scholarly journals Tolerance and humoral immune response to the yellow fever vaccine in sickle cell disease children treated with hydroxyurea: a multicentre prospective study

2021 ◽  
Author(s):  
Berengere Koehl ◽  
Camille Aupiais ◽  
Nelly Schinckel ◽  
Pierre Mornand ◽  
Marie-Hélène Odièvre ◽  
...  
Keyword(s):  
Immune Response ◽  
Sickle Cell Disease ◽  
Adverse Events ◽  
Prospective Study ◽  
Antibody Titre ◽  
Yellow Fever ◽  
Sickle Cell ◽  
Cell Disease ◽  
Protective Antibody ◽  
Antibody Titres

Abstract Background Sickle cell disease (SCD) children are frequent travellers to countries where yellow fever (YF) is endemic, but there are no data regarding the safety and immunogenicity of the vaccine in such children treated with hydroxyurea (HU). The main objective of this study was to compare the tolerance and immune response to YF vaccination in SCD children treated or not with HU. Method SCD children < 18 years attending the international travel clinics of three large paediatric centres and requiring a first YF vaccination were included in a prospective study. Adverse events were collected 2 weeks after vaccination. YF vaccine antibody titres were measured ~6 months after vaccination. Results Among the 52 SCD children vaccinated against YF, 17 (33%) were treated with HU. Only mild adverse events, mainly fever and local reaction, were observed in the HU group with a similar frequency in the non-HU group (57 and 35%, respectively, P = 0.30). YF antibody titres were measured in 15/17 patients in the HU group and 23/35 patients in the non-HU group after a median of 6.0 months (3.5–8.5) following vaccination. The geometric mean of YF antibody titre was similar in both groups. A protective antibody level was observed in 85% of the children in the HU group vs 100% in the non-HU group (P = 0.14), suggesting a lower effectiveness of the vaccine in patients on HU similarly to what has been described in patients on immune suppressive therapy for other vaccines. Conclusion YF vaccination seems to be safe and efficient in SCD children treated with HU. Considering the potential risk of severe complications in cases of YF while travelling in Africa for those patients, the benefit-to-risk ratio argues for YF vaccination in all SCD children. Control of a protective antibody titre may also be useful to ascertain an adequate response in those treated with HU.

scholarly journals Alteration of humoral, cellular and cytokine immune response to inactivated influenza vaccine in patients with Sickle Cell Disease

PLoS ONE ◽  
2019 ◽  
Vol 14 (10) ◽  
pp. e0223991
Author(s):  
Carole Nagant ◽  
Cyril Barbezange ◽  
Laurence Dedeken ◽  
Tatiana Besse-Hammer ◽  
Isabelle Thomas ◽  
...  
Keyword(s):  
Immune Response ◽  
Sickle Cell Disease ◽  
Influenza Vaccine ◽  
Sickle Cell ◽  
Cell Disease

scholarly journals Neuropathic Pain in Children with Sickle Cell Disease: The Hidden Side of the Vaso-Occlusive Crisis

Children ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. 84
Author(s):  
Jeanne Sigalla ◽  
Nathalie Duparc Alegria ◽  
Enora Le Roux ◽  
Artemis Toumazi ◽  
Anne-Françoise Thiollier ◽  
...  
Keyword(s):  
Risk Factors ◽  
Neuropathic Pain ◽  
Sickle Cell Disease ◽  
Sex Ratio ◽  
Prospective Study ◽  
Sickle Cell ◽  
Clinical Presentation ◽  
Early Stage ◽  
Cell Disease ◽  
A Prospective Study

The majority of hospitalizations of patients with sickle cell disease (SCD) are related to painful vaso-occlusive crises (VOCs). Although the pain of VOC is classically nociceptive, neuropathic pain (NP) has also been demonstrated in SCD patients. The aim of our study is to specify the prevalence of NP during VOCs in SCD children using a dedicated scale and to measure its characteristics. We performed a prospective study that included SCD children hospitalized for an acute VOC. The presence of NP was sought with the DN4 scale on the second and fourth days of hospitalization. A total of 54 SCD children were included in the study. Overall, 41% of the patients (n = 22) experienced neuropathic pain during the VOC, mostly at an early stage (Day 2). The median age, the sex ratio, the location of the pain, and the morphine consumption were similar for patients with and without NP. Our study shows that neuropathic pain is very common during VOCs in SCD children. The absence of identified risk factors should prompt us to be vigilant regardless of the patient’s age, sex, and clinical presentation.

Adjuvant interventions with opioids for vaso-occlusive crisis in sickle cell disease: A mixed treatment network meta-analysis of randomized controlled clinical trials

2020 ◽  
Vol 16 (4) ◽  
pp. 267-275
Author(s):  
Kannan Sridharan, MD, DM ◽  
Gowri Sivaramakrishnan, MDS
Keyword(s):  
Nitric Oxide ◽  
Sickle Cell Disease ◽  
Adverse Events ◽  
Magnesium Sulfate ◽  
Sickle Cell ◽  
Meta Analysis ◽  
Favorable Effect ◽  
Secondary Outcome ◽  
Cell Disease ◽  
Number Of Patients

Objective: Vaso-occlusive crisis is the most common clinical feature requiring opioid analgesics in patients with sickle cell disease. We conducted a network meta-analysis to compare the drugs that can be used as add-on with opioids for vaso-occlusive crisis.Design: Network meta-analysis of randomized clinical trials.Patients: Sickle cell disease patients with vaso-occlusive crisis receiving adjuvants to opioids for pain management.Main outcome measures: A number of patients with complete pain relief and pain scores assessed either by visual analog or by a numerical rating scale were the primary outcomes. Adverse events and dose of opioids (in morphine equivalents) for pain alleviation between the treatment arms were the secondary outcome measures.Results: Eleven studies evaluating the addition of ketorolac, magnesium sulfate, ketoprofen, ibuprofen, methadone, inhalational nitric oxide, methylprednisolone, and arginine with morphine were obtained. The pooled analysis showed a favorable effect in the pain reduction for the additions of arginine {–2 [–3.39, –0.61]} and ibuprofen {–1.7 [–3.26, –0.14]} with morphine. Arginine has high probability of being the “best” in the pool followed by ibuprofen. No significant differences were observed in the risk of adverse events {ketoprofen—0.84 [0.42, 1.65]; magnesium sulfate—1.81 [0.64, 5.81]; and arginine—2.08 [0.18, 24.31]}. A significant lower dose of opioid was required when given adjunctive to arginine, inhalational nitric oxide, and methylprednisolone.Conclusion: We observed that arginine and ibuprofen could produce additional analgesic effects when combined with morphine in vaso-occlusive crisis.

Adverse Events in Sickle Cell Patients with Nocturnal Hypoxia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3793-3793
Author(s):  
Andrew D. Campbell ◽  
Megumi Okumura ◽  
Ndidi Unaka ◽  
Sally Hutchinson ◽  
Onyinye Onyekwere
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Sickle Cell Disease ◽  
Adverse Events ◽  
Sickle Cell ◽  
Case Series ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Obstructive Sleep ◽  
The Relationship

Abstract The relationship between hemoglobin dexoygenation and sickling is well known. However, the relationship between hypoxia and severity of disease in sickle cell patients has not been well established. Recently, nocturnal hypoxemia has been associated with higher incidence of CNS events including strokes, and elevated TCDs. We present our case series on 13 patients(12 SS, 1 SC) with sickle cell disease (SCD) who have nocturnal hypoxia. Approximately 75 patients were screened at the University of Michigan Sickle Cell clinic for nocturnal hypoxia either by symptoms of obstructive sleep apnea or by longitudinal baseline clinic 02 saturations (02 Sat <92%). Of the 13 hypoxic pts, median baseline O2 Sat 90%(n=13, mean 90) and the median nocturnal O2sat (Nctnl 02 sat) 84%(n=13, mean 80%) with 10/13 with moderate-severe nocturnal hypoxia (O2sats<85%)based on sleep studies. Multiple adverse events noted in the cohort were pulmonary hypertension (PHTN TRJV>2.5, n=9, median 2.74/mean 2.74,) frequent pain episodes(>3visits to ER or hospitalizations/year, n=7, with 5 pts >5/year ), recurrent acute chest syndrome( ≥ 3 episodes, n= 10), CNS events (n=3 silent infarcts, vascular stenosis), priapism( (n=4, among 6 males ). Also reported were possible causes of the underlying hypoxia including obstructive sleep apnea(OSA)(n=7 of 11 pts), asthma(n= 10 of 13 pts), and chronic lung disease( n=8). In conclusion, the persistence of nocturnal hypoxia in pediatric sickle cell disease could possibly contribute to the development of severe complications of sickle cell disease. Treatment of underlying hypoxia (ie nighttime oxygen, maximize asthma treatment, T&A for OSA)may help prevent complications and lead to the improvement clinical symptoms. Further, chronic nocturnal hypoxia may complicate pulmonary disease and accelerated the development of PHTN. More studies are needed to clarify the mechanism of hypoxia in SCD. Table I. Clinical &Demographic Data of 13 SCD Patients with Nocturnal Hypoxia. Age:(6–22y/o, mean 15) Sex: M=6 F=7 Clinical: Total Mild Mod Sev. Genotype: SS=12, SC=1 Mean Range Nctnl Hypoxia(<%) 13 3 5(<85) 5(<80) Baseline O2 Sat(%) 90 +3.0 86–97 Obstr Sleep Apnea 7 3 3 1 Nctnl 02 sat (%) 80+8.4 59–87 Pulm HTN 9 4 4 1 Total #Apneic Events(11) 65.6+80 6–256 Rest. Lung Ds. 8 2 5 1 Obstr. Apneic Events(7) 27+68.5 0–221 # of Episodes <3 3–4 >4 Hypopneic Events(9) 32.5+38 0–132 ACS 2 5 5 TRJet Velocity 2.74+.42 2–3.5 Severe Pain Crises/yr 1 2 5

Safety and Efficacy of Sildenafil Therapy for Doppler-Defined Pulmonary Hypertension in Patients with Sickle Cell Disease: Preliminary Results of the Walk-PHaSST Clinical Trial.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 571-571 ◽  
Author(s):  
Roberto F Machado ◽  
Robyn J Barst ◽  
Nancy A Yovetich ◽  
Kathryn L Hassell ◽  
Jonathan C. Goldsmith ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Sickle Cell Disease ◽  
Adverse Events ◽  
Arterial Pressure ◽  
Sickle Cell ◽  
Research Funding ◽  
Cell Disease ◽  
Safety And Efficacy ◽  
Preliminary Results ◽  
Significant Difference

Abstract Abstract 571 Background: Pulmonary hypertension (PH) is associated with increased mortality in patients with sickle cell disease (SCD). Methods: Walk-PHaSST (treatment of Pulmonary Hypertension and Sickle cell disease with Sildenafil Therapy) is a multi-center (10 United States and United Kingdom Centers), placebo-controlled, double-blind 16-week trial evaluating the safety and efficacy of oral sildenafil for the treatment of Doppler-defined PH (tricuspid regurgitant jet velocity [TRV] ≥2.7m/s) in adults and children (aged >12 years) with SCD. The primary endpoint was the six-minute walk distance (6MWD). The study was designed with a planned screening of approximately 1000 subjects, to enroll 132 subjects for inclusion in the nested Main Interventional Trial (MIT). In the screening trial, subjects were evaluated by history and physical examination, laboratory screening, transthoracic Doppler echocardiography and 6MWD. Randomized subjects were stratified by TRV (2.7-2.9 m/s and ≥3.0 m/s), and those in upper strata underwent a right heart catheterization (RHC). Preliminary Results: Of the 722 screened subjects, 150 (26%) had both a TRV ≥2.7 m/s AND 6MWD of 150-500 meters (m), qualifying for MIT enrollment. A total of 74 subjects (13%) were randomized into the MIT. The study was prematurely stopped due to a statistically significant increase in serious adverse events (SAEs) in the sildenafil arm after 33 subjects had completed the 16 week assessments and 74 subjects (37 sildenafil: 23 female, 47 ± 12 years, TRV 3.0 ± 0.4 m/s, 6MWD 378 ± 93 m; 37 placebo: 23 female, 44 ± 14 years, TRV 2.9 ± 0.3 m/s, 6MWD 381 ± 75 m) had been randomized in the MIT. To evaluate safety and efficacy, all 74 subjects were evaluated, with pre-defined primary and secondary endpoint analysis and imputation rules for missing data. Baseline gender, hemoglobin phenotype, TRV and 6MWD were similar between sildenafil and placebo (all p>0.05). There was a significant increase in SAEs in the sildenafil arm (46% vs. 22% of randomized subjects; p=0.048) but no significant difference in adverse events (AEs; 76% vs. 68%; p=0.607). Sickle cell anemia with crisis (hospitalization defining the SAE) accounted for the significant difference in SAEs (35% vs. 11%; p=0.025). In reference to AEs, patients on sildenafil tended to have more headache (27% vs. 14%; p=0.247) and more blurred vision (11% vs. 3%; p=0.358). No other SAEs or AEs by organ system or preferred term were significantly different (all p > 0.43). There were no AEs classified as life-threatening and there was one death in the placebo arm. To assess potential efficacy, all 33 subjects with TRV of ≥3.0 m/s underwent RHC and received a single test dose of 60 mg of sildenafil; data are currently availabel for 22 of those subjects. Although this dose of sildenafil acutely decreased mean pulmonary arterial pressure (p=0.01), and mean systemic arterial pressure (p<0.01), the change in pulmonary vascular resistance was not significant. There were no apparent safety issues with the acute sildenafil dosing (e.g. priapism). After 16 weeks of sildenafil, there was no difference in the change in TRV (adjusted mean change from baseline: sildenafil -0.10 ± 0.08 m/s, placebo -0.13 ± 0.8 m/s; p=0.7) or in 6MWD (adjusted mean change from baseline: sildenafil -17 ± 20.9 m, placebo +1.4 ± 21.8 m; p=0.47). On the Brief Pain Inventory (BPI), sildenafil subjects reported worsening pain during walking (p=0.07; p=0.17) and less enjoyment of life (p=0.09; p=0.04) vs. placebo at the interim visits (6 and 10 week, respectively). For subjects in the sildenafil group, no difference was detected in 6MWD for those experiencing a VOC vs. those without a VOC (adjusted mean 386 ± 15.9 m; 372 ± 11.7 m; p=0.39). Preliminary Conclusions: In conclusion, sildenafil significantly increased rates of VOCs requiring hospitalization vs. placebo. The premature study termination for safety concerns limited the sample size for efficacy assessments; however, further investigation may be warranted in a more select group of patients with optimized hydroxyurea and transfusion therapy. Based on the completed analyses, no relationship has been established between experiencing pain (via serious VOC) and 6MWD. Additional analyses will focus on determining whether pain (as measured by BPI) is correlated with change in 6MWD. Finally, these data suggest a potential role for the cyclic cGMP axis in the pathobiology of VOC and sickle cell disease related pain. Disclosures: Barst: Pfizer: Consultancy, Research Funding. Gibbs:Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees. Girgis:Pfizer: Research Funding. Badesch:Pfizer: Consultancy, Research Funding.

A Randomized Trial of the Safety and Benefit of Transfusion Vs. Standard Care In the Prevention of Sickle Cell-Related Complications In Adults: a Preliminary Report From the Phase II NHLBI Comprehensive Sickle Cell Centers (CSCC) Study of Neuropsychological Dysfunction and Neuroimaging Abnormalities In Neurologically Intact Adult Patients with Sickle Cell Disease

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3221-3221 ◽  
Author(s):  
Elliott Vichinsky ◽  
Lynne Neumayr ◽  
Jeffrey I Gold ◽  
Michael W Weiner ◽  
Jeffrey Kasten ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Adverse Events ◽  
Randomized Trial ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Preliminary Report ◽  
Standard Care ◽  
Neurocognitive Function ◽  
Cell Disease ◽  
Transfusion Therapy

Abstract Abstract 3221 Background: Most adult sickle cell anemia patients have received transfusion therapy. However, prospective studies evaluating the efficacy of transfusions in preventing sickle cell-related complications are lacking. The Phase II Neuropsychological Adult Sickle Cell Anemia Study is a randomized trial of chronic transfusion vs. standard of care in patients with abnormal neurocognitive function in order to determine the safety and benefits of transfusion therapy on neurocognitive function. A secondary goal of the study is to evaluate the benefit of chronic transfusion on the frequency and severity of acute sickle cell events; this is a preliminary report of this specific aim. Methods: Eligibility required normal neurological exam, WAIS III PIQ score ≤ 90, hemoglobin ≤ 9 g/dL, hemoglobin SS electrophoresis, and age between 21 and 55 years. Patients were randomly assigned to receive either standard care or transfusions. The transfusion goal was to maintain a hemoglobin of 2 g/dL rise over baseline with matched red cells for D, C/c, E/e, and Kell antigens. The protocol required simple transfusions at approximately 4 week intervals. Chelation therapy was not part of the study design. Patients underwent serial clinical and laboratory evaluations with central analysis of all clinical and transfusion events and complications. Laboratory testing of subjects in the transfusion arm included quantitative hemoglobin S/A, hemoglobin concentration, ferritin levels, and red cell antibody screening; a full hematology/chemistry panel was performed for all subjects at baseline, the study mid-point, and at the end of the study. Results: There were 20 patients in the transfusion arm (TX arm) with a mean age of 29 years vs. 16 patients in the standard care arm (SC arm) with a mean age of 30.5 years. The baseline data in the TX arm was similar to the SC arm: hemoglobin 7.8 vs. 8.0 g/dL; hematocrit 22.6% vs. 23.1%; hemoglobin F 10.5% vs. 12.5%. Thirty-five percent of patients randomized to the TX arm had a history of acute chest syndrome (ACS) vs. 31% in the SC arm; 30% of patients in the TX arm were on hydroxyurea compared to 50% in the SC arm. The TX arm patients have received an average of 5.6 transfusions (2 units per transfusion) with only one subject requiring an acute transfusion (5%); in contrast, 4 SC arm patients (25%) were transfused for acute events for a total of 7 units (average 1.8 per patient). The transfusion therapy improved the average hematologic status of patients: hemoglobin S% decreased from 85% to 32% (p=0.0003); hemoglobin and hematocrit increased from 7.6 to 9.4 g/dL (p=0.0052) and 22% to 28%, (p=0.007), respectively. Bilirubin declined from 3.6 to 2.4 mg/dL (p=0.042). In contrast, only bilirubin showed a significant decrease in the SC arm. In the TX arm, serum ferritin rose an average of 1318 to 2368 (p=.001); there was no change in liver function. There were no clinical transfusion reactions in the 120 study transfusions (360 units); however, one patient on routine screening reported a transient anti-D antibody without clinical or laboratory changes. Clinical Results: Adverse events were higher in the SC arm. Total number of adverse events in the TX arm were 23 (1.2 per person) vs. 66 in (4.1 per person) in the SC arm. There were 5 hospitalizations in the TX arm and 21 in the SC care arm, with a median number of hospitalized days per hospitalization of 5.0 and 6.0 respectively. The total number of serious events was 6 in the TX arm (0.3 per person) vs. 23 in the SC arm (1.4 per person). The total number of vaso-occlusive events in the TX arm were 14 (0.7 per person) vs. 57 (3.6 per person) in the SC arm. Acute pulmonary events occurred in 25% (4 patients) of the SC arm vs. none in the TX arm. Conclusions: This is preliminary data from the first prospective randomized study of the safety and efficacy of transfusion therapy in adults with SCD. We demonstrate the safety of transfusion therapy. Compared to standard therapy, transfusions improve or stabilize critical laboratory markers, decrease serious sickle cell anemia-related adverse events, and decrease in hospitalizations. Increase in ferritin is an expected outcome in transfused patients since chelation was not a part of this transfusion protocol. On completion of the study, the potential benefits of transfusion therapy on sickle cell disease morbidity including neurocognitive function will be reported. Disclosures: Field: Novartis Pharm: Honoraria.

Clinical Benefit and Costs’ Evaluation of Erythocytapheresis Compared to Manual Exchange Transfusion for Children with Sickle Cell Disease: A Single Center Experience

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4091-4091
Author(s):  
Laurence Dedeken ◽  
Phu Quoc Lê ◽  
Laurence Rozen ◽  
Hanane El Kenz ◽  
Sophie Huybrechts ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Adverse Events ◽  
Sickle Cell ◽  
Median Duration ◽  
Exchange Transfusion ◽  
Biological Data ◽  
Acute Chest Syndrome ◽  
Continuous Control ◽  
Cell Disease ◽  
Previously Treated

Abstract Chronic transfusion in sickle cell disease (SCD) remains the gold standard therapy for primary and secondary stroke prevention and is indicated for patients with recurrent severe vaso occlusive crisis (VOC) or acute chest syndrome (ACS). Automatized apheresis (AA) has several advantages compared to manual exchange transfusion (MET): shorter procedure, continuous control of fluid balance, etc. The aim of our study was to assess the safety and efficacy of AA in SCD patients previously treated with MET at Hôpital Universitaire des Enfants Reine Fabiola, Brussels, Belgium and to evaluate the change of the costs related to transfusion and chelation overtime. From January 2012, the AA program for SCD patients started in our institution. Patients on chronic transfusion program (CTP) and previously treated with MET were eligible to switch to AA if sufficient peripheral venous access to allow AA without the use of central venous line and if weight ≥ 30kg. On CTP, target HbS was <30% in case of stroke risk and <50% for other indications. Data on biological values, duration of the procedure, intervals between procedures as well as adverse events were recorded for the last 6 months on MET and compared to the data on AA. The overall costs of last year on MET, 1st year and 2nd year on AA were analysed. The cost of packed red blood cell (RBC), one-day care facility, apheresis kit and chelation were recorded. For patients on AA for less than 2 years, costs for the 2nd year were extrapolated taking into account the data from the 6 previous months. Data were collected for this analysis until June 2014. Friedman test was used to compare treatment across years and Dunn's Multiple Comparison Test to compare each year of treatment among them. Ten patients switched from MET to AA at a median age of 11.8 years (range, 9.6-16.8y). The median duration of MET before start of AA was 1.9 years (range 0.5-4.4y). The median duration of AA was 1.7 years (range 1-2.4y). Four patients are on AA for > 2 years, 4 ≥ 20 months and 2 > than 12 months. Indications for CTP were overt stroke (2), pulmonary hypertension (2), recurrent VOC/ACS (5) and poorly tolerated severe anemia (1). All patients remained stable without any SCD related event, except one child who presented seizures without evidence of new stroke and for whom anticonvulsivant therapy was resumed. HbS level remained in the target values for all patients despite a slightly but significantly higher value on AA. The ferritin level and the duration of the procedure decreased significantly (Table 1). The 2 patients on iron chelation stopped it after 10 and 1 AA procedures. Interval between 2 AA was significantly longer than on MET (P<0.0001). On 181 procedures, 9 adverse events (4.9%) required medical intervention: transient hypotension (1), symptomatic hypocalcemia (2), transient headache (2), fever (1), nausea-vomiting (1) and abdominal pain (2). On AA, the requirement of packed RBC was significantly higher than on MET. During the 1st year, costs of AA were significantly higher than MET (132937€ vs.107560€; P=0.01). Nevertheless, during the 2nd year of treatment, the costs of AA were not significantly different from those on MET (102965€ vs. 107560€). Indeed chelation could be stopped in patients previously treated. AA is useful and safe for SCD patients requiring exchange transfusion program. It is less time consuming for nurses and patients, improves iron overload and interval between 2 procedures is significantly reduced. Despite higher costs related to the increase packed RBC requirement, the costs of AA and MET in the Belgian Health Care System are the same as chelation could be stopped in previously treated patients. Abstract 4091. Table 1.Changes in age, weight, biological data and procedure parameters on MET and on AA On METOn AAP value 1st year 2nd yearMedianRangeMedianRangeMedianRangeMedian age (years)11,89,7-16,812,810,8-17,713,311,8-18,6<0,0001Median weight (kg)45,530,4-66,349,933,8-72,05336,1-76,0<0,0001Median height (cm)153,5138-178161143-180165145-182<0,0001Hb (g/L)9,958,6-10,89,958,8-10,6109,2-11,7NSHb S (%)33,525-424028,5-424631-480,0002Ferritin (µg/L)666182-151225552-8111489-622<0,001Duration of procedure (min)245195-36087,375,5-1269164-1540,0002Interval between procedures (d)2821-293428-35,54228-42<0,0001Packed RBC requirement (ml/kg)18,315,1-2032,227,4-36,13026,8-36<0,0001Packed RBC requirement (unit)39,515-796749-12065,538-137<0,0001 Disclosures No relevant conflicts of interest to declare.

Incidence and Risk of Delayed Hemolytic Transfusion Reaction in Sickle Cell Disease Patients Based on a Prospective Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 95-95 ◽  
Author(s):  
France Pirenne ◽  
David Narbey ◽  
Philippe Chadebech ◽  
Armand Mekontso-Dessap ◽  
Pablo Bartolucci ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Prospective Study ◽  
Sickle Cell ◽  
Acute Chest Syndrome ◽  
Transfusion Reaction ◽  
Cell Disease ◽  
Hemolytic Transfusion Reaction ◽  
Delayed Hemolytic Transfusion Reaction ◽  
Prospective Longitudinal

Abstract Background Delayed hemolytic transfusion reaction (DHTR) is a life threatening complication of transfusion in sickle cell disease (SCD). This syndrome is underestimated because of a clinical picture that resembles a vaso-occlusive crisis (VOC) and the frequent absence of detectable antibodies. Several retrospective studies have evaluated the frequency of DHTR based on case reports. We conducted a prospective, longitudinal, single center study to determine the incidence of DHTR and the risk of developing DHTR depending on the transfusion regimen: chronic versus punctual. Methods and patients SCD patients aged over 18 years, undergoing a transfusion, were enrolled in this study. A total of 697 transfusion episodes (TE) in 312 patients were included during 30 months. Some patients had multiple TE during the period. The post transfusion outcome of the patients was assessed up to one month after the included TE. DHTR was confirmed based on the rapid disappearance of HbA (> 50% 15 days post-transfusion) associated with two of the following criteria up to three weeks after transfusion: VOC symptoms, dark urine, worsening anemia, increased LDH. Transfusion episodes were divided into chronic (336 TE in 111 patients) and punctual (361 TE in 201 patients). Chronic transfusions were defined as regular transfusions to treat chronic complications or for primary/secondary prevention of complications. Short transfusion program during pregnancy was considered as punctual transfusions if patients were not previously regularly transfused. The study obtained approval of the local Ethics Committee. Results Follow-up of the patients after transfusion showed 15 DHTR during the study. They all developed in punctually transfused patients. Thus, patients who are transfused punctually have a significantly higher risk of developing DHTR than those in a regular transfusion program (p < 0.001). When considering only punctual transfusions, the incidence of DHTR is 4.2% per transfusion episode (IC 95% [2.6; 6.9]) and 7.5% per patient during the 30 months of the study (IC 95% [4.6; 12.4]). In these DHTR cases, the transfusion indication was surgery (n = 6), pregnancy (n = 3), acute chest syndrome (n = 3), stroke (n = 1), profound anemia (n = 1), and VOC prevention before a school exam (n = 1 case). Two patients died of multi-organ failure following severe intravascular hemolysis. The median hemoglobin decrease for all DHTR cases after the triggering transfusion was 4.4 g/dl [IQR 3.6-5.2]; the highest LDH level was 879 [IQR 680-1423]. Ten patients developed newly formed antibodies, but only five among them displayed antibodies with significant serological features (anti-Fya, anti-S, anti-Jka, anti-HI). In the five other cases, the antibodies were of unspecified specificity or auto antibodies in the RH blood group (the genetic RH background was known). Finally, antibodies were undetectable for five cases, confirmed by long-term patient follow up. Conclusion This prospective study demonstrates, for the first time, that DHTR is a frequent reaction in adult SCD patients, developing only in occasionally transfused patients. This finding highlights that adult patients with regular transfusion who did not previously encountered DHTR are not susceptible to developing this severe reaction. A mechanism linked to acute situations can be suggested as already shown for the induction of allo-immunization. However, many cases developed without detectable antibodies, confirming the complex pathophysiology of this syndrome. A bio-clinical scoring system to predict DHTR, based on this study, is under development and will be presented. Disclosures Michel: Roche: Research Funding.

Sign in / Sign up

Export Citation Format

Share Document