HLA Antibodies and Their Association with Blood Product Exposures in Pediatric Patients Undergoing Cardiac Transplantation

2021 ◽  
Author(s):  
Susana Cruz‐Beltran ◽  
Andrea Lane ◽  
Shivani Seth ◽  
Kati Miller ◽  
Reneé H. Moore ◽  
...  
Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2285-2285
Author(s):  
Ashanka M Beligaswatte ◽  
Eleni Tsiopelas ◽  
Ian Humphreys ◽  
Greg Bennett ◽  
Kathryn Robinson ◽  
...  

Abstract Abstract 2285 Background: HLA allo-immunized patients often receive matched platelets only after demonstrating platelet transfusion refractoriness (PTR). If further risk stratification was possible, high risk patients could be considered for pre-emptive HLA-matched platelets, cryopreserved autologous platelets, or possibly thrombopoietin analogues. Micro-bead flow cytometry is widely used to detect anti-HLA antibodies, and mean fluorescence intensities (MFI) obtained from these assays correlate with antibody titers. We asked whether MFIs could be used to stratify the risk of PTR among allo-immunized patients. Study design: We retrospectively identified 387 patients who received an autologous stem cell transplant or induction therapy for acute leukemia, between January 2005 and March 2012. All patients had a serum sample taken for HLA antibody assay within 6 weeks of commencing cellular blood product transfusions. No patient was scheduled to receive prophylactic HLA matched platelets. The primary endpoint was the development of PTR. To minimize the influence of sensitization occurring after screening, only outcomes during the first 2 weeks from commencing cellular blood product transfusions were considered. PTR was defined as having received ≥ 2 consecutive RDPLT transfusions associated with an 18–24h corrected count increment of < 2.5 at 18 – 24 hours. Antibody testing was performed using a micro-bead flow cytometry assay (Lifecodes LifeScreen Deluxe, with positive results confirmed by Lifecodes Class I ID assay, Gen-Probe Transplant Diagnostics, Stamford, CT) either during the treatment period, or on serum samples stored at −30°C. Mean fluorescence intensities (MFI) were acquired using a Luminex 100 analyzer (Luminex Corporation, Austin, TX), and analyzed using Lifecodes Quicktype v2.5.5 (Gen-Probe Transplant Diagnostics, Stamford, CT). We defined the predictor variable avgMFI to be the average MFI of the 7 individual beads in the assay, weighted by whether the presence of antibodies was confirmed or not: where w = 1 if the presence of antibodies is confirmed, and 0 otherwise; and subscript i refers to the ith class I bead. Results: Antibodies were detected in 57 (14.7%) patients of whom 45 (78.9%) were female. A total of 1443 random donor platelet (RDPLT) transfusions (mean platelet count 2.4×1011/unit) were studied. Sixty six (17%) patients developed PTR, of whom 28 had detectable antibodies; 29 of 321 patients who did not develop PTR also tested positive. Among antibody positive patients, median avgMFI for refractory patients was 4589 versus 349 for patients who were not, Wilcoxon rank sum test P< 0.0001. (Figure 1). The area under the receiver operating characteristic curve for avgMFI as a predictor of PTR was 0.8633 (95% confidence interval: 0.7664 – 0.9602). Higher avgMFIs also correlated with a broader range of target antigens, likely due to increasingly avid binding to cross-reactive epitopes. (Spearman's r = 0.7736 for correlation between avgMFI and panel reactive antibody percentages (cPRA), calculated in reference to the general American population, and used here as a surrogate for the range of antibody specificities). cPRA was >80% in 25/27 patients with avgMFI>1000, suggesting poor ability to discriminate among patients with moderate to high antibody titers, and was not an independent predictor of PTR. Hence, while the increased probability of encountering a cognate antigen on a RDPLT may partly explain the correlation between avgMFI and PTR, the avidity of binding, represented in vitro by the MFIs, appears to be a more significant determinant of risk. In conclusion, we provide evidence for the concept that PTR risk due to HLA allo-immunization is usefully predicted by the MFIs of antibodies detected using micro-bead flow cytometry. Our model allows cut-offs for identifying high risk patients to be based on the degree of risk acceptable in a given clinical situation. This should enable hematology units to develop risk-adapted strategies for supporting allo-immunized thrombocytopenic patients. Disclosures: No relevant conflicts of interest to declare.


2015 ◽  
Vol 34 (4) ◽  
pp. S302-S303
Author(s):  
P. Shah ◽  
A.M. Jackson ◽  
M.C. Philogene ◽  
S.S. Desai ◽  
N.A. Burton ◽  
...  

2015 ◽  
Vol 34 (8) ◽  
pp. 1095-1102 ◽  
Author(s):  
Claire A. Irving ◽  
Andrew R. Gennery ◽  
Vaughan Carter ◽  
Jonathan P. Wallis ◽  
Asif Hasan ◽  
...  

2012 ◽  
Vol 31 (4) ◽  
pp. S140
Author(s):  
C. Irving ◽  
V. Carter ◽  
A. Gennery ◽  
G. Parry ◽  
A. Hasan ◽  
...  

2009 ◽  
Vol 87 (6) ◽  
pp. 864-871 ◽  
Author(s):  
John D. Smith ◽  
Iman M. Hamour ◽  
Margaret M. Burke ◽  
Balikrishnan Mahesh ◽  
Rachel E. Stanford ◽  
...  

2010 ◽  
Vol 8 (3) ◽  
pp. 0-0
Author(s):  
Rita Sudikienė ◽  
Radvilė Malickaitė ◽  
Virgilijus Lebetkevičius ◽  
Virgilijus Tarutis ◽  
Kęstutis Ručinskas ◽  
...  

Rita Sudikienė1,2 , Radvilė Malickaitė2 , Virgilijus Lebetkevičius2 , Virgilijus Tarutis2 , Kęstutis Ručinskas2 , Vytautas Sirvydis2 1Vilniaus universiteto Vaikų ligų klinika2Vilniaus universiteto Širdies ir kraujagyslių ligų klinika, Santariškių g. 2, LT-08661 Vilnius El. paštas: rita.sudikienė@santa.lt Įvadas: Kardiomiopatijos ir įgimtos širdies ydos yra paskutinės stadijos, nepagydomo širdies nepakankamumo priežastys vaikų amžiuje. Efektyviausias gydymo metodas yra širdies transplantacija. Endomiokardo biopsija yra pripažinta atmetimo diagnostikos aukso standartu, tačiau echokardiografija yra svarbiausias neinvazinis tyrimas po širdies persodinimo. Darbo tikslas: Įvertinti Vilniaus širdies chirurgijos centre vaikams atliktų širdies transplantacijų rezultatus ir palyginti su literatūros duomenimis. Echokardiografijos tyrimu mėginti optimizuoti parametrus, kuriais vadovaujantis būtų galima įtarti ankstyvuosius atmetimo požymius, juos susieti su biopsijos duomenimis, imunologiniais ir biocheminiais pakitimais. Ligoniai metodai: Vilniaus širdies chirurgijos centre nuo 2001 metų atliktos penkios širdies transplantacijos vaikams. Pagrindinės komplikacijos: atmetimo reakcija, infekcija ir imunosupresinio gydymo šalutinis poveikis. Pagrindinis dėmesys skirtas diastolinės funkcijos vertinimui echokardiografiniu būdu. Rezultatai: Echokardiografijos metodu vertinant mitralinio vožtuvo žiedo judesio greitį sistolėje ir diastolėje (Sm ir E’) ir transmitralinio ankstyvos diastolės mitralinio vožtuvo greičio E ir E’ santykį (E/E’), buvo rasta koreliacija su 2R atmetimo reakcija, ši koreliacija patvirtinta biopsijos duomenimis bei natriuretinio peptido (BNP) padidėjimu. Nustatyta, kad kiekvienam pacientui yra svarbi jo paties echokardiografinių duomenų ir BNP kaita (pasikeitimas iki 10 % susijęs su atmetimu). Išvados: Širdies transplantacija yra veiksmingos kraštutinai sunkaus vaikų širdies nepakankamumo gydymo metodas. Prieš širdies transplantaciją būtina įvertinti recipiento santykinės rizikos veiksnių, tinkamai paruošti transplantacijai didelės rizikos pacientus, kad būtų išvengta ūminio atmetimo reakcijos ankstyvuoju laikotarpiu. Būtina indukcinio gydymo standartizacija. Echokardiografijos metodu tiriant diastolinę funkciją, pagal E, E’ greičius bei jų santykį E/E’, taip pat BNP pokyčius galima įtarti ar paneigti atmetimo reakciją ir sumažinti širdies biopsijų skaičių. Echokardiografija yra labai svarbus metodas humoraliniam transplantato atmetimui nustatyti, kai biopsijos atsakymas neigiamas. Reikšminiai žodžiai: vaikų širdies transplantacija, transplantato atmetimas, imunosupresija po transplantacijos Cardiac transplantation in pediatric patients: experience of vilnius cardiac surgery center Rita Sudikienė1,2 , Radvilė Malickaitė2 , Virgilijus Lebetkevičius2 , Virgilijus Tarutis2 , Kęstutis Ručinskas2 , Vytautas Sirvydis2 1Vilnius University Clinic of Children’s Diseases2Vilnius University, Clinic of Cardiovascular Diseases, Santariškių str. 2, LT-08661 Vilnius, Lithuania E-mail: rita.sudikienė@santa.lt Pediatric heart transplantation is a surgical therapy for dilated cardiomyopathy and for complex congenital heart defects. Endomiocardial biopsies have remained a gold standard to detect the rejection. Echocardiography remains the main noninvasive method of the follow-up. We report the experience of the Vilnius hHeart sSurgery cCenter. Assessment of the diastolic dysfunction by tissue doppler and correlation with biopsy and BNP was assessed. E/E‘ <7 and BNP >100 pg/ml was associated with 0-1R rejection, E/E‘ >7 and BNP> 200 pg/ml was related with 2R rejection. Keywords: cardiac transplantation in pediatric patients


2011 ◽  
Vol 32 (5) ◽  
pp. 615-620 ◽  
Author(s):  
Victoria Scott ◽  
Ryan J. Williams ◽  
Daniel S. Levi

2018 ◽  
Vol 37 (4) ◽  
pp. S114
Author(s):  
M.L. Sell ◽  
A.L. Haney ◽  
K. Sprott ◽  
A. Burnette ◽  
H. Henderson ◽  
...  

2000 ◽  
Vol 119 (2) ◽  
pp. 324-330 ◽  
Author(s):  
John A. Hawkins ◽  
John P. Breinholt ◽  
Linda M. Lambert ◽  
Thomas C. Fuller ◽  
Tracie Profaizer ◽  
...  

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