Corrected Count Increment Research Articles

Continuous Platelet Transfusion As a Potential Desensitization Regimen in HLA Class I Alloimmune-Mediated Platelet Refractoriness

Background: The development of HLA antibodies is responsible for 4-8% of platelet transfusion refractoriness (PTR). The presence of HLA antibodies is a clinical complication that is generally managed by the selection of products that are negative for the antigens cognate to the patient's antibodies. Often, this selection is facilitated by targeted recruitment of donors with known HLA types. However, for very broadly HLA-alloimmunized patients, compatible products may be exceedingly scarce or completely unavailable, precluding the ability to consistently provide products the patient will likely increment to and benefit from. Here we describe a case of a patient with severe aplastic anemia (platelet count chronically <1 K/uL) and platelet transfusion refractoriness secondary to broad HLA-alloimmunization (98% PRA). HLA compatible products were unavailable due to the patient's rare HLA type and breadth of antibodies, and attempts at procuring compatible products via multiple national agency searches were unsuccessful. Thus, the patient could only be supplied with HLA incompatible products, which yielded insufficient post-transfusion platelet corrected-count increments (CCI). Her course was eventually complicated by multifocal intracranial hemorrhages, necessitating ICU admission with aggressive platelet transfusion support, immune-targeting therapy consisting of IVIg, and aminocaproic acid and recombinant activated factor VIIa.Methods: A continuous platelet infusion, or “platelet drip,” was employed in order to provide platelet transfusion support in the face of her severe thrombocytopenia with profound refractoriness. This consisted of consecutive transfusions of 4-6 equivalent unit apheresis platelet products (“doses”) transfused over 4 hours with a 15 minute post-transfusion CBC obtained from Q8 to Q12 hours to assess platelet increments. This ultimately resulted in 24-30 equivalent unit platelet product infusions/day.Results: Two days into the continuous platelet infusion, the patient began incrementing appropriately to occasional platelet products (CCI>>5) and, consequently, the infusions were able to sustain a platelet count >10K/uL, with a range of 20-70 K/uL, over the subsequent week. The improved counts, along with the patient's improved clinical condition and stable imaging findings showing resolving intracranial hemorrhages, allowed the transfusion support to be goal-directed targeting a prophylactic platelet threshhold of 10K/uL. Continued monitoring of the patient's CCIs enabled the identification of permissive antigens (i.e., allogeneic platelets with HLA antigens predicted to be incompatible with the patient's serum by solid-phase testing but were found to result in satisfactory increments); this knowledge allowed progressive widening of her permissive donor pool and enabled continued prophylactic support as needed. After three weeks the patient was able to be discharged from the ICU.Subsequent HLA class I antibody screens using flow-cytometry based single antigen bead (SAB) technology revealed progressive decrease in the patient's mean fluorescence intensity for most of her antibody specificities, with the majority of her class I A antibodies falling to undetectable or near-undetectable levels (while previously >5000 MFI). Simple regression analysis (RStudio 1.0.153, R version 3.4.1) was used to test to how level of exposure to individual HLA platelet antigens (as measured by the number of doses with a given antigen) affected subsequent MFI levels. The results of the regression indicate that pre MFI and exposure explain 70.6% of the variance (R2=0.706, F(2,78)=93.7, p=<2.2e-16). It was found that exposure is a significant predictor of decreased MFI (b=-107.20, p=0.01422). High initial MFI was strongly associated with high subsequent MFI (b=0.75, p= <2.2e-16).Conclusions: This data raises the possibility that large bolus platelet infusions could not only be of immediate therapeutic benefit in patients with HLA-alloimmune-mediated platelet refractoriness, but may also accelerate the evanescence of the responsible antibodies. Further research is warranted to explore this possibility, and to ascertain the potential magnitude of this effect in comparison to competing factors such as natural evanescence and/or B-cell immunosuppressive or immunomodulatory therapies. DisclosuresNo relevant conflicts of interest to declare.

Post-Transfusion Overall Survival for HLA- Alloimmunized Platelet Refractorythrombocytopenic Leukemia Patients

BACKGROUND: Platelet alloimmunization and refractoriness is an established complication of platelet (PLT) transfusion, known to be treatment-limiting with potential life-threatening complications for hemato-oncologic patients undergoing chemotherapy (Hess et al.). Previous studies have explored the association of PLT refractoriness with lymphocytotoxic antibody positivity, more frequent platelet transfusion and platelet age (Slichter et al, Blood, 2005). They have also developed cross matching or HLA matching for donor selection as the basis of managing refractory patients. However, the impact of patient characteristics on the clinical outcomes of refractoriness is not fully understood.Objective: To analyze overall survival (OS) of PLT refractory leukemia patients transfused with HLA-matched platelets in association with the demographic and clinical characteristics of these patients.METHODS: We analyzed the demographics, clinical characteristics and platelet refractoriness (defined as two consecutive <24 hr post-transfusion corrected platelet count increments (CCI) of < 5 K/uL), ABO matching (fully compatible, minor mismatch or major mismatch), and HLA match grade (A, B, C). The threshold for transfusion was <7 K/uL and only patients with recorded platelet counts pre- and post-transfusion were included. The majority of post-transfusion counts were performed < 24 hrs. Transfusion efficacy was defined as having: i) difference in platelet counts > 5 pre- and post-transfusion; ii) ABO match or compatible; iii) HLA match grade A or B1.We included two measurements for overall survival (OS): from the date of the first transfusion and also from the last transfusion to the date of last follow-up or date of death. A PLT transfusion record for each measure was obtained using a majority rules algorithm. Group differences in OS were assessed using the log-rank test. For differences in PLT counts, the median value for each patient was used. The association between mean PLT count difference, age, and weight with OS was evaluated using univariate Cox proportional regression models.RESULTS: We identified 33 leukemia patients who received a total of 145 HLA-matched platelet transfusions from 2010-2017. A majority [60%] of the patients had a diagnosis of acute myeloid leukemia or myelodysplastic syndrome and received ≤2 HLA-matched platelet transfusions. Complex cytogenetics was identified in 7 of 23 (30%) patients, while the majority (97%) showed broad reactivity against HLA Class I and Class II antigens. Less than half (45%) of the platelets transfused were HLA match grade B and a third of the platelets (35%) were ABO compatible.The median OS was 16.7 months and the 1-year OS rate was 64%. A significant association between post-transfusion OS with age [p=0.016] and complex cytogenetics [p=0.013] was observed. However, no significant association between OS and gender, weight, ethnicity, and the number of pregnancies was noted. Although the median OS was longer for patients with ABO match/compatible transfusions (vs. incompatible), HLA match grades B2/B3/C platelets (vs. A/B1), and >2 platelets transfusions (vs. ≤ 2), none of these differences were statistically significant (Table 1).CONCLUSIONS: In summary, our findings reveal a significant association of OS was noted with age and complex cytogenetics in platelet refractory hemato-oncologic patients who received HLA-matched platelet transfusions. This association prompts further investigation into how patient profiles may be used in HLA-alloimmunized patients with platelet refractoriness. However, this may need to be studied in a larger cohort of patients in the future. [Display omitted] DisclosuresDiNardo:Celgene: Honoraria, Research Funding; Agios: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Daiichi-Sankyo: Honoraria, Research Funding. Cortes:ImmunoGen: Consultancy, Research Funding; ARIAD: Consultancy, Research Funding; Novartis Pharmaceuticals Corporation: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Teva: Research Funding; Sun Pharma: Research Funding; Pfizer: Consultancy, Research Funding. Kantarjian:Delta-Fly Pharma: Research Funding; Amgen: Research Funding; Novartis: Research Funding; Bristol-Meyers Squibb: Research Funding; Pfizer: Research Funding; ARIAD: Research Funding.

Human leukocyte antigen (HLA)-incompatible mean fluorescence intensity-selected platelet products have corrected count increments similar to HLA antigen-matched platelets.

Donor specific antibody sum mean fluorescence intensity (MFI) values have been successfully used in transplant medicine to assess risk for organ rejection. However, little is known regarding whether MFI values could be similarly used to aid in platelet product selection. We have developed a novel protocol where MFI values are used to offer human leukocyte antigen (HLA)-incompatible platelet products when HLA antigen-matched products are not available. We aimed to evaluate the efficacy of this protocol. We performed a 4-year retrospective chart review for all patients who received at least one MFI-selected platelet product. A corrected count increment (CCI) was calculated for each transfusion event. A mixed effects model was used to investigate the association between CCIs for MFI-selected, HLA antigen matched, and random donor platelet transfusions. A random effects expectation-maximization regression tree was used to define the extent to which other patient variables, such as age, sex, and diagnosis impacted the CCI for each platelet transfusion. Twenty highly HLA alloimmunized patients received a total of 591 platelets. MFI-selected platelet (low MFI) transfusions had a significantly higher median CCI 0-6 hour post-transfusion (13,559, interquartile range [IQR]: 8275-18,736) compared to random donor platelets (2121, IQR: 0-10,368, p< 0.0001). There was no significant difference in median CCI between HLA antigen matched and MFI selected platelet transfusions (p= 0.2). Mixed effects and regression modeling revealed that MFI-selected platelet products had a significantly higher CCI than non-matched platelets, even when accounting for other significant patient variables. MFI-selected HLA-incompatible platelet products could provide a comparable alternative to traditional HLA antigen-matched platelet products.

Does time of CCI measurement affect the evaluation of platelet transfusion effectiveness?

The measurement of corrected count increment at 1-h post-transfusion (CCI-1 h) of platelet concentrate (PC) transfusion is recommended, but in the revised Japanese Guideline (2017) it was changed to “after 10-min to 1-h”, following the revision of the guidelines from Western countries. Here, we aimed to investigate on the feasibility to apply the CCI measured at 10-min or 30-min post-transfusion as the surrogate of CCI-1 h. Peripheral blood was collected at 10-min, 30-min and 1-h post-transfusion of PC and the effectiveness of the transfusion was analyzed based on the CCI. In the period from December 2017 to February 2020, 8 patients, who received multiple PC transfusion (total 208) at our institution, were analyzed. We performed the univariate analyses to examine the relationship between CCI value and the categorical variables, p-value <0.1 was obtained for gender (p = 2.91 × 10−19), fever after transfusion (p = 0.0163). The qualitative variables, namely measurement time (p = 0.0553), also showed p-value <0.1. Using these factors as covariates in the mixed effect model, we found that the measurement time (p = 0.0007) had a significant effect on the CCI value when looking at fixed effects. Although there is a tendency for decreased CCI values with time progression, the slope of the change in the mixed model was -0.00307, indicating that the CCI difference among the 3 measurements was small. Here we provide evidence that CCI measured at 10-min and 30-min post-transfusion give results comparable to those measured at 1-h post-transfusion, under the Japanese practice of platelet transfusion, which relies on 100 % single-donor apheresis PC, and ABO-identical whenever possible.

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.

Human Leukocyte Antigen Class I Antibodies and Response to Platelet Transfusion in Patients Undergoing Liver Transplantation

BackgroundPatients undergoing liver transplantation (LT) frequently receive platelet transfusion (PLT) to minimize their risk of hemorrhage. Alloimmunization to platelets may lead to refractoriness to PLT. Data on the implications of platelet alloimmunization in patients undergoing LT remain limited. We examined the effect of human leukocyte antigen class I (HLA-I) antibodies on PLT refractoriness and short-term outcomes after LT. MethodsPeritransplant clinical and PLT factors were reviewed for all adult liver or simultaneous liver–kidney transplantations from 2012 to 2017. Sensitized patients (SE) with pretransplant HLA-I calculated panel-reactive antibody ≥20% were compared with unsensitized patients (US) with calculated panel-reactive antibody <20%. The mean follow-up was 21.4 mo. ResultsAlloimmunization was observed in 39% of the study cohort. SE (n = 28) received 272 PLTs, and US (n = 44) received 246 PLTs. History of pregnancy was higher among SE than US (P < 0.01); otherwise, both groups had similar clinical characteristics. SE had higher rates of PLT refractoriness (66% versus 47%; P < 0.01) than US. The mean platelet corrected count increment was lower among SE compared with US up to 100 min after PLT (P < 0.05). Alloimmunization and simultaneous liver–kidney transplantation independently predicted refractoriness on multivariate logistic regression (P < 0.05). Early allograft rejection and patient survival rates were comparable for both groups. ConclusionsLT patients experienced high rates of HLA-I alloimmunization and PLT refractoriness. SE had higher rates of refractoriness and lower mean corrected count increment after transfusion compared with US. Our study suggests that further research to evaluate the utility of HLA-matched PLTs in HLA-I alloimmunized LT patients is warranted.

Retrospective cohort studies of repeat donors reveal donor‐dependent variability in the recovery of transfused platelets

The in vivo recovery of transfused platelets is variable and often unpredictable. Although many recipient-dependent factors are well described, donor-dependent variables remain poorly understood. To explore donor-dependent variables we conducted 2 retrospective studies of platelet transfusion outcomes in repeat donors. One study analyzed multiple autologous, radiolabeled platelet transfusions, and a second study analyzed multiple clinical platelet transfusions from a small cohort of repeat donors. In 36 subjects, multiple within-subject determinations of recovery and survival of radiolabeled autologous platelets revealed a relative consistency in platelet recoveries within donors compared to the range of recoveries among donors. Intraclass correlation coefficients for platelet recovery were 43% to 93%. In 524 ABO-compatible clinical platelet transfusions derived from seven donors, a linear mixed-effects model revealed significant donor-dependent differences in corrected count increments for units stored for 4 or 5 days. These two studies indicate reproducible donor-dependent differences in transfused platelet recovery, suggesting a possible heritable influence on the quality of transfused platelets.

Transfusion outcome for volume- and plasma-reduced platelet concentrates for pediatric patients

Background and ObjectivesPlasma reduction in platelet concentrate (PC) products has been reported to prevent large volume load and transfusion-related adverse reactions (TRARs). However, volume reduction might be associated with a poor transfusion response because of a deterioration in platelet (PLT) quality. Because PLT quality control and transfusion responses for recently washed PCs using PLT additive solutions are superior, we investigated the clinical safety and transfusion efficacy of volume-reduced washed PCs in pediatric patients. Materials and MethodsWe prepared a simplified resuspended PC product (RPC) as a washed PC. Regular RPC (R-RPC) included equivalent volumes of bicarbonate Ringer's solution and anticoagulant citrate dextrose solution A (BRS-A) as the resuspension solution. Half RPC (H-RPC) was prepared by adding a half volume of BRS-A. Twenty-four pediatric patients were scheduled for transfusions with R-RPC and H-RPC up to 4 times. R-RPC was transfused 42 times into 24 patients. H-RPC was transfused 41 times into 23 patients. ResultsNeither product was observed to cause TRARs. Although the calculated PLT recovery for H-RPC was significantly reduced, the posttransfusion corrected count increment (24 h) did not differ. Moreover, similar results were observed for vital signs during transfusion. ConclusionVolume-reduced washed PC can be transfused without causing TRARs, differences in vital signs, or inferior transfusion responses. Volume-reduced washed PC also provides the advantages of shortened transfusion times and reduced volume loads. Although a standard technique for stable resuspension is necessary, volume-reduced washed PC may be a beneficial option for children, including neonates, or individuals with cardiovascular or renal problems.

Platelet Count Increment after Transfusion of Fresh and Stored Platelet Concentrates in Children with Acute Lymphoblastic Leukaemia

Background: Therapeutic platelet transfusion is necessary to prevent bleeding due to thrombocytopenia in childhood acute lymphoblastic leukaemia (ALL). Platelet concentrates may be transfused as fresh platelet concentrate immediately or with five days of storage after collection Objectives: To compare the platelet count increment between fresh and stored platelet concentrate transfusion in children with acute lymphoblastic leukaemia. Methodology: This observational study was carried out in the Department of Clinical Pathology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, in collaboration with the Department of Transfusion Medicine and Paediatric Haemato-Oncology, BSMMU, Dhaka. Seventy-two children diagnosed as acute lymphoblastic leukaemia were included in this study. ABO identical whole-blood derived platelet-rich-plasma platelet concentrates (PRP-PCs) were transfused within 24 hours of preparation or 1-5 days of storage. Effectiveness of platelet transfusion was carried out by measuring platelet count prior to transfusion, subsequently 1 hour and 24 hours of transfusion. Result: Post transfusion platelet count at 1 hour and 24 hours with fresh platelet concentrates (FPC) and stored platelet concentrates (SPC) were not statistically significant. Post transfusion platelet increment at 1 hour and 24 hours were also similar in both FPC and SPC. Corrected count increment (CCI) at 1 hour in FPC and SPC were 20.5±10.1 and 18.6 ±6.5 respectively and was statistically not significant (P: 0.168). CCI at 24 hours were 15.5±9.1 and 13±5.8 which were also statistically not significant. Percentage platelet recovery at 1 hour and 24 hours in both FPC and SPC were statistically not significant. But these values in SPC were consistently lower than that of FPC. All the values of FPC and SPC were well apart from the lower limit of CCI and percentage platelet recovery (PPR). It was also observed that 85.1% satisfactory platelet transfusion was achieved with FPC and rest of 14.9% was platelet refractory cases. In 79.5% cases satisfactory platelet transfusion were achieved with SPC and refractory cases were 20.5 %. Conclusion: One to five day’s stored PRP-PCs are as effective as fresh PRP-PCs to achieve satisfactory platelet increment.

Evaluation and monitoring of response to platelet transfusion therapy: experience from a tertiary care center

ABSTRACT Objective: Refractoriness to platelet transfusion is defined as Corrected Count Increment (CCI) <5000 after two sequential ABO identical transfusions. Immune causes include alloimmunization to HLA and/or platelet-specific antigens. Analysis of various factors leading to platelet refractoriness would help in the management of the patient in a timely manner. Materials and Methods: A prospective observational study on platelet transfusions from November 2013 to June 2015 was conducted. Demographic information, pre, and post-transfusion platelet counts and relevant clinical details were noted. Among patients who were considered refractory to platelet transfusions, platelet factor 3 assay was performed to detect antiplatelet antibodies. Data were analyzed using SPSS software. A P value of <0.05 was considered to be statistically significant. Results: A total of 1190 patients received platelet transfusions during the study period. Among these only 339 (28.5%) patients received transfusions on two or more occasions, of which 237 (69.91%) were considered non-refractory. Among the 102 (30.1%) refractory cases non-immune causes for refractoriness were present in 97 (95.1%) patients and antiplatelet antibody was positive in 18 (17.64%) patients. Bleeding and medication have shown to have significantly contributed to refractoriness (p = 0.025 and 0.003) respectively. Use of medication was independently associated with refractoriness. Conclusion: Non-immune causes are more profound in leading to a poor response to platelet transfusions. Recognizing the cause of poor response and treating the underlying cause would help in getting a better response.

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.

Clinical efficacy of platelet transfusion therapy in patients with leukemia and analysis of risk factors for ineffective transfusion.

Clinical efficacy of platelet transfusion therapy in patients with leukemia was investigated to analyze risk factors for ineffective transfusion. A total of 105 cases of patients with leukemia admitted to The First Affiliated Hospital of Bengbu Medical College from August 2016 to November 2018 were selected as research subjects. A total of 49 patients received transfusion of apheresis platelet suspension, and were group A. Fifty-six patients who received mixed multi-person platelet suspension were group B. The percentage plate recovery (PPR) and corrected count increment (CCI), interleukin-11 (IL-11) and soluble glycoprotein 130 (sgp130) levels were compared between the two groups, and the correlation of PPR and CCI with serum IL-11 and sgp130 levels was analyzed. Multivariate logistic regression was used to analyze the independent risk factors affecting ineffective transfusion in patients with leukemia. After transfusion, PPR and CCI in both groups were significantly higher than those before transfusion (P<0.05). IL-11 was significantly increased in both groups after transfusion, and sgp130 was significantly decreased in the two groups after transfusion (P<0.05). Serum IL-11 level in leukemia patients was positively correlated with PPR and CCI (r=0.7693, P<0.001), (r=0.7760, P<0.001), and serum sgp130 level in leukemia patients was negatively correlated with PPR and CCI (r=-0.7086, P<0.001), (r=-0.7733, P<0.001). There were differences between the effective group and the ineffective group in transfusion frequency, fever, infection and splenomegaly (P<0.05). Fever (OR, 0.382; 95% CI, 0.183-0.972) and infection (OR, 0.367; 95% CI, 0.140-0.956) were independent risk factors for ineffective transfusion. In conclusion, apheresis platelet or mixed multi-person platelet suspension transfusion can significantly improve the disorder of platelet count in patients with leukemia, and improve the clinical efficacy. Fever and infection are independent risk factors leading to ineffective transfusion.

Clinical outcome of platelet transfusion using platelet-rich plasma-derived platelets and buffy coat-removed platelets in patients with dengue fever – A comparison

Background and Objectives: Platelet transfusions are widely used to treat thrombocytopenia of various etiology. There are two different methods of preparation of platelet concentrate from whole blood: one is platelet-rich plasma method (PRP) and the buffy coat removed (BCR) method. This study aimed to compare the clinical outcome of patients with dengue fever transfused with platelets prepared by PRP method and BCR method. Methodology: A total of 100 patients with thrombocytopenia due to dengue fever were enrolled in the study, with fifty patients in each group. The outcome of patients transfused with PRP-derived platelets and BCR platelets was compared on the basis of absolute and corrected count increment (CCI), percent platelet recovery, and incidence of posttransfusion reactions. Results: The mean absolute count increment in patients who received BCR-platelet concentrate (BCR-PC) was 23,900/μl ± 7022.56/μl. The mean absolute count increment in patients who received PRP-derived PC was 18,910/μl ± 7482.42/μl. The difference was statistically significant with P = 0.001. The mean CCI of PRP group was 12,847 ± 5146.76 and in the BCR group, it was 12,897 ± 4266.82, and this difference was not statistically significant (P = 0.957). None of the patients transfused with BCR platelets reported a transfusion reaction, whereas one out of fifty (2%) patients transfused with PRP platelets had febrile nonhemolytic transfusion reaction. Conclusion: On the basis of count increment, CCI, percent platelet recovery, and incidence of posttransfusion reactions, BCR platelet transfusions showed a better outcome than PRP platelet transfusions.

Transfusion Medicine Equations Made Internet Accessible.

Multiple mathematical equations inform the practice of transfusion medicine. These equations apply to a wide range of topics: dosage of blood products, calculation of fluid volumes, and even specific treatment decisions (e.g. corrected count increment for determination of platelet refractoriness). The calculation of these equations can be complicated, prone to error, and time-consuming. A trusted source is needed to accurately perform these calculations 24 hours a day without error and without monetary cost. We sought to build internet-enabled calculators relevant to the practice of transfusion medicine. We partnered with MDCalc, an online host of medical calculators with 1 million monthly users in 196 countries, to design and host the calculators. The calculators guide users in the application of transfusion medicine equations by providing indications for use, inputs for the equations variables, error-checking, warnings for bad inputs, and interpretive guidance of the result. The following calculators were built: blood volume, corrected count increment (CCI), plasma dosage, cryoprecipitated antihemophilic factor dosage, approximate number of units for compatibility testing, maternal-fetal hemorrhage Rh(D) immune globulin dosage, intrauterine RBC transfusion dosage, neonatal polycythemia partial exchange, theoretical removal of a substance by plasmapheresis, sickle cell RBC exchange volume, peripheral blood stem cell collection, and a calculator relevant to donor lymphocyte infusion. Clinicians can now utilize this reputable and highly visible online source to access these common transfusion medicine equations at any time with an internet-enabled device (https://www.mdcalc.com/search?filter=transfusion+medicine).

Post-transfusion platelet responses in critically ill cancer patients with hypoproliferative thrombocytopenia.

Platelet transfusion is aimed at increasing platelet counts to prevent or treat bleeding. Critically ill cancer patients with hypoproliferative thrombocytopenia are high consumers of blood products. We herein described their post-transfusion platelet responses in the intensive care unit (ICU) and analyzed the determinants of poor post-transfusion increments. This was a single-center 9-year (2009-2017) retrospective observational study. Patients with malignancies and presumed or proven hypoproliferative thrombocytopenia who had received at least one platelet transfusion in the ICU were included. Poor post-transfusion platelet increments were defined as body surface-adjusted corrected count increment (CCI) <7, or alternatively as weight-adjusted platelet transfusion recovery (PTR) <0.2. Patients were deemed refractory to platelet transfusions when two consecutive ABO-compatible transfusions resulted in poor platelet increments. A total of 1470 platelet transfusions received by 326 patients were analyzed. Indications for platelet transfusions were distributed into prophylactic (44.5%), peri-procedural (18.1%) and therapeutic (37.4%). Regardless of indications, 54.6% and 55.4% of transfusion episodes were associated with a CCI <7 or a PTR <0.2. Factors independently associated with poor post-transfusion increments were lower body mass index, spleen enlargement, concurrent severity of clinical condition, fever ≥39°C, antibiotic therapy and increased storage duration of platelet concentrates. Eventually, 48 patients developed refractoriness to platelet transfusion, which was associated increased incidence of bleeding events. Platelet transfusions are often associated with poor increments in critically ill cancer patients with hypoproliferative thrombocytopenia. The findings suggest amenable interventions to improve the platelet transfusion practices in this setting.

Cytokine Release Syndrome Is an Independent Risk Factor Associated with Platelet Transfusion Refractoriness after CAR-T Treatment for Relapsed/Refractory Acute Lymphoblast Leukemia

Platelet transfusion refractoriness (PTR) has been widely observed in hematopoietic stem cell transplantation (HSCT) and chemotherapy in some researches. However, PTR not only has unclear mechanism but no recognized standard treatment guidelines, even has a life-threatening effect on hematological patients. Our study is aim to evaluate the rate of PTR and related factors of PTR in patients with refractory/relapsed acute lymphocytic leukemia (R/R ALL) who received chimeric antigen receptor T cell therapy (CAR-T). We retrospectively collected the data of 49 R/R ALL patients between July 2011 and June 2019 in our single center, and divided them into chemotherapy group and CAR-T group, including 26 patients only receiving chemotherapy and 23 undergoing CAR-T therapy. All R/R ALL patients underwent multiple first lines or second lines of chemotherapies. As for CAR-T group, the fludarabine and cyclophosphamide were administrated three days to lower the tumor burden before CAR-T cell infusion. Age, sex, height, weight, the platelet count before and after transfusion, transfusion unit are all included in our data. In terms of the CAR-T group ,we also collect the peak body temperature , the peak c-reactive protein ,CRS grade , IL6 , IL10 , IFN-γ. The pre-transfusion and post-transfusion platelet count were obtained after each transfusion, the 12h CCI&lt;5000 (corrected count increment) is used to evaluate if the patient has PTR. By chi-square test, we found 13 patients became PTR in all patients, of 2 patients (15.4%) is in chemotherapy group while 11 (84.6%) is in CAR-T group. Moreover, 7.7% (2/26) PTR in chemotherapy group is markedly lower than 47.8% (11/23) in CAR-T group (P=0.001). The associated factors with PTR in this study is cytokine release syndrome (CRS) grade. Then we found the significant elevated cytokine levels in CAR-T group. By Mann-Whitney U test, the mean levels of IL-6 in PTR group versus non-PTR group were 6.58 vs 17.91 (p&lt;0.001). Serum mean levels of IL-10 in PTR group versus non-PTR group were 7.58 vs 16.82 respectively (p=0.001) while serum levels of IFN-γ were 6.58 versus 17.91 respectively (P&lt;0.001). With the decline of cytokines, the 12h CCI of partial patients with PTR will be increased than before, some patients even recover to normal platelet transfusion increment. The rate of PTR in patients undergoing CAR-T therapy was much higher than those who received chemotherapy only. CRS was the only independent risk factor associated with PTR after CAR-T treatment. High serum levels of cytokines (IL-6, IL-10 and IFN-γ) during CRS might contribute to is PTR. Disclosures No relevant conflicts of interest to declare.

Evaluation of Efficacy and Safety of Cold-Stored Platelets in Healthy Human Subjects Treated with Dual Antiplatelet Therapy

Background: Platelets are currently stored at 22°C (room temperature-stored) for clinical purposes. This approach has numerous downsides including limited storage time due to risk of bacterial growth, and increased costs caused by bacterial testing or pathogen reduction. Platelets stored at 4ºC (cold-stored) were the standard of care in the 1960s and 70s, and while they generally perform better than room temperature-stored platelets in in vitro assays, functional studies in vivo have yielded contradictory results. Methods: Eight healthy human participants were included in the analysis of this randomized, cross-over study. A double unit of apheresis platelets was collected from each subject for autologous transfusion. Platelets were stored for 5 days at either 4ºC, or 22ºC, based on randomization. On day 5, platelets were transfused 12-24 hours after participants received a loading dose of acetylsalicylic acid and clopidogrel. An array of platelet function testing was done at baseline, after loading dose, and after transfusion (1h, 4h, 24h). The first round was followed by a wash-out period of at least 10 days, and a second sequence of collection, antiplatelet loading dose, and transfusion with platelets stored under alternate conditions from the first sequence. The primary endpoint was defined as post-transfusion platelet αIIbβ3 integrin activation in response to agonists for pathways inhibited by dual antiplatelet therapy, measured by the VerifyNOW assay. Secondary endpoints included platelet function testing by bleeding time, VASP-phosphorylation, light transmission aggregometry, and flow cytometric analysis of platelet αIIbβ3 integrin activation and α-granule secretion. Results: All cold-stored platelet units passed quality control analyses, and no platelet aggregates were observed at the end of the storage period. One room temperature-stored unit had to be discarded due to quality control failure. Transfusion of a double unit with 5 day cold-stored platelets was tolerated well by all recipients. The absolute number of transfused platelets did not differ significantly between the cold-storage arm and the room temperature storage arm. The corrected count increment did not differ significantly at 1h after transfusion, but was significantly lower in the cold-stored group at the 4h, and 24h time points. The primary endpoint, platelet function testing by VerifyNOW, showed reversal of the effect of acetylsalicylic acid with both products at 1h and 4h post transfusion, but platelet inhibition re-appeared after 24h post transfusion in the cold-storage arm, presumably due to accelerated clearance of cold-stored platelets. No significant differences were observed between the two products in the VerifyNOW assay for clopidogrel. The bleeding time (a secondary endpoint) did not differ significantly at any time point between the cold-stored and room temperature-stored transfusion group. However, the bleeding time improved or remained unchanged in all recipients transfused with room temperature-stored platelets, whereas, transfusion of cold-stored platelets caused prolongation of the bleeding time in 50% of recipients. Surprisingly, platelets isolated from recipients of room temperature-stored platelets aggregated significantly better in response to collagen compared to platelets isolated from recipients of cold-stored platelets at 1h and 4h post transfusion. Other secondary endpoints, including VASP-phosphorylation, αIIbβ3 integrin activation and α-granule secretion by flow cytometry, and platelet aggregation in response to arachidonic acid and ADP did not differ significantly between the two treatment groups. Conclusion: We report the first safety and efficacy data of 5 day cold stored platelets in plasma. Unexpectedly, some endpoints demonstrate agonist- and assay-dependent inferiority of cold-stored platelets at early and late time points. Further studies are needed to determine the maximum storage time, and the efficacy of cold-stored platelets in actively bleeding patients and patients with platelet dysfunction. Disclosures No relevant conflicts of interest to declare.

Impact of Amotosalen/UVA Pathogen Inactivated Platelet Components on Outcomes after Allogeneic Hematopoetic Stem Cell Transplantation: A Single Center Analysis

Background: Platelet component (PC) transfusion is required for allogeneic hematopoietic stem cell transplantation (HCT) recipients. Contamination with infectious pathogens (bacteria, viruses, or protozoa) and T-cells is a risk factor for transfusion-transmitted infection (TTI) and transfusion associated graft-versus-host disease (TA-GVHD). Pathogen inactivation (PI) treatment of PC with amotosalen-UVA (PI-PC, INTERCEPT Blood System, Cerus Corp) in platelet additive solution (PAS) without bacterial screening, gamma irradiation, CMV serology, and with 7-day storage has been the standard of care in Switzerland since 2011 to manage risk of TTI and TA-GVHD. PI-PC have replaced conventional PC (C-PC) prepared in PAS with gamma irradiation and 5 day storage. We previously reported platelet usage in two consecutive five year periods at the University Hospital of Basel. Mean PI-PC dose was higher (3.0 vs. 2.8 x 1011, p=0.001) and mean storage duration longer (4.2 vs. 3.4 days: p=0.001) than with C-PC. PC expiration wastage was reduced with 7-day PI-PC storage vs. 5-day storage (1.5% vs. 8.7%). For HCT recipients, days of PC support; PC use per patient; and RBC use per patient were similar, despite 24.3% lower corrected count increments (CCI) with PI-PC. Now, we report the impact of these observations on treatment related mortality (TRM) and overall survival (OS) 100 days after HCT. Patients and Methods: A two-period retrospective cohort study was conducted to evaluate PI-PC impact on outcomes of consecutive first allogeneic HCT recipients from January 2006 to December 2010 (Period 1, P1), when gamma-irradiated apheresis C-PC were used, and Period 2 (P2) from January 2011 to December 2017, when apheresis and whole blood-derived PI-PC were used. The review utilized 100-day OS and 100-day TRM to determine the impact of PI-PC on HCT outcomes. Descriptive statistics were used for continuous variables and log-rank analysis for survival outcomes. Univariate analysis was performed using Pearson χ2 statistics. Multivariate Cox regression modelling analyses included: PC period (P1, P2), donor match (HLA identical/twin, matched related, matched unrelated), disease state (early, intermediate, late), and conditioning regimen (reduced intensity, myeloablative) with TRM as the outcome. This was an IRB approved single-center analysis. Results: In P1 and P2, 256 and 557 consecutive first-time allogeneic HCT recipients were included, respectively. By univariate analysis, the distribution of European Group for Bone Marrow Transplantation (EBMT) risk scores (grouped 0-2, 3-4, 5-7) and mean patient age were higher during P2 (p = 0.001 and p &lt;0.001, respectively). Primary disease status (p = 0.039); stem cell source (p &lt;0.001); GVHD prophylaxis with ATG (p &lt;0.001); total body irradiation (p &lt;0.001); and conditioning regimen (p &lt;0.001) were different between P1 and P2. Donor match (p=0.084) and disease status (p = 0.628) were similar in P1 and P2. TRM at day 100 post HCT was significantly less (31/557, 5.5%) for PI-PC recipients in P2 vs. C-PC recipients in P1 (37/256, 14.5%, p&lt;0.001). Overall proportion of survivors at day 100 post HCT was significantly greater for PI-PC recipients (507/557, 91.0 %) compared to C-PC recipients (209/256, 81.6%, p &lt;0.001). By multivariate Cox regression analysis, P2 with PI-PC component support was associated with improved TRM (p = 0.001; adjusted hazard ratio 0.433; 95% confidence interval: 0.262, 0.716). Donor match (p = 0.019), disease state (p = 0.022), and myeloablative conditioning (p = 0.034) were associated with significantly poorer TRM (Table). Stem cell source was not significant (p=0.157) in the model. Hemorrhage was reported as cause of death in 1/50 (2.0%) patients during P2 with PI-PC and 4/47 (8.5%) patients during P1 with C-PCs. Conclusions: Universal implementation of PI-PC in routine with extended storage to 7 days in P2 was associated with reduced TRM and better overall survival 100 days post HCT, despite transplantation of older patients with higher EBMT risk scores. Multivariate analysis revealed an adjusted hazard ratio of 0.433 (95% C.I. 0.262, 0.716) for TRM by 100 days, suggesting better outcomes in P2. This retrospective analysis at a single site indicated that PI-PC treated with amotosalen /UVA stored up to 7 days did not have a negative impact on TRM and OS in HCT recipients, and was an integral part of improving clinical outcomes at our institution. . Table. Disclosures Heim: Novartis: Research Funding. Irsch:Cerus Corporation: Employment, Equity Ownership. Lin:Cerus Corporation: Employment, Equity Ownership. Benjamin:Cerus Corporation: Employment, Equity Ownership. Corash:Cerus Corporation: Employment, Equity Ownership.

Efficacy of cross-match compatible platelets in multi transfused haemato-oncology patients refractory to platelet transfusion

BackgroundPlatelet refractoriness, which leads to platelet transfusion failure resulting in significant morbidity and long hospital stay, is routinely not investigated. AimsTo determine the efficacy of cross-match compatible platelets in multi-transfused alloimmunized hemato-oncological patients refractory to platelet transfusion. Materials and method149 ABO compatible single donor apheresis platelet transfusions given to 38 alloimmunized refractory patients. Corrected Count Increment (CCI) <5000 (1 h) was taken to define refractoriness. Solid-phase red cell adherence assay was used to determine the alloimmunization status and platelet cross-matching. Post Transfusion Platelet Increment, CCI and the Percentage Platelet Recovery were used to monitor the effectiveness of platelet transfusion. ANOVA test followed by Post hoc test Tukey HSD used to compare group means and classified into three groups depending upon the cross-matching and compatibility status. Categorical data was analysed for various outcomes using Pearson's chi square test or Fischer exact test. ResultPatients showed statistically significant recovery in terms of PPI, CCI and PPR at 1 h post SDAP transfusions when they received cross-matched compatible platelets. The one-hour CCI was significantly higher for cross-match-compatible platelets (19173 ± 2692) than for incompatible (5888 ± 1526) and for uncross-matched (8140 ± 1480). Forty four (97.8%) of 45 cross-matched compatible platelet transfusion episodes showed a satisfactory response in terms of PPI and CCI values as compared to 50 % and 53.9% in uncross-matched group respectively (p < 0.0001). ConclusionPlatelet cross-matching is an effective intervention in the management of multi-transfused alloimmunized Haemato-oncological patients, refractory to platelet transfusion.