1-hour Corrected Count Increment Research Articles

Analysis of platelet transfusion efficacy during extracorporeal membrane oxygenation (ECMO) treatment in pediatric patients post-cardiac surgery-a retrospective cohort study.

Postoperative extracorporeal membrane oxygenation (ECMO) may be necessary for pediatric patients following cardiac surgery, with associated risks of thrombocytopenia and bleeding. Prophylactic platelet transfusions are utilized to mitigate these risks, but the effectiveness of platelet transfusion cannot be reliably predicted. The aim of this study was to investigate the effect of platelet transfusion during postoperative treatment with ECMO in children undergoing cardiac surgery and to explore the optimal transfusion thresholds to reduce the number of platelet transfusions in patients and reduce the risk of death. We included in our study patients from the Pediatric Cardiac Surgery Department at the First Affiliated Hospital of Tsinghua University who underwent cardiac surgery and received ECMO treatment from January 1, 2019, to December 31, 2023, and received platelets transfusion at least once during the ECMO therapy. The platelet counts were determined both before and 24 hours posttransfusion of the platelet product. The corrected count increment (CCI) was calculated for the effectiveness estimation of platelet transfusion. The research subjects were divided into 3 groups based on the platelet count before transfusion (pretransfusion platelet count ≤30×109/L was the low-threshold group, pretransfusion count 31-50×109/L was the medium-threshold group, and ≥51×109/L was the high-threshold group) and the effective rates of each group were calculated. A total of 11 patients received 47 platelet transfusions, an average of 4.27 ± 1.67 per patient. According to the 24-hour postinfusion platelet (Plt) corrected critical control increase index (24-hour CCI) ≥4500, the infusion was considered to be effective, and ineffective when the CCI was <4500. Out of these, 22 transfusions (46.8%) proved effective, whereas 25 (53.2%) were deemed ineffective. The effective transfusion rates across the 3 groups were 69.2%, 50%, and 27.7%, respectively. The efficacy of platelet transfusion may be higher if a low threshold of platelet transfusion is chosen during ECMO treatment, on the premise of ensuring life safety.

Alloantibody Levels, Immunoglobulin Degradation Products, and Platelet Transfusion Response over Successful Desensitization of Severe Alloimmune Platelet Refractoriness with a Novel IgG-Targeted Enzyme Therapeutic

INTRODUCTION Alloimmune platelet refractoriness (APR), an insufficient response to platelet transfusion due to anti-HLA alloantibodies, affects ~25% of acute myeloid leukemia (AML) patients. In APR, HLA- or crossmatch-compatible platelet units may not be identifiable, precluding transfusion and increasing hemorrhage risk. Single antigen bead testing (SAB) semi-quantitates antibody levels against cognate HLA antigens in units of mean fluorescence intensity (MFI). MFI &amp;gt;3,000 suggests an incompatible platelet antigen for transfusion. Imlifidase, an IgG-specific cysteine protease, cleaves IgG first into single-cleaved IgG (scIgG) with limited Fc-mediated function, then into inactive F(ab') fragments 1. We previously reported successful desensitization and provision of permissive platelet transfusions in an APR patient following desensitization treatment with imlifidase. Here we report pre- and post-desensitization alloantibody (PDAb) levels in correlation with IgG degradation products and response to single donor platelet transfusion. CASE As described previously 2, a 43-year-old highly sensitized (calculated PRA [cPRA] 99.9%) woman with AML and history of life-threatening thrombocytopenic hemorrhage secondary to APR presented for matched-unrelated donor stem cell transplantation. Nationwide, few compatible platelet units were identified to support her through the anticipated platelet nadir. Following conventional desensitization, cPRA did not change significantly. Following imlifidase-desensitization [0.25 mg/kg IV (D-1 and D1)], cPRA decreased significantly. 7 single-donor, antigen-avoidance platelet units produced corrected count increments (CCI) [median (interquartile range) of 6,000 (500-7500)]. The patient experienced no hemorrhage and was discharged stable, post-platelet engraftment on D+19. METHODS With IRB approval, patient data and samples (D-16; D-1 post-conventional desensitization with rituximab and therapeutic plasma exchange; D0 post-imlifidase dose 1; D2 post-imlifidase dose 2; and D7, D14 and D29 follow-up samples) were collected. Serial dilutions of patient D-1 serum were tested with SAB (LABScreen single antigen, One Lambda/ThermoFisher, West Hills, California). SDS-PAGE (gradient gel, non-reduced conditions), Western Blot (antiF(ab') detection), and SAB were performed and acceptable antigens (to molecular specificity, targeted by MFI ≤3,000) were compared over the clinical course. Summative MFIs targeting transfused single donor platelet units were compared with 1-hour CCI. Wilcoxon matched-pairs signed rank for matched, nonparametric values and Chi-squared or Fisher's exact for categorical variables were used. P &amp;lt;0.05 was significant. RESULTS/DISCUSSION The D-1 sample (post-conventional desensitization, pre-imlifidase) showed exquisite HLA sensitization. The highest Class A and B antibodies demonstrated an effective MFI of &amp;gt;4,000,000, each (Fig. A). PDAb and the number of unacceptable antigens decreased significantly in D0 (post-imlifidase) vs. D-1 (pre-imlifidase) samples; Intact IgG and scIgG were eliminated from the D0 and D2 samples (Fig. B). Of 7 single donor platelet transfusions, the 5 producing adequate response were each targeted by a summative MFI ≤4,000 (median 4,000 MFI, range 300-4,000). The 2 units producing inadequate CCI response were targeted by summative MFI &amp;gt;4,000 (5,050, 4,900-5,200), suggesting a threshold summative MFI precluding adequate response. CONCLUSIONS Here we show that the patient's pre-desensitization alloantibody levels significantly exceeded the analytical range of the SAB; PDAb levels declined significantly from baseline, correlating with lack of intact IgG and scIgG following imlifidase; and permissive transfusions (CCI &amp;gt;5,000) were seen to platelets targeted by ≤4,000 summative MFI. These results suggest imlifidase is capable of effective desensitization despite profound baseline sensitization, with rapid cleavage of intact IgG to F(ab'), resulting in the temporary reduction of unacceptable antigens. Larger scale investigation of imlifidase in desensitization of APR patients requiring significant transfusion over a limited period of time, along with investigation into transfusion strategies in desensitized APR, are warranted. REFERENCES Am J Transpl. 2022;22(3):691-697.Blood. 2022;140 (Suppl. 1):8562-3. .

Efficacy of UVC-treated, pathogen-reduced platelets versus untreated platelets: a randomized controlled non-inferiority trial.

Pathogen reduction (PR) technologies for blood components have been established to reduce the residual risk of known and emerging infectious agents. THERAFLEX UV-Platelets, a novel ultraviolet C (UVC) light-based PR technology for platelet concentrates, works without photoactive substances. This randomized, controlled, double-blind, multicenter, non-inferiority trial was designed to compare the efficacy and safety of UVC-treated platelets to that of untreated platelets in thrombocytopenic patients with hematologic-oncologic diseases. The primary objective was to determine non-inferiority of UVC-treated platelets, assessed by the 1-hour corrected count increment (CCI) in up to eight per-protocol platelet transfusion episodes. Analysis of the 171 eligible patients showed that the defined non-inferiority margin of 30% of UVC-treated platelets was narrowly missed as the mean differences in 1-hour CCI between standard platelets versus UVC-treated platelets for intention-to-treat and per-protocol analyses were 18.2% (95% Confidence Interval [CI]: 6.4-30.1) and 18.7% (95% CI: 6.3-31.1), respectively. In comparison to the control, the UVC group had a 19.2% lower mean 24-hour CCI and was treated with an about 25% higher number of platelet units, but the average number of days to the next platelet transfusion did not differ significantly between both treatment groups. The frequency of low-grade adverse events was slightly higher in the UVC group and the frequencies of refractoriness to platelet transfusion, platelet alloimmunization, severe bleeding events, and red blood cell transfusions were comparable between groups. Our study suggests that transfusion of pathogen-reduced platelets produced with the UVC technology is safe but non-inferiority was not demonstrated. (clinicaltrials gov. Identifier: DRKS00011156).

Efficacy of HLA-compatible Platelet Transfusion for Patients with Acute Myeloid Leukemia Refractory to Platelet Transfusion

Abstract Introduction/Objective Acute myeloid leukemia (AML) patients often require transfusion support during induction chemotherapy. Platelet transfusion refractoriness (PTR) may develop due to HLA alloimmunization. Management of immune-refractory patients with HLA-compatible platelet transfusions is labor intensive and associated with increased costs. The purpose of this study is to evaluate the efficacy of HLA-compatible platelet units in AML patients. Methods Newly diagnosed AML patients undergoing induction chemotherapy in our institute between 2015 and 2018 were identified. Platelet counts and platelet transfusion data from initiation of chemotherapy until platelet recovery (&amp;gt; 20K/µL and increased consistently) were extracted. A 24-hour posttransfusion corrected count increment (CCI) was calculated to evaluate the efficacy of each platelet transfusion. PTR was declared if a patient had a 24-hour CCI &amp;lt; 4K following two consecutive transfusions. Student’s t-test was used for statistical analysis. Results were presented as mean ± SE, * if p &amp;lt; 0.05. Results We identified 39 patients with newly diagnosed AML. PTR developed in 22/39 (56%) patients during induction chemotherapy. The average CCI was higher among those without PTR compared to those with PTR (8,408 ± 585 vs. 2,923 ± 360*), and overall platelet transfusion burden (in number of units) was lower (7.29 ± 1.0 vs. 18.55 ± 1.71*). HLA antibodies were identified in 3/22 (14%) PTR patients, as 6/22 (27%) were tested. The average CCI during HLA matched transfusions for these 3 patients was higher than that with random units (2,059 ± 149 vs. -126 ± 306*). Compared to HLA-negative PTR patients receiving random units, the average CCI for HLA-compatible transfusions was still lower, though not significantly (2,059 ± 149 vs. 3,099 ± 390, p = 0.33), while the number of HLA- compatible units transfused was significantly higher (31.0 ± 3.0 vs. 16.6 ± 1.45*). Conclusion In a cohort of newly diagnosed AML patients undergoing induction chemotherapy whose PTR was associated with detectable HLA antibodies, transfusion support with HLA-matched products did not lead to reduced overall platelet transfusion rates and CCI remains in the refractory range. This suggests that use of HLA matched platelets among newly diagnosed AML patients with PTR, even in the setting of detectable HLA antibodies, does not appear to result in reduced overall product utilization.

Efficacy of HLA virtual cross-matched platelet transfusions for platelet transfusion refractoriness in hematopoietic stem cell transplantation.

Cross-matched platelet (cross-matched PLT) transfusion is effective for immune-mediated platelet transfusion refractoriness (PTR), but is more costly and time-consuming for physical cross-match than using standard PLT units. Recent studies have reported the utility of human leucocyte antigens (HLA) virtual cross-matched PLT (HLA-matched PLT) that is defined as HLA-A/B matched or no antibody against donor-specific antigen. Here, we evaluated the effect of HLA-matched PLTs for PTR in post hematopoietic stem cell transplant (HSCT) recipients. Our study included a total of 241 PLTs in 16 patients who underwent HSCT at Okayama University Hospital between 2010 and 2017, receiving either HLA-matched or cross-matched PLTs. We calculated the 24-hour corrected count increments (CCI-24) to evaluate the effect of PLTs. A CCI-24 ≥ 4500 was considered to be a successful transfusion. We analyzed 139 cross-matched PLTs and 102 HLA-matched PLTs. In the immune-mediated PTR, the rate of successful transfusion was 60.5% for cross-matched PLT and 63.4% for HLA-matched PLT (p = 0.825). On the other hand, the median CCI-24 for cross-matched PLT transfusions and HLA-matched PLT transfusions were 1856 and 5824 (p < 0.001), with a success rate of 28.1 and 54.1% in cases with non-immune-mediated PTR, respectively (p = 0.001). The effectiveness of HLA-matched PLT is not inferior to cross-matched PLT. This result indicates that physical cross-match can be omitted in post HSCT PTR.

HLA-matched platelet transfusions are effective only in refractory patients with positive HLA antibody screening.

Recipients of platelet transfusions with 1-hour corrected count increments (1hCCIs) of 7.5 or less on two subsequent platelet transfusions with random platelets may benefit from human leukocyte antigen (HLA)-matched platelet concentrates. We aimed to quantify the efficacy of HLA-matched platelets concentrates expressed in 1hCCIs. We performed a cohort study among consecutive refractory patients who received HLA-matched platelet concentrates in the Netherlands between 1994 and 2017. We performed mixed-model linear regression comparing 1hCCIs after HLA split-antigen-matched transfusions with 1hCCIs after HLA-mismatched transfusions, adjusted for within-patient correlations. A donor-to-patient match was categorized as a split-match if all donor HLA-A and -B antigens were present in the patient as well; that is, donor and patient were HLA identical or compatible. Subgroup analyses were performed for patients with positive or negative HLA antibody screens. Finally, the additional effect of ABO mismatches on 1hCCIs was investigated. The 1hCCI after an HLA-matched transfusion was 14.09 (95% reference interval, 1.13-29.89). This was 1.94 (95% confidence interval [CI], 0.74-3.15) higher than 1hCCI after HLA-mismatched transfusions. In patients with negative HLA antibody screening tests, HLA matching did not affect 1hCCIs. Conditional on HLA matching, 1hCCIs decreased by 3.70 (95% CI, -5.22 to -2.18) with major ABO mismatches. Matched platelet concentrates yielded maximal 1hCCIs, whereas mismatched transfusions still resulted in adequate increments. There is no indication for HLA-matched platelets in patients with negative antibody screens.

Diagnostic Management Team: Platelet Refractory Algorithm and Consult

Abstract Platelet refractoriness occurs when a patient fails to achieve appropriate platelet count increment following platelet (plt) transfusion. Approximately 30% to 40% of cases are due to human leukocyte antigen (HLA) alloantibodies and 2% to 10% are due to human platelet antigen (HPA) alloantibodies, which can be detected by various assays. The results of these tests are then used to guide selection of appropriate units, such as crossmatch-compatible (XM) and HLA-matched (HLAm) plts. Given the various steps and tests involved in diagnosing and managing plt refractoriness, clinicians may order unnecessary tests resulting in delays in patient care. In April 2018, our institution formed a diagnostic management team (DMT) to establish an algorithmic approach to testing, diagnosing, and transfusing plt refractory patients. We performed a retrospective review of clinician requests for XM or HLAm plts over a 9-month period prior to the launch of the DMT and compared that to requests placed during the initial 9-month period following the launch of the DMT. We collected the date transfusion medicine (TM) service was notified and the time to complete the following: 1-hour corrected count increment (CCI), ELISA indirect antibody screen, HLA flow cytometry PRA screen, HLA single antigen bead (SAB), and obtain the first XM or HLAm plt unit for the patient. There were 12 and 20 patients evaluated for plt refractoriness pre- and post-DMT, respectively. The median time to complete the ELISA indirect antibody screen was 2 days pre- and post-DMT, respectively. Eight percent of patients never had an ELISA screen performed pre-DMT. All patients meeting plt refractory criteria had ELISA screens performed post-DMT. Median time to complete HLA testing decreased from 4 days to 2 days and all patients who had positive FlowPRAs had subsequent SABs performed post-DMT compared to only 40% of patients pre-DMT. The median times to obtain the first XM unit were 6 and 5 days and the first HLAm unit was 5 and 6 days pre- and post-DMT, respectively. One patient had a CCI above 7,500 and four patients had negative screening ELISA and FlowPRA tests after the launch of the DMT. No further testing was performed and they continued to receive ABO-compatible (ABOc) plt units. Since the launch of the DMT, there is improved consistency regarding what tests are performed and standardization of the sequence in which the appropriate tests are ordered. We have reduced unnecessary testing by identifying patients with nonimmune-mediated etiologies of plt refractoriness. Divergence from the algorithm is the main issue encountered during the initial 9-month period following implementation of the DMT. This divergence stemmed from lack of consistent education about plt refractoriness and the DMT. We believe better adherence to the algorithm will lead to decreased product acquisition time and further improve efficiency.

Transfusion of pathogen-reduced platelet components without leukoreduction.

BACKGROUNDLeukoreduction (LR) of platelet concentrate (PC) has evolved as the standard to mitigate risks of alloimmunization, clinical refractoriness, acute transfusion reactions (ATRs), and cytomegalovirus infection, but does not prevent transfusion‐associated graft‐versus‐host disease (TA‐GVHD). Amotosalen–ultraviolet A pathogen reduction (A‐PR) of PC reduces risk of transfusion‐transmitted infection and TA‐GVHD. In vitro data indicate that A‐PR effectively inactivates WBCs and infectious pathogens.STUDY DESIGN AND METHODSA sequential cohort study evaluated A‐PR without LR, gamma irradiation, and bacterial screening in hematopoietic stem cell transplant (HSCT) recipients. The first cohort received conventional PC (control) processed without LR, but with gamma irradiation and bacterial screening. The second cohort received A‐PR PC (test) processed without: LR, bacterial screening, or gamma irradiation. The primary efficacy outcome was the 1‐hour corrected count increment. The primary safety outcome was treatment‐emergent ATR. Secondary outcomes included clinical refractoriness, and 100‐day status for engraftment, TA‐GVHD, HSCT‐GVHD, infections, and mortality.RESULTSMean corrected count increment (× 103) of 33 test PC recipients was similar (18.9 ± 8.8 vs. 16.6 ± 8.4; p = 0.296) to that of 31 control PC recipients. Test recipients had a reduced, but nonsignificant, incidence of ATR (test = 9.1%, Control = 19.4%; p = 0.296). The frequencies of clinical refractoriness (0 of 33 vs. 4 of 31 patients) and refractory transfusions (6.6% vs. 19.3%) were lower in the test cohort (p = 0.05 and 0.02), respectively. No patient in either cohort had TA‐GVHD. Day 100 engraftment, HSCT‐GVHD, mortality, and infectious disease complications were similar between cohorts.CONCLUSIONSThis study indicated that A‐PR PC without LR, gamma irradiation, or bacterial screening is feasible for support of HSCT.

HLA-selected platelets for platelet refractory patients with HLA antibodies: a single-center experience.

Platelet refractoriness due to HLA immunization represents a problem in transfusion management of thrombocytopenic hematology patients. Refractory patients can be managed by HLA-selected platelet transfusions, but the optimal matching strategy is debated and how the degree of HLA mismatch influences transfusion outcome is poorly studied. We studied 32 hematology patients who received 142 matched platelet units between 2007 and 2016. Four matching strategies were compared: 1) genomic HLA typing at the two digit level, performed using polymerase chain reaction-sequence-specific oligonucleotide probing; 2) serologic "eplet score" calculated using HLAMatchmaker; 3) cross-matching using lymphocyte cytotoxicity; and 4) matching based on donor-specific antibody (DSA) specificity, determined using Luminex. A 1-hour corrected count increment (CCI) of more than 7.5 × 109 /L was considered a successful response. Selection of platelets with either a complete HLA match or an acceptable HLA mismatch based on genomic typing and DSA information, each predicted 86% successful transfusion responses. For HLA-mismatched transfusions, the eplet score correlated with CCI and the fraction of successful transfusions, but less well compared to DSA matching. Cytotoxic crossmatching was least predictive. For transfusions across one to four DSAs, the antibody reaction strength correlated with the 1-hour CCI, but many transfusions were successful despite the presence of DSA. A complete HLA-A and -B match or an acceptable mismatch based on DSA should guide identification of donors. Still, transfusions across DSAs are often successful, emphasizing that the presence of DSA is necessary but not sufficient for platelet clearance.

Efficacy of HLA-Matched PLT Transfusions for Platelet Transfusion Refractoriness in HSCT Patients

Introduction: Cross-matched platelet (cross-matched PLT) transfusions are effective for immune-mediated platelet transfusion refractoriness (PTR). However, cross-matched PLT is more costly and takes more effort to cross match than a standard PLT unit. Recently, the utility of virtual HLA cross-matched PLT (HLA-matched PLT) has been reported. HLA-matched PLT is defined as HLA-A/B matched or cross-reactive groups excluded. Cross-matched PLTs are collected from donors selected based on patient's HLA class I antibody and HLA typing of the donor. The products are supplied after confirmation of cross-matched negative. Hematopoietic stem cell transplantation (HSCT) patients frequently receive many transfusions before HSCT. Therefore, HLA antibody is often detected, which causes PTR. After HSCT, many complications, such as infection, bleeding, and thrombotic microangiopathy, may occur, which can cause PTR. Inadequate post-transfusion PLT increment occurs in more than 50% of PLT transfusions in patients undergoing HSCT. Here, we evaluated the effect of HLA-matched PLT for PTR in post-HSCT recipients.Methods: The records of all patients who underwent HSCT at Okayama University Hospital between 2010 and 2017 were reviewed to identify patients who received either cross-matched or HLA-matched PLT products after HSCT for hematologic malignancy. All patients had HLA Class I antibody and immune-mediated PLT transfusion refractoriness (PTR). An analysis of the initial episode of the PLT transfusion refractoriness was conducted for each patient. The following data were recorded for each patient: disease, age, sex, body surface area, HSCT donor source, HLA typing (Class I), HLA Class I antibody screen, WHO Grade 3 to 4 bleeding episodes, complications, death, and platelet-corrected count increment (CCI). Non-immune mediated causes were defined as an episode of fever (≥38 °C), bleeding (Grade 3 to 4), DIC, infection, thrombotic microangiopathy, sinusoidal obstructive syndrome, and splenomegaly. PLT products (cross-matched and HLA-matched units) were supplied by the Japanese Red Cross Society. The exact PLT content of each unit was obtained from the Japanese Red Cross Society. The 24-hour corrected count increments (CCI-24) were calculated to evaluate the effect of PLT transfusions. A CCI-24 more than 4500/μL was considered a successful transfusion.Results: Sixteen patients received a total of 241 PLT transfusions; 139 PLT transfusions were cross-matched, and 102 PLT transfusions were HLA-matched. The median CCI-24 for cross-matched PLT transfusions and HLA-matched transfusions was 2626/μL and 6137/μL, respectively, (p<0.001). The percentage of successful transfusions was 38.1% for cross-matched PLT and 57.8% for HLA-matched PLT, respectively, (p<0.001). Eighty-four PLT transfusions were used under situations without cause for non-immune mediated PTR. The percentage of successful transfusions (median CCI-24) was 62.8% (6684/μL) for cross-matched PLT and 65.1% (7108/μL) for HLA-matched PLT(p=0.825). Of the 241 transfusions, 157 (65.1%) transfusions were used under situations with cause for non-immune mediated PTR. When patients had non-immune mediated PTR, the percentage of successful transfusions was only 28.1% for cross-matched PLT and 51.1% for HLA-matched PLT (p=0.001). The median CCI-24 was 1856/μL for cross-matched PLT and 5824/μL for HLA-matched PLT (p<0.001). HLA-matched PLT resulted in a higher response, and episodes of bleeding and splenomegaly were lower by multiple linear regression analysis (Table 1).Conclusions: HLA-matched PLT was not inferior to cross-matched PLT for post-HSCT PTR. Both cross-matched PLT and HLA-matched PLT resulted in a similar response for immune-mediated PTR, but HLA-matched PLT was superior for non-immune mediated PTR. The difference of selection method between cross-matched PLT and HLA-matched PLT may influence the effectiveness of the transfusion. The reasons of superior CCI-24 result in HLA-matched PLT are currently under investigation. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Therapeutic Effect of Platelet Transfusion in Patients with Acute Lymphocytes Treated with CART Therapy

Background: CART therapy is the most effective method for the treatment of acute lymphoblastic leukemia (ALL) right now, which accompanied with severe cytokine storms (CRS) during treatment, resulting in severe platelet destruction and reduction. So the treatment of platelet transfusion is particularly important to the CART therapy. However, there is no clinical consensus on when given platelet transfusion can patients obtain the maximum benefit.Methods: In the study, 14 ALL patients were enrolled for the CART treatment. The patients with platelet transfusion refractoriness (PTR) were excluded for non-immune factors such as large spleen and high fever. Blood routine and cytokines such as IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, and IL-17A were monitored during treatment. Body temperature should be less than 38 degrees before transfusion of platelets. Analyze the efficacy of platelet transfusion in patients before the CART treatment, the time with CRS, and after the CRS. The platelet transfusion effect was determined by 24-hour corrected count increment (CCI) (greater than 7.5 considered as effective, otherwise as invalid).Results: All the patients in the study were treated with platelet transfusion before CART treatment. There was a CSR-3 level in every patients during the treatment. Four of them didn't get platelet transfusion as the lowest platelet count is more than 10×109/L without bleeding tendency. Ten of them received platelet transfusion treatment during CRS and the average of the cytokine were higher than before (IL-2 (12.65±21.08 pg/ml), IL-6 (8540.57±6791.91 pg/ml), IL-10 (1547.46±2939.45 pg/ml), IFN-γ (2846.49±2480.88 pg/ml),P<0.01). The 24 hour CCI of the 10 patients before CART treatment were 10.91±3.27, during CRS were 4.18±4.28, and after CRS were 8.72±2.93 (P<0.01). During the CRS, 24 hour CCI is higher in patients with platelet count below 5×109/L than patients with platelet count between 5-10×109/L(P<0.01).Conclusion: CRS during CART treatment accelerated platelet consumption, resulting PTR. Platelet transfusion could not be given to patients when they were experiencing the most serious CSR without bleeding tendency, but it can be considered when the platelet count is less than 5×109/L,Key Words: acute lymphoblastic leukemia, severe cytokine storms, platelet transfusion.Fig 1: the relationship between 24 hour CCI and the highest IL-6:The IL-6 is so high that we reduced it by one thousand times in the figure. The 24 hour CCI is negatively correlated with IL - 6, P<0.01, R=-0.92. DisclosuresNo relevant conflicts of interest to declare.

Pathogen Inactivated Platelet Components Used without Leukofiltration, or Gamma Irradiation Show Comparable Therapeutic Efficacy and Safety to Gamma Irradiated and Non-Leukofiltered Conventional Products for the Support of HSCT Patients in Hong Kong

▪Introduction: Depending on the conditioning intensity and graft source, mosthematopoietic stem cell transplant(HSCT) patients invariably experience a cytopenic phase of at least 2-3 weeks and require transfusion support until engraftment. All transfused blood components post-transplant need to be gamma irradiated to prevent transfusion associated graft versus host disease (TA-GVHD). Platelet component (PC) manufacturing methodologies differ around the globe. Currently, Hong Kong HSCT patients are supported with individual platelet rich plasma (PRP) PCs without leukocyte filtration (NLF), tested by short-term aerobic cultures for bacterial contamination (STABC), and gamma irradiated. When new PC manufacturing methodologies are considered for adoption, it is important to assess the immediate and longer term effects on transfused patients. Amotosalen+UVA light (A-UVA) pathogen reduction technology (INTERCEPT™ Blood System, Cerus Corporation, Concord, CA) inactivates bacteria, viruses, parasites and leukocytes by efficient covalent adduct modification of DNA and RNA. Treatment with A-UVA prevents TA- GVHD in an animal model, inhibits clonal T cell proliferation, prevents allogeneic antigen stimulation in mixed lymphocyte reactions, and inhibits transcription mediated cytokine production and early activation antigen expression (Corash et al, BMT 2004). The common strategy of prescribing gamma irradiated PC only for suspected "high risk" patients is sub-optimal, as failure to identify recipients at risk for TA-GVHD was responsible for 50% of reported cases (Kopolovic et al. Blood 2016). Treatment of PC with A-UVA addresses two key issues for HSCT patients: bacterial contamination, and universal prevention of TA-GVHD. Here, we compared the clinical support of HSCT patients with conventional PCs (C-PC) vs. an equivalent HSCT group supported with A-UVA PCs (I-PC) using a sequential patient cohort design within a single HSCT clinical center.Methods: I-PCs were prepared from 5 pooled ABO-matched, NLF buffy coat PCs in platelet additive solution and treated with A-UVA replacing gamma irradiation and bacterial detection. C-PCs were prepared from 5 ABO-matched, STABC-negative, NLF PRP PCs, and treated with gamma irradiation. Each patient could receive up to 5 PC transfusions. The primary efficacy endpoint was the 1-hour corrected count increment (CCI) and the primary safety endpoint was the proportion of patients (P) with acute transfusion reactions (ATR). Follow-up data on mortality, hematopoiesis engraftment, and immune status were collected up to 100 days post HSCT.Results: Patient demographics and type of HSCT were similar between patient cohorts. 33 patients received 76 A-UVA PCs and 31 patients received 89 C-PCs. The mean days of platelet support (p=0.618) and mean 1-hour CCIs per patient averaged for all transfusions were comparable (p=0.296) between the I- PC and conventional C-PC cohorts (Table). The proportion of patients with AEs was lower (p=0.021) for the I-PC group (Table), and no related SAEs were observed during the entirety of trial. Survival at 100 days post HSCT and rates of remission were similar between the cohorts (Table). The ATR rate trended lower, although not significantly different (p=0.296), in the I- PC group (Table). Follow-up data showed that the patients had comparable neutrophil and platelet engraftment (Table) with comparable immune system reconstitution by 100 days post HSCT. No cases of TA-GVHD were observed in either cohort.Conclusions: A-UVA-treated PCs prepared without LF, gamma irradiation, and bacterial detection can replace C-PCs for support of HSCT patients resulting in comparable post transfusion CCI responses and short and intermediate term clinical outcomes, while offering additional protection against transfusion transmitted bacteria and emerging or untested pathogens. [Display omitted] DisclosuresSim Pui Yin:Cerus Corporation: Other: Investigator sponsored trial. Leung Yuk Yan:Cerus Corporation: Other: Investigator sponsored trial. Lam Chun Kit:Cerus Corporation: Other: Investigator sponsored trial. Tsoi Wai:Cerus Corporation: Other: Investigator sponsored trial. Lee Cheuk:Cerus Corporation: Other: Investigator sponsored trial. Lie Kwok Wai:Cerus Corporation: Other: Investigator sponsored trial. Huang:Cerus Corporation: Employment. Rico:Cerus Corporation: Employment. Lin:Cerus corp: Employment. Corash:Cerus Corporation: Employment. Stassinopoulos:Cerus Corporation: Employment.

Transfusion of ABO-Incompatible HLA-Matched Platelets as Support for Patients with Acute Myeloid Leukaemia Undergoing Chemotherapy

Background: ABO-incompatible human leukocyte antigen (HLA)-matched platelets are used to manage thrombocytopenic patients with anti-HLA-A and/or anti-HLA-B (HLA-A/B) antibodies when ABO-identical donors are not available. This study assessed the effectiveness of ABO-incompatible HLA-matched platelets in an unselected group of patients with acute myeloid leukaemia (AML) undergoing cytotoxic chemotherapy. Material and Methods: The study cohort consisted of 12 AML patients undergoing cytotoxic chemotherapy and administered HLA-matched single donor platelet transfusions. Patients positive for anti-HLA-A/B antibodies were defined as candidates for HLA-matched platelet transfusion. The effectiveness of platelet transfusions was determined by measuring corrected count increments (CCIs). Results: The 12 patients received a total of 128 HLA-matched platelet transfusions. The median CCIs 1 hour after ABO-minor and -major incompatible HLA-matched transfusions were 11.4 (range: 3.2-24.9) and 12.4 (range: 3-37), respectively. There were no significant differences in 1- and 24-hour CCIs among ABO-identical and ABOminor and major incompatible transfusions. Discussion: ABO-incompatible HLA-matched platelets are effective in supporting thrombocytopenic AML patient’s positive for anti-HLA-A/B antibodies and undergoing cytotoxic chemotherapy.

Hemostatic Efficacy of Pathogen-Inactivated Blood Components

Pathogen inactivation (PI), or pathogen reduction technology, reduces the infectious risk of plasma and platelet transfusions, and also affects clotting factor activities and platelet viabilities. Plasma is treated with solvent-detergent to disrupt enveloped viruses, or with photoactive agents methylene blue plus light, or amotosalen (AM) or riboflavin (RF) plus ultraviolet (UV) light, to disrupt pathogen nucleic acids. PI plasmas have average clotting factor activities of 75 to 85% of untreated plasma. PI plasmas are generally equivalent to regular plasma in randomized clinical trials (RCTs) in regard to coagulation test corrections and bleeding outcomes, except for one trial in which RF plasma was inferior for prothrombin time correction. Platelets are treated with UV plus RF or AM. In RCTs, the mean 1-hour corrected count increments from PI platelets are 66 to 94% (trials median, 75%) of those from untreated platelets. PI platelets also have lifespans of 4 to 5 days after 5 days of storage, compared with 6 to 7 days for untreated platelets. Bleeding outcomes comparing PI versus non-PI platelets in RCTs have been equivalent, except one study with more bleeding on AM platelets. Platelet treatment with UVC light alone for PI has entered clinical trials.

Review of in vivo studies of dimethyl sulfoxide cryopreserved platelets.

A literature review was conducted to assess the efficacy and safety of dimethyl sulfoxide (DMSO) cryopreserved platelets for potential military use. In vivo DMSO cryopreserved platelet studies published between 1972 and June of 2013 were reviewed. Assessed were the methods of cryopreservation, posttransfusion platelet responses, prevention or control of bleeding, and adverse events. Using the Department of Defense's preferred 6% DMSO cryopreservation method with centrifugation to remove the DMSO plasma before freezing at -65°C and no postthaw wash, mean radiolabeled platelet recoveries in 32 normal subjects were 33% ± 10% (52% ± 12% of the same subject's fresh platelet recoveries), and survivals were 7.5 ± 1.2 days (89% ± 15% of fresh platelet survivals). Using a variety of methods to freeze autologous platelets from 178 normal subjects, mean radiolabeled platelet recoveries were consistently 39% ± 9%, and survivals, 7.4 ± 1.4 days. More than 3000 cryopreserved platelet transfusions were given to 1334 patients. There were 19 hematology/oncology patient studies, and, in 9, mean 1-hour corrected count increments were 11 100 ± 3600 (range, 5700-15 800) after cryopreserved autologous platelet transfusions. In 5 studies, bleeding times improved after transfusion; in 3, there was either no improvement or a variable response. In 4 studies, there was immediate cessation of bleeding after transfusion; in 3 studies, patients being supported only with cryopreserved platelets had no bleeding. In 1 cardiopulmonary bypass study, cryopreserved platelets resulted in significantly less bleeding vs standard platelets. In 3 trauma studies, cryopreserved platelets were hemostatically effective. No significant adverse events were reported in any study. In summary, cryopreserved platelets have platelet recoveries that are about half of fresh platelets, but survivals are only minimally reduced. The platelets appear hemostatically effective and have no significant adverse events.

Hemostatic Function and Transfusion Efficacy of Apheresis Platelet Concentrates Treated with Gamma Irradiation in Use for Thrombocytopenic Patients

Background: During the transfusion of blood components, the transfer of allogeneic donor white blood cells (WBCs) can mediate transfusion-associated graft-versus-host disease (TA-GVHD). To minimize the reaction, exposure of blood products to gamma irradiation is currently the standard of care. The aim of our study was to evaluate and compare hemostatic function, transfusion efficacy, and safety of gamma-irradiated single-donor apheresis platelet concentrates (PCs) and of conventional non-irradiated PCs in patients with chemotherapy-induced thrombocytopenia. Methods: 20 double-dose single-donor leukoreduced PCs were split in two identical units; one was gamma-irradiated with 25 Gy (study arm A) and the other remains non-irradiated (study arm B). Both units were stored under equal conditions. Hematologic patients were randomly assigned to receive gamma-irradiated or conventional non-irradiated PCs. Hemostatic function was evaluated by thrombelastography (TEG). TEG measurements were taken pre transfusion and 1 and 24 h post transfusion. TEG profiles were measured, noting the time to initiate clotting (R), the angle of clot formation (α), and the maximum amplitude (clot strength (MA)). Whole blood samples were collected from these thrombocytopenic patients at 1 and 24 h for PLT count increments (CIs) and corrected count increments (CCIs) with assessments of transfusion efficacy. Time to next PLT transfusion, transfusion requirement of RBCs, active bleeding, and adverse events (AEs), were analyzed. Results: No differences could be found in hemostatic function parameters (MA, R, and α) between study arms A and B (all p values > 0.096) pre transfusion as well as 1 and 24 h post transfusion. No differences between study arms A and B were observed for mean (± standard deviation (SD)) 1-hour CCI (12.83 ± 6.33 vs. 11.59 ± 5.97) and 24-hour CCI (6.56 ± 4.10 vs. 5.76 ± 4.05). Mean 1-hour CI and 24-hour CI were not significantly different in both study arms (p = 0.254 and p = 0.242 respectively). Median time to the next PC transfusion after study PC was not significantly different between groups: (2.4 vs. 2.2 days, p = 0.767). No differences could be found in transfusion requirement of red blood cells (p = 0.744) between both study arms. There were also no regarding bleeding, adverse events, and acute transfusion reaction(s). Conclusions: This study confirms safety of gamma-irradiated PCs for treatment thrombocytopenia. Hemostatic function, transfusion efficacy, bleeding, and safety of single-donor apheresis PCs treated with gamma irradiation versus untreated control PCs are comparable.

Cross-match-compatible platelets improve corrected count increments in patients who are refractory to randomly selected platelets.

Cross-match-compatible platelets are used for the management of thrombocytopenic patients who are refractory to transfusions of randomly selected platelets. Data supporting the effectiveness of platelets that are compatible according to cross-matching with a modified antigen capture enzyme-linked immunosorbent assay (MAC-ELISA or MACE) are limited. This study aimed to determine the effectiveness of cross-match-compatible platelets in an unselected group of refractory patients. One hundred ABO compatible single donor platelet transfusions given to 31 refractory patients were studied. Patients were defined to be refractory if their 24-hour corrected count increment (CCI) was <5×10(9)/L following two consecutive platelet transfusions. Platelets were cross-matched by MACE and the CCI was determined to monitor the effectiveness of platelet transfusions. The clinical sensitivity, specificity, positive predictive value and negative predictive value of the MACE-cross-matched platelets for post-transfusion CCI were 88%, 54.6%, 39.3% and 93.2%, respectively. The difference between adequate and inadequate post-transfusion 24-hour CCI for MACE cross-matched-compatible vs incompatible single donor platelet transfusions was statistically significant (p=0.000). The 24-hour CCI (mean±SD) was significantly higher for cross-match-compatible platelets (9,250±026.6) than for incompatible ones (6,757.94±2,656.5) (p<0.0001). Most of the incompatible cross-matches (73.2%) were due to anti-HLA antibodies, alone (55.3% of cases) or together with anti-platelet glycoprotein antibodies (17.9%). The clinical sensitivity and negative predictive value of platelet cross-matching by MACE were high in this study and such tests may, therefore, be used to select compatible platelets for refractory patients. A high negative predictive value demonstrates the greater chance of an adequate response with cross-matched-compatible platelets.

Comparison of transfusion efficacy of amotosalen‐based pathogen‐reduced platelet components and gamma‐irradiated platelet components

Trials of transfusions of platelets (PLTs) treated with amotosalen-based pathogen reduction (PR) showed lower corrected count increments (CCIs) compared to conventional PLT components (PCs). However, PR-PLTs and conventional PCs often differed in various factors besides PR. We compared transfusion efficacy of single-donor apheresis PCs treated with PR or gamma irradiation. Hematologic patients were assigned to receive PR-PLTs or gamma-irradiated conventional PCs, both prepared in PLT additive solution (PAS). One-hour CCI (primary endpoint), 24-hour CCI, time to next PLT transfusion, and transfusion requirement of red blood cells and plasma were analyzed. Forty-four patients assigned to PR-PLTs received 220 PR-PLTs and 136 conventional PCs; 72 controls received 517 conventional PCs. No differences between patient groups were observed for mean (±standard deviation [SD]) 1-hour CCI (11.4 [±4.9] for PR-PLT vs. 11.0 [±4.9] for controls), mean (±SD) 24-hour CCI (6.1 [±4.4] for PR-PLTs vs. 6.2 [±4.8] for controls), and for the other evaluated outcomes. No differences between PC types were observed for mean (±SD) 1-hour CCI (10.6 [±6.7] for PR-PLTs vs. 9.9 [±6.2] for conventional PCs) and mean 24 hour-CCI (3.3 [±3.9] for PR-PLTs vs. 4.2 [±5] for conventional PCs). Thirty-five percent of PR-PLTs and 38% of conventional PCs (p = 0.63) were associated with 1-hour CCIs of less than 7.5. Inadequate 24-hour CCIs were observed for 72% of PR-PLTs and 64% of conventional PCs (p = 0.002). Transfusion efficacy of single-donor apheresis PCs in PAS treated with amotosalen PR versus gamma irradiation is comparable.

Longitudinal management with crossmatch‐compatible platelets for refractory patients: alloimmunization, response to transfusion, and clinical outcomes (CME)

The use of crossmatch-compatible platelets (PLTs) improves posttransfusion corrected count increments (CCIs) in patients with alloimmune PLT refractoriness. However, few reports address the efficacy of utilizing this strategy for patients requiring intensive PLT transfusion therapy lasting several weeks to months. Medical records of patients with two or more PLT crossmatch assays performed between 2002 and 2010 were reviewed. All patients were refractory to random single-donor apheresis PLT units, defined as two consecutive 1-hour posttransfusion CCIs of less than 7500. A commercial solid-phase adherence assay was used for crossmatching. Seventy-one patients were included. A median of four crossmatch assays were performed per patient (range, 2-17). Mean percent reactivity in initial (58.6%) versus last (55.3%) crossmatch assay for each patient demonstrated no trend toward progressive alloimmunization (p = NS). A total of 738 crossmatched PLT units were administered with a mean ± standard deviation CCI of 7000 ± 7900 (n = 443 units with adequate 1-hr posttransfusion counts), a significant improvement over random PLTs (p < 0.001). Patients with an initial crossmatch reactivity of greater than 66% were significantly more likely to demonstrate at least one panreactive crossmatch assay, impacting the availability of compatible PLTs for optimum transfusion support. One patient (1.4%) developed WHO Grade IV bleeding. Progressive alloimmunization to mismatched antigens does not impact medium-term transfusion support with crossmatched PLTs. Increased reactivity in the initial crossmatch assay can serve as a trigger to initiate workup for HLA-matched PLTs as a second-line approach. However, for most patients, medium-term transfusion support with crossmatched PLTs offers an effective and rapid first-line approach to management of PLT transfusion refractoriness.

A comparison of volume‐reduced versus standard HLA/HPA–matched apheresis platelets in alloimmunized adult patients

Our blood bank prepares, on indication or request, a volume-reduced (VR) platelet (PLT) product with greater than 95% reduced plasma content and a 15-fold higher PLT concentration, potentially minimizing adverse reactions due to plasma, in particular for human leukocyte antigen (HLA)/human PLT antigen (HPA)-matched PLTs when minor ABO incompatibility cannot be avoided. Here we compared the clinical effectiveness of VR apheresis PLTs (APs) with standard APs. We performed a single-center cohort study among consecutive alloimmunized patients who received either HLA/HPA-matched standard APs and/or VR-APs between 1994 and 2008. The endpoints were corrected count increments (CCIs), time to next transfusion, and frequency of adverse reactions. The CCI of VR PLTs was calculated using the PLT dose before volume reduction. Using a random effects model, 851 transfusions to 68 patients were evaluated for CCI and 731 transfusions to 64 patients for time to next transfusion. The frequency of reported adverse reactions was compared between the groups. The 1-hour CCI was 23% (95% confidence interval [CI], 9%-42%; p < 0.001) lower and the 24-hour CCI was 17% (95% CI, -11% to 59%; p = 0.278) lower after VR-APs. The mean time to next transfusion was similar: standard APs, 3.1 days (95% CI, 2.7-3.5); and VR-APs, 2.8 days (95% CI, 2.5-3.2). Eight adverse reactions were reported: 4 of 619 in the standard AP group and 4 of 1202 in the VR-AP group. VR-APs showed lower 1- and 24-hour CCIs than standard-APs, which can be largely explained by the lower PLT dose of VR-APs. The benefits of plasma reduction should seriously be outweighed given these lower increments.