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.

Clinical and Economic Issues in Multiply Transfused Sickle Cell Disease (SCD) Patients.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1889-1889
Author(s):  
Vishwas S. Sakhalkar ◽  
Diana M. Veillon ◽  
James D. Cotelingam ◽  
Linda M. Hawthorne ◽  
Gloria C. Caldito ◽  
...  
Keyword(s):  
Subsequent Development ◽  
Blood Type ◽  
P Value ◽  
Blood Group Antigens ◽  
Chi Square ◽  
Exact Test ◽  
Number Of Patients ◽  
Before And After ◽  
Patient Groups ◽  
Transfusion Reactions

Abstract Aim: To study alloantibody (alloAB)/autoAB formation and transfusion reactions in 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. Statistical analysis was performed using the Chi square test and Fischer’s exact test. Results: During 1990–2004, 500 SCD patients received 16,617 pRBCs in our hospital. 387 received pRBCs crossmatched for ABO and Rh only; 121 (31.3%) developed alloantibodies (alloABs). Table 1: Transfusion characteristics of patients forming alloABs Data on pts forming alloABs CEK matched patients CEK unmatched pRBC Transfusion (Tn) patients (387) ≥ 1 ABs ≥ 2 ABs ≥ 3 ABs ≥ 4 ABs ≥ 5 ABs Number of patients (% of total) 6/113 (5%) 121/387(31%) 57/121 (47%) 29/57 (51%) 16/29 (55%) 11/29 (69%) # of Tn before AB-Median (range) 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 AB 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 1 12 4 2 1 0 There were 37 transfusion reactions: 9 febrile, 24 allergic and 4 dHTRs, none was life-threatening. 21 pts developed multiple alloABs simultaneously after a single transfusion; 15 additionally developed warm autoABs. >13% patients transfused CEK unmatched units developed ABs to C, E, K and other antigens. Once allosensitized, there was an ↑ chance of subsequent development of multiple alloABs with fewer transfusions. Table 2: Incidence of antibody formation in patient groups Major patient groups Total # of pts Total # of transfusions Number of allo ABs (%of pts) [Incidence/1000 pRBCs] Number of autoABs (%of pts) [Incidence/1000 pRBCs] All Non-CEK Total Warm P value (CEK vs Regular) - # of pts <0.001 0.03 0.005 0.02 CEKmatched 113 2354 6 (5%)[2.55] 5(4%)[2.12] 1 (0.88%)[0.425] 1 (1%)[0.46] Regular (ABORh) 387 14263 240(31%)[16.8] 76 (13%)[5.33] 39 (10%)[2.73] 30 (8%)[2.1] alloAB forming pts 121 7338 240[32.71] 76[10.36] 34 (28%)[4.63] 30 (25%)[4.1] No alloAB pts 266 6925 N/A N/A 5 (2%)[0.7] 0 P value(alloAB vs non-alloAB) - # of pts N/A N/A <0.001 <0.001 Of 266 patients who did not develop any alloABs, 5 had cold and no warm autoABs. 113 patients received 2354 CEKneg pRBCs only (from 1997), 6 (p<0.01) had one alloAB each, 1 warm autoAB and no reactions. Technologists required 30 more minutes and $153 extra in reagent costs for extended CEK match. 90% of our donors are Caucasian. Conclusions: Utilizing CEK negative pRBCs ↓↓ alloAB(p<0.01), autoAB (p<0.001) formation and eliminated transfusion reactions in our multiply transfused SCD patients. Universal availability of leukopoor pRBCs (from 1997) may have eliminated febrile reactions. There was ↓ alloAB formation for C, E, K and other blood group antigens. Though unlikely, Rh neg and CEKneg pRBCs may also be negative for other minor antigens. AutoAB formation (and allergic reactions)especially ↑ in patients with multiple and simultaneous alloAB formation. CEK matching made it easier to find pRBCs due to less formation of alloABs. However, it resulted in marked overuse of Rh neg pRBCs and extra cost and effort to find CEKneg pRBCs for every transfusion. For cost efficacy, one might consider CEKneg pRBCs after first alloAB.

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&lt;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&lt;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&lt;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&lt;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) &lt;0.001 &lt;0.001

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.

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 &lt;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&lt;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.

High-Throughput DNA Analysis for Red Blood Cell Antigens Facilitates the Transfusion Support with Antigen-Matched Blood in Sickle Cell Disease Patients.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 555-555
Author(s):  
Lilian Castilho ◽  
Ghazala Hashmi ◽  
Marion E. Reid ◽  
Tasmia Shariff ◽  
Michael Seul ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Blood Group ◽  
Sickle Cell ◽  
High Throughput ◽  
Dna Analysis ◽  
Blood Type ◽  
Blood Group Antigens ◽  
Nucleotide Polymorphisms ◽  
Cell Disease ◽  
Fast Procedure

Abstract Background: Transfusion dependent patients as those with Sickle Cell Disease (SCD) patients become alloimmunized and have the potential to form additional antibodies with such frequency that antigen-negative blood is preferred to prevent further alloimmunization. Blood group genotyping is playing a supporting role in the routine blood banks, especially for provision of antigen-matched blood for these patients. However, current techniques for genomic typing are all labor-intensive and require manual set up and analysis by gel electrophoresis. As a result, DNA microarrays are being developed for the single nucleotide polymorphisms (SNPs) detection in the blood group genes to provide a fast procedure and an automated analysis of numerous blood group polymorphisms. We evaluated the usefulness of DNA microarray to provide a means to precisely match donor blood to the antigen-negative type of SCD patients. Method: A total of 12 DNA samples from patients with SCD (homozygous for HbS) and 84 DNA samples from blood donors, were analyzed by the HEA Beadchip (Hashmi et al, 2005) containing a total of 18 SNPs (FYA/B, FY-GATA, FY265, DOA/B (nt 378, 624, 793), COA/B, LWA/B, DIA/B, SC1/SC2, M/N, S/s, LUA/B, KEL1/2, JKA/B, DO323, DO350, HgbS) in a single reaction. Results: A genotype result was obtained for all SNPs tested on 96 samples within 4 hours of the start of testing. Results obtained by Beadchip analysis in donors were used to provide antigen-matched blood for FYA/B, FY-GATA, FY265, DOA/B, M/N, S/s KEL1/2, JKA/B, for all 12 SCD patients. This technology provided a fast procedure and facilitated the transfusion support with antigen-matched blood in SCD patients allowing the reduction of alloimunization to blood group antigens. Conclusion: This high-throughput DNA analysis has the potential not only to increase the inventory of antigen-negative blood but also to facilitate the matching of RBC component to the recipient’s blood type. It also contributes to the management of transfusions in SCD patients by allowing a more accurate selection of donor units. The application of microarray technology in transfusion medicine may have a tremendous impact on further improvement of the safety of blood transfusion.

Experience of an Interdisciplinary Pediatric Pain Service

PEDIATRICS ◽  
1991 ◽  
Vol 88 (6) ◽  
pp. 1226-1232
Author(s):  
Barbara S. Shapiro ◽  
David E. Cohen ◽  
Kenneth W. Covelman ◽  
Carol J. Howe ◽  
Sam M. Scott
Keyword(s):  
Sickle Cell Disease ◽  
Patient Care ◽  
Sickle Cell ◽  
Health Care Professionals ◽  
Tertiary Care ◽  
Direct Patient Care ◽  
Team Approach ◽  
Cell Disease ◽  
Number Of Patients ◽  
Physician Time

This article is a report of our experience with an interdisciplinary pain service in a large tertiary care pediatric hospital. During the first 2 years of operation, we received 869 consultations and referrals from more than 19 hospital divisions. Postoperative pain was the most frequent reason for consultation (56% of patients). Patients with pain related to cancer and sickle cell disease comprised 25% of the consultations. The remaining patients had a wide variety of primary diagnoses and causes of pain. We calculated the time spent by pain service physicians in direct patient care. The majority (63%) of physician time was spent with a small number of patients (17%). Most of these patients had pain that was unrelated to surgery, cancer, or sickle cell disease, and many posed dilemmas in diagnosis and treatment. Physician time was correlated directly to the use of psychologic and physical therapies for the pain, involving multiple team members. This experience supports the demand for an interdisciplinary pain service in a tertiary care children's hospital. A significant amount of physician time is necessary to provide patient care and to maintain a team approach, however, and pediatricians and other health care professionals who aim to implement such services should be cognizant of the time required.

scholarly journals Utility of Procalcitonin in Differentiating Acute Chest Syndrome from Vaso-Occlusive Crisis in Sickle Cell Disease

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 10-11
Author(s):  
Satish Maharaj ◽  
Simone Chang ◽  
Karan Seegobin ◽  
Marwan Shaikh ◽  
Kamila I. Cisak
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Complete Blood Count ◽  
Conflicts Of Interest ◽  
Statistical Significance ◽  
Acute Chest Syndrome ◽  
Adult Males ◽  
Cell Disease ◽  
Unequal Variances ◽  
Recorded Data

Background: Acute chest syndrome (ACS) frequently complicates sickle cell disease (SCD) and is a leading cause of hospitalization and mortality. Many factors have been implicated in ACS, including infections, thrombosis, fat and pulmonary emboli. However, a clear etiology is not defined in 50% of the cases and ACS is considered a clinical endpoint for different pathogenic processes (Vichinsky et al 2000). The non-specific nature of ACS makes diagnostic tests challenging, and there are no serum tests clinical used to aid diagnosis. Procalcitonin (PCT) is a prohormone of calcitonin and serum PCT rises within hours of an inflammatory stimulus. PCT has clinical utility as a marker of severe systemic inflammation, infection, and sepsis (Becker et al. 2008). Few studies have evaluated PCT as a biomarker for ACS in patients presenting with vaso-occlusive crises (VOC). Two studies have reported no difference in PCT (Biemond et al. 2018 and Stankovic et al 2011), while one study reported higher PCT between ACS and VOC (Patel et al 2014). Methods: We retrospectively reviewed 106 patients with SCD who presented to the emergency department with fever and painful crises during 2015-2019. The patients were divided into two categories based on discharge diagnoses - patients with VOC only (n=88) and patients with ACS (n=18). Inclusion criteria for both groups were patients with SCD, 17 years and older and PCT measurement on presentation. Exclusion criteria were defined as patients who had received empiric antibiotics prior to PCT testing. Data collected on presentation included genotype, age, gender, complete blood count, PCT, creatinine, total bilirubin and hydroxyurea use. Length of stay was recorded. Data was analyzed between the two groups using descriptive statistics and accounting for unequal variances, withp-value set at 0.05 for significance. Results: Demographics and clinical characteristics are summarized in Table 1 (Figure). The sample included primarily adult males (77%), with about two-thirds on hydroxyurea. Genotype HbSS (73.6%) was most prevalent followed by HbSC (22.6%) and HbSβ (3.8%). The ACS group had a higher percentage of HbSS, lower use of hydroxyurea and higher mean bilirubin. Mean PCT for the ACS group was 0.52 ng/mL (range, 0.05-2.04), compared to 0.31 ng/mL (range, 0.02-6.82) in the VOC group; withp=0.084. ROC analysis showed a PCT&gt;0.5ng/mL had 39% sensitivity and 85% specificity for ACS in this sample. Conclusion: In this sample, PCT on presentation was higher in those with ACS compared to VOC, but this difference did not achieve statistical significance. Further study in a larger population would be useful to evaluate this finding. Disclosures No relevant conflicts of interest to declare.

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.

Does Treatment with Hydroxyurea and Opioids Affect Age of Death in Sickle Cell Disease Patients?

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4808-4808
Author(s):  
Charlene M. Flahiff ◽  
Jude C Jonassaint ◽  
Charles R. Jonassaint ◽  
Soheir S. Adam ◽  
Marilyn J. Telen ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Treatment Modality ◽  
Group Analysis ◽  
Treatment Modalities ◽  
Age At Death ◽  
Cell Disease ◽  
Number Of Patients ◽  
Living Group ◽  
Age Of Death

Abstract Hydroxyurea (HU) is used to treat sickle cell disease and has been shown to decrease painful episodes (Charache, 1995) and possibly vaso-occlusive episodes associated morbidity and mortality (Steinberg, 2003). Opioids are often prescribed in adult patients for daily management of their chronic pain. The aim of the current study was to determine the age at death and the effect of treatment with HU and/or opioids prior to death in patients who died from sickle cell disease (SCD) related complications and to compare these parameters to those in our current patients population. Methods: Age, daily treatment with opioids, and HU treatment were determined for 185 patients currently followed at the Duke Comprehensive Sickle Cell Center (DCSCC) and for 50 patients who died between 2002 and 2008 due to SCD complications and who were regularly followed at the DCSCC for their care. The two cohorts, living and deceased patients were divided based on their treatment modality into the following 4 groups: opioid only, HU only, both drugs, and neither drug. Non-parametric chi-square test was performed to determine whether the treatment modality distribution was different in the deceased group compared to the living group. Analysis of variance was done to determine the relationship between treatment group and age at death. Results and Discussion: The distribution of treatment modalities in the deceased group was significantly different than that of the living group. The opioids only group had the largest number of patients in the deceased cohort (44%), and this percentage was almost twice that of the living group (25%). (Fig. 1) Moreover, 72 % of the deceased patients were treated with opioids vs. only 53 % of the living patients, perhaps because the sicker patients are often treated with daily opioids. However, the age of death in the opioids only group was 44 ± 15.5 years. (Fig. 2) In the living group, treatment with both drugs or with no drugs were equivalent (28%), while in the deceased group, more patients were treated with both drugs (28%) compared to no drug treatment (18%). The HU only group had the lowest number of deaths (10%), and the percentage of patients in this group was nearly half that the one of the living group (19%). This group also was the oldest at death (58 ±16 years). Age at death was also significantly higher in this group than in each of the other 3 groups (p&lt;0.05). The low use of HU in the deceased cohort, along with the higher age of death, support the reported effectiveness of this drug in reducing morbidity associated with SCD. The age of the living patients receiving treatment with both drugs was the same as that of the deceased. Similarly the age of the non treated living patients was comparable with that of the deceased group. Interestingly, the interaction of the 2 therapeutic interventions (HU and opiates) had a significant effect on the age at death (p=0.003). We conclude that opioid treatment, either alone or in conjunction with HU, appears to have a significant effect on the age at death and warrants further investigation.

Implementation of a European Cohort to Follow Sickle Cell Children and Adults Treated with Hydroxycarbamide

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 564-564
Author(s):  
Mariane De Montalembert ◽  
Frédéric Galacteros ◽  
Jean Antoine Ribeil ◽  
Uwe Kordes ◽  
Jean Benoit Arlet ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Safety Profile ◽  
Conflicts Of Interest ◽  
Subcutaneous Tissue ◽  
Acute Chest Syndrome ◽  
Control Group ◽  
Cell Disease ◽  
Skin Reactions ◽  
Number Of Patients

Abstract Hydroxycarbamide (HU) is a myelosuppressive drug marketed since 1968 for the treatment of hematological cancer, and authorized since 2007 in Europe as orphan medicinal product for the prevention of recurrent vaso-occlusive crises including acute chest syndrome in adults and children older than 2 years with sickle cell disease (SCD). ESCORT-HU (European Sickle Cell Disease Cohort – Hydroxyurea) is a multicenter prospective non interventional study implemented in Europe to collect more information about the safety profile of HU and morbi-mortality in SCD patients treated with HU. The study responds to EMA (European Medicines Agency) request and has been approved by the Ethical of Necker Enfants Malades Hospital (Paris, France).The ongoing study involves the largest number so far of patients with SCD treated with HU. Primary endpoints of ESCORT HU are to determine frequency of adverse events, and possible consequent changes of HU treatment. Secondary endpoints are to evaluate morbi-mortality of the disease although in the absence of control group. From June 2008 to June 2014, 483 patients (255 females; 228 males) were enrolled from 3 European countries, Greece (24%), Germany (19%), and France (56%). 67% patients were adults, median aged 37.35 yrs (17-83.5) and 33% were children, median aged 11.06 yrs (2.6-16.9). genotypes were HbS/HbS in 71.4% cases, and compound heterozygotous HbS/β-thalassemia in 22.8 % (Table 1). 137 (28.4%) patients experienced 421 events (Table 2). 132 (32.2%) of these events may be attributed to HU. The safety profile is roughly similar in children and adults. As expected the most frequent side effects were firstly blood disorders (n=86 events, 42.4%) such as neutropenia or thrombocytopenia. In all cases, these cytopenias were rapidly resolved with the transitory stop of HU. 71 events related to skin and subcutaneous tissue disorders were observed, mostly cutaneous dryness, skin reactions, alopecia and nails or skin pigmentation; 4 patients had a leg ulcer (34.8%). Most of these events are ongoing or stabilized despit the decrease of HU. No secondary cancer has been reported until now. Even if HU is an old drug with a relatively well-known safety profile, some uncertainties remain in terms of long-term safety as well as tolerance in the youngest people. The main interest of ESCORT HU is to offer the possibility of safety surveillance of hydroxycarbamide in European sickle cell patients. Table 1 Demographic data Adults Children < 17 years old Total Number of patients 322 (67%) 161 (33%) 483 Females/Males 183/139 72/89 255/228 Median age (yrs) (range) 37.35 (17-83.5) 11.06 (2.6-16.9) 28.58 Genotype SS 206 (64%) 139 (86.3%) 345 (71.4%) SC 1 (0.3%) 3 (1.86%) 4 (0.8%) Sβ0 51 (15.8%) 11 (6.8%) 62 (12.8%) Sβ+ 46 (14.2%) 2 (1.2%) 48 (9.9%) Other 18 (5.5%) 6 (3.7%) 24 (4.9%) Treatment with HU before enrollment in ESCORT HU No of pts 232 83 315 (65%) Median duration (range) of HU treatment before ESCORT HU 8.2 yrs (0.5 ans-24 yrs) 3. 1 yrs ( 71 days – 8.9 yrs) 6.85 (71 days-24 years)] HU ESCORT Daily mean dose (mg/kg/d) 16.11 ± 4.79 19.63 ± 4.69 17.32 ± 4.94 Abstract 564. Table 2 The most frequent events of hydroxycarbamide in the two populations of SCD patients ADULTS CHILDREN No ofGerman(%) No of adults No ofEpisodes(%) No of children Total(% /411) Events Related to HU treatment (Siklos®)(%**) Blood and lymphatic system disorders (%) 32 (17.7) 22 54 (31.03) 28 86 (20.9) 56 (65.1) Skin and subcutaneous tissue disorders (%) 42 (23.2) 28 29 (16.7) 19 71 (17.3) 46 (64.8) Nervous system disorders Headache (24), Dizziness/vertigo (14), 32 (17.7) 23 12(6.9) 10 44 (10.7) 11 (25) Gastrointestinal disorders Nausea (14), diarrhea (8), other (14) 20 (11) 17 23 (13.2) 16 43 (10.4) 7 (16.3) Metabolic and nutrition disorders: vit D deficiency (17), weight gain (5) 13 (7) 11 18 (18.3) 18 36 (8.75) 4 (11.1) Fever 11 (6) 10 12(6.9) 7 23 (5.6) 1 (4.3) Cardiac disorders (hypertension, bradycardia, chest pain, cardiomegaly) 4 4 2 2 6 1 (16.6) General disorders : fatigue 5 5 0 0 5 0 Hepatobiliary disorders 2 2 0 0 2 0 Neoplasms benign, malignant and unspecified (incl. cysts and polyps) Harmatoma, benign vulvar sebaceous cyst 2 2 0 0 2 0 Renal & urinary disorders 2 2 0 0 2 0 Reproductive system and breast disorders 3 3 0 0 3 0 Other 13 13 21 14 34 6 (17.1%) 181 80 /181(24.8%) 174 57 / 174(35.4%) 411 132/411 (32.2%) ** compared to the total number of “system organ class” events Disclosures No relevant conflicts of interest to declare.

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