PLTs of blood group A1 donors express increased surface A antigen owing to apheresis and prolonged storage

BACKGROUND: In contrast to RBC transfusion, where ABO mismatch is potentially lethal, immunologic ABO matching has been considered less critical for PLTs. Nonetheless, PLTs bear ABO blood group antigens, some of them expressing very high levels. STUDY DESIGN AND METHODS: The expression of A antigen was investigated by flow cytometry on resting and stimulated human PLTs of 100 A and 10 O group donors, as well as on 17 PLT concentrates (PCs) after apheresis and daily during a 6-day storage, to determine possible changes in expression of A antigen on PLT surface. RESULTS: Considerable variation of A antigen expression on PLT surface of A1 group individuals was observed; A2 group PLTs could not be distinguished from O group PLTs. The variability of A antigen on A group PLTs also became evident on investigating PLT lysates by ELISA. A1 group PCs showed a significant increase of A antigen expression on their surface owing to apheresis (p = 0.001) and to storage (p = 0.0091). CONCLUSION: Apheresis and prolonged storage of A1 group PCs independently led to overexpression of A antigen on the PLT surface. This may make such PCs more susceptible to destruction by anti-A of O or B group recipients.     

Alterations of platelet function and clot formation kinetics after in vitro exposure to anti‐A and ‐B

BACKGROUND: ABO‐mismatched platelets (PLTs) are commonly transfused despite reported complications. We hypothesized that because PLTs possess A and B antigens on their surface, ABO‐mismatched transfused or recipient PLTs could become activated and/or dysfunctional after exposure to anti‐A or ‐B in the transfused or recipient plasma. We present here in vitro modeling data on the functional effects of exposure of PLTs to ABO antibodies. STUDY DESIGN AND METHODS: PLT functions of normal PLTs of all ABO types were assessed before and after incubation with normal saline, ABO‐identical plasma samples, or O plasma samples with varying titers of anti‐A and anti‐B (anti‐A/B). Assays used for this assessment include PLT aggregation, clot kinetics, thrombin generation, PLT cytoskeletal function, and mediator release. RESULTS: Exposure of antigen‐bearing PLTs to O plasma with moderate to high titers of anti‐A/B significantly inhibits aggregation, prolongs PFA‐100 epinephrine closure time, disrupts clot formation kinetics, accelerates thrombin generation, reduces total thrombin production, alters PLT cytoskeletal function, and influences proinflammatory and prothrombotic mediator release. CONCLUSIONS: Our findings demonstrate a wide range of effects that anti‐A/B have on PLT function, clot formation, thrombin generation, PLT cytoskeletal function, and mediator release. These data provide potential explanations for clinical observations of increased red blood cell utilization in trauma and surgical patients receiving ABO‐nonidentical blood products. Impaired hemostasis caused by anti‐A/B interacting with A and B antigens on PLTs, soluble proteins, and perhaps even endothelial cells is a potential contributing factor to hemorrhage in patients receiving larger volumes of ABO‐nonidentical transfusions.     

Platelet Transfusion – the Art and Science of Compromise

Summary

Many modern therapies depend on platelet (PLT) transfusion support. PLTs have a 4- to 7-day shelf life and are frequently in short supply. In order to optimize the inventory PLTs are often transfused to adults without regard for ABO compatibility. Hemolytic reactions are infrequent despite the presence of ‘high titer’ anti-A and anti-B antibodies in some of the units. Despite the low risk for hemolysis, some centers provide only ABO identical PLTs to their recipients; this practice might have other beneficial outcomes that remain to be proven. Strategies to mitigate the risk of hemolysis and the clinical and laboratory outcomes following ABO-matched and mismatched transfusions will be discussed. Although the PLTs themselves do not carry the D antigen, a small number of RBCs are also transfused with every PLT dose. The quantity of RBCs varies by the type of PLT preparation, and even a small quantity of D+ RBCs can alloimmunize a susceptible D− host. Thus PLT units are labeled as D+/–, and most transfusion services try to prevent the transfusion of D+ PLTs to D– females of childbearing age. A similar policy for patients with hematological diseases is controversial, and the elements and mechanisms of anti-D alloimmunization will be discussed.KeyWords: Platelets, ABO, Rh, Mismatch, Hemolysis, Alloimmunization, Antibody     

Practices associated with ABO‐incompatible platelet transfusions: a BEST Collaborative international survey

BACKGROUND: There is a lack of evidence for guiding the best strategy for ABO selection of platelet (PLT) transfusions. As a baseline for future studies, the BEST Collaborative performed an international survey of current practices in this area. STUDY DESIGN AND METHODS: An international survey was sent via BEST members to transfusion services and hospitals requesting the demographics of the transfused patient population, ABO matching policies, anti‐A and anti‐B measurements in PLT concentrates (PCs), and practices regarding ABO‐incompatible PC transfusions to adult and pediatric patients. RESULTS: We received 126 responses from 14 countries, 59% from Europe. Most of them were from local/community (42%) and university hospitals (39%) serving between 500 and 1500 beds; 50.4% transfused fewer than 1000 PCs per year. One‐fifth of respondents (19.4%, mainly local/community hospitals) did not have a written policy for selecting ABO‐incompatible PCs. Significant practice variation was reported when ABO‐mismatched PLTs were given to adults: for PCs suspended in 100% plasma, 29% to 43% of respondents selected any ABO group available; 52% to 61% selected units with compatible supernatant; and, in the case of minor ABO incompatibility, 43% to 54% did not take any specific action. In contrast if ABO‐identical PCs were not available for a pediatric recipient, for PCs resuspended in 100% plasma, 71% to 82% selected PCs so the supernatant plasma would be compatible with patient's red blood cells. CONCLUSION: Considerable practice variation exists when transfusing ABO‐incompatible PCs, suggesting an opportunity for research to inform evidence‐based practices.     

Providing ABO-identical platelets and cryoprecipitate to (almost) all patients: approach, logistics, and associated decreases in transfusion reaction and red blood cell alloimmunization incidence

BACKGROUND: There are multiple benefits to transfusing only ABO‐identical blood components. Historically our institution routinely transfused ABO‐nonidentical platelets (PLTs) and cryoprecipitate to surgical patients. In April 2005, we implemented a policy of transfusing only ABO‐identical components whenever feasible, regardless of outdating or logistic considerations. STUDY DESIGN AND METHODS: Technical staff closely monitored product usage and adjusted blood center orders based on recent utilization and planned transfusions. When unable to provide ABO‐identical PLTs, ABO‐compatible PLTs were washed to remove incompatible plasma. Data on outdating were collected for 18 months before and after implementation. We compared transfusion reaction and red blood cell (RBC) alloimmunization incidence for 4 years preceding (2001‐2004) and subsequent (2006‐2009) to implementation. RESULTS: In the year after implementation, only 11 of 410 surgical patients received ABO‐nonidentical PLTs (2.7%). There was a 5.6% increase in outdating of PLTs. Transfusing ABO‐identical components was associated with significant reductions in febrile (?46%; 8.0 to 4.3 per 10,000 components; p < 0.0001) and allergic transfusion reactions (?23%; from 7.0 to 5.4 per 10,000 components; p = 0.025). A progressive reduction in de novo RBC alloimmunization incidence also occurred (?50% by 2009; p = 0.03). CONCLUSIONS: Providing ABO‐identical PLTs to almost all patients was feasible in our setting by changing ordering and inventorying procedures and making the ABO‐identical policy a staff priority. Unexpected and striking reductions in febrile and allergic reactions and RBC alloimmunization were observed, of uncertain causal relationship to this ABO policy change, which will require further study.     

A randomized controlled clinical trial evaluating the performance and safety of platelets treated with MIRASOL pathogen reduction technology

BACKGROUND: Pathogen reduction of platelets (PRT‐PLTs) using riboflavin and ultraviolet light treatment has undergone Phase 1 and 2 studies examining efficacy and safety. This randomized controlled clinical trial (RCT) assessed the efficacy and safety of PRT‐PLTs using the 1‐hour corrected count increment (CCI_1hour) as the primary outcome. STUDY DESIGN AND METHODS: A noninferiority RCT was performed where patients with chemotherapy‐induced thrombocytopenia (six centers) were randomly allocated to receive PRT‐PLTs (Mirasol PRT, CaridianBCT Biotechnologies) or reference platelet (PLT) products. The treatment period was 28 days followed by a 28‐day follow‐up (safety) period. The primary outcome was the CCI_1hour determined using up to the first eight on‐protocol PLT transfusions given during the treatment period. RESULTS: A total of 118 patients were randomly assigned (60 to PRT‐PLTs; 58 to reference). Four patients per group did not require PLT transfusions leaving 110 patients in the analysis (56 PRT‐PLTs; 54 reference). A total of 541 on‐protocol PLT transfusions were given (303 PRT‐PLTs; 238 reference). The least square mean CCI was 11,725 (standard error [SE], 1.140) for PRT‐PLTs and 16,939 (SE, 1.149) for the reference group (difference, ?5214; 95% confidence interval, ?7542 to ?2887; p < 0.0001 for a test of the null hypothesis of no difference between the two groups). CONCLUSION: The study failed to show noninferiority of PRT‐PLTs based on predefined CCI criteria. PLT and red blood cell utilization in the two groups was not significantly different suggesting that the slightly lower CCIs (PRT‐PLTs) did not increase blood product utilization. Safety data showed similar findings in the two groups. Further studies are required to determine if the lower CCI observed with PRT‐PLTs translates into an increased risk of bleeding.     

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

BACKGROUND: 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. STUDY DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.     

Factors influencing moderate to severe reactions to PLT transfusions: experience of the TRAP multicenter clinical trial

BACKGROUND: During the Trial to Reduce Alloimmunization to Platelets (TRAP Trial), data were prospectively collected for 8769 PLT transfusions regarding the frequency of moderate to severe PLT transfusion reactions. STUDY DESIGN AND METHODS: At seven centers, 598 patients were randomly assigned to receive unmodified pooled random-donor PLT concentrates (PCs), UV-B-irradiated PCs, filtered PCs, or filtered random-donor apheresis PLTs. RESULTS: Moderate to severe transfusion reactions were an increase in temperature of at least 2 degrees C, chills with rigors, extensive urticaria, dyspnea, cyanosis, or bronchospasm. These reactions occurred with 2.2 percent of the transfusions in 22 percent of the patients. Transfusion reactions were associated with WBC counts of more than 5 x 10(6) per transfusion (p = 0.002) and transfusions stored for more than 48 hours (p = 0.02). PLT counts before transfusion were significantly lower for transfusions associated with reactions (p = 0.005). Neither UV-B irradiation nor apheresis PLTs independently influenced reaction rates. The PLT increment at 1 hour after transfusion was lower for transfusions associated with reactions (p = 0.004), and the frequency of reactions was higher in PLT refractory patients (p < 0.001). CONCLUSIONS: The provision of either fresh and/or WBC-reduced PLTs may decrease the frequency of PLT transfusion reactions and improve PLT transfusion efficacy.     

Platelets photochemically treated with amotosalen HCl and ultraviolet A light correct prolonged bleeding times in patients with thrombocytopenia

BACKGROUND: Photochemical treatment (PCT) with amotosalen HCl with ultraviolet A illumination inactivates pathogens and white blood cells in platelet (PLT) concentrates. STUDY DESIGN AND METHODS: In a Phase II crossover study, 32 patients with thrombocytopenia received one transfusion of PCT and/or one transfusion of untreated (reference) apheresis PLTs. Hemostatic efficacy was assessed with the cutaneous template bleeding time and clinical observations. RESULTS: Paired bleeding time data for PCT and reference transfusions were available for 10 patients. Mean pretransfusion bleeding times were 29.2 +/- 1.6 minutes in the PCT group and 28.7 +/- 2.5 minutes in the reference group. After transfusion of a dose of PLTs of at least 6.0 x 10(11), mean 1-hour posttransfusion template bleeding times corrected to 19.3 +/- 9.5 minutes in the PCT group and 14.3 +/- 6.5 minutes in the reference group (p = 0.25). In 29 patients receiving paired PCT and reference transfusions, mean 1-hour posttransfusion PLT count increments were 41.9 x 10(9) +/- 20.8 x 10(9) and 52.3 x 10(9) +/- 18.3 x 10(9) per L for PCT and reference, respectively (p = 0.007), and mean 1-hour posttransfusion PLT corrected count increments (CCIs) were 10.4 x 10(3) +/- 4.9 x 10(3) and 13.6 x 10(3) +/- 4.3 x 10(3) for PCT and reference, respectively (p < 0.001). The time to next PLT transfusion was 2.9 +/- 1.2 days after PCT transfusions versus 3.4 +/- 1.3 days after reference transfusions (p = 0.18). Clinical hemostasis was not significantly different after PCT and reference transfusions. CONCLUSION: PCT PLTs provided correction of prolonged bleeding times and transfusion intervals not significantly different than reference PLTs despite significantly lower PLT count increments and CCIs.     

Platelet dose consistency and its effect on the number of platelet transfusions for support of thrombocytopenia: an analysis of the SPRINT trial of platelets photochemically treated with amotosalen HCl and ultraviolet A light

BACKGROUND: The SPRINT trial examined efficacy and safety of photochemically treated (PCT) platelets (PLTs). PCT PLTs were equivalent to untreated (control) PLTs for prevention of bleeding. Transfused PLT dose and corrected count increments (CIs), however, were lower and transfusion intervals were shorter for PCT PLTs, resulting in more PCT than control transfusions. PLT dose was analyzed to determine the impact of the number of PLTs transfused on transfusion requirements. STUDY DESIGN AND METHODS: Transfusion response was compared for patients with all doses of >or=3.0 x 10(11) and the complementary subset of patients with any dose of fewer than 3.0 x 10(11). Analyses included comparison of bleeding, number of PLT and red blood cell (RBC) transfusions, transfusion intervals, and CIs between PCT and control groups within each PLT dose subset. RESULTS: Mean PLT dose per transfusion in the PCT group was lower than in the control group (3.7 x 10(11) vs. 4.0 x 10(11); p<0.001). More PCT patients received PLT doses of fewer than 3.0 x 10(11) (n=190) than control patients (n=118; p<0.01). Comparisons of patients receiving comparable PLT doses showed no significant differences between PCT and control groups for bleeding or number of PLT or RBC transfusions; however, transfusion intervals and CIs were significantly better for the control group. CONCLUSIONS: When patients were supported with comparable doses of PCT or conventional PLTs, the mean number of PLT transfusions was similar. Lower CIs and shorter transfusion intervals for PCT PLTs suggest that some PLT injury may occur during PCT. This injury does not result in a detectable increase in bleeding, however.     

Patient and product factors affecting platelet transfusion results

BACKGROUND: Providing patients with platelet (PLT) transfusions requires important logistic resources and represents a considerable cost factor. Optimizing PLT transfusions is in the interest of not only patient safety but also economic importance. Only few studies have evaluated factors associated with transfusion results. STUDY DESIGN AND METHODS: In a prospective single-center study, 9923 mainly prophylactic PLT transfusions given to 672 patients treated for hematologic malignancies between 1997 and 2004 were investigated. Patient and product factors were analyzed. Transfusion efficacy was measured by the corrected count increment (CCI), and side effects were recorded. RESULTS: The mean CCI of all transfusions was 14.05 (standard deviation, 9.5). The CCI correlates with the transfusion interval. PLT transfusions that resulted in a transfusion interval of 1 day or less had significantly lower CCI of 11.3 than transfusions that resulted in a transfusion interval of 2 days or more (15.57). Allogeneic stem cell transplant recipients had a significantly lower transfusion efficacy (CCI mean, 13.3) whereas patients treated with antithymocyte globulin (ATG) had better CCIs (17.2) compared to patients who were treated with chemotherapy only. Longer PLT storage time and ABO mismatch had a negative impact on transfusion efficacy. PLTs stored in PLT additive storage solution were less effective than PLTs stored in their own autologous plasma. CONCLUSION: Manipulation of PLT products may result in lower transfusion efficacy as illustrated by the introduction of PLT additive storage solution in this report. The higher number of products used per patient may negatively impact on advantages gained by the transfusion of "safer" PLT products.     

CTLA4‐Ig prevents alloantibody production and BMT rejection in response to platelet transfusions in mice

BACKGROUND: Platelet (PLT) transfusions can induce humoral and cellular alloimmunity. HLA antibodies can render patients refractory to subsequent transfusion, and both alloantibodies and cellular alloimmunity can contribute to subsequent bone marrow transplant (BMT) rejection. Currently, there are no approved therapeutic interventions to prevent alloimmunization to PLT transfusions other than leukoreduction. Targeted blockade of T‐cell costimulation has shown great promise in inhibiting alloimmunity in the setting of transplantation, but has not been explored in the context of PLT transfusion. STUDY DESIGN AND METHODS: We tested the hypothesis that the costimulatory blockade reagent CTLA4‐Ig would prevent alloreactivity against major and minor alloantigens on transfused PLTs. BALB/c (H‐2^d) mice and C57BL/6 (H‐2^b) mice were used as PLT donors and transfusion recipients, respectively. Alloantibodies were measured by indirect immunofluorescence using BALB/c PLTs and splenocytes as targets. BMTs were carried out under reduced‐intensity conditioning using BALB.B (H‐2^b) donors and C57BL/6 (H‐2^b) recipients to model HLA‐identical transplants. Experimental groups were given CTLA4‐Ig (before or after PLT transfusion) with control groups receiving isotype‐matched antibody. RESULTS: CTLA4‐Ig abrogated both humoral alloimmunization (H‐2^d antibodies) and transfusion‐induced BMT rejection. Whereas a single dose of CTLA4‐Ig at time of transfusion prevented alloimmunization to subsequent PLT transfusions, administration of CTLA4‐Ig after initial PLT transfusion was ineffective. Delaying treatment until after PLT transfusion failed to prevent BMT rejection. CONCLUSIONS: These findings demonstrate a novel strategy using an FDA‐approved drug that has the potential to prevent the clinical sequelae of alloimmunization to PLT transfusions.     

Clinically significant anti‐A1 in a presumed ABO‐identical hematopoietic stem cell transplant recipient: a case report

BACKGROUND: Subgroups of the blood group A (ABO) are generally not considered ABO incompatible for hematopoietic progenitor cell (HPC) transplant. CASE REPORT: A 54‐year‐old female presented for HPC transplantation for acute leukemia. No HLA‐matched donor was identified, so she received a peripheral blood stem cell graft from an HLA‐mismatched unrelated donor. On pretransplant testing, both the donor and the recipient typed as blood group A. On Day +67 after transplant, the recipient had a transfusion reaction consisting of an increase in temperature, rigors, and shaking chills during infusion of a unit of group A red blood cells (RBCs). A transfusion reaction workup revealed an ABO discrepancy with both anti‐A (1+) and anti‐B (3+) identified in the patient's serum as well as a positive direct antiglobulin test with monoclonal anti‐IgG antisera. Anti‐A₁ were identified serologically and in an eluate. Hemolysis was clinically significant, requiring blood transfusion. No ABO typing discrepancies were found on pretransplant testing in either the recipient or the donor. DNA sequencing for blood group A subgroups performed after the transfusion reaction on blood collected before the transplant showed the donor to be type A₁ and the recipient as A₂. Unfortunately, the patient experienced graft failure requiring reconditioning and reinfusion of additional cells from the original HPC donor. On Day +94 after the second transplant, the patient died with severe acute gastrointestinal graft‐versus‐host disease. CONCLUSION: This report describes a blood group A₂ patient who developed an anti‐A₁ causing clinically significant hemolysis after HPC transplant from an A₁ donor.     

Evaluation of in vitro storage properties of prestorage pooled whole blood–derived platelets suspended in 100 percent plasma and treated with amotosalen and long-wavelength ultraviolet light

BACKGROUND: Amotosalen, a psoralen, has been utilized for photochemical treatment (PCT) of apheresis platelets (PLTs) and pooled buffy coat PLTs suspended in additive solution. In the United States, the source of many PLT transfusions is from whole blood–derived PLTs prepared by the PLT‐rich plasma (PRP) method. This study investigated the in vitro PLT properties of amotosalen‐PCT of leukoreduced pools of PLTs prepared by the PRP method and suspended in 100 percent plasma. STUDY DESIGN AND METHODS: On Day 1 of storage, 12 leukoreduced (n = 6) or 10 leukoreplete (n = 6) ABO‐identical PLT concentrates were pooled, separated into two pools of 6 or 5 units, respectively, and leukoreduced (leukoreplete pools only). Each pool of 5 or 6 units was then photochemically treated (designated “test”: amotosalen plus 3.0 J/cm² long‐wavelength ultraviolet light followed by amotosalen/photoproduct removal) while the remaining identical pool (designated “control”) was untreated. PLT in vitro assays were performed on test and control pools during 7‐day storage. RESULTS: PCT resulted in slightly reduced pH in test pools compared to that of matched control pools after 5 days of storage (5‐unit pools: test, 6.96 ± 0.12 vs. control, 7.15 ± 0.09, p = 0.0033; 6‐unit pools: test, 6.90 ± 0.10 vs. control, 7.07 ± 0.09, p < 0.0001). Test pools adequately maintained many other in vitro properties including PLT morphology, hypotonic shock response, and extent of shape change parameters during 5‐day storage, which, like pH, also differed from those of controls. The pH of test and control pools declined on Day 7, with 1 of 6 test pools (either 5 or 6 units) having a pH value of less than 6.20, while all control pools had pH values of more than 6.66. CONCLUSION: PCT of leukoreduced PLT pools of whole blood–derived PLTs in 100 percent plasma maintained adequate PLT in vitro variables through 5 days of storage.     

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

BACKGROUND: 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. STUDY DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Posttransfusion platelet count increments after ABO‐compatible versus ABO‐incompatible platelet transfusions in noncancer patients: an observational study

BACKGROUND: Major incompatible platelet (PLT) transfusions have been associated with inferior posttransfusion PLT count increments compared with ABO‐compatible transfusions. However, most studies to date have been small and involved hematology/oncology patients. STUDY DESIGN AND METHODS: We conducted a prospective observational study in predominantly nononcologic patients to determine whether ABO‐compatible (defined as ABO identical and minor incompatible) PLT transfusions resulted in superior posttransfusion PLT count increments. We collected data on consecutive inpatients at Hamilton General Hospital receiving a PLT transfusion during a 50‐month period. We compared the absolute count increment (ACI) and corrected count increment (CCI) values in ABO‐compatible versus incompatible PLT transfusions. Linear regression was performed to adjust for factors potentially affecting the posttransfusion PLT count response. Univariate models were applied to each explanatory variable with p values of less than 0.10 considered potentially significant. Multivariate models were applied to all potential explanatory variables of interest. p values of less than 0.05 were considered significant. RESULTS: A total of 1030 transfusions were included in the primary analysis, 73.7% of which were ABO compatible. The median ACI was 35 (interquartile range [IQR], 18‐55) for compatible transfusions versus 31 (IQR, 13‐51) for incompatible transfusions (p = 0.1480). The median posttransfusion CCI (n = 686) was 18.6 (IQR, 10.2‐28.4) for compatible transfusions versus 15.2 (IQR, 4.7‐25.7) for incompatible transfusions (p = 0.0499). CONCLUSIONS: ABO‐compatible transfusions in nononcologic patients are associated with a significantly better CCI although the observed difference is small (approx. 20%) and may not be clinically significant.     

Prospective monitoring of plasma and platelet transfusions in a large teaching hospital results in significant cost reduction

BACKGROUND: Plasma and platelets (PLTs) are often transfused to correct mild to moderately abnormal laboratory values. Our objective was to reduce unnecessary plasma and PLT transfusions to nonbleeding patients by prospective triage and education of end users in evidence‐based hemostasis and transfusion medicine practices. STUDY DESIGN AND METHODS: Using the Parkland Memorial Hospital's transfusion service and admission database as the data source, this study comprises the comparison of transfusion data on plasma and PLT use between pre‐ (2000‐2002) and posttriage (2003‐2006) periods. Yearly transfusion and wastage data on red blood cells (RBCs), plasma, and PLTs and yearly hospital admissions, trauma visits, and surgical procedures were extracted retrospectively for the study. RESULTS: The study revealed that implementation of triage resulted in a significant reduction of plasma (60%) and PLT (25%) transfusions, saving more than $3,000,000 over 4 years. CONCLUSIONS: Prospective triage and evidence‐based transfusion practice education reduced unnecessary plasma and PLT transfusions and health care costs.     

Therapeutic efficacy and safety of photochemically treated apheresis platelets processed with an optimized integrated set

BACKGROUND: This multicenter, randomized, controlled, double-blind Phase III clinical study evaluated the therapeutic efficacy and safety of apheresis platelets (PLTs) photochemically treated (PCT) with amotosalen and ultraviolet A light (INTERCEPT Blood System, Baxter Healthcare Corp.) compared with conventional apheresis PLTs (reference). STUDY DESIGN AND METHODS: Forty-three patients with transfusion-dependent thrombocytopenia were randomly assigned to receive either PCT or reference PLT transfusions for up to 28 days. RESULTS: The mean 1- and 24-hour corrected count increments were lower in response to PCT PLTs (not significant). When analyzed by longitudinal regression analysis, the estimated effect of treatment on 1-hour PLT count was a decrease of 7.2 x 10(9) per L (p = 0.05) and on 24-hour PLT count a decrease of 7.4 x 10(9) per L (p = 0.04). Number, frequency, and dose of PLT transfusions; acute transfusion reactions; and adverse events were similar between the two groups. There was no transfusion-associated bacteremia. Four PCT patients experienced clinical refractoriness; however, only one exhibited lymphocytotoxicity assay seroconversion. Antibodies against potential amotosalen-related neoantigens were not detected. CONCLUSION: PCT PLTs provide effective and safe transfusion support for thrombocytopenic patients.     

Clinical safety of platelets photochemically treated with amotosalen HCl and ultraviolet A light for pathogen inactivation: the SPRINT trial

BACKGROUND: A photochemical treatment (PCT) method utilizing a novel psoralen, amotosalen HCl, with ultraviolet A illumination has been developed to inactivate viruses, bacteria, protozoa, and white blood cells in platelet (PLT) concentrates. A randomized, controlled, double-blind, Phase III trial (SPRINT) evaluated hemostatic efficacy and safety of PCT apheresis PLTs compared to untreated conventional (control) apheresis PLTs in 645 thrombocytopenic oncology patients requiring PLT transfusion support. Hemostatic equivalency was demonstrated. The proportion of patients with Grade 2 bleeding was not inferior for PCT PLTs. STUDY DESIGN AND METHODS: To further assess the safety of PCT PLTs, the adverse event (AE) profile of PCT PLTs transfused in the SPRINT trial is reported. Safety assessments included transfusion reactions, AEs, and deaths in patients treated with PCT or control PLTs in the SPRINT trial. RESULTS: A total of 4719 study PLT transfusions were given (2678 PCT and 2041 control). Transfusion reactions were significantly fewer following transfusion of PCT than control PLTs (3.0% vs. 4.1%; p = 0.02). Overall AEs (99.7% PCT vs. 98.2% control), Grade 3 or 4 AEs (79% PCT vs. 79% control), thrombotic AEs (3.8% PCT vs. 3.7% control), and deaths (3.5% PCT vs. 5.2% control) were comparable between treatment groups. Minor hemorrhagic AEs (petechiae [39% PCT vs. 29% control; p < 0.01] and fecal occult blood [33% PCT vs. 25% control; p = 0.03]) and skin rashes (56% PCT vs. 42% control; p < 0.001) were significantly more frequent in the PCT group. CONCLUSION: The overall safety profile of PCT PLTs was comparable to untreated PLTs.     

Function of platelets in apheresis platelet concentrates and in patient blood after transfusion as assessed by Impact‐R

BACKGROUND: Platelet (PLT) transfusion is a mainstream therapy for preventing or treating bleeding episodes in patients with thrombocytopenia. The efficacy is usually estimated from the corrected count increment of PLTs after transfusion, which does not assess PLT function. We therefore evaluated PLT function in blood samples of patients with thrombocytopenia before and after transfusion. STUDY DESIGN AND METHODS: PLT function was assessed in 24 chemotherapy‐treated patients and in the PLT concentrates (PCs) by the Impact‐R (DiaMed). This device evaluates PLT adhesion and aggregation recorded as surface coverage (%) and size of aggregates (AS µm²). P‐selectin expression was determined by flow cytometry. RESULTS: The PCs were stored for a median of 70 hours before transfusion. An analysis stratified by the median storage of PCs (<70 hr or >70 hr) showed no differences in the SC, the AS, and P‐selectin expression between these concentrates' groups. Transfusion resulted in an increase of adhering PLTs in the patients after transfusion. There were no differences in the AS and in P‐selectin expression before and after transfusion, but the AS increased after transfusion upon ex vivo exposure to adenosine 5′‐diphosphate. P‐selectin expression was significantly lower in the patient group receiving PCs stored for more than 70 hours. CONCLUSION: The current trial shows the feasibility of using the Impact‐R to assess the function of transfused PLTs in the patient's blood stream.