research paper
The impact of a regular erythrocytapheresis programme on the acute and chronic complications of sickle cell disease in adults
Anna Kalff,1 Claire Dowsing2 and Andrew Grigg2 Departments of 1Laboratory Haematology and 2
Clinical Haematology, Royal Melbourne
Hospital, Vic., Australia
Received 2 December 2009; accepted for 12 February 2010 Correspondence: Dr A Kalff, Diagnostic Haematology, Royal Melbourne Hospital, Grattan Street, Parkville, Vic. 3006, Australia. E-mail:
[email protected];
[email protected]
Summary Thirteen adult patients aged 22–63 (median 30) years with sickle cell disease (SCD) were enrolled in a regular erythrocytapheresis (ECP) programme at a single institution between December 1998 and November 2008. The indications for enrolment were recurrent painful crises (PC), acute chest syndrome (ACS), silent cortical ischaemia, pulmonary hypertension, multiorgan crises and pregnancy. Endpoints retrospectively evaluated included the incidence of SCD-related acute events requiring hospitalization following and prior to regular ECP, the development of new and progression of pre-existing related end-organ damage, the effectiveness in reducing HbS levels acutely and prior to the next exchange and the transfusion-related complications. Sixteen acute sickle-related events occurred in five patients in 846 months of patient follow-up. In all patients with reliable data available pre-ECP, the frequency of such events was reduced following commencing regular ECP. No patient experienced stroke, multi-organ crises or developed new and/or progression of end-organ dysfunction. Regular ECP reduced HbS levels to the target of 18 years of age) with complicated SCD despite maximally tolerated, contra-indication to or refusal to take hydroxycarbamide (HC). The eligible complications included those published as conventional consensus criteria for ECP programme (Lottenberg & Hassell, 2005), specifically a life-threatening multi-organ crisis or acute chest syndrome. We expanded the eligibility to include ‡1 hospital admission/year for an acute painful crisis, a ‘controversial’ consensus indication (Lottenberg & Hassell, 2005) and pregnancy, the latter based on the observation that, compared with simple transfusion, ECP has been shown to improve perinatal outcome (Koshy et al, 1988; Morrison et al, 1991).
ª 2010 Blackwell Publishing Ltd, British Journal of Haematology, 149, 768–774
Regular Erythrocytapheresis for SCD Complication Patients with silent cortical infarcts (SCI) were also included due to the significant associated morbidity (including lower IQ and other neurocognitive impairment) and high risk for progression in children with either new SCI or overt stroke (Pegelow et al, 1995; Armstrong et al, 1996); we elected to extrapolate these findings to young adults. Cognisant of the considerable cost of ECP with respect to nurse time, consumables and the utilization of red cells, we conducted a detailed retrospective evaluation of the effectiveness of the programme, with the approval of the Ethics committee of our hospital.
Methods Automated red cell exchange was performed by an apheresis nurse (single dedicated nurse from 2002) responsible for the program using the COBE Spectra apheresis system – red blood cell exchange programme (RBCX), whole blood:ACD ratio of 13:1. Patients were exchanged via peripheral venous cannulae or arterio-venous fistula, generally at an initial frequency of 4 weeks and subsequently at 4–6 week intervals, except for one patient who was exchanged at 3 weekly intervals during pregnancy. The number of red cell units transfused and frequency of ECP were determined by patient weight, clinical symptomatology and response of HbS concentrations (target post-exchange HbS 24 h) (Craft et al, 1993) was assessed by MRI at initiation of therapy in 12 patients and repeated in patients with abnormalities at baseline (yearly) or with clinical suspicion of neurological events. Renal function was assessed yearly by estimation of glomerular filtration rate (eGFR, normal >90 ml/min/1Æ73 m2) and urinalysis, with formal assessment of proteinuria in those with > trace on dipstick by 24 h urine collection and protein quantification. Iron overload was assessed by serum ferritin assays four times per year; evaluation of liver iron concentrations by biopsy or MRI was not performed. Liver function tests (LFTs), fasting glucose, testosterone/oestrogen, luteinizing hormone (LH), follicle stimulating hormone (FSH) and thyroid stimulating hormone (TSH) and viral screening for hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus (HIV) were performed annually. Cost assessments were calculated based on data provided by the institutional finance department and the ARCBS and were estimated in the patient group who had reliable data prior to commencement of therapy with respect to hospital admissions for sickle complications. The annual cost of the ECP programme per patient was compared to savings from reduced hospital admissions.
Results Thirteen patients (three females; 10 males) of median age 30 years (range 22–63) with homozygous sickle cell anaemia (HbSS) (n = 8) or sickle b+ thalassaemia (HbS/b+) (n = 5) were enrolled between December 1998 and November 2008. No patient has discontinued ECP following commencement. Table I details the individual patient data. The most common indications for commencement were frequent painful crises (n = 7) and acute chest syndrome (n = 3). Seven patients were not treated with HC due to patient concerns regarding potential long-term side effects on fertility. Four patients had recurrent crises despite HC therapy, three of whom had a HbF level >20% prior to initiation of ECP. HC was discontinued in one patient due to myelosuppression. Of the 12 non-pregnant patients, one was commenced on 6 weekly exchanges with the remainder on 4 weekly exchanges. After a median of 5–6 months, 10 patients were reduced to 5 weekly exchanges; five were then reduced to 6 weekly exchanges after a median of 15 months. The majority of patients (10 of 13) are currently exchanged every 5–6 weeks (Table I). With a median duration of follow-up of 70 months (8–119), the median number of ECP procedures per patient was 68 (7–90), total red cells units exchanged was 299 (43–493) and red cells per exchange was 5Æ7 units (4Æ4–6Æ1).
ª 2010 Blackwell Publishing Ltd, British Journal of Haematology, 149, 768–774
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A. Kalff et al Table I. Patient Transfusion characteristics.
Patient number Sex
Age (years) Diagnosis Indication
1 2 3 4 5 6 7 8 9 10 11 12 13
35 41 30 27 62 47 27 63 25 33 22 22 24
M M M F M M M F M F M M M
S/B+ SS S/B+ SS SS SS SS S/B+ SS SS S/B+ S/B+ SS
Prior Follow-up HC therapy (m)
PC 101 PC 88 ACS 70 Pregnancy 53 PC 112 ACS 119 PC, ACS 65 PC 84 MOC 84 PHT 9 PC 26 PC 27 SCI 8
Yes* No No Yes Yes§ Yes* Yes* Yes* No Yes* No No Yes
Current Red cell exchanges Frequency (weeks) (n)
Total red cell units
HbS prior to start of ECP programme (%)
Mean HbS immediately post each ECP (%)
Mean HbS immediately prior to each ECP (%)
72 90 68 40 72 82 47 68 69 8 23 24 7
411 493 299 240 392 449 208 357 400 47 138 144 43
82Æ1 67Æ7 73Æ8 82Æ7 79Æ1 77Æ9 75Æ1
25 25Æ3 28Æ5 21Æ8 27 30Æ8 22Æ1 19Æ8 28Æ6 18Æ5 25Æ1 26Æ1 32Æ6
47Æ1 45Æ1 44Æ7 44Æ9 51Æ9 49Æ6 41Æ6 40Æ7 52Æ7 43 46Æ8 48Æ6 59Æ3
6 4 5 3 6 6 6 6 6 5 5 5 4
SS, homozygous HbS; S/B+, compound heterozygote HbS; B+, thalassaemia; PC, painful crisis; ACS, acute chest syndrome; MOC, multi-organ crisis; PHT, pulmonary hypertension; SCI, silent cortical infarcts. *HC failure/intolerance as contributor to initiation of ECP therapy. HbS not assessable as these patients received intermittent simple transfusion prior to commencing regular ECP. Hydroxycarbamide (HC) therapy deferred/ceased due to planned pregnancy, fertility concern, not failure. §Unknown why HC discontinued.
Table II. Pre-ECP HbS% in three patients after commencing regular ECP. HbS % pre-exchange Pre-exchange number
Patient 13
Patient 12
Patient 11
Baseline 2 3 4 5 6 7
75Æ6 63Æ2 78 51Æ6 50Æ5 48Æ3 48Æ3
82Æ9 77Æ9 58Æ5 47Æ5 40Æ3 39Æ2 40
80Æ2 79Æ1 51Æ8 41Æ6 38 38Æ8 39Æ9
Table II demonstrates the gradual fall in pre-ECP HbS% following commencement of regular exchanges (4 weekly) in three patients. Beyond the fifth exchange, the mean HbS% in these patients prior to and immediately following each ECP procedure was 47% and 26%, respectively. In patients on 6 weekly exchanges, HbS% was
