Long-term Erythrocytapheresis Research Articles

Long-Term Erythrocytapheresis Did Not Prevent Development of Severe Pulmonary Hypertension in Sickle Cell Disease

Background The WHO classifies pulmonary hypertension into five different groups based on pathophysiology, clinical presentation, and therapeutic options. The development of pulmonary hypertension (PH) in sickle cell disease (SCD) is multifactorial and can cause devastating complications. Erythrocytapheresis is utilized in patients with SCD who have multiple comorbidities or are unresponsive to first-line treatments like hydroxyurea. It is hypothesized that treatment with long-term erythrocytapheresis (LTE) could slow the progression to pulmonary hypertension by modifying the pathophysiology of the disease process. However, limited clinical data supports this transfusion modality [1]. Case Description The patient is a 17-year-old female with a history of SCD, obstructive sleep apnea (OSA), nocturnal hypoxemia, and recurrent pain crises maintained on LTE every four weeks for the past seven years. She had previously failed hydroxyurea therapy. She underwent a tonsillectomy and adenoidectomy seven years ago to treat OSA. The patient had an echocardiogram five years ago, which showed normal biventricular function and tricuspid regurgitation jet velocity. Recently she presented to the emergency department with cough, shortness of breath, fever, diarrhea, and nausea lasting for three days. Initial assessment revealed elevated liver enzymes, elevated BNP, hyperbilirubinemia, hemoglobin of 9.5 g/dL, and oxygen saturations in the 80's. Echo revealed right ventricular dysfunction and right atrial and ventricular enlargement with a tricuspid regurgitation jet velocity of 4.29 m/s and estimated right ventricular systolic pressure 90% systemic, as seen in figure 1. The patient was admitted to the PICU under concern of pulmonary hypertension crisis. She underwent a right cardiac catheterization three days into her admission and was diagnosed with severe pulmonary hypertension with a mean pulmonary artery pressure of 49 mmHg. Pulmonary capillary wedge pressure was 11 mmHg, and pulmonary vascular resistance was calculated to be 18 wood units x m 2 with 20 PPM of nitric oxide and 80% FiO2 the PVR decreased to 11 woods units x m 2 (figure 2). CTA showed subsegmental thrombosis and vascular surgery was consulted for evaluation for endarterectomy, but they decided she was not a surgical candidate. She was initiated on anticoagulation therapy with enoxaparin, sildenafil, and bosentan. Conclusions The cause of PH in this patient appears to be multifactorial. Possible etiologies include SCD-related, primary pulmonary hypertension, or subsegmental pulmonary embolism. Although LTE is increasingly used in the management of SCD, providers should not assume that a patient receiving this treatment will not progress to develop complications. Some patients on LTE may also develop progressive CNS vasculopathy and are still at risk for developing hypertension. Patients with SCD should be screened for PH if they are symptomatic or have comorbid conditions. This patient had a history of nocturnal hypoxemia and OSA, which some studies indicate are associated with pulmonary hypertension in adolescents with SCD. Screening for nocturnal hypoxemia and OSA is recommended in SCD to identify patients at high risk of PH development [2].

Effects of Erythrocytapheresis Procedures on Delayed Bone Marrow Conversion in Sickle Cell Disease

The imaging appearances of the skeletal system have been well documented in sickle cell disease (SCD) but there is limited information about the impact of SCD treatments on skeletal abnormalities. We present two patients with SCD maintained on long-term erythrocytapheresis and the changes to their skeletal abnormalities on neuroimaging with this treatment. We observed a reversal of the bone marrow conversion process and the skull appearance was age appropriate without any radiographic findings of iron overload in the patients.

Long-term Erythrocytapheresis Is Associated With Reduced Liver Iron Concentration in Sickle Cell Disease.

Erythrocytapheresis procedures are increasingly used in sickle cell disease. Serum ferritin and noninvasive magnetic resonance imaging measurements of liver iron concentration (LIC) are frequently used to monitor iron overload secondary to hypertransfusion. There is a paucity of data describing the impact of long-term erythrocytapheresis (LTE) on LIC. We measured magnetic resonance imaging liver and cardiac iron on LTE subjects and stratified them into 2 groups: higher LIC (>3 mg/g) and lower LIC (<3 mg/g). χ(2) and t test were used to test for differences between the 2 groups. Logistic regression and generalized linear mixed-effects models were used to test what impacted LIC. None of 29 sickle cell disease subjects maintained on LTE had high cardiac iron concentration. LIC was associated with serum ferritin (r=0.697, P<0.001) but was not associated with the total number of LTE procedures (r=-0.088, P=0.656) or total number of simple transfusions (r=0.316, P=0.108). The total number of LTE procedures was not associated with serum ferritin (r=0.040, P=0.838), the total number of simple transfusions (r=-0.258, P=0.184), or LIC group (r=-0.111, P=0.566). There was no significant correlation between duration of LTE maintenance and LIC.

Long Term Erythrocytapheresis Is Associated with Reduced Liver Iron Concentration in Sickle Cell Disease

Background:Observational studies and randomized clinical trials have demonstrated that RBC transfusions can alleviate or prevent many complications of sickle cell disease (SCD). Obligatory iron loading is most problematic for those receiving chronic simple transfusions and is managed with chelation therapy to prevent hepatic, cardiac, and endocrinologic complications. Erythrocytapheresis procedures are increasingly used in SCD as they achieve dilution of hemoglobin S without significantly raising the total hematocrit. Some guidelines for the management of iron overload use serum ferritin levels, but non-invasive measurements of liver iron concentration (LIC) using validated and widely available MRI techniques have been described. There is a paucity of data elucidating the impact of long-term erythrocytapheresis (LTE) on LIC. We evaluated LIC with MRI and serial serum ferritin measurements among a population of SCD patients maintained on LTE at a single institution.Methods:Subjects with SCD maintained on the LTE program included those with elevated TCD, history of stroke, recurrent acute chest syndrome, or frequent pain crises unresponsive to hydroxyurea therapy. Serial serum ferritin measurements were followed and chelation with deferasirox was initiated for consistent ferritin level >1000 ng/mL. MRI of liver and cardiac iron was measured on all LTE subjects with non-contrast MRI techniques. A total of n=31 subjects maintained on LTE were enrolled and stratified into two groups: high LIC, ≥5mg/g of dry tissue (n=4, 12.9%) and low LIC, <5mg/g (n=27, 87.1%). Chi-squared and t-test were used to test for differences between the two groups. Logistic regression was used to test what impacted the odds of having a high LIC, while generalized linear mixed-effects modeling was used to test what impacted LIC.Results:None of the subjects had high cardiac iron concentration. Subjects with high LIC were significantly older (17.8 vs. 13.1, p=0.032) and were more likely to be female (100% vs. 44.4%, p=0.038). The duration of LTE was not associated with high and low levels of LIC (8.25 vs. 6.15, p=0.240, Figure 1), levels of LIC (r=0.247, p=0.188, Figure 2), or serum ferritin (r=0.077, p=0.680). The total number of simple of transfusions was not associated with serum ferritin (r=-0.177, p=0.558) or LIC (r=-0.022, p=0.910). Serum ferritin was not significantly associated with LIC (r=0.296, p=0.112, Figure 3). One of the 4 patients with high LIC required chelation with deferasirox for ferritin >1000 ng/mL. Three of the 31 subjects required iron chelation with deferasirox.Conclusions:There was no significant correlation between duration of LTE and LIC. The impact of cumulative simple transfusions on LIC was obviated by maintenance LTE. These findings are consistent with reports that LTE is associated with reduced transfusional iron overload. The lack of significant association between serum ferritin and LIC suggest that validated MRI measurements of LIC may have greater sensitivity for identifying patients with iron overload and guidelines for iron chelation should consider LIC rather than serum ferritin alone. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Impact of long-term erythrocytapheresis on growth and peak height velocity of children with sickle cell disease.

Children with sickle cell disease (SCD) lag in weight and height and have a delayed growth spurt compared to normal children. We studied the effect of long-term erythrocytapheresis (LTE) on the growth of children with SCD and the age at which they attained peak height velocity. A retrospective chart review was performed recording weight, height, and body mass index (BMI) measurements of 36 patients with SCD who received LTE every 3-5 weeks for an average duration of 5 years. The z-scores for weight, height, and BMI of these patients were compared with that of patients with SCD from the Cooperative Study of Sickle Cell Disease (CSSCD) and a sub-set of 64 controls matched for age, sex, and initial growth parameter z-scores at the start of LTE. The z-scores for all parameters improved significantly for our patients on LTE compared to match controls from CSSCD and the entire pediatric CSSCD cohort (P-value: <0.01). Peak height velocity was achieved 2 months earlier for females (P-value: 0.94) and 11 months earlier for males (P-value: 0.02), who started LTE before 14 years of age, compared to matched CSSCD controls. The study subjects who had not been on regular simple transfusions prior to starting LTE had a mean serum ferritin of 681 ng/ml after LTE for an average duration of 63 months. LTE improves the growth of children with SCD without the risk of iron overload.

Long-term red blood cell exchange in children with sickle cell disease: Manual or automatic?

Little information is available on erythrocytapheresis in children with sickle cell disease, and no comparison has ever been made with manual exchanges in a long-term blood exchange program. We matched a historical cohort of five patients who received 60 erythrocytapheresis procedures with five who received 124 manual exchanges. Long-term erythrocytapheresis was feasible and well-tolerated even in children of low weight. In a long-term approach, automated exchanges were more efficient in maintaining a low HbS level, and exchanges could be spaced out. This approach appears especially useful in the cases where the HbS level must be maintained below 30%.

Short-Term Femoral Catheter Insertion: A Promising Alternative to Consistently Allow Long-Term Erythrocytapheresis Therapy in Children with Sickle Cell Anemia

Erythrocytapheresis procedures, increasingly used in the management of patients with severe complications of sickle cell disease, are limited by adequate venous access. We have successfully used short-term femoral catheter insertion, during a 6.5-year period for a total of 443 procedures, to perform long-term erythrocytapheresis in 18 consecutive children with sickle cell disease.

Complications of implantable venous access devices in patients with sickle cell disease

Implantable venous access devices (VADs) are used in sickle cell disease (SCD) for patients with poor venous access to facilitate chronic blood transfusions and manage acute complications. We attempted to define the frequency of bloodstream infections (BSI) and thrombosis in adults and children with SCD and VADs. We performed a single-institution, retrospective review of VAD-associated infection and thrombosis in patients with SCD. Thirty-two patients (median age 20 years, range, 1-59) had 86 VADs placed (median, 2.7 VADs per patient, range, 1-7) with a total of 41,292 catheter days (median, 1,376 days; range, 323-3,999). Mean catheter lifespan in adults (691 days ± 123) was not significantly higher than children (614 days ± 154). A total of 66 VAD-associated BSI (1.59 infections per 1,000 catheter days) occurred in 17 of 32 (53%) patients. Children with VADs had fewer BSI (3 of 10; 30%) than adults (14 of 22; 64%, P = 0.08). 24 catheter-associated thromboses (0.49 thromboses per 1,000 catheter days) occurred in 10 of 32 (41%) of patients. Children also had fewer VAD-associated-thrombosis (1 of 10; 10%) than adults (9 of 22; 40%, P = 0.08). In conclusion, the use of VADs in SCD was linked to a significant rate of infection and thrombosis.

Cardiopulmonary Stress Testing in Children With Sickle Cell Disease Who are on Long-term Erythrocytapheresis

The purpose of the study was to assess the feasibility and safety of symptom-limited cardiopulmonary stress testing (CPST) in children with sickle cell disease (SCD), who are on long-term erythrocytapheresis. Maximal symptom-limited CPST was performed in 16 children with SCD who were maintained on long-term erythrocytapheresis and the exercise response in this patient cohort was compared with those of a healthy control population. All patients completed the CPST without any complications. Twelve patients with SCD had significant reduction in aerobic capacity [peak oxygen consumption (VO2) <80% predicted]. No patient demonstrated evidence of myocardial ischemia. In summary, symptom-limited CPST can be performed safely in a subgroup of children with SCD and can yield valuable clinical information.

Quantitative assessment of ventricular function in sickle cell disease: Effect of long‐term erythrocytapheresis

Previous studies on cardiac function in patients with sickle cell disease (SCD) demonstrated abnormalities of systolic and diastolic function including elevated left ventricular myocardial performance index (LVMPI) on chronic transfusion protocols. LVMPI has been validated as a useful and easy non-invasive measure of overall cardiac function. Up to now, there are no reported studies on cardiac function in patients with SCD maintained on long-term erythrocytapheresis (LTE). We recorded LVMPI in 22 patients with SCD aged 3-20 years and we compared the results between non-transfused patients (NT-SCD) and patients on LTE (T-SCD). Males with SCD had higher mean LVMPI than females (P = 0.04). There were significant differences among T-SCD, severe NT-SCD, and mild NT-SCD patients with respect to hemoglobin (Hb) levels (P = .003) and TR velocity (P = .03). T-SCD patients showed elevated LVMPI compared to NT-SCD patients with severe and mild disease (P = 0.002). Pair-wise comparisons demonstrated that T-SCD patients had LVMPI that was significantly higher than NT-SCD (mild) patients (P = 0.01). Our study demonstrates that patients SCD on LTE have cardiac dysfunction based on elevated LVMPI. This may be a reflection of the global severity of disease. Our findings merit further investigation with serial monitoring of LVMPI on a larger number of patients with SCD.

Assessment of cerebral tissue oxygenation in patients with sickle cell disease: effect of transfusion therapy.

This study used spatially resolved transcranial near-infrared spectroscopy (NIRS) to compare brain tissue oxygenation in sickle cell disease (SCD) patients with that of healthy children. In addition, NIRS was used to measure the dynamic response of cerebral oxygen balance to erythrocytapheresis. Transcranial NIRS measurements were obtained from 25 children with SCD who were not receiving transfusion or hydroxyurea therapy (NT-SCD). These patients were divided into two subgroups, those with mild (n = 10) or severe (n = 15) SCD symptoms. In addition, NIRS measurements were performed in 16 SCD patients with severe disease maintained on long-term erythrocytapheresis (T-SCD) and in 35 control children. The lowest mean brain tissue oxygen saturation occurred in the NT-SCD subgroup with severe symptoms (48 +/- 9%; P < 0.001 vs. control). NT-SCD patients with mild symptoms had higher saturation (62 +/- 8%; P < 0.001 vs. control), while the highest appeared in the control group (72 +/- 7%). In T-SCD patients, however, brain tissue oxygen saturations were higher than severely symptomatic NT-SCD children and similar to mildly symptomatic NT-SCD children (65 +/- 7%). Non-invasive measurements of brain tissue oxygenation with NIRS revealed that abnormal oxygen saturation levels in SCD patients correlated with the severity of their clinical manifestations. Additionally, cerebral oxygen balance seems to be favorably affected by erythro-cytapheresis.

Erythrocytapheresis therapy to reduce iron overload in chronically transfused patients with sickle cell disease

Chelation therapy with deferoxamine is effective in preventing the risk of transfusional iron overload, but treatment failure is common because of noncompliance. To reduce the transfusional iron load, we have evaluated longterm erythrocytapheresis in 14 subjects with sickle cell disease and stroke (11) or other complications (3) as an alternative to simple transfusion. Subjects were treated with erythrocytapheresis using the Haemonetics V50 (Haemonetics Corp, Braintree, MA) to maintain the target pretransfusion hemoglobin S (Hb S) level less than 50% for 6 to 71 months. The transfusional iron load and the donor blood usage were analyzed for a 6- to 36-month study period and were compared with similar data from a subset of 7 subjects previously treated with conventional (target Hb S &lt; 30%) and modified (target Hb S &lt; 50%) simple transfusion protocols. The effect of erythrocytapheresis on iron accumulation was determined by assessment of serum ferritin levels in the absence of iron chelation. The mean transfusional iron load and donor blood usage with erythrocytapheresis were 19 +/- 14 mg iron/kg/yr (range, 6 to 50) and 188.4 +/- 55.2 mL packed-red blood cells (RBC)/kg/yr (range, 107 to 281), respectively. Of 6 subjects receiving no iron chelation therapy, 5 maintained normal or nearly normal serum ferritin levels during 11 to 36 months of erythrocytapheresis. In comparison with conventional simple transfusion and modified simple transfusion, erythrocytapheresis reduced iron loading by 87% (P &lt; .01) and 82% (P &lt; .01), respectively, but increased donor blood usage by 23% and 73%, respectively. Subjects with pre-erythrocytapheresis Hb levels &gt; or = 8.0 g/dL had lower iron accumulation (P &lt; .001) and less donor blood usage (P &lt; .005) than subjects with Hb levels &lt; or = 8.0 g/dL. Although donor blood usage is increased in comparison with simple transfusion, long-term erythrocytapheresis markedly reduces or prevents iron accumulation. This form of transfusion therapy allows the cessation of iron chelation in well-chelated subjects and, if used as the initial form of transfusion therapy, may prevent long-term complications of sickle cell disease without risk of iron overload and the need for chelation therapy.

Erythrocytapheresis Therapy to Reduce Iron Overload in Chronically Transfused Patients With Sickle Cell Disease

AbstractChelation therapy with deferoxamine is effective in preventing the risk of transfusional iron overload, but treatment failure is common because of noncompliance. To reduce the transfusional iron load, we have evaluated long-term erythrocytapheresis in 14 subjects with sickle cell disease and stroke (11) or other complications (3) as an alternative to simple transfusion. Subjects were treated with erythrocytapheresis using the Haemonetics V50 (Haemonetics Corp, Braintree, MA) to maintain the target pre-transfusion hemoglobin S (Hb S) level less than 50% for 6 to 71 months. The transfusional iron load and the donor blood usage were analyzed for a 6- to 36-month study period and were compared with similar data from a subset of 7 subjects previously treated with conventional (target Hb S < 30%) and modified (target Hb S < 50%) simple transfusion protocols. The effect of erythrocytapheresis on iron accumulation was determined by assessment of serum ferritin levels in the absence of iron chelation. The mean transfusional iron load and donor blood usage with erythrocytapheresis were 19 ± 14 mg iron/kg/yr (range, 6 to 50) and 188.4 ± 55.2 mL packed-red blood cells (RBC)/kg/yr (range, 107 to 281), respectively. Of 6 subjects receiving no iron chelation therapy, 5 maintained normal or nearly normal serum ferritin levels during 11 to 36 months of erythrocytapheresis. In comparison with conventional simple transfusion and modified simple transfusion, erythrocytapheresis reduced iron loading by 87% (P < .01) and 82% (P < .01), respectively, but increased donor blood usage by 23% and 73%, respectively. Subjects with pre-erythro-cytapheresis Hb levels ≥8.0 g/dL had lower iron accumulation (P < .001) and less donor blood usage (P < .005) than subjects with Hb levels ≤ 8.0 g/dL. Although donor blood usage is increased in comparison with simple transfusion, long-term erythrocytapheresis markedly reduces or prevents iron accumulation. This form of transfusion therapy allows the cessation of iron chelation in well-chelated subjects and, if used as the initial form of transfusion therapy, may prevent long-term complications of sickle cell disease without risk of iron overload and the need for chelation therapy.