was similar to that in other clinical studies. Lack of recognition and reporting was marked, even though changes in vital signs were monitored in the context of the Early Warning Score. This study points to a missing link in the transfusion chain, namely recognising the vital signs of circulatory overload during or shortly after transfusion as being a serious adverse transfusion reaction.
Michael Sarai, Aaron M Tejani
Loop diuretics for patients receiving blood transfusions.
Cochrane Database Syst Rev. 2015 Feb 16;(2):CD010138. doi: 10.1002/14651858.CD010138.pub2. Epub 2015 Feb 16.
Abstract/Text
BACKGROUND: Blood transfusions are associated with significant morbidity and mortality. Prophylactic administration of loop diuretics (furosemide, bumetanide, ethacrynic acid, or torsemide) is common practice, especially among people who are at risk for circulatory overload, pulmonary oedema or both.
OBJECTIVES: This review aimed to determine if the prophylactic administration of loop diuretics (furosemide, bumetanide, ethacrynic acid, or torsemide) provides a therapeutic advantage (that is, a favourable risk benefit ratio) in adults and children who are recipients of any blood product transfusion versus placebo, no treatment, or general fluid restriction measures.
SEARCH METHODS: We searched the Cochrane Renal Group's Specialised Register to 13 January 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review.
SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTs assessing a loop diuretic in patients receiving any blood transfusion were considered for inclusion.
DATA COLLECTION AND ANALYSIS: Two authors independently assessed study quality and extracted data. Study authors were contacted for additional information. Results were to be expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. Mean effect sizes were to be calculated using the random-effects models.
MAIN RESULTS: We included four studies that involved 100 participants. Furosemide was the only diuretic investigated in all four studies.None of the included studies assessed the clinically important outcomes noted in our protocol. The studies focused on various markers of respiratory function. An improvement in fraction of inspired oxygen (in favour of furosemide) was noted in one study. An improvement in pulmonary capillary wedge pressure (in favour of furosemide) was noted in two studies.
AUTHORS' CONCLUSIONS: There was insufficient evidence to determine whether premedicating people undergoing blood transfusion with loop diuretics prevents clinically important transfusion-related morbidity. Due to the continued use of prophylactic loop diuretics during transfusions, and because this review highlights the absence of evidence to justify this practice, well-conducted RCTs are needed. Given the high mortality, severe morbidity and increasing incidence of transfusion-associated circulatory overload, determining the therapeutic utility of pre-transfusion loop diuresis is an urgent need.
E Tseng, J Spradbrow, X Cao, J Callum, Y Lin
An order set and checklist improve physician transfusion ordering practices to mitigate the risk of transfusion-associated circulatory overload.
Transfus Med. 2016 Apr;26(2):104-10. doi: 10.1111/tme.12284. Epub 2016 Feb 10.
Abstract/Text
OBJECTIVES AND BACKGROUND: There are few studies of quality interventions to mitigate the risk of transfusion-associated circulatory overload (TACO). Our aim was to reduce TACO risk in patients admitted to internal medicine at our hospital, by addressing gaps in transfusion practice.
MATERIALS AND METHODS: A 3-month baseline audit of red blood cell (RBC) transfusion orders was conducted. An intervention consisting of a transfusion order set and physician checklist was developed and implemented based on identified gaps, followed by a 3-month post-intervention audit. Compliance with appropriateness criteria for RBC transfusion was ascertained, along with documentation of transfusion rate, diuretic usage and consent.
RESULTS: A total of 97 transfusion orders from 68 inpatients and 95 orders from 62 inpatients were audited in the baseline and post-intervention groups, respectively. Compliance with appropriateness criteria was similar pre- and post-intervention (87 versus 85%, P = 0·81). Specification of transfusion rate improved (84 versus 98%, P < 0·01), and diuretics were appropriately ordered more frequently for patients with TACO risk factors (37 versus 64%, P < 0·01). Timing of diuretics shifted from between or post-transfusion to pre-transfusion (35 versus 86%, P < 0·01), without increases in hypokalemia or acute kidney injury. No case of TACO was observed during the study. Documentation of specific risks discussed during consent discussion improved (4 versus 23%, P < 0·01).
CONCLUSION: A checklist and order set are tools that can improve the quality of transfusion orders by increasing the judicious use of pre-transfusion diuretics and augmenting the specification of transfusion rate. These interventions could be adapted to electronic order formats to improve transfusion safety.
© 2016 British Blood Transfusion Society.
Guangxi Li, Sonal Rachmale, Marija Kojicic, Khurram Shahjehan, Michael Malinchoc, Daryl J Kor, Ognjen Gajic
Incidence and transfusion risk factors for transfusion-associated circulatory overload among medical intensive care unit patients.
Transfusion. 2011 Feb;51(2):338-43. doi: 10.1111/j.1537-2995.2010.02816.x. Epub 2010 Aug 17.
Abstract/Text
BACKGROUND: Transfusion-associated circulatory overload (TACO) is a frequent complication of blood transfusion. Investigations identifying risk factors for TACO in critically ill patients are lacking.
STUDY DESIGN AND METHODS: We performed a 2-year prospective cohort study of consecutive patients receiving blood product transfusion in the medical intensive care unit (ICU) of the tertiary care institution. Patients were followed for development of transfusion-related complications. TACO was defined as acute hydrostatic pulmonary edema occurring within 6 hours of transfusion. In a nested case-control design, transfusion characteristics were compared between cases (TACO) and controls after matching by age, sex, and ICU admission diagnostic category. In a secondary analysis, patient characteristics before transfusion were compared between cases (TACO) and randomly selected controls.
RESULTS: Fifty-one of 901 (6%) transfused patients developed TACO. Compared with matched controls, TACO cases had a more positive fluid balance (1.4 L vs. 0.8 L, p = 0.003), larger amount of plasma transfused (0.4 L vs. 0.07 L, p = 0.007), and faster rate of blood component transfusion (225 mL/hr vs. 168 mL/hr, p = 0.031). In a secondary analysis comparing TACO cases and random controls, left ventricular dysfunction before transfusion (odds ratio [OR], 8.23; 95% confidence interval [CI], 3.36-21.97) and plasma ordered for the reversal of anticoagulant (OR, 4.31; 95% CI, 1.45-14.30) were significantly related to the development of TACO.
CONCLUSION: Volume of transfused plasma and the rate of transfusion were identified as transfusion-specific risk factors for TACO. Left ventricular dysfunction and fresh-frozen plasma ordered for the reversal of anticoagulant were strong predictors of TACO before the onset of transfusion.
© 2010 American Association of Blood Banks.
M A Popovsky
Transfusion and the lung: circulatory overload and acute lung injury.
Vox Sang. 2004 Jul;87 Suppl 2:62-5. doi: 10.1111/j.1741-6892.2004.00453.x.
Abstract/Text
Chester Andrzejewski, Mark A Casey, Mark A Popovsky
How we view and approach transfusion-associated circulatory overload: pathogenesis, diagnosis, management, mitigation, and prevention.
Transfusion. 2013 Dec;53(12):3037-47. doi: 10.1111/trf.12454. Epub 2013 Oct 28.
Abstract/Text
K C Anderson, H J Weinstein
Transfusion-associated graft-versus-host disease.
N Engl J Med. 1990 Aug 2;323(5):315-21. doi: 10.1056/NEJM199008023230506.
Abstract/Text
輸血用血液製剤の安全対策の導入効果と輸血によるHBV, HCV及びHIV感染のリスク．輸血情報1804-159日本赤十字社，2018.
H Takeda, K Matsubayashi, H Sakata, S Sato, T Kato, S Hino, K Tadokoro, H Ikeda
A nationwide survey for prevalence of hepatitis E virus antibody in qualified blood donors in Japan.
Vox Sang. 2010 Nov;99(4):307-13. doi: 10.1111/j.1423-0410.2010.01362.x.
Abstract/Text
BACKGROUND AND OBJECTIVES: In previous studies, we reported the transmission of hepatitis E virus (HEV) by transfusion, and the frequent detection of HEV markers in Japanese blood donors with elevated ALT levels. For the current study, we carried out a nationwide survey of the prevalence of IgG anti-HEV in qualified blood donors throughout Japan.
MATERIALS AND METHODS: The 12,600 samples from qualified blood donors were collected from seven blood centres (1800 per centre) representing nearly all regions of Japan. Samples were from age- and sex-matched blood donors who tested negative for all the current blood screening tests. The samples were screened using the in-house IgG anti-HEV ELISA. Sequentially, the positive samples were tested by the commercial IgG anti-HEV ELISA.
RESULTS: Of 12,600 samples, 431 (3·4%) were regarded as positive for IgG anti-HEV. The prevalence of IgG anti-HEV was higher in eastern Japan (5·6%) than in western Japan (1·8%) (P<0·001), and was also age-dependent and higher in men (3·9%) than in women (2·9%) (P=0·002).
CONCLUSION: The spread of the domestic infection of HEV was observed in qualified blood donors in Japan. A higher prevalence of IgG anti-HEV was observed in male donors, older donors and in donors residing in eastern Japan. Further studies are necessary to clarify the potential risk of transfusion-transmission of HEV in Japan.
© 2010 The Author(s). Vox Sanguinis © 2010 International Society of Blood Transfusion.
Yukihiko Kimura, Akihiko Gotoh, Seiichiro Katagiri, Yuji Hoshi, Shigeharu Uchida, Atsushi Yamasaki, Yoko Takahashi, Katsuyuki Fukutake, Toru Kiguchi, Kazuma Ohyashiki
Transfusion-transmitted hepatitis E in a patient with myelodysplastic syndromes.
Blood Transfus. 2014 Jan;12(1):103-6. doi: 10.2450/2013.0081-13. Epub 2013 Oct 2.
Abstract/Text
坪内博仁，熊田博光，清澤研道ら：免疫抑制・化学療法により発症するB 型肝炎対策―厚生労働省「難治性の肝・胆道疾患に関する調査研究」班 劇症肝炎分科会および「肝硬変を含めたウイルス性肝疾患の治療の標準化に関する研究」班合同報告―． 肝臓 2009;50:38-42.
医療機関での輸血後感染症に関する全数調査について．輸血情報0804-112日本赤十字社，2008.
血液製剤等に係る遡及調査ガイドライン（改訂版）平成20年12月26日一部改正．血液製剤の使用にあたって 第4版．じほう，2009；103-153．.
Jong Wook Lee
Iron chelation therapy in the myelodysplastic syndromes and aplastic anemia: a review of experience in South Korea.
Int J Hematol. 2008 Jul;88(1):16-23. doi: 10.1007/s12185-008-0117-0. Epub 2008 Jul 5.
Abstract/Text
Emerging clinical data indicate that transfusion-dependent patients with bone marrow-failure syndromes (BMFS) are at risk of the consequences of iron overload, including progressive damage to hepatic, endocrine, and cardiac organs. Despite the availability of deferoxamine (DFO) in Korea since 1998, data from patients with myelodysplastic syndromes, aplastic anemia, and other BMFS show significant iron overload and damage to the heart and liver. The recent introduction of deferasirox, a once-daily, oral iron chelator, may improve the availability of iron chelation therapy to iron-overloaded patients, and improve compliance in patients who may otherwise find adherence to the DFO regimen difficult.
Takahiro Suzuki, Masao Tomonaga, Yasushi Miyazaki, Shinji Nakao, Kazuma Ohyashiki, Itaru Matsumura, Yutaka Kohgo, Yoshiro Niitsu, Seiji Kojima, Keiya Ozawa
Japanese epidemiological survey with consensus statement on Japanese guidelines for treatment of iron overload in bone marrow failure syndromes.
Int J Hematol. 2008 Jul;88(1):30-5. doi: 10.1007/s12185-008-0119-y. Epub 2008 Jun 27.
Abstract/Text
Many patients with bone marrow failure syndromes need frequent transfusions of red blood cells, and most of them eventually suffer from organ dysfunction induced by excessively accumulated iron. The only way to treat transfusion-induced iron overload is iron chelating therapy. However, most patients have not been treated effectively because daily/continuous administration of deferoxamine is difficult for outpatients. Recently, a novel oral iron chelator, deferasirox, has been developed, and introduction of the drug may help many patients benefit from iron chelation therapy. In this review, we will discuss the current status of iron overload in transfusion-dependent patients, and the development of Japanese guidelines for the treatment of iron overload in Japan, which were established by the National Research Group on Idiopathic Bone Marrow Failure Syndromes in Japan.
Maria Domenica Cappellini, John Porter, Amal El-Beshlawy, Chi-Kong Li, John F Seymour, Mohsen Elalfy, Norbert Gattermann, Stéphane Giraudier, Jong-Wook Lee, Lee Lee Chan, Kai-Hsin Lin, Christian Rose, Ali Taher, Swee Lay Thein, Vip Viprakasit, Dany Habr, Gabor Domokos, Bernard Roubert, Antonis Kattamis, EPIC Study Investigators
Tailoring iron chelation by iron intake and serum ferritin: the prospective EPIC study of deferasirox in 1744 patients with transfusion-dependent anemias.
Haematologica. 2010 Apr;95(4):557-66. doi: 10.3324/haematol.2009.014696. Epub 2009 Nov 30.
Abstract/Text
UNLABELLED: Background Following a clinical evaluation of deferasirox (Exjade) it was concluded that, in addition to baseline body iron burden, ongoing transfusional iron intake should be considered when selecting doses. The 1-year EPIC study, the largest ever investigation conducted for an iron chelator, is the first to evaluate whether fixed starting doses of deferasirox, based on transfusional iron intake, with dose titration guided by serum ferritin trends and safety markers, provides clinically acceptable chelation in patients (aged >or=2 years) with transfusional hemosiderosis from various types of anemia.
DESIGN AND METHODS: The recommended initial dose was 20 mg/kg/day for patients receiving 2-4 packed red blood cell units/month and 10 or 30 mg/kg/day was recommended for patients receiving less or more frequent transfusions, respectively. Dose adjustments were based on 3-month serum ferritin trends and continuous assessment of safety markers. The primary efficacy end-point was change in serum ferritin after 52 weeks compared with baseline.
RESULTS: The 1744 patients enrolled had the following conditions; thalassemia (n=1115), myelodysplastic syndromes (n=341), aplastic anemia (n=116), sickle cell disease (n=80), rare anemias (n=43) and other transfused anemias (n=49). Overall, there was a significant reduction in serum ferritin from baseline (-264 ng/mL; P<0.0001), reflecting dosage adjustments and ongoing iron intake. The most common (>5%) adverse events were gastrointestinal disturbances (28%) and skin rash (10%). Conclusions Analysis of this large, prospectively collected data set confirms the response to chelation therapy across various anemias, supporting initial deferasirox doses based on transfusional iron intake, with subsequent dose titration guided by trends in serum ferritin and safety markers (clinicaltrials.gov identifier: NCT00171821).
L J Anderson, S Holden, B Davis, E Prescott, C C Charrier, N H Bunce, D N Firmin, B Wonke, J Porter, J M Walker, D J Pennell
Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload.
Eur Heart J. 2001 Dec;22(23):2171-9.
Abstract/Text
AIMS: To develop and validate a non-invasive method for measuring myocardial iron in order to allow diagnosis and treatment before overt cardiomyopathy and failure develops.
METHODS AND RESULTS: We have developed a new magnetic resonance T2-star (T2*) technique for the measurement of tissue iron, with validation to chemical estimation of iron in patients undergoing liver biopsy. To assess the clinical value of this technique, we subsequently correlated myocardial iron measured by this T2* technique with ventricular function in 106 patients with thalassaemia major. There was a significant, curvilinear, inverse correlation between iron concentration by biopsy and liver T2* (r=0.93, P<0.0001). Inter-study cardiac reproducibility was 5.0%. As myocardial iron increased, there was a progressive decline in ejection fraction (r=0.61, P<0.001). All patients with ventricular dysfunction had a myocardial T2* of <20 ms. There was no significant correlation between myocardial T2* and the conventional parameters of iron status, serum ferritin and liver iron. Multivariate analysis of clinical parameters to predict the requirement for cardiac medication identified myocardial T2* as the most significant variable (odds ratio 0.79, P<0.002).
CONCLUSIONS: Myocardial iron deposition can be reproducibly quantified using myocardial T2* and this is the most significant variable for predicting the need for ventricular dysfunction treatment. Myocardial iron content cannot be predicted from serum ferritin or liver iron, and conventional assessments of cardiac function can only detect those with advanced disease. Early intensification of iron chelation therapy, guided by this technique, should reduce mortality from this reversible cardiomyopathy.
P Kirk, M Roughton, J B Porter, J M Walker, M A Tanner, J Patel, D Wu, J Taylor, M A Westwood, L J Anderson, D J Pennell
Cardiac T2* magnetic resonance for prediction of cardiac complications in thalassemia major.
Circulation. 2009 Nov 17;120(20):1961-8. doi: 10.1161/CIRCULATIONAHA.109.874487. Epub 2009 Oct 2.
Abstract/Text
BACKGROUND: The goal of this study was to determine the predictive value of cardiac T2* magnetic resonance for heart failure and arrhythmia in thalassemia major.
METHODS AND RESULTS: We analyzed cardiac and liver T2* magnetic resonance and serum ferritin in 652 thalassemia major patients from 21 UK centers with 1442 magnetic resonance scans. The relative risk for heart failure with cardiac T2* values <10 ms (compared with >10 ms) was 160 (95% confidence interval, 39 to 653). Heart failure occurred in 47% of patients within 1 year of a cardiac T2* <6 ms with a relative risk of 270 (95% confidence interval, 64 to 1129). The area under the receiver-operating characteristic curve for predicting heart failure was significantly greater for cardiac T2* (0.948) than for liver T2* (0.589; P<0.001) or serum ferritin (0.629; P<0.001). Cardiac T2* was <10 ms in 98% of scans in patients who developed heart failure. The relative risk for arrhythmia with cardiac T2* values <20 ms (compared with >20 ms) was 4.6 (95% confidence interval, 2.66 to 7.95). Arrhythmia occurred in 14% of patients within 1 year of a cardiac T2* of <6 ms. The area under the receiver-operating characteristic curve for predicting arrhythmia was significantly greater for cardiac T2* (0.747) than for liver T2* (0.514; P<0.001) or serum ferritin (0.518; P<0.001). The cardiac T2* was <20 ms in 83% of scans in patients who developed arrhythmia.
CONCLUSIONS: Cardiac T2* magnetic resonance identifies patients at high risk of heart failure and arrhythmia from myocardial siderosis in thalassemia major and is superior to serum ferritin and liver iron. Using cardiac T2* for the early identification and treatment of patients at risk is a logical means of reducing the high burden of cardiac mortality in myocardial siderosis. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00520559.
Dudley J Pennell, John B Porter, Maria Domenica Cappellini, Lee Lee Chan, Amal El-Beshlawy, Yesim Aydinok, Hishamshah Ibrahim, Chi-Kong Li, Vip Viprakasit, Mohsen S Elalfy, Antonis Kattamis, Gillian Smith, Dany Habr, Gabor Domokos, Bernard Roubert, Ali Taher
Deferasirox for up to 3 years leads to continued improvement of myocardial T2* in patients with β-thalassemia major.
Haematologica. 2012 Jun;97(6):842-8. doi: 10.3324/haematol.2011.049957. Epub 2012 Jan 22.
Abstract/Text
BACKGROUND: Prospective data on cardiac iron removal are limited beyond one year and longer-term studies are, therefore, important.
DESIGN AND METHODS: Seventy-one patients in the EPIC cardiac substudy elected to continue into the 3(rd) year, allowing cardiac iron removal to be analyzed over three years.
RESULTS: Mean deferasirox dose during year 3 was 33.6 ± 9.8 mg/kg per day. Myocardial T2*, assessed by cardiovascular magnetic resonance, significantly increased from 12.0 ms ± 39.1% at baseline to 17.1 ms ± 62.0% at end of study (P<0.001), corresponding to a decrease in cardiac iron concentration (based on ad hoc analysis of T2*) from 2.43 ± 1.2 mg Fe/g dry weight (dw) at baseline to 1.80 ± 1.4 mg Fe/g dw at end of study (P<0.001). After three years, 68.1% of patients with baseline T2* 10 to <20 ms normalized (≥ 20 ms) and 50.0% of patients with baseline T2* >5 to <10 ms improved to 10 to <20 ms. There was no significant variation in left ventricular ejection fraction over the three years. No deaths occurred and the most common investigator-assessed drug-related adverse event in year 3 was increased serum creatinine (n = 9, 12.7%).
CONCLUSIONS: Three years of deferasirox treatment along with a clinically manageable safety profile significantly reduced cardiac iron overload versus baseline and normalized T2* in 68.1% (32 of 47) of patients with T2* 10 to <20 ms.
Eli Konen, Husam Ghoti, Orly Goitein, Asher Winder, Tammi Kushnir, Yael Eshet, Eliezer Rachmilewitz
No evidence for myocardial iron overload in multitransfused patients with myelodysplastic syndrome using cardiac magnetic resonance T2 technique.
Am J Hematol. 2007 Nov;82(11):1013-6. doi: 10.1002/ajh.20980.
Abstract/Text
The method of cardiovascular T2 magnetic resonance imaging (MRI) allows in vivo estimation of iron in the heart and liver and was used to measure the degree of iron overload in 10 transfused MDS patients (average 90 blood units) and in 3 patients with congenital hemolytic anemia. In all MDS patients iron overload was found in the liver but not in the heart. Patients with congenital anemias had iron in both organs despite iron chelation. It is possible that in MDS more time and more transfusions are required to induce iron accumulation in the myocardium. Therefore, cardiac MRI may serve as a diagnostic tool to assess if and when iron chelation is indicated.
(c) 2007 Wiley-Liss, Inc.
