Red cell transfusion has an important role in the management of sickle cell disease (SCD) in both emergency and elective settings. However, because of insufficient randomised data, it is not always clear when or how to use red cell transfusion. A companion guideline, Guidelines on red cell transfusion in sickle cell disease Part I: principles and laboratory aspects, addresses the general principles of transfusion practice in SCD (Davis et al, 2016, BJH in press). The present guideline examines current available evidence on indications for transfusion in SCD. This may not be appropriate for all clinical scenarios and clinical decisions must be based on individual patient considerations. In both guidelines, the term sickle cell disease refers to all genotypes of the disease, and sickle cell anaemia to the homozygous state (SS). The writing group was selected by the British Committee for Standards in Haematology (BCSH) General Haematology and Transfusion Task Forces with input from other experts in Haemoglobinopathy. PubMed, MEDLINE and Embase were searched systematically for publications on red cell transfusion in SCD from 1960 to May 2016 using a combination of search terms related to: (i) sickle cell (including sickle, sickle cell, sickle cell disease, sickle cell anaemia, haemoglobin SC disease, sickle cell crisis), (ii) transfusion (including transfusion, blood transfusion, red cell transfusion), (iii) transfusion indications (including aplastic crisis, parvovirus, sequestration (splenic, liver, hepatic), acute chest syndrome (ACS), stroke, silent cerebral infarcts, multi-organ failure, girdle syndrome, intrahepatic cholestasis, surgery, pregnancy, and (iv) transfusion complications (including alloimmunisation, haemolytic transfusion reactions, iron overload, viral infections). Opinions were also sought from experienced haematologists with a special interest in the care of SCD patients. The guideline was reviewed by the members of the General Haematology Task Force of the BCSH prior to being sent to a sounding board of approximately 50 UK haematologists, the BCSH and the British Society for Haematology (BSH) Committee. Comments were incorporated where appropriate. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) nomenclature was used to evaluate levels of evidence and to assess the strength of recommendations. The GRADE criteria are specified in the BCSH guidance pack http://www.bcshguidelines.com/BCSH_PROCESS/EVIDENCE_LEVELS_AND_GRADES_OF_RECOMMENDATION/43_GRADE.html and the GRADE working group website http://www.gradeworkinggroup.org. Consideration of sickle cell patients for transfusion, particularly long-term regimens, should weigh up the potential benefits against potential risks (Grade 1C). Regular transfusion to maintain HbS <30% should be offered as initial treatment to children with SS or S/βo thalassaemia aged 2–16 years judged to be at high risk for a first stroke on the basis of Transcranial Doppler ultrasonography (TCD) (Grade 1A). Hydroxycarbamide treatment should be considered for the primary prevention of stroke in children with sickle cell anaemia and high TCD velocities but not severe Magnetic Resonance Angiography (MRA)-defined cerebral vasculopathy after an initial period of transfusions (Grade 1A). The duration of the initial period of transfusion should be tailored to the individual patient but should be for a minimum of 1 year; the transition to hydroxycarbamide should be done gradually and transfusion should be withdrawn after the hydroxycarbamide has been escalated to the maximum tolerated dose. Regular transfusion to maintain HbS <30% effectively reduces the incidence of recurrence of cerebral infarction (defined as a stroke or a new or enlarged silent cerebral infarct) in children with sickle cell anaemia and S/βo thalassaemia aged 5–15 years. Treatment options including transfusion should be discussed with families of children who are found to silent cerebral Transfusion should be offered to children who are to be at risk for recurrence of infarction after of benefits and risks (Grade 1A). transfusion to maintain HbS <30% is for the prevention of stroke to sickle cell disease in both children and (Grade or children who present with or of acute stroke should be to maintain HbS <30% with stroke to sickle cell disease should transfusions long-term (Grade transfusion is for SS patients (Grade 1A). transfusion is for SC patients (Grade 1C). Transfusion is for sickle cell patients of all genotypes (Grade 1C). sickle cell patients with other genotypes should be and of surgery, and a management should be to the for transfusion (Grade 1C). care should be to all of including and and are in all sickle cell patients (Grade 1C). patients emergency surgery, the and of the should be in the of transfusion. transfusion should be not in to transfusion is to an to surgery, it is to to to the patient or (Grade Transfusion is and may be in acute sickle complications as aplastic and severe acute chest syndrome (Grade Transfusion should be considered in the patient with acute multi-organ failure, syndrome (Grade and patients with severe (Grade should be discussed with the Transfusion for other of acute anaemia individual and should be discussed with the Transfusion may be by transfusion or on clinical the guidance of the (Grade transfusion is not for sickle pregnancy, but should be considered for on long-term transfusions for stroke prevention or for of severe sickle complications should with transfusions (Grade Transfusion should be considered in with anaemia or with acute SCD complications chest syndrome, stroke (Grade In selected patients with severe disease, blood transfusion be in disease, in in Hydroxycarbamide is as first treatment for prevention of acute chest syndrome or with chest syndrome (Grade 1A). Regular transfusion should be considered for patients treatment or for hydroxycarbamide is or not (Grade Transfusion is not to state anaemia has not a period of to levels with (Grade 1C). is evidence transfusion the duration of a Transfusion is not in but should be considered is a in from or to or complications (Grade 1C). The of transfusion to acute has not been in randomised patients a or general may a transfusion. should be discussed with the (Grade Transfusion has been to the incidence of in children transfusions to maintain HbS <30% for prevention of recurrence of cerebral infarction (Grade 1A). However, is on the use of transfusion for the of in transfusion is considered for indications where is insufficient evidence for or disease, sickle cell a should be in with the and should be considered on (Grade The indications for red cell transfusion in SCD from in transfusion be to where use is or A of risk and of red cell transfusion should be for or The indications be in of anaemia is the and where of sickle haemoglobin may be appropriate In both transfusion is as of the management of an acute of or for the prevention or management of disease transfusions may be or be of a long-term transfusion The to patient with SCD should be by at with the appropriate elective transfusions should be by or in with a should be the state in SCD is the of the of haemoglobin and is not in an or transfusion. anaemia in SCD has been as a in haemoglobin the state et al, the of the anaemia is for appropriate haemoglobin sequestration and should of transfusion, and blood and to should the and of anaemia to should be in patients with acute of state anaemia with and is to with et al, et al, et al, is severe with a of approximately state et al, et al, transfusion to state is all is to maintain the of blood et al, et al, et al, of to of et al, the to the state patients be to at the of clinical with of and of from et al, may present with and including acute et al, et al, or acute including stroke et al, et al, In transfusion after initial transfusion may be appropriate. sequestration is by an acute in and et al, in severe may in and et al, et al, sequestration in the first years of et al, the has it may particularly in with disease as SC disease in infarction may not in et al, management of transfusion to the to state et al, Transfusion with emergency or and blood may be to and anaemia in In transfusion of red cell to the haemoglobin to the state is to the and and Transfusion of of red levels should be to the risk of when red to the et al, et al, patients with sequestration should be discussed with the is a high recurrence et al, et al, and is in patients who or is not with an long-term risk of or et al, Regular transfusion to maintain HbS <30% not the risk of recurrence or for after sequestration to clinical in a et al, sequestration with acute with a in and in the to transfusion or transfusion et al, et al, has been et al, in acute the of red the may acute and transfusion of of red is A haemolytic transfusion or must be in patients with acute anaemia of a transfusion et al, et al, et al, may be because it is the are to a The and management of been in the companion guideline, Guidelines on red cell transfusion in sickle cell disease Part I: principles and laboratory (Davis et al, BJH in press). of should be discussed with the both for on management and because of the long-term of and risk of Transfusion is not in to state transfusion is not and to as the Transfusion may be is a in from or 50 or complications acute in to is in acute sickle as et al, and acute multi-organ syndrome et al, The role of transfusion in is in chest syndrome and multi-organ transfusion is for acute blood anaemia hydroxycarbamide transfusion is to an acute as acute aplastic or the of the et al, et al, et al, et al, et al, The of are of the or of hydroxycarbamide but may not for et al, et al, In patients with sickle cell a of haemoglobin as the disease and the anaemia may be severe to transfusion to state haemoglobin is for patients with acute of anaemia as a of aplastic or sequestration (Grade should be in sequestration because of the risk of to the of red the Transfusion is not in but should be considered is anaemia, or complications (Grade 1C). Transfusion for other of acute anaemia individual and should be discussed with the (Grade 1C). Transfusion to the is where is evidence of acute and a and should be in patients with with clinical of et al, of and with blood transfusion be and to acute a is to to blood available of other transfusion and transfusion with in et al, et al, A transfusion for a is in to acute in SS patients with it is in the et al, and should be considered in patients with a on but may also be at severe of on the individual and clinical or the are et al, transfusion is in patients with of severe who to to initial transfusion, or patients with a where is for transfusion et al, et al, et al, is evidence as to the transfusion. In a of is but should be by the clinical et al, Guidelines for the and management of are available from the BCSH et al, The of transfusion and the of transfusion in acute stroke not been in randomised transfusion to HbS to <30% is for acute stroke Society transfusion should be the stroke has in the of severe acute anaemia in aplastic are on the of transfusion on the stroke red cell transfusion may and by and to the of an is evidence from a transfusion for a first stroke at the of stroke is with a risk of a stroke to transfusion et al, is important to the and to the at a of as a high with may the for acute stroke care in the UK patients with stroke to be to stroke stroke must are in to care for SCD patients with stroke who are to stroke emergency transfusion be in a of care has not been for must with the of SCD children with acute stroke appropriate including transfusion and are to the use of red cell transfusion in the acute management of stroke or to recurrence and it is should be sought for individual This is a severe syndrome may a severe is particularly to in patients with SCD and a high haemoglobin The patient with multi-organ with in and and The syndrome to transfusion et al, This is a severe sequestration syndrome by or and sequestration in the and et al, in the and is in the present with and and to with a silent and of on to of the chest blood transfusion is a of and transfusion or transfusion may be in anaemia, blood and the clinical This is a and with et al, et al, of the and in is a high from or is treatment but transfusion to be The treatment of in acute is by the of to the et al, This initial should not be a transfusion is transfusion been for acute management of in randomised and evidence of of or duration of has been et al, et al, management is initial are not et al, for the of acute a general the patient may from transfusion, as with other et al, patients not to initial may be from transfusion to should patients are to patients must be discussed with the with to transfusion Transfusion is in of acute chest syndrome with Transfusion may be by or transfusion on clinical the guidance of the (Grade or children with or of acute stroke should be to sickle haemoglobin <30% with stroke to sickle cell disease should transfusions (Grade Transfusion should be considered in the patient with acute multi-organ failure, syndrome (Grade and patients with severe (Grade should be discussed with the The of transfusion to acute has not been in randomised patients a or general may a transfusion. should be discussed with the (Grade The to transfusion are for the primary prevention of stroke et al, and prevention of silent cerebral in et al, is also evidence for the of transfusions in stroke in children et al, et al, transfusion has been for a of including prevention of and chest In of is also evidence of of hydroxycarbamide et al, et al, and transfusion should be where hydroxycarbamide is or transfusion is the of stroke, the to assess should be and the risks and benefits for the patient of transfusion should be to transfusion should be by the red cell transfusion is the of treatment for the primary and prevention of stroke to SCD. for the of transfusion for primary stroke prevention is available for children but the principles may be for patients Regular red cell transfusion to maintain HbS <30% is for the primary prevention of stroke in children with SS or S/βo thalassaemia with TCD velocities of in the or cerebral in et al, Regular red cell transfusion the risk of an initial stroke by et al, This was in the in where children transfusions were were to a stroke or to to TCD velocities who on transfusion The role of hydroxycarbamide in TCD velocities in children severe cerebral vasculopathy or prior who transfusions for at 1 for primary stroke prevention has been in the TCD to et al, In randomised hydroxycarbamide at maximum tolerated was to transfusions after patients randomised to hydroxycarbamide been transfusions This hydroxycarbamide is to transfusions for the of TCD velocities and be used as a to primary stroke after of initial transfusion Transfusion to maintain HbS <30% should be offered to children at high risk of stroke Transcranial Doppler (TCD) Transfusion is the initial treatment to stroke in children (Grade 1A). Hydroxycarbamide treatment should be considered for the primary prevention of stroke in children with high TCD velocities but not severe cerebral vasculopathy after an initial period of transfusion of at 1 (Grade 1A). The duration of the initial period of transfusion should be tailored to the individual the transition to hydroxycarbamide should be done gradually and transfusion should be withdrawn after the hydroxycarbamide has been escalated to the maximum tolerated dose. The role of transfusion in the management of children with sickle cell anaemia aged 5–15 years with silent cerebral was in the et al, In randomised children with SS or S/βo thalassaemia with silent cerebral and or TCD velocities were randomised to transfusions to a of and HbS <30% or care for years. The primary was recurrence of as a stroke, or new or enlarged silent cerebral The group a risk of recurrence of infarction of to the was to a in stroke incidence a in silent by The a Magnetic Resonance of the to children who may from or et al, However, is to in children years the group in the of silent cerebral Treatment options including transfusion should be discussed with families of children who are found to silent cerebral Transfusion should be offered to children who are as being at risk for recurrence of infarction after of benefits and risks (Grade 1A). The risk of stroke in children with SCD is In a of patients with a of or the recurrence was a with of the of the initial et al, been randomised the use of transfusion to for prevention of stroke in SCD. et al, et al, et al, et al, and et al, et al, all a clear of transfusion in the risk of recurrence in patients who or of cerebral In the to a transfusion to HbS <30% with hydroxycarbamide for the of stroke prevention and of iron overload, were of stroke in the patients with in the et al, The was because the stroke risk in the hydroxycarbamide was the it was not by a in iron the transfusion and a to children with sickle cell anaemia, stroke and iron the risk of stroke is not by transfusions et al, et al, et al, transfusions to maintain HbS <30% the to stroke recurrence in children with SCD. is evidence from a patients on transfusion for stroke prevention may be on a of HbS with risk of stroke been for at years after the initial stroke et al, transfusion to maintain HbS <30% is for the prevention of stroke to sickle cell disease in children (Grade with sickle cell anaemia are at risk of and the risk of stroke is after the of stroke is in the group et al, TCD has not been in and is for systematically stroke to evaluate the of transfusion for primary stroke prevention in SCD not been are on the management of patients been on long-term transfusions for primary stroke prevention the transition and of patients is a for individual and with and should the benefits and risks of on transfusion or with as or may be the initial of sickle cell disease, should be for other on transfusion for stroke prevention in SCD is et al, the risk of is to be high practice is to transfusions in who a stroke to SCD Society transfusion to maintain HbS <30% is for the prevention of stroke to sickle cell disease in (Grade The duration of transfusion is from the patients who were on transfusion for a up period of for primary stroke prevention a stroke risk patients who transfusions after The of the hydroxycarbamide is and to blood transfusions for primary stroke prevention in children severe cerebral vasculopathy or prior who been on transfusion for at a et al, However, the not the duration of transfusions prior to the to the duration of initial period of transfusions is on a patients who a stroke, the risk of stroke is in the first years after the initial et al, et al, et al, et al, a HbS <30% is important The benefits of transfusions period are stroke has been of transfusions in of children who been on a transfusion for as as years et al, transfusion for stroke prevention may to Society but the to transfusions should be tailored to the of individual it should be reviewed and must be discussed with the patient has been where the stroke has in the of acute aplastic crisis), transfusions may be after years is at Transfusion is the initial treatment of for children at high risk of stroke based on TCD (Grade 1A). is severe cerebral vasculopathy or prior of hydroxycarbamide may be offered to children after at 1 of transfusions (Grade but the duration of transfusions should be tailored to the individual transfusion should be offered to children and who a stroke to sickle cell disease (Grade chest syndrome is a of SCD being a risk for in SS patients years et al, et al, and of patients et al, transfusion is in incidence and to et al, et al, In the was in with patients with an incidence of et al, However, is a clear of hydroxycarbamide for prevention et al, et al, transfusion should be considered hydroxycarbamide is or Hydroxycarbamide is as first treatment for acute chest syndrome or Regular transfusion should be considered for patients treatment or for it is (Grade The of sickle cell is a of disease SS patients who are to a because of are at risk of et al, and high are also with a et al, transfusion may be of in patients with In a long-term blood transfusion the for from to patient In the the for in patients was for patients on care patient et al, In the incidence of were by transfusion with an incidence of et al, However, hydroxycarbamide is in the of and in both and children et al, et al, and et al, hydroxycarbamide is the first for patients with with transfusion being for who not or in hydroxycarbamide is by or transfusion, should be considered in patients with where hydroxycarbamide is or (Grade Transfusion has been used in a of sickle cell related where clinical or In patients with disease, transfusion may be considered in disease, in a and Transfusion has also been used in patients in the et al, et al, transfusion in the treatment of with the of and and and has been for The incidence of and was by transfusion in the randomised with incidence of and et al, but in the management of patients with disease has not been in randomised Transfusion has been used for other including et al, et al, and sickle et al, et al, In the from transfusion has but must Transfusion for indications where evidence is should be based on a after (Grade and particularly transfusion reduces the risk of complications et al, et al, should be to all of care including and as as and and is to should be in where is to transfusion, the to This has been with insufficient randomised on in practice in et al, and in other been both of transfusion et al, et al, et al, and transfusion et al, et al, et al, et al, A transfusion was with a of complications for SS patients and for SC patients at all risk levels et al, However, not all patients should be the chest syndrome and but randomised to or transfusion et al, et et et risk risk et of et transfusion transfusion and transfusion et of et transfusion transfusion and transfusion et of et transfusion transfusion and transfusion et et et 50 transfusion transfusion et et transfusion in of and 1 and 1 The evidence to transfusion from the Transfusion in et al, This was a randomised in a of SS and thalassaemia patients risk and risk were to transfusion or transfusion transfusion transfusion to HbS et al, of risk was in with the of criteria et al, important complications and were found in SS and to patients and The was for of all in of patients with in patients. or transfusion was in the patients who not been et al, the of the at was the evidence to transfusion in SS patients and In a of SS and patients et al, a transfusion to haemoglobin was to be as as transfusion to haemoglobin and HbS <30% in complications and was with a risk of However, it must be the of transfusion was not and of the patients transfusion. in of patients in the transfusion was the for a of including transfusion. in the transfusion of the patients transfusion the transfusion was as as transfusion. The of or transfusion was not in the where the transfusion was transfusion or transfusion to a of and HbS et al, of patients transfusion, for the of a transfusion in complications for the in the is not to the of of transfusion and transfusion should be tailored to the individual as the of surgery, the of the SCD and patients may from transfusion, of transfusion in for sickle genotypes other However, it is to transfusion for and risk is to a of transfusion should be considered for patients surgery, patients with severe SCD and with for the role of transfusion in emergency is In the on in patients of were emergency et al, all were patients and were of SS and of as were or of SS and of the for were for elective and emergency it is not to assess the on transfusion on for SCD patients emergency in in were for patients emergency et al, In a where transfusion was used and et al, in patients emergency it is not clear patients were The important is to not emergency because of transfusion. A is to a transfusion to patients who and to with the is and the is it is to to are to the patient or is a of evidence to SC and other sickle a for transfusion in the incidence of sickle complications for SC patients at all levels of risk et al, SC patients of cell complications and patients. A transfusion was for risk particularly et al, The has evidence for the of transfusion for SS patients with a of elective et al, The may not be to other However, on the basis of the it is transfusion to an of be considered a in SS elective or as in the et al, other patients it is is judged on in with the Transfusion should be considered when the risk of chest or is but has to be in Transfusion is also for with and and in or The of transfusion an but available evidence transfusion is not to transfusion in to et al, et al, transfusion is for patients surgery, has not been in transfusion transfusion to or is for SS patients and (Grade 1A). transfusion is for all patients with SS (Grade 1C). transfusion is for patients with SC risk and (Grade 1C). other patients should be and of surgery, and a management should be to the for transfusion (Grade 1C). patients emergency surgery, the and of the should be in the of transfusion. transfusion not in to surgery, transfusion should be to a of the is and risk is but transfusion in an to surgery, it is to to are to the patient or (Grade 1C). cell disease in is with an risk of both and complications et al, et al, et al, et al, complications and as and an of et al, et al, complications and of et al, et al, In a of in of and and were to care et al, is a randomised SS who were or transfusion in the first or HbS to a group of SS who transfusion for or et al, This found a in the incidence of and in other complications in the group transfusions but in and complications or the were in a group of SC and thalassaemia who were for or In of the transfusions was not to patients with SCD or and use of transfusions in was not However, a of including and high risk of et al, with evidence for a of transfusion et al, et al, et al, et al, et al, et al, not et al, et al, The by et a for complications in the in patients on the to transfusions from the of in SS patients. In a high of sickle and other severe sickle complications a of transfusions to maintain HbS from to for all sickle patients et al, but was not transfusion for A evidence from of other a in the of transfusion clear transfusion with to However, the of a and and the randomised by et transfusion is with a in and the of the et al, a of the and data, the use of transfusion is a with a of severe as and stroke, on transfusion prior to pregnancy, and with sickle cell or of anaemia pregnancy, should transfusion Society transfusion should also be considered for with other or or with a should be in with SCD is and care is to The of care is management by and haematologists who are experienced in the care of SCD patients. transfusion is not for sickle pregnancy, but should be considered for on long-term transfusions for stroke prevention or for of severe sickle complications should with transfusions (Grade Transfusion should be considered in with anaemia or with acute SCD complications chest syndrome, stroke (Grade This guideline be reviewed years of of the the and in is to be and at the of to the the British Society for Haematology the for the of of the a of were in evidence and writing the are to for the

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