Effectiveness of a top up transfusion programme in preventing cerebrovascular damage in a birth cohort of sickle cell disease

Regular transfusions are effective in managing strokes in paediatric sickle cell patients. However, there are associated risks, including alloimmunisation and iron overload. This study evaluated the efficacy of top-up transfusions in primary and secondary stroke prevention in a single tertiary paediatric centre in Central London. Forty-seven children with sickle cell disease who received transfusions in the last decade were included. No patient on a primary stroke prevention transfusion programme had a cerebrovascular event during the study period but 9.5% on secondary stroke prevention programme did. Twenty-one per cent of patients in this cohort converted to exchange transfusions following transfer to adult services, of which 11% had subsequent strokes. Targeted pre-transfusion haemoglobin S % was not always met; 43% of HbS% readings in a 12- month period were above the set target of 30% and 37% were above the set target of 50%. About a third of patients had evidence of severe hepatic iron overload, but no significant cardiac iron. 25% of patients became alloimmunised, but not severe enough to warrant discontinuation of the transfusion programme. Although transfusions are effective for primary stroke prevention, iron overload remains a significant burden.

Download Full-text

A Single Institution Study of Chronic Erythrocytapheresis for Secondary Stroke Prevention in Children and Young Adults with Sickle Cell Disease

Blood ◽

10.1182/blood.v120.21.4754.4754 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4754-4754

Author(s):

Nadia L Cheek ◽

Robert L Saylors ◽

Raghu Ramakrishnaiah ◽

Suzanne Saccente ◽

Xinyu Tang ◽

...

Keyword(s):

Sickle Cell Disease ◽

Iron Overload ◽

Sickle Cell ◽

Stroke Prevention ◽

Organ Damage ◽

Secondary Stroke Prevention ◽

Cell Disease ◽

End Organ Damage ◽

Children And Young Adults ◽

The Mean

Abstract Abstract 4754 Introduction: The current standard of care for secondary stroke prevention in children and young adults with sickle cell disease and cerebral infarction is chronic simple transfusion (ST). Published data indicate that at least 18% of patients treated with chronic ST will experience a second overt infarct and at least 28% will experience additional silent infarcts. Since 1996, we have used chronic erythrocytapheresis (RCE) instead of chronic ST in our hospital to treat all patients with either overt infarction or abnormal transcranial doppler (TCD) with silent infarction. Here we present clinical, radiographic, and laboratory data from this group of patients treated with chronic RCE for secondary stroke prevention. Methods: This was a retrospective study of all patients treated with chronic RCE for either overt infarction or for an abnormal TCD with silent infarction at Arkansas Children's Hospital from 1996 through 2011. We reviewed clinical records and serial MRI/MRA scans and determined the time to progression from the time of the initial diagnosis of an overt or silent infarct to the time of the second overt or silent infarct. Events were classified as overt infarcts if the MRI demonstrated acute cerebral ischemia, based on increased signal intensity on T2-weighted images and restricted diffusion on diffusion-weighted images, and abnormal neurologic findings correlated with the abnormalities identified on MRI. Events were classified as silent infarcts if the MRI demonstrated new lesions 3 mm or greater in a single dimension with increased signal intensity on T2-weighted images and there were no corresponding abnormal neurologic findings. We also studied the pre-procedure hemoglobin S concentration (%S), pre-procedure ferritin levels, volume of blood transfused per kilogram, necessity for chelation medication, and presence of end-organ damage. Results: We identified 24 patients, ranging in age from 2 to 18 years at the initiation of chronic RCE, who were treated with 2539 RCE procedures during the study period. These patients were treated with RCE every two to six weeks with the goal of maintaining their pre-RCE %S at less than 30%. Progressive cerebral infarcts occurred in 42% (10 of 24) of the patients while receiving chronic RCE (Figure 1): 3 were overt (13%) and 7 were silent (29%). There were no additional infarcts observed after patients had been on chronic RCE for greater than 5 years. Eight patients (33%) experienced increased vasculopathy and 3 patients (13%) had an improvement in vasculopathy while on therapy. The mean pre-procedure %S concentration was 29%. The mean pre-procedure ferritin was 1188 ng/ml but approximately 60% of the patients had ferritin levels under 1000 ng/ml and only three patients required chelation. Patients received a mean of 45.5 ml/kg of packed red blood cells per procedure. There was no evidence of end-organ damage secondary to iron overload. Discussion: We determined that children with sickle cell disease and cerebral infarction experience additional silent and overt strokes despite intensive treatment with chronic RCE. The proportion of patients developing new overt infarcts in our study (13%) was slightly lower than that in a recent multi-institution study (18%; Hulbert et al, Blood 117:772, 2011) but the proportion of patients developing new silent infarcts in our study (29%) was no different (28%). Although patients receiving RCE have increased blood product utilization as compared with patients receiving ST, only three patients required chelation medication and none experienced end-organ damage secondary to iron overload. We conclude that chronic RCE is no more effective than chronic ST for secondary stroke prevention, that chronic RCE prevents the iron overload and need for chelation that is common with chronic ST, and that other forms of therapy are needed to prevent the progressive accumulation of cerebral infarcts in these patients. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Chronic Manual Exchange Transfusions Compared with Erythrocytapheresis in Children and Teens with Sickle Cell Disease

Blood ◽

10.1182/blood.v124.21.4927.4927 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4927-4927

Author(s):

Debbie Woods ◽

Robert J. Hayashi ◽

Melanie E. Fields ◽

Monica L. Hulbert

Keyword(s):

Sickle Cell Disease ◽

Iron Overload ◽

Sickle Cell ◽

Stroke Prevention ◽

Secondary Stroke Prevention ◽

Cell Disease ◽

Double Lumen ◽

Transfusion Therapy ◽

Catheter Complications ◽

Hb S

Abstract Background: Children and young adults with sickle cell disease (SCD) are at high risk of strokes and are frequently treated with red blood cell (RBC) transfusions. RBCs may be given by simple transfusion, manual exchange transfusion (ME), or erythrocytapheresis (ECP) with a goal of suppressing hemoglobin (Hb) S while minimizing transfusion-induced iron overload. There have been no formal comparisons of these modalities, and practices for transfusion management vary among institutions. We compared transfusion therapy outcomes among patients with SCD undergoing transfusion therapy for primary or secondary stroke prevention, hypothesizing that children would be more likely to achieve Hb S suppression and ferritin goals while receiving ECP. We also compared complications of transfusion therapy across transfusion modalities. Methods: This is a single-institution retrospective cohort study of 38 patients with SCD who received chronic transfusion therapy for primary or secondary stroke prevention from 1/1/2008 through 12/31/2012. Per institutional practice, younger patients receive ME for stroke prevention; they are offered ECP when their size is adequate for a large-bore double-lumen implantable port, but may choose to continue ME. The pre-transfusion Hb S goal is <30% for at least 2 years, then may be liberalized to <50% for subjects without either abnormal transcranial Doppler ultrasound or infarct recurrence. Hb S percentage and ferritin were measured prior to each transfusion. Patients on transfusion therapy for 6 or more months were included; one child who had a stroke after brain tumor biopsy was excluded. Subjects were censored at last date of follow-up or date of hematopoietic stem cell transplant. The following factors were evaluated: duration and mode of transfusion therapy, achievement of Hb S suppression goal, ferritin levels, and catheter complications. Categorical variables were compared with Fisher’s exact test and medians with the Mann-Whitney U-test in SPSS version 21 (IBM, Armonk, NY). Results: During the study period, 38 subjects (42% male) met all inclusion criteria. Of these, 5 received exclusively ECP, 17 received exclusively ME, and 16 received both modalities during the study period. For the most recent 12-month period of data for each participant, 13 received ECP and 25 received ME. There was no association between modality of transfusion and the proportion of visits during which subjects achieved their pre-transfusion Hb S goal during the 12-month period. The median proportion of visits achieving the Hb S goal was 0.80 for ECP (IQR 0.40-1.0) versus 0.50 for ME (IQR 0.28-0.90) (p=0.27). Furthermore, there was no significant difference in ferritin concentrations between transfusion modalities: median 875 ng/ml for ECP (IQR 578-2659) versus median 1527 ng/ml for ME (IQR 731-2568) (p=0.56). Children who had ever received ECP had a significantly longer total duration of transfusion therapy (median 97 months, IQR 51.5-134) than those receiving ME only (median 28 months, IQR 12.5-47) (p<0.001). Among 21 subjects who had ever received ECP, 15 (71.4%) experienced one or more catheter complications, including infection, thrombosis, catheter leakage, or venous stenosis, compared with 1/17 subjects (5.8%) who had never received ECP (OR for catheter complications 40 for subjects who had ever received ECP, 95% CI 4.29, 372.4, p <0.001). Five subjects switched from ECP to ME due to stenosis of the great vessels that precluded double-lumen port replacement. Conclusions: Children with SCD receiving ECP and ME for stroke prevention in this cohort had similar achievement of Hb S suppression goals and iron overload management. Additional patient-specific factors may be responsible for variations in pre-transfusion Hb S and ferritin concentrations. Catheter complications were significantly more common in children and adolescents receiving ECP compared with ME, likely due to the large-bore double-lumen port utilized for ECP at our center. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Liver Stiffness Measurement by Vibration Controlled Transient Elastography Does Not Correlate to Hepatic Iron Overload in Children With Sickle Cell Disease

Journal of Pediatric Hematology/Oncology ◽

10.1097/mph.0000000000001726 ◽

2020 ◽

pp. 1

Author(s):

Peter Costa ◽

Bryan Rudolph ◽

Debora Kogan-Liberman ◽

Deepa Manwani ◽

Ellen J. Silver ◽

...

Keyword(s):

Sickle Cell Disease ◽

Iron Overload ◽

Sickle Cell ◽

Transient Elastography ◽

Liver Stiffness ◽

Hepatic Iron ◽

Cell Disease ◽

Liver Stiffness Measurement ◽

Stiffness Measurement ◽

Hepatic Iron Overload

Download Full-text

Silent cerebral infarcts occur despite regular blood transfusion therapy after first strokes in children with sickle cell disease

Blood ◽

10.1182/blood-2010-01-261123 ◽

2011 ◽

Vol 117 (3) ◽

pp. 772-779 ◽

Cited By ~ 154

Author(s):

Monica L. Hulbert ◽

Robert C. McKinstry ◽

JoAnne L. Lacey ◽

Christopher J. Moran ◽

Julie A. Panepinto ◽

...

Keyword(s):

Magnetic Resonance ◽

Sickle Cell Disease ◽

Blood Transfusion ◽

Sickle Cell ◽

Stroke Prevention ◽

Secondary Stroke Prevention ◽

Cell Disease ◽

Cerebral Infarcts ◽

Eligibility Criteria ◽

Transfusion Therapy

Abstract Children with sickle cell disease (SCD) and strokes receive blood transfusion therapy for secondary stroke prevention; despite this, approximately 20% experience second overt strokes. Given this rate of second overt strokes and the clinical significance of silent cerebral infarcts, we tested the hypothesis that silent cerebral infarcts occur among children with SCD being transfused for secondary stroke prevention. A prospective cohort enrolled children with SCD and overt strokes at 7 academic centers. Magnetic resonance imaging and magnetic resonance angiography of the brain were scheduled approximately every 1 to 2 years; studies were reviewed by a panel of neuroradiologists. Eligibility criteria included regularly scheduled blood transfusion therapy. Forty children were included; mean pretransfusion hemoglobin S concentration was 29%. Progressive cerebral infarcts occurred in 45% (18 of 40 children) while receiving chronic blood transfusion therapy; 7 had second overt strokes and 11 had new silent cerebral infarcts. Worsening cerebral vasculopathy was associated with new cerebral infarction (overt or silent; relative risk = 12.7; 95% confidence interval, 2.65-60.5, P = .001). Children with SCD and overt strokes receiving regular blood transfusion therapy experience silent cerebral infarcts at a higher rate than previously recognized. Additional therapies are needed for secondary stroke prevention in children with SCD.

Download Full-text