Blood transfusion usage among adults with sickle cell disease a single institution experience over ten years

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1 research paper Blood transfusion usage among adults with sickle cell disease a single institution experience over ten years Emma Drasar, 1,2 Norris Igbineweka, 1 Nisha Vasavda, 1 Matthew Free, 2 Moji Awogbade, 2 Marlene Allman, 2 Aleksandar Mijovic 2 and Swee Lay Thein 1,2 1 Molecular Haematology, Division of Gene and Cell Based Therapy, King s College London School of Medicine, and 2 Haematological Medicine, King s College Hospital, Denmark Hill, London, UK Received 14 July 2010; accepted for publication 9 September 2010 Correspondence: Swee Lay Thein, King s College London School of Medicine, The James Black Centre, 125 Coldharbour Lane, London SE5 9NU, UK. sl.thein@kcl.ac.uk Summary Transfusion of red blood cells is a major therapeutic option in sickle cell disease (SCD). There is strong evidence for its efficacy, particularly in primary and secondary stroke prevention in children, however, its use in other areas remains controversial. This study assessed the patterns of transfusion in the adult cohort attending King s College Hospital over a 10-year period, from 2000 to Total blood usage has increased significantly (P = 0Æ006) during this time, with 78% of the blood received by only 6% of the patients. The increase is explained by increased automated red cell exchange and increased usage for planned and acute transfusions for sickle-related complications. Keywords: blood transfusion, sickle cell disease, iron overload. Sickle cell disease (SCD) is the most prevalent inherited blood condition worldwide (Modell & Darlison, 2008; Weatherall, 2010). In the UK and northern Europe SCD numbers are growing faster than any other serious genetic disease; newborn screening identified more than 350 babies born in the 2007/ 2008 year (NHS sickle cell and thalassaemia screening programme 2009) with an estimated affected individuals in the UK. Currently there are two main therapeutic options in the management of sickle cell disease hydroxycarbamide and blood transfusion (Claster & Vichinsky, 2003). Transfusion of normal red blood cells provides benefit by correcting the low-oxygen capacity caused by the anaemia as well as improving microvascular perfusion by reducing the proportion of sickle red cells in circulation. Regular blood transfusion also suppresses endogenous erythropoiesis and the production of sickle haemoglobin. Although the clinical benefits of blood transfusion for patients with SCD have long been recognized, complications associated with transfusion have limited its use. With improved red cell phenotyping and matching for transfusion, more sensitive microbiological testing of blood donors, and development of iron chelating agents, blood transfusion usage in the treatment of SCD appears to be increasing. The use of transfusion in secondary prevention of stroke was first described in the 1970s (Lusher et al, 1976) and is now used routinely in paediatric and adult patients. Several key studies in the last decade have proven the efficacy of blood transfusion in the prevention as well as treatment of acute and chronic complications of SCD, including life-long or long-term blood transfusion in primary prevention of stroke in high-risk children [Stroke Prevention in Sickle Cell Anaemia (STOP) and STOP2 studies], (Adams et al, 1998; Adams & Brambilla, 2005) and acute chest syndrome (Vichinsky et al, 2000; Styles et al, 2007). Further, the unintended benefits of chronic transfusion, such as reduced frequency of chest syndrome and acute pain episodes and hospitalization are added incentives for compliance with continuing blood transfusion (Miller et al, 2001). These recent developments have prompted the expanding use of blood transfusion to new areas where the evidence base is not so clear, such as treatment of non-healing leg ulcers. Blood transfusion can be a simple top-up of additional units of blood without removal of sickle blood, or exchange (automated or manual) with the removal of sickle blood that is replaced by normal red cells (Wahl & Quirolo, 2009). We present the changing practice in blood transfusion among adult patients with SCD attending King s College Hospital (KCH) over a 10-year period. First published online 31 January 2011 doi: /j x ª 2011 Blackwell Publishing Ltd, British Journal of Haematology, 152,

2 Blood Transfusion Usage in Adults with Sickle Cell Disease Materials and methods This retrospective analysis included all adult patients ( 16 years) attending KCH, London, between 1st January 2000 to 31st December Data were extracted from the KCH sickle database, KCH transfusion databases (PathNet (Ipswitch Inc, Lexington MA, USA) and Winpath Clinisys, Surrey, UK), the KCH electronic patient record system (EPR isoft Group, Sydney, Australia), and patient case notes. Two 2-year periods, 1st January 2000 to 31st December 2001 and 1st January 2008 to 31st December 2009, were selected to compare blood transfusion practices for acute complications when inpatient admissions were recorded. For a more accurate representation of sickle-related complications, the sub-analysis excluded planned surgical admissions and admissions for renal dialysis. There were limitations to the data collected, as full clinical data (discharge summaries, clinic letters etc) were only available in the EPR from The resulting data were analysed as (i) all transfusions, (ii) planned transfusions and (iii) acute transfusions that were usually prescribed for inpatients. Categorical variables were summarized using means and percentages. Continuous variables were summarized using one or more of mean, standard deviation (SD) and percentages. Due to the non-gaussian distribution of our data the Mann Whitney U test was used to compare the sample means. The results were considered significant when P < 0Æ05. (A) (B) Results A total of 659 patients (55% female) attended KCH over the 10-year period; the number of patients seen each year increased steadily each year from 232 (in 2000) to 463 (in 2008) with a slight drop to 434 patients in 2009 (Fig 1A). The SCD population consisted of 66% HbSS (435 patients), 28% HbSC (185 patients), 4% Sb + thalassaemia (26 patients), 2% Sb 0 thalassaemia (13 patients). Within each year the proportion of male and female sickle patients, and sickle genotypes remained relatively stable (Fig 1A). The patients ranged from 16 to 71 years of age with a mean age of 35 years at the last hospital attendance. During the 10-year study period, a total of 8171 units were transfused (including inpatient and outpatient transfusions); 390 (59%) of the 659 patients did not require any blood transfusion, whereas 261 (41%) patients had at least one unit of blood. Not surprisingly, the amount of blood used was not equally distributed between the genotypes. Over the 10-year period, although HbSS patients comprised 66% of the cohort they used a mean value of 88% (SD 5%) of all red cells transfused with 9% of red cells given to HbSC patients. There has been a steady increase in blood transfusion over the 10-year period from 395 units (1Æ7 units per patient year) in 2000, to 1676 units (3Æ86 units per patient year) in 2009 (Fig 1B). The percentage of patients transfused each year has increased from 15% in 2000 to 19% in There has also Fig 1. (A) Distribution of patient genotypes ( ). (B) Total blood usage among patients with SCD ( ). been a significant (P =0Æ006) increase in the mean units transfused per patient, from 11 (95% confidence interval [CI] 5Æ9 16Æ3) in 2000 to 21 (95% CI 15Æ7 25Æ9) in The major proportion of blood used throughout the 10-year study period was for planned transfusion (mean 65% SD 6%) (Fig 1B). Six per cent of patients received 78% of blood transfused; all of these 37 patients were on chronic transfusion programmes (18 for secondary stroke prevention, six for renal failure and anaemia, six for frequent acute pain not responding to hydroxycarbamide, two for chronic sickle lung disease, two for leg ulcers, one for sickle hepatopathy, one for control of recurrent priapism, and one for preservation of renal graft). For planned transfusions, the volume of blood used increased from 1 unit/patient year in 2000 to 2Æ90 units/patient year in 2009 (Fig 1B). The most dramatic increase occurred between ª 2011 Blackwell Publishing Ltd, British Journal of Haematology, 152,

3 E. Drasar et al 2005 and The reasons for this were twofold: the increased use of automated exchange transfusion and the general increased usage for the control of sickle-related complications. In 2000 the majority of planned transfusions were given as topup (61% of planned blood usage); however, in 2009, automated exchange transfusion accounted for 81% of all blood used in planned transfusions. There has also been an expansion in blood usage for other sickle-related complications during the study period. In 2000, of the seven patients (all HbSS) on planned transfusions, two were transfused for secondary prevention of stroke, and the remainder for endstage renal failure and symptomatic anaemia. In contrast, the 2009 cohort on planned transfusion, consisted of 31 patients (28 HbSS, 3 HbSC) who received transfusion for a far wider range of indications 16 for secondary stroke prevention, six for renal impairment and anaemia, three for control of frequent acute pain, two for treatment of recalcitrant leg ulcers, and one each for sickle hepatopathy, recurrent priapism, preservation of renal graft, and chronic sickle lung disease with pulmonary hypertension. Transfusion details of patients admitted in 2000/2001 and 2008/2009 are shown in Table I. Although there were 56% more patients in 2008/2009 compared to 2000/2001 (490 vs. 314 respectively), the age range and mean age of both patient groups were similar. In 2000/2001, 17Æ8% of the patients received blood transfusion compared to 23Æ9% in 2008/2009, although the ratio of acute to planned transfusion was similar in both groups. Of the 137 patients admitted in 2000/2001, 28Æ5% (39) received blood transfusions in contrast to 42Æ8% (86) of the 201 patients admitted in 2008/2009 for sicklerelated complications. The data showed an overall increase in usage of blood in 2008/2009 that is not age-related, most of it for acute admissions related to sickle complications. To reflect the use of blood transfusions directly related to acute sickle-related complications, we analysed inpatient transfusions excluding those related to end stage renal failure and planned surgery. In the 2-year period , there were 380 acute admissions for 137 of the 314 patients (526 patient years); 55 patients (18%) had one admission, and 81 Table I. Transfusion record of sickle patients in and / /2009 No. (%) Age (mean), years No. (%) Age (mean), years Unique patients (31Æ2) (31Æ4) Transfused 56 (17Æ8%) (29Æ3) 117 (23Æ9) (32Æ7) Acute 39 (69Æ6) (31Æ2) 86 (73Æ5) (33Æ1) Planned 17 (30Æ4) (27Æ9) 31 (26Æ5) (29Æ7) Un-transfused 258 (82Æ2) (31Æ8) 373 (76Æ1) (34Æ6) Total admitted Transfused 39 (28Æ5) (31Æ2) 86 (42Æ8) (33Æ1) Un-transfused 98 (71Æ5) (31Æ3) 115 (57Æ2) (30) (26%) had more than two admissions, of which three (1%) had 10 or more admissions. In , there were 520 acute admissions for 201 of the 490 patients (897 patient years); 101 patients (20Æ6%) had one admission, and 100 (20Æ4%) had more than two admissions, of which five patients (1%) had 10 or more admissions. A total of 241 units were transfused in compared to 594 in with a significant increase (P = 0Æ01) in the number of units transfused per admission from 0Æ68 (95% CI 0Æ44 0Æ93) to 1Æ5 (95% CI 1Æ08 1Æ94). Twenty-five per cent of the 520 acute admissions in 2008/2009 resulted in transfusion compared with 17% of the 380 admissions in 2000/2001. For both and , the reasons for acute admission were very similar in pattern and distribution (Fig 2A). Acute pain accounted for the majority of admissions (84% and 80% respectively), followed by chest complications (11% and 13% respectively), renal or abdominal problems (4% and 5% respectively), and neurological problems (2% and 3% respectively) (Fig 2A). In , chest complications accounted for the majority (43%) of the blood used, followed by acute pain (20%), whereas in , acute pain and chest complications accounted for the major portion of blood used, 37% and 35%, respectively (Fig 2B). The length of inpatient stay per admission was significantly different (P = 0Æ01), the mean duration being 8Æ07 d in (95% CI 6Æ83 9Æ31) and 6Æ76 d in (95% CI 5Æ87 7Æ65). However, the reduced length of stay may not necessarily be a direct result of the increased use of transfusion; it could be related to a change in culture in the treatment of SCD with fewer patients being long-term inpatients. Discussion We conclude that blood usage in the KCH sickle cell cohort has increased significantly in the past 10 years. This was due in part to an increase in exchange transfusion (39% of all transfused units in 2000/2001 to 71% of all transfused units in 2008/2009) after correction for increase in patient number. There was also an increased use in top-up transfusion for acute and chronic sickle-related complications. The majority of blood received was by a small proportion of patients. SCD-Hb SS received the majority of transfusions both as planned and in the acute setting (90% in and 88% in ). Blood transfusion for acute sickle-related complications has also increased significantly, the majority for admissions related to acute pain. Currently, there is no therapeutic equivalent to blood transfusion for many of the severe acute complications of SCD. Although hydroxycarbamide has decreased the incidence of pain and hospitalization and the frequency of blood transfusions in responders (Charache et al, 1995; Zimmerman et al, 2004; de Montalembert, 2007; Lanzkron et al, 2008), its use does not appear to have impacted blood transfusion usage among the adults with SCD, at least in KCH. As more of the paediatric sickle population on long-term blood transfusion 768 ª 2011 Blackwell Publishing Ltd, British Journal of Haematology, 152,

4 Blood Transfusion Usage in Adults with Sickle Cell Disease (A) (B) Fig 2. (A) Indications for unplanned admissions for SCD patients during and (B) Percentage of blood used according to acute sickle-related complications during and for primary prevention of stroke transition to adult care, the expectation is that a greater, not fewer, number of patients will be on long-term blood transfusion. This change in pattern of blood usage amongst sickle patients in KCH is likely to reflect similar practices in other sickle cell centres in the UK. Future multi-centre prospective studies are required to clarify indications for transfusion therapy in SCD; its usage for some indications (eg. chronic leg ulceration) has no clear evidence base. The increasing number of patients on blood transfusion will need an increased vigilance for monitoring and management of secondary iron loading complications (Cappellini et al, 2010). In addition, the NHS Blood and Transplant needs to devise strategies to expand the pool of donors of African descent, and to minimize red cell alloimmunization by using novel techniques, including molecular genotyping, of patients and donors. Acknowledgements We thank Claire Steward for help in preparation of the manuscript. References Adams, R.J. & Brambilla, D. (2005) Discontinuing prophylactic transfusions used to prevent stroke in sickle cell disease. New England Journal of Medicine, 353, Adams, R.J., McKie, V.C., Hsu, L., Files, B., Vichinsky, E., Pegelow, C., Abboud, M., Gallagher, D., Kutlar, A., Nichols, F.T., Bonds, D.R. & Brambilla, D. (1998) Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial doppler ultraso- ª 2011 Blackwell Publishing Ltd, British Journal of Haematology, 152,

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