Autoantibody Formation in Sickle Cell Disease Patients Receiving Multiple Blood Transfusions.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3186-3186
Author(s):  
Vishwas S. Sakhalkar ◽  
Diana M. Veillon ◽  
James D. Cotelingam ◽  
Deborah M. McCaskill ◽  
Gloria C. Caldito ◽  
...  
Keyword(s):  
Immune System ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Medical Center ◽  
Blood Type ◽  
P Value ◽  
Cell Disease ◽  
Exact Test ◽  
Patient Groups ◽  
Autoantibody Formation

Abstract Aim: To study autoantibody (autoAB) formation in our sickle cell disease (SCD) patients before and after instituting the practice of transfusing C, E, K blood type negative (CEKneg) packed red blood cell (pRBC) units. Material and Methods: We retrospectively reviewed blood bank records of all SCD patients that were transfused pRBCs since 1990 to date. Statistical analysis was performed using the Chi square test and Fischer’s exact test. Results: During 1990–2004, a total 500 SCD patients (240 male, 260 female) received 16,617 pRBCs in our medical center. Of these, 387 (178m, 209f) received 7338 sickle negative ‘regular’ pRBC units crossmatched only for ABO and Rh blood types. 121 (31.3%, 56m, 65f) patients received 7338 pRBCs and developed alloantibodies (alloABs), and those patients developed 4 cold and 30 warm autoABs. 266 patients (68.7%, m, f; 6925 transfusions) never developed alloABs, but 5 patients developed cold and no warm autoABs. 16 patients developed autoABs (15 warm) simultaneously in addition to the multiple alloABs after a single pRBC transfusion. 113 patients (62m, 51f) always received 2354 CEKneg pRBCs (from 1997), 6 patients (4m, 2f; p<0.01) developed one alloAB each and only 1 warm autoAB.Patients receiving CEK matched pRBCS developed autoABs at 6 times↓frequency. It was found that the technologist required 30 more minutes and $153 extra in reagent costs for this extended CEK match. It was found that most Rh negative pRBC units were also CEKneg. 90% of our donors are Caucasian. The patients who received only ABORh matched transfusions and yet did not develop alloABs, also did not develop any warm autoABs compared to 30 warm autoABs encountered in corresponding patients that developed alloABs (p<0.001). Extended antigen matching (by an additional C,E,K antigen match) ↓ alloAB and autoAB formation. In some patients, allosensitization possibly activates the immune system into a hyperactive state leading to further, earlier, multiple and simultaneous alloAB and autoAB formation. Conclusions: This study showed that utilizing CEK negative pRBCs dramatically ↓ autoAB formation in our SCD patients. Patients that did not develop alloABs also did not develop any warm autoABs (p<0.001). AutoAB formation was more common in patients that developed multiple alloABs simultaneously, but did not result in any significant complications. These patients were also more prone to develop allergic reactions (p<0.002), prompting speculation whether allosensitization possibly activates the immune system into a hyperactive state or if certain patients are gentically more predisposed to allosensitization or both. In our population, extended antigen matching made it easier to transfuse blood units due to less formation of alloABs and autoABs. However, it resulted in a significant overuse of Rh negative pRBCs and extra cost and effort to find CEKneg pRBCs for every transfusion. Table: Incidence of autoantibody formation in patient groups Major patient groups # of pts # of pRBCs Number of autoABs (% of patients)[Incidence/1000 Tx ] Total Warm P value (CEK vs Regular) 0.005 0.02 CEKmatched Tn pts 113 2354 1 (0.88%)[0.425] 1 (1%)[0.46] Regular (ABORh) 387 14263 39 (10%)[2.73] 30 (8%)[2.1] alloAB forming pts 121 7338 34 (28%)[4.63 ] 30 (25%)[4.1] No alloAB forming pts 266 6925 5 (2%)[0.7] 0 P value(alloAB vs non-alloAB) <0.001 <0.001

Alloantibody Formation in Sickle Cell Disease Patients Receiving Multiple Transfusions.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3795-3795
Author(s):  
Vishwas S. Sakhalkar ◽  
Diana M. Veillon ◽  
James D. Cotelingam ◽  
Gloria C. Caldito ◽  
Deborah M. McCaskill ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Blood Type ◽  
Blood Group Antigens ◽  
Adult Males ◽  
Cell Disease ◽  
Chi Square ◽  
Exact Test ◽  
Number Of Patients ◽  
Patient Groups

Abstract Aim: To study allosensitization in our sickle cell disease (SCD) patients before and after instituting the practice of transfusing C, E, K blood type negative (CEKneg) packed red blood cell (pRBC) units. Material and Methods: We retrospectively reviewed blood bank records of all SCD patients that were transfused pRBCs since 1990 to date. Statistical analysis was performed using the Chi square test and Fischer’s exact test. Results: See table 1. Table I: General data of various patient groups Major patient groups Total pt # (%) Sex (m/f) Pt age in yrs, Median (range) Total pRBC units Median Tn #/pt(range) 121 (31.3%, 56m, 65f) developed alloantibodies (alloABs). Grand total of all patients 500 240/260 22 (0.7–79) 16617 14 (1–524) CEK (& ABO) matched tn pts 113 62/51 8 (0.5–35) 2354 10 (1–143) Regular (ABORh) matched Tn pts 387 (100) 178/209 26 (0.7–79) 14263 18 (1–524) AlloAB forming patients 121 (31.3) 56/65 29 (5–70) 7338 26 (1–500) Non-alloAB forming pts 266 (68.7) 122/144 25 (0.7–79) 6925 12 (1–524) Table II: Transfusion characteristics of patients forming alloantibodies Data on pts forming alloantibodies CEK matched patients CEK unmatched pRBC Transfusion (Tn) patients(387) >0 ABs >1 ABs >2 ABs >3 ABs >4 ABs Number of patients 6/113 121/387(31%) 57/121 (47%) 29/57 (51%) 16/29 (55%) 11/29 # of Transfusions before AB formation 9.5 (0–106) 7 (0–270) 2 (0–106) 0 (0–89) 0 (0–180) 0 (0–16) # of pts with > 5 Tn before alloAB formed 4/6(67%) 68/121(56%) 21/57(37%) 5/29(17%) 4/16(25%) 1/11(9%) # of pts with >30 Tn before AB formed 1 12 4 2 1 0 There were 33 patients with anti-C, 74 with anti-E, and 57 with anti-K ABs (a total of 164, incidence of 2.235 CEK alloABs/100 transfusions{Tn}). 266 patients (6925 Tn, 68%) did not develop any alloABs. 21 patients developed multiple alloABs simultaneously after a single transfusion. pRBC Tn was 1½ times more likely to lead to alloAB formation in adult females (p=0.006) and children (p=0.011) over adult males. >13% patients transfused with CEK unmatched units developed ABs to C, E, K and other antigens. 2/3 patients never developed ABs. Once allosensitized, there was an sustained ↑ chance of developing a 2nd (& later) AB (50% Vs 31% for first timers) with fewer Tn (usually <5). A small number of patients developed alloABs later (>30 pRBCs). Patients receiving CEK matched pRBCs developed non-CEK ABs at 2½ times lower frequency than the corresponding group of patients. It was found that the technologist required 30 more minutes and $153 extra in reagent costs for this extended CEK match. Most Rh negative pRBC units were also CEKneg. 90% of our donors are Caucasian. Conclusions: This study showed that utilizing CEK negative pRBCs dramatically ↓ alloAB(p<0.01) formation in our SCD patients, including C, E, and K and other minor blood group antigens. Patients transfused without C, E, K antigen match developed ABs to C, E, K, and other antigens. In some patients, allosensitization possibly activates the immune system into a hyperactive state leading to further, earlier, multiple and simultaneous alloAB and autoAB formation. Though unlikely, Rh negative and CEKneg pRBCs may also be negative for other minor antigens. Extended antigen matching made it easier to find proper blood units due to less formation of alloABs. However, it resulted in overuse of Rh negative pRBCs and effort to find CEKneg pRBCs for every transfusion.

Transfusion Reactions in Sickle Cell Disease (SCD) Patients Receiving Multiple Blood Transfusions.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 946-946
Author(s):  
Vishwas S. Sakhalkar ◽  
Diana M. Veillon ◽  
James D. Cotelingam ◽  
Linda M. Hawthorne ◽  
Gloria C. Caldito ◽  
...  
Keyword(s):  
Medical Center ◽  
Blood Type ◽  
P Value ◽  
Transfusion Reaction ◽  
Chi Square ◽  
Exact Test ◽  
Number Of Patients ◽  
Before And After ◽  
Patient Groups ◽  
Transfusion Reactions

Abstract Aim: To study transfusion reactions in our SCD patients before and after instituting the practice of transfusing C, E, K blood type negative (CEKneg) packed red blood cell (pRBC) units. Material and Methods: We retrospectively reviewed blood bank records of all SCD patients transfused pRBCs since 1990. Statistical analysis was performed using the Chi square test and Fischer’s exact test. Results: During 1990–2004, 500 SCD patients received pRBCs in our medical center. Of these, 387 received pRBC units crossmatched only for ABO and Rh blood types and suffered 37 transfusion reactions. Table I: General data of various patient groups Major patient groups Number of patients Median age in yrs # of pRBCs Tx Total (%) Sex (m/f) (range) Total units Median (range) Grand total of all patients 500 240/260 22 (0.7–79) 16617 14 (1–524) CEK (&ABO) matched transfusion patients 113 62/51 8 (0.5–35) 2354 10 (1–143) Regular (only ABORh) matched Tx patients 387 (100) 178/209 26 (0.7–79) 14263 18 (1–524) AlloAB forming patients 121 (31.3) 56/65 29 (5–70) 7338 26 (1–500) Non-alloAB forming pts 266 (68.7) 122/144 25 (0.7–79) 6925 12 (1–524) Table 2: Transfusion reactions in various patient groups Major patient groups Total # of pts Total # of pRBCs Transfusion reactions (% of pts) [Incidence/1000 Tx] Total Febrile Allergic dHTR CEK matched pts 113 2354 0 0 0 0 Regular (ABORh) Tx pts 387 14263 37 (10%)[2.594] 10 23 (6%)[1.61] 4 (1%)[0.28] AlloAB forming pts 121 7338 23 (19%)[3.134] 4 (3%)[0.55] 15 (12%)[2.04] 4 (3%)[0.55] Non-alloAB forming pts 266 6925 14 (5%)[2.0] 6(2%)[0.87] 8 (3%)[1.16] 0 P value (alloAB vs non-alloAB) # of pts 0.25 0.684 0.266 - P value (alloAB vs non-alloAB) # of Tx <0.001 0.809 0.002 - 121 developed alloantibodies (alloABs). 113 patients always received CEKneg pRBCs (from 1997). The technologist required 30 more minutes and $153 extra in reagent costs for this extended CEK match. Most Rh negative pRBC units were also CEKneg. 90% of our donors are Caucasian. Discussion: ’Non-alloAB forming’ patients who received ABORh matched transfusions were 4 times less likely (and twice less likely when number of transfusions was considered) to develop allergic transfusion reaction (p=0.002), compared with ’alloAB forming’ counterparts. Similar finding is seen in patients receiving CEK matched pRBCs. It would be interesting to know if ’slow/rapid/non alloAB producer patients had any genetic predisposition accounting for early/slow/non-development of ABs and transfusion reactions or if alloAB formation transforms the immune system to a hyper-reactive state leading to autoAB formation/allergic reaction. Conclusions: This study showed that utilizing extended antigen (C, E, K) matching for pRBC transfusion ↓↓ alloAB(p<0.01) and autoAB(p=0.005) formation in our SCD patients and eliminated transfusion reactions. Universal availability of leukopoor pRBCs may have eliminated febrile reactions. AlloAB forming patients were more prone to develop allergic transfusion reaction (p=0.002). AutoAB formation was more common in patients with alloABs and did not cause complications. dHTRs were rare and mild. CEK matching made it easier to find and transfuse blood due to less formation of ABs and reactions. However, it resulted in marked overuse of Rh negative pRBCs, extra cost and additional effort to find CEKneg pRBCs for every transfusion.

scholarly journals 3458 Temporal Trends and Outcomes of Opioid Abuse among Adolescents & Young Adult Sickle Cell Disease Patients

2019 ◽  
Vol 3 (s1) ◽  
pp. 54-55
Author(s):  
Nnaemeka E Onyeakusi ◽  
Adebamike Oshunbade ◽  
Fahad Mukhtar ◽  
Adeyinka Adejumo ◽  
Semiu Gbadamosi ◽  
...  
Keyword(s):  
Young Adults ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Temporal Trends ◽  
Opioid Abuse ◽  
P Value ◽  
Total Charge ◽  
Inpatient Mortality ◽  
Cell Disease ◽  
Sickle Cell Crisis

OBJECTIVES/SPECIFIC AIMS: In this study, we aim to describe temporal trends in opioid abuse among adolescents and 11-21years and young adults 22-35years with Sickle cell disease hospitalized for sickle cell crisis. We also aim to evaluate clinical and healthcare utilization outcomes of opioid abuse in the same population. In addition, we hope to assess for difference in effect by age category. METHODS/STUDY POPULATION: Our study is a cross-sectional study of data secondarily sourced from the 2007-2014 National Inpatient Sample(NIS), a component of the Healthcare Utilization Project (HCUP). Variables were identified using ICD-9-CM codes. We selected inpatient stays for patients aged 11-35 years admitted for sickle cell crisis. Opioid abuse was the primary outcome of interest. Secondary outcomes were inpatient mortality, total charge, length of stay and select clinical outcomes. We analyzed our data for trends and outcomes. We performed trend analysis of prevalence rates between 2007-2014 by age categories. Propensity-Matched Score regression models were deployed to assess for associations between opioid abuse and outcomes while adjusting for relevant covariates. Sub-group analysis of opioid abuse by age was assessed for outcomes of interest. Trend analysis was performed on Joinpoint Software v4.6.0, (National Cancer Institute, NIH, Bethesda, MD). Outcome analysis was performed on SAS v9.4 (SAS Institute, Cary, NC). Statistical significance was set at 95% and p-value of 0.05, two-tailed. RESULTS/ANTICIPATED RESULTS: Of 86,827 inpatients admitted for sickle cell crisis, 2,363 (2.73%) had a diagnosis of opioid abuse while 84,464 (97.27%)did not abuse opioids. 27,004 (31.01%) of admitted patients were 11-21 years while 59,823 (68.99%) were 21-35 years. We found statistically significant APCs (Annual Percentage Change) showing increasing trends in both age categories for years under review, (18.47% [95% CI 15.39-21.63]; p-value <0.001 in young adults vs. 10.31% [95% CI 3.58-17.49]; p-value 0.009 in adolescents). The difference in APCs between both age categories were also significant (−8.16% [95% CI [−14.26-2.05]; p-value 0.009). There were no parallelism or coincidence in the trend lines. Opioid abuse was found to be associated with significantly longer length of stay (7.74 vs 6.05 days), higher total charge ($40,797 vs $32,164), (aOR 1.44; 95% CI [1.19-1.75]) seizures, sepsis (aOR 1.62; 95% CI [1.35-1.94]) and pulmonary hypertension (aOR 1.36; 95% CI [1.12-1.66]). No significant association was found for inpatient mortality, transfusion, cardiac dysrhythmias, pulmonary embolism and acute kidney injury. Significant interaction existed between opioid abuse and age for total charge (for $41,869 vs $29,371 among adolescents & $40,632 vs $32,550 among young adults; interaction p-value 0.03). DISCUSSION/SIGNIFICANCE OF IMPACT: Trends show a significant increase in the prevalence of opioid abuse among adolescents and an increasingly higher prevalence when adolescents transition to young adults. Opioid abuse among sickle cell patients is associated with significant poor healthcare resource utilization and clinical outcomes. Public health interventions to prevent worsening opioid abuse prevalence are expected to improve patient outcomes.

Autoantibody Formation and Alloimunization in Sickle Cell Disease Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4099-4099
Author(s):  
Marcia C.Z. Novaretti ◽  
Eduardo Jens ◽  
Thiago Pagliarini ◽  
Andreia L. Rodrigues ◽  
Pedro E. Dorlhiac-Llacer ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Study Group ◽  
Cell Disease ◽  
The One ◽  
Design And Methods ◽  
The Impact ◽  
Transfusion History ◽  
Autoantibody Formation

Abstract Background: Alloantibody and autoantibody formation to red blood cell (RBC) antigens is one of the observed complications in sickle cell disease patients (SCD). The incidence of alloimmunization and autoantibodies in this selected group of patients is particularly high, although the clinical implication of autoantibodies in sickle cell disease patients is not clear. The purpose of this study is to evaluate the rate of alloantibody and autoantibody formation in SCD patients. Study design and methods: A retrospective analysis of transfused sickle cell disease patients followed at Fundacao Pro-Sangue Hemocentro de Sao Paulo between 1988 and 2004 were retrieved. Data on transfusion history, were correlated with development of alloantibodies and autoantibodies. Results: The study group was composed by 43 sickle cell disease patients followed for a mean of 89 months (22–116). The number of RBC units transfused (mean) was 64 (4–208). The development of the first alloantibody was detected after a mean of 40 months (1–107) after the first transfusion in our institution. Out of these patients, 31 (72.1%) were identified with RBC alloantibodies; 9 of these patients (21%) had both allo and autoantibodies to RBC antigens, whereas 5 (55.6%) developed autoantibodies after alloimmunization. The one remainder had only autoantibodies. Conclusion: The alloimmunization rate was extremely high (72.1%) and can be partially explained because of the extended time of follow-up (mean of 89 months). Different from the literature the development of autoantibodies preceeded alloantibodies in 44.4%. The impact of this observation in clinical practice warrants further investigation.

Genetic Polymorphisms Associated with Priapism in Sickle Cell Disease.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 789-789
Author(s):  
Laine Elliott ◽  
Allison E. Ashley-Koch ◽  
Jude Jonassaint ◽  
Jennifer Price ◽  
Jason Galloway ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Linkage Disequilibrium ◽  
Sickle Cell Disease ◽  
Candidate Genes ◽  
Sickle Cell ◽  
P Value ◽  
Cell Disease ◽  
P Values ◽  
History Of ◽  
Male Patients

Abstract Priapism, a painful and prolonged erection, has been reported to occur in 30–45% of male patients with sickle cell disease (SCD). However, little is known about the pathological processes and genetic risk factors that contribute to the occurrence of priapism. The identification of genetic variables that are associated with priapism may therefore help define both critical pathophysiologic mechanisms not otherwise apparent, as well as patients at increased risk. We examined genetic variation in our sample of 199 unrelated, adult (&gt;18 years), male patients with Hb SS and Hb Sβ0-thalassemia, 83 (42%) of whom reported a history of priapism. Candidate genes for association with priapism were identified based on their involvement in adhesion, coagulation, inflammation, and cell signaling. Additionally, we examined genes involved in NO biology (NOS2, NOS3, SOD1, SLC4A1). Finally, we also examined polymorphisms in the KLOTHO gene, which has previously been associated with priapism. We examined a total of 389 SNPs in 48 candidate genes. Except for the gene encoding the β2 adrenergic receptor, SNP genotyping was performed by TaqMan, using Assays-on-Demand or Assays-by-Design genotyping products (Applied Biosystems). Allele tests were used to detect genetic associations with priapism. Strong evidence of association was found for SNP rs7526590 in the transforming growth factor-β receptor, type III (TGFBR3) gene (p=.00058), SNP rs10244884 in the aquaporin (AQP1) gene (p=.00068), and SNP rs3768780 in the integrin αV (ITGAV) gene (p=0.00090). A second ITGAV SNP (rs3768778), in linkage disequilibrium (r2=.59) with the first, also showed association with priapism (p=.00888). The A1 subunit of coagulation factor XIII (F13A1) had four SNPs (hcv1860621, rs1032045, rs1674074, rs381061) with p-values less than 0.010 (p-values = 0.00156, 0.00415, 0.00648, and 0.00712, respectively). The linkage disequilibrium among these F13A1 SNPs is negligible (r2 &lt;.15). We also adjusted for multiple testing using the Benjamini-Hochberg procedure (significance threshold &lt;.10). SNP rs7526590 in TGFBR3, SNP rs10244884 in AQP1 and SNP rs3768780 in ITGAV each had a false discovery rate (FDR) p-value of .09834. SNP rs1674074 in F13A1 had an FDR p-value of .12733. The other SNPs in F13A1 had large FDR p-values, close to .30. We did not detect an association between priapism and genetic variation in the Klotho gene, as was previously reported by Nolan et al. (2005). Specifically, SNPs rs2249358, rs211234 and rs211239 showed a virtually identical distribution of genotypes for individuals with and without a history of priapism. However, our population is not identical to the previous study, which included patients as young as 10 years old. In conclusion, our data support the hypothesis that genetic variation is associated with risk for priapism among males with SCD and suggest that genes involved in the TGFβ pathway, coagulation, cell adhesion and cell hydration pathways may be important.

Impact of Hydroxyurea on Thrombin Antithrombin Complex and Vaso-Occlusive Crisis in Pediatric Sickle Cell Disease.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5525-5525
Author(s):  
Mohsen Saleh Elalfy ◽  
Ashraf M. Abdelmonem ◽  
Soha Youssef ◽  
Heba Ismail
Keyword(s):  
Sickle Cell Disease ◽  
Blood Transfusion ◽  
Sickle Cell ◽  
Coagulation System ◽  
P Value ◽  
Cell Disease ◽  
Significant Difference ◽  
Healthy Control ◽  
Pain Crisis

Abstract Background: Several studies suggest that increased activity of the coagulation system may be important in the pathogenesis of vascular occlusion in sickle cell disease. Hydroxyurea (HU) has been shown to reduce the frequency of vaso-occlusive manifestations in both adults and children with sickle cell disease (SCD). Aim: To analyze the effect of HU on Thrombin-Antithrombin (TAT) as a marker of thrombin generation and hypercoagualbility in SCD and to find out the relation between TAT level and vaso-occusive crisis. Subjects and Method: we evaluated 37 child with sickle cell hemoglobinopathy (mean age 10.92±5.39 years) and 15 normal control children (mean age 9.75±6.34 years). Informed consent was obtained from patients and/or guardians and study approval by local IRB was obtained. Twenty-two patients (59.5%) were on HU, 15 (41.5%) patients did not receive HU, 7 (46.7%) of them were transfusion dependant. TAT assay was done in vitro using a sandwich enzyme immunoassay. Results: Mean patients’ age at institution of HU was 8.54± 3.85 years with median treatment duration of 4.5 years. Causes for initiating HU therapy were frequent blood transfusion in 11 patients (50%), frequent pain crisis (≥ 3/year) in 9 patients (41%), severe anemia and parents refusing blood transfusion in 1 patient (4.5%) and stroke in another patient (4.5%). HU dose was 20.82±4.95 mg/kg/day. We measured TAT in all patients and compared them to healthy control. There was significant difference in TAT level in sickle cell patients (198.86±185.7) compared to healthy control 2.91±0.94, [P value < 0.0001]. When the level of TAT was compared between the HU and non-HU groups we found that patients on HU had statistically significant lower TAT level (172.36 vs.225.37) [P=0.039]. There was also a significant negative correlation between HU dose and TAT level (p=0.03). A significant positive correlation between number of vaso-occlusive crisis/year [P=0.03], frequency of pain crisis/year [P=0.04], duration of pain crisis [P=0.03] and TAT level was observed. Conclusion: Hydroxyurea has significant inhibitory effect on thrombogenesis in sickle cell patients, which may be another mechanism for reducing vaso-occlusive crisis. Sickle cell children with higher TAT level had more frequent and severe vaso-occlusive crisis.

RH Gene Polymorphisms Are Risk Factor for Alloimmunization in Patients with Sickle Cell Disease.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 455-455 ◽  
Author(s):  
Connie M. Westhoff ◽  
Sunitha Vege
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Cost Effective ◽  
Blood Group Antigens ◽  
Cell Disease ◽  
Negative Effects ◽  
Transfusion Therapy ◽  
Risk Patients ◽  
Patient Groups ◽  
Red Cell Transfusion

Abstract Transfusion therapy for treatment of sickle cell disease (SCD) is predicted to increase, following the significant benefit of chronic red cell transfusion demonstrated by the stroke prevention trial (STOP). Despite progress in mitigating negative effects of transfusion therapy with the use of iron chelating agents, alloimmunization remains a significant problem. Patients with SCD have a higher incidence of antibody production compared to other patient groups undergoing chronic transfusion. To limit alloimmunization, many programs transfuse SCD patients with RBCs that are phenotype-matched for the most immunogenic blood groups, Rh and K, and some programs also supply RBCs from African-American (AA) donors. Although this approach reduces the incidence of alloantibody production, it is resource- and cost-prohibitive for many programs, and, importantly, some patients (∼5%) still become alloimmunized. The development of high-throughput genotyping for blood group antigens will make antigen-matching cost effective; therefore, it is important to determine why some patients become alloimmunized despite antigen-matching. We investigated the antibody specificity and sequenced the RH genes in 46 SCD patients who were alloimmunized, despite having received Rh and K matched units. The antibodies identified included anti-D, or -C, or -e, and/or antibodies to high-prevalence antigens. None had anti-E. RH gene sequencing revealed that 20 patients had a RHD-CE(3–7)-D hybrid gene in which RHD exons 3 through 7 are replaced with reciprocal exons from RHCE. The resulting Rh protein encodes an altered C antigen. This D-CE-D gene was also linked to an RHce allele encoding altered e antigen. These patients had anti-C and/or anti-e in their serum (i.e.-hrB). We screened healthy AA donors and found that the prevalence of the hybrid RHD-CE(3–7)-D gene in this population is 5–8%. The remaining 26 patients were homozygous for mutations in RHce and had produced anti-e, and some also had mutations in RHD and had produced anti-D. These results suggest that inheritance of a RHD-CE-D gene or altered RHce, with or without altered RHD, underlies Rh alloimmunization in SCD. The altered Rh proteins are not distinguished with current serologic typing reagents. Therefore, these patients are not truly Rh antigen matched. The development of RH genotyping platforms offers a potential solution to prevent alloimmunization by identifying SCD patients who are homozygous for variant alleles and at risk for production of alloantibodies to Rh antigens. The 5–8% of donor units with the same RH genotype could be directed to these high risk patients.

Improvement In Acute Management of Vaso-Occlusive Pain In Pediatric Sickle Cell Disease with Use of a Clinical Pathway

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2660-2660
Author(s):  
Katherine Ender ◽  
Jennifer Freed ◽  
John Babineau ◽  
Mary Tresgallo ◽  
William Schechter ◽  
...  
Keyword(s):  
Pain Management ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Clinical Pathway ◽  
Clinical Pathways ◽  
Capture Rate ◽  
Tertiary Care ◽  
P Value ◽  
Time Interval ◽  
Cell Disease

Abstract Abstract 2660 Background: Sickle cell disease causes considerable morbidity and mortality. Three guidelines exist for the management of vaso-occlusive pain, although studies have shown that these guidelines are not well followed and that there is considerable variation in care. Investigations of clinical pathways for pediatric sickle cell pain have not been published to our knowledge, but research in other pediatric conditions has shown that the implementation of clinical pathways can improve medical care. We initiated an investigation of the effects of a pain management pathway for sickle cell vaso-occlusive crisis in the emergency department (ED) with the hypothesis that the introduction of a clinical pathway would improve the efficiency and efficacy of acute pain management. Methods: We conducted a prospective, cohort study from February 2009 to March 2010 in an urban, tertiary care ED. We collected data from patients aged 3–18 years old with sickle cell disease who presented to the ED with vaso-occlusive crisis (VOC) pain. Baseline data was collected for five months prior to the introduction of the clinical pathway, followed by a four-week time interval in which the ED physicians and nurses were in-serviced on the pathway, followed by six months in which data was collected with the clinical pathway in place. Our pathway, which is in checklist format with instructions for triage, monitoring, medication administration, and timing of assessments and interventions, was developed by representatives from the divisions of Pediatric Hematology, Pediatric Emergency Medicine, and Pediatric Pain Medicine, Symptom Management and Palliative Care and based upon current standard-of-care guidelines. Results: Over the eleven month study period, 68 patients were enrolled. Random chart audits revealed a 75% capture rate. Significant improvement was demonstrated in time interval to first analgesic from 74 minutes to 42 minutes (p value 0.02), time interval to first opioid from 94 minutes to 46 minutes (p value < 0.01), and time interval to subsequent assessment of pain score from 110 minutes to 72 minutes (p value 0.02). The percentage of patients who received ketorolac also increased from 57% to 82% (p value 0.03). Change in pain scores was not significantly different, nor was admission rate. Conclusions: Implementation of a pain management pathway for sickle cell VOC led to an improvement in the time interval to administration of first analgesic and time interval to pain re-assessment, bringing these aspects of patient management closer to accepted guidelines. Whether improvement can be made in admission rates, change in pain ratings, and patient satisfaction will require further study. Disclosures: No relevant conflicts of interest to declare.

Timing of the Initiation of Hydroxyurea and Hematologic Outcomes in Patients with Sickle Cell Disease (SCD)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1004-1004
Author(s):  
Shaina Willen ◽  
Nirmish Shah ◽  
Courtney Thornburg ◽  
Jennifer Rothman
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Significant Relationship ◽  
Medical Center ◽  
Fetal Hemoglobin ◽  
Clinical Severity ◽  
Cell Disease ◽  
Younger Age ◽  
The Mean

Abstract Abstract 1004 Hydroxyurea (HU) is approved for use in adults with Sickle Cell Disease (SCD) and increases the production of fetal hemoglobin (HbF). Increased HbF is associated with decreased clinical severity in adults and children with SCD, such as decreased numbers of vaso-occlusive events, transfusions, and hospitalizations. Higher HbF at initiation of HU is predictive of HbF response, but association between age of hydroxyurea initiation and HbF response has not been investigated. We hypothesize that starting hydroxyurea at an early age may improve hematological and clinical response. In order to determine if younger age at hydroxyurea initiation affects the percentage of HbF achieved with hydroxyurea, we conducted a retrospective cohort study. We identified subjects enrolled in the Duke University Medical Center Comprehensive Sickle Cell program who initiated hydroxyurea when they were less than 17.99 years of age and were prescribed hydroxyurea for at least six months. The following data were abstracted from the medical record between December 1996 and April 2011: age, hemoglobin, percentage HbF, and mean corpuscular volume (MCV) at start of HU and at maximum tolerated dose (MTD) of HU therapy. The correlation coefficient and p-values for various parameters were calculated. Seventy-three patients (41 males and 32 females) were included in the analysis. The mean age at hydroxyurea initiation was 5.5 years (1.2–14.1). The mean hydroxyurea dose at MTD was 28.6 ± 3.2 mg/kg/day. At initiation, the mean hemoglobin was 8.2 ± 1.2 g/dL, the mean MCV was 83±7.4 fl and mean HbF was 10 ± 5.7%. At MTD, the mean hemoglobin was 9.4 ± 1.1 g/dL, the mean MCV was 99 ± 11.1 fl, and the mean HbF was 21.7 ± 9.4%. As expected, at MTD, an elevated MCV was correlated with elevated fetal hemoglobin (r2= 0.19, p= 0.0001) [Table 1]. There was a statistically significant relationship between the age at HU initiation and the HbF at MTD (r2= 0.08, p= 0.015) [Figure 1] as well as the age at HU initiation and the hemoglobin at MTD (r2= 0.19, p= 0.016). The relationship between the age at starting HU and the overall change in HbF (DHbF) was not statistically significant (r2= 0.01, p= 0.41). There was not a statistically significant relationship between age at HU initiation and the MTD of HU (r2= 0.003, p= 0.61). The 6 patients started on HU at age less than 2 years (mean 1.5 ± 0.3 years) maintained a mean elevated HbF of 19.1 ± 5% at last documented follow-up with follow-up ranging from 1.4–13 year of uninterrupted hydroxyurea use. Starting hydroxyurea therapy at a younger age appears to improve HbF response as measured at MTD, although there is variability in the level of fetal hemoglobin attained. There is not an association seen with the DHbF or dose at MTD and age at hydroxyurea initiation. In summary, starting hydroxyurea at a younger age, when HbF is >20%, leads to persistence of HbF production and overall improvement in hematological efficacy. This was not simply the result of achieving MTD at a younger age before physiologic decline of HbF. Disclosures: Off Label Use: Hydroxyurea for complications of sickle cell disease in pediatrics. Shah:Eisai: Research Funding; Adventrx: Consultancy.

Reduction of the Six-Minute Walk Distance in Children with Sickle Cell Disease Is Correlated with Silent Infarct: Results From a Cross-Sectional Evaluation in a Single Center in Belgium.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2107-2107
Author(s):  
Rudy Chapusette ◽  
Laurence Dedeken ◽  
Phu-Quoc Le ◽  
Catherine Heijmans ◽  
Christine Devalck ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Exercise Capacity ◽  
Sickle Cell ◽  
P Value ◽  
Cell Disease ◽  
Walk Distance ◽  
Cross Sectional ◽  
History Of ◽  
Minute Walk Distance ◽  
Minute Walk

Abstract Abstract 2107 The 6-minute walk test (6MWT) evaluates the sub-maximal functional exercise capacity and can be used together with the tricuspid regurgitant jet velocity (TRV) and pro-BNP to screen pulmonary hypertension in adults with sickle cell disease (SCD). A reduced 6-minute walk distance (6MWD) is observed in adults with SCD with chronic pain, hip avascular necrosis and osteopenia. In children with SCD, baseline elevated TRV is associated with a decline in age-standardized 6MWD. The aim of our study is to explore the submaximal exercise capacity of children with SCD followed at the Hôpital Universitaire des Enfants Reine Fabiola, Brussels, Belgium and to analyze the factors affecting the 6MWT and the 6MWD. Since September 2011, all patients with SCD above 6 years of age were screened with the 6MWT as part of their follow-up in order to test if their functional capacity was altered. The age-standardized predicted value of the 6MWD was established as reported by Geiger. The 6MWT was considered as normal if the 6MWD was more than 80% of the age-standardized predicted value, moderately decreased between 60–80%, and severely altered less than 60%. Baseline hematological values, clinical events, cerebro-vascular disease, cardio-pulmonary parameters and disease-modifying treatment (DMT) were compared between those with normal and abnormal 6MWT and according to the 6MWD. Forty-six patients (20 boys and 26 girls) with a median age of 12 yrs were investigated. Forty-three were HbSS or HbSβ°, 2 HbSC and 1 HbSβ+. Thirty-two patients had a normal 6MWT and 14 an abnormal 6MWT. Only one patient had a severely altered test. These 2 groups were similar for age, sex, genotype and history of vaso-occlusive crisis or acute chest syndrome (ACS) as well as for the number of patients receiving DMT (either hydroxyurea (HU) or chronic transfusion). The proportion of patients with normal, conditional or abnormal transcranial doppler was also similar in both groups. Silent infarct (SI) on routine cerebral magnetic resonance imaging was found in 42.9% in the group with abnormal 6MWT versus only 19.4% in the group with normal 6MWT (p= 0.087). Pulmonary functional test, blood pressure, heart rate, systolic function and TRV were identical in both groups and only one patient had TRV >2.5m/sec. Baseline pulse oxymetry was slightly but significantly decreased in patients with abnormal 6MWT (98 versus 100%; p=0.022). Biological parameters were not statistically different between both groups. The 6MWD was not modified according to Hb, MCV, HbF, LDH and reticulocytes count or previous history of clinical event, except for the presence of SI (Table 1). Patients with or without SI were similar for age, sex, previous ACS or painful crisis as well as for hemolytic parameters (LDH: 945 versus 825 UI/l, p=0.832; reticulocytes: 273 versus 329 × 103/μl, p=0.548) and basal Hb (9.7 versus 8.8 g/dl, p=0.06). However patients without SI had significantly higher HbF and MCV values, and lower PMN count reflecting that most of them were treated with HU. In this cross-sectional study, the majority of children with SCD have a normal 6MWT. Abnormal 6MWT was not predicted by any clinical or biological features despite a trend to more SI in the group of children with abnormal test. In this series with only one high TRV patient, the sole factor which influences the 6MWD is the presence of SI. The lower exercise capacity of children with SCD with silent stroke may reflect some subclinical motor or sensitive impairment. Our data suggest also that HU might prevent SI which needs to be confirmed by larger prospective studies. Table 1. 6-minute walk distance (6MWD) in 46 SCD children according to their biological values and clinical complications Mean 6MWD in meters (SD) p value Mean Age in years (SD) p value Hemoglobin (g/dl) · ≥ 9 (N = 24) 531.5 (95.4) 0.173 11.2 (2.8) <0.001 · < 9 (N = 22) 569.8 (92.2) 14.5 (2.7) MCV (fL) · ≥ 90 (N = 24) 536.1 (100.7) 0.251 12.6 (3.5) 0.518 · < 90 (N = 22) 568.3 (86.8) 13.2 (2.8) HbF (%)* · ≥ 10% (N = 30) 544.0 (101.7) 0.360 13.2 (3.5) 0.352 · <10% (N = 15) 570.1 (81.8) 12.6 (2.4) LDH (UI/l) · ≥ 1000 (N = 14) 526.8 (86.5) 0.229 11.8 (3.0) 0.105 · < 1000 (N = 32) 562.3 (97.4) 13.4 (3.1) Previous ACS* · Yes (N = 38) 548.6 (98.3) 0.625 13.5 (3.1) 0.453 · No (N = 7) 566.9 (85.5) 12.5 (4.2) Silent Infarct · Yes (N = 12) 502.5 (113.9) 0.035 12.1 (2.2) 0.374 · No (N = 34) 568.9 (82.0) 13.2 (3.4) * Missed information for 1 patient. Disclosures: No relevant conflicts of interest to declare.

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