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.     

Four crossmatch methods to select platelet donors

We employed four crossmatch techniques to select platelet donors for refractory patients. Forty-four donor-recipient pairs were studied in 32 patients. Analysis of effectiveness of platelet transfusions revealed that only 18 percent of transfusions gave a borderline response; the remainder were either effective or not effective at all. The corrected predictive values of three crossmatch tests were as follows: enzyme-linked immuno-specific assay, 81 percent; platelet immunofluorescence test, 73 percent; and lymphocytotoxicity, 70 percent (p greater than 0.05). The predictive value of these tests did not differ in HLA-matched versus unmatched platelet transfusions. Donor selection by lymphocytotoxicity compatibility did not appear to be useful if donors were selected by either of the other two methods. The fourth test, antiglobulin-modified lymphocytotoxicity, offered no advantage over lymphocytotoxicity. Our data suggest that platelet crossmatching assays are a useful adjunct to the selection process for the platelet donor in addition to ABO, Rh, and HLA matching.     

Complement (C1q) fixing solid-phase screening for HLA antibodies increases the availability of compatible platelet components for refractory patients

BACKGROUND: Immune refractoriness to platelet (PLT) transfusion is primarily due to HLA antibody. Patients at our institution are identified as refractory due to HLA by a Luminex‐based immunoglobulin (Ig)G–single‐antigen‐bead (SAB) assay, but in highly sensitized patients, antigen‐negative compatible donors cannot be found due to the high sensitivity of the IgG‐SAB method. We developed an assay that detects only HLA antibodies binding the first complement component (C1q). We hypothesized that the C1q‐SAB method might be more relevant than the IgG‐SAB method because the antibodies identified may activate the complement cascade causing PLT destruction. STUDY DESIGN AND METHODS: Thirteen highly sensitized refractory patients received 177 PLT units incompatible by the IgG‐SAB method. They were retrospectively retested by the C1q‐SAB method. Calculated percent reactive antibody (CPRA) and HLA antibody specificities were compared between the two methods and corrected count increment (CCI) values were analyzed. Additionally the impact of ABO compatibility on CCI responses was evaluated. RESULTS: The mean CPRA value was significantly lower by C1q‐SAB (60%) than by IgG‐SAB (94%; p < 0.05). Patients showed significantly better CCI (10.6 × 10⁹ ± 0.8 × 10⁹/L) with C1q‐compatible (n = 134) than with C1q‐incompatible PLTs (n = 43) (2.5 × 10⁹ ± 0.9 × 10⁹/L/m²; p < 0.0001). ABO compatibility did not significantly impact the CCI values (p < 0.0001). Our results show that 75% of PLT units previously considered incompatible were actually compatible. CONCLUSION: For highly refractory patients to PLT transfusion, the C1q‐based SAB binding assay may be a better method for identifying clinically relevant HLA antibodies and selecting PLT units that will result in acceptable CCI.     

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.     

Structural epitope matching for HLA‐alloimmunized thrombocytopenic patients: a new strategy to provide more effective platelet transfusion support?

BACKGROUND: During the past three decades, HLA matching for platelet (PLT) transfusion of refractory thrombocytopenic patients has been based on serologic cross-reactivity between HLA-A and HLA-B antigens. Although many blood banks are using this matching strategy, the general experience is that such matched PLT transfusions are often ineffective. STUDY DESIGN AND METHODS: This report describes a new HLA matching algorithm that considers structurally defined epitopes recognized by antibodies. HLAMatchmaker is a computer program that determines histocompatibility at the amino acid level initially designed as triplets (i.e., linear sequences of three residues in molecular surface-exposed positions) but now updated as eplets representing patches of antibody-accessible polymorphic residues surrounded by residues within a 3-A radius. The eplet version of HLAMatchmaker is also useful in the analysis of HLA antibody reactivity patterns of alloimmunized patients so that acceptable mismatches can be identified. CONCLUSION: An HLA epitope-based matching protocol is proposed that may permit a more effective PLT transfusion management of refractory patients. This protocol includes high-resolution HLA-A, -B, and -C typing of patients and donors, serum screening to identify acceptable mismatches, and the identification of suitable donors in a donor database that incorporates HLAMatchmaker as a search engine. HLAMatchmaker programs can be downloaded from the Web site http://tpis.upmc.edu/tpis/HLAMatchmaker/.     

Epitope‐based matching for HLA‐alloimmunized platelet refractoriness in patients with hematologic diseases

BACKGROUND: For HLA‐alloimmunized patients, platelet (PLT) concentrations are provided either at matched HLA‐A and HLA‐B loci or by serologic cross‐reactivity groups (CREG) matching strategy. However, this method has some limitations. STUDY DESIGN AND METHODS: In this study, the epitope‐based matching (EBM) method was evaluated for selecting proper HLA‐typed PLTs for patients with PLT transfusion refractoriness. Bead‐based single‐antigen HLA antibody detection method and HLAMatchmaker software were used to define the epitopes recognized by HLA‐specific antibodies and to select compatible PLTs for nine patients with alloimmunized refractoriness. Corrected count increments (CCIs) were prospectively determined to compare successful transfusion rates among different matching methods in 142 PLT transfusions. In addition, HLA antibodies were serially detected to see whether any emerging antibodies appeared after receiving the EBM‐matched PLTs. RESULTS: The transfusion success rates evaluated with 1‐hour CCIs for perfect matching or lacking any mismatching at HLA‐A and ‐B locus (A/BU)‐matched, CREG‐matched, and EBM‐matched PLTs were 85.2, 63.2, and 83.7%, respectively. Compared to CREG‐matched PLTs, EBM‐matched PLTs showed better transfusion results (p = 0.035). In the follow‐up study (7 months; range, 3‐13 months), no emerging HLA‐specific antibodies were detected after receiving EBM‐matched PLTs. CONCLUSIONS: EBM performed on the basis of bead‐based single‐antigen HLA antibody detection coupled with the HLAMatchmaker program is recommended in choosing proper PLTs for refractory patients when A/BU‐matched PLTs were not available.     

Platelet crossmatches of single-donor platelet concentrates using a latex agglutination assay

A latex agglutination assay was evaluated for the purpose of identifying compatible platelet donors for alloimmunized recipients. Assay reagents were prepared by adsorbing detergent-solubilized, donor- specific platelets to polystyrene latex beads. Semiquantitative results for up to 30 donors can be completed in less than 1 hour. These reagents retained their immunoreactivity for at least 3.5 months. A retrospective study has established the assay's upper limit of compatibility. The prospective study evaluated transfusions to a group of multiply transfused patients. Part I evaluated 143 crossmatched, single-donor platelet transfusions given to 50 patients. In 96 percent of the cases, a positive crossmatch was associated with an unsuccessful transfusion outcome; in 84 percent of the transfusions, a negative crossmatch predicted a satisfactory platelet increment. The overall predictability, sensitivity, and specificity were 87, 62, and 99 percent, respectively. Part II evaluated 105 transfusions given to the 43 patients (of 50) in whom no incidence of fever, sepsis, or bleeding could be documented. A positive crossmatch was 96-percent efficient in predicting an unsuccessful transfusion, whereas a negative crossmatch was associated with an adequate platelet increment following 89 percent of the transfusions. The overall predictability was 91 percent, the sensitivity was 72 percent, and the specificity was 99 percent. Within- run and between-run variations were 6.3 and 6.2 percent, respectively. These results demonstrate that detergent-solubilized platelet antigens, immobilized on latex particles, can be used in a cost-effective crossmatching procedure.     

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.     

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.     

The clinical impact of platelet refractoriness: correlation with bleeding and survival

BACKGROUND: Despite supportive care with platelet (PLT) transfusions, bleeding complications occur in a substantial number of patients with thrombocytopenia due to cytotoxic therapy. Moreover, refractoriness to PLT transfusions remains a frequently encountered problem. The clinical impact of PLT transfusion failure was investigated in 117 patients, part of a randomized PLT transfusion trial, which excluded patients with HLA and/or HPA alloantibodies. STUDY DESIGN AND METHODS: Between October 2003 and April 2005, a multicenter randomized controlled trial, testing the clinical efficacy of PLTs stored in plasma compared to PLT additive solution (PAS II), was performed. Using multiple regression analysis of observational data of patients randomized in one of the participating centers, the occurrence of PLT transfusion refractoriness was analyzed for a relation with bleeding complications and patient survival. RESULTS: PLT transfusion failure occurred at least once in 49.6 percent of the patients. Mild to moderate bleeding complications occurred in 19 percent of the patients. PLT transfusion failure was, independently from thrombocytopenia, positively associated with bleeding complications (odds ratio, 3.4; 95% confidence interval, 1.1‐11). Moreover, patients experiencing one or more 24‐hour PLT transfusion failures had, compared to patients always showing a sufficient 24‐hour increment, a significantly reduced median survival of 491 days (interquartile range [IQR], 156‐858 days) versus 825 days (IQR, 355‐996 days), respectively. In a Cox regression model, the effect on survival was independent of therapy, diagnosis, and age. CONCLUSION: Our results suggest that PLT transfusion failure might be a sensitive clinical marker for the occurrence of bleeding and impaired patient survival. PLT transfusion failure, bleeding complications, and decreased survival could be manifestations of a more severe degree of endothelial damage.     

Combined granulocyte and platelet transfusions. Development of alloimmunization as reflected by decreasing cell recovery values

Twenty-three patients undergoing induction therapy for acute myelogenous leukemia (AML) received a total of 191 combined prophylactic granulocyte (PMN) and platelet (PLT) concentrates on alternate days (median 8, range 3–12 per patient). Each transfusion was assessed by monitoring the patient for reactions and by estimating the recovery of PMN in the circulation at 1 hour and of PLT at 1 and 20 hours. Seventeen patients developed alloimmunization to PLT from at least one donor, defined as either a PLT recovery of less than 15 percent at 1 hour and/or less than 10 percent at 20 hours. In this group there was a progressive reduction in PMN and PLT recovery with increasing transfusion number, strongly suggesting alloimmunization to both cells. Thirty-four transfusions were accompanied by transfusion reactions, thirty-two of which occurred in ten patients who had PMN recoveries of less than 5 percent after at least one transfusion (median 2.5, range 1–6 transfusions per patient). Actuarial calculations predicted that 70 percent of patients would become alloimmunized to PLT from at least two individuals after receiving 11 transfusions. These results suggest that combined PMN and PLT transfusion are associated with the rapid development of alloimmunization.     

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.     

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.     

Correlation of platelet crossmatch results by Solid Phase Red Cell Adherence Assay (SPRCA) with post-transfusion platelet count increment in adult hemato-oncology patients of a tertiary care oncology centre in India

AimsTo assess platelet crossmatch result by SPRCA and find its correlation with post-transfusion platelet count increment among adult hemato-oncology patients.MethodsA prospective observational pilot study of 50 adult hematologic malignancy patients previously transfused, but not already known to be transfusion-refractory and without any nonimmune causes for inadequate response to platelet transfusion were included after obtaining informed consent. They were transfused one unit of ABO identical single donor platelet. Ten minutes to 1 -h post-transfusion CCI was calculated.CCI ≥ 7500 was considered as adequate response. Post-transfusion crossmatching by SPRCA was performed by using preserved platelet samples from donor units with the serum of the respective patient. Statistical analysis of the correlation between platelet crossmatch results and CCI was done.ResultsOut of 50 crossmatches, 78% (39/50) showed compatible and 22% (11/50) showed incompatible results. Among 39 compatible results, 87.2% (34/39) showed adequate CCI and 12.8% (5/39) showed inadequate CCI. Among 11 incompatible results, 18.2% had adequate CCI and 81.8% had inadequate CCI. The difference between the response in terms of CCI to compatible and incompatible crossmatches was found to be statistically significant (p < 0.05). Other variables like age, sex, number of previous transfusions and underlying clinical condition of the patient were not found to have any effect on the compatibility of crossmatch.ConclusionsTransfusion of crossmatched platelets to non-refractory, multiply transfused hematological malignancy patients without serious illness might provide a small benefit over transfusing randomly selected platelets, though these data must be confirmed with a larger sample size.     

The impact of apheresis platelet manipulation on corrected count increment

BACKGROUND: Concentrating and washing apheresis platelets (APs) substantially reduce the number of allergic transfusion reactions likely due to removal of plasma. However, these processes may damage platelets (PLTs). This study evaluated whether concentrating or washing APs decrease the corrected count increment (CCI). STUDY DESIGN AND METHODS: This retrospective study evaluated individuals who initially received unmanipulated APs and subsequently received concentrated and/or washed APs at a large university hospital between 1998 and 2009. Concentrated units were prepared by reducing the plasma volume of APs by a goal of more than 67%. Washed units were prepared by washing the APs with 1 L of normal saline. The CCI (PLTs [×10⁶]× m²/L) for all transfusions was calculated. Hypothesis testing was performed with t tests for continuous variables and chi‐square tests for dichotomous variables. RESULTS: We evaluated 121 individuals: 46 patients who received unmanipulated, concentrated, and then washed APs; 59 patients who received unmanipulated and then concentrated APs; and 16 patients who received unmanipulated and then washed APs. Patient demographics were similar among the three groups. The mean CCI for unmanipulated AP transfusions at 0 to 2 hours posttransfusion was significantly higher than concentrated and washed PLT transfusions (p < 0.001). When accounting for PLT loss due to manipulation, concentrating APs did not impact the CCI. However, the CCI remained significantly lower for washed products at all time points after transfusion (40.7% mean reduction at 20‐24 hr, p < 0.001). CONCLUSIONS: Washing APs significantly reduces PLT count recovery and survival, as demonstrated by a significantly reduced CCI.     

Selection of platelets for refractory patients by HLA matching and prospective crossmatching

A multi-site clinical study compared platelets chosen for refractory patients by prospective platelet crossmatching using stored donor platelets and HLA-based selection. Seventy-three patients who were refractory to random-donor platelets received two plateletpheresis components, one chosen by HLA-based criteria and the other by crossmatching. Patients were carefully evaluated to exclude nonimmune factors that could adversely affect transfusion results. Each of the five study sites used a crossmatch procedure with which it had experience. Results from this study indicate the following: 1) The overall rate of successful transfusion was similar when an HLA-based method of donor selection that includes all grades of matching and mismatching was compared to a crossmatch-based method of donor selection. 2) HLA-based selection that restricts recipients to grade A and BU matches was superior to a selection method based upon crossmatching alone. Donor selection based on HLA matching (grades A or BU) was also superior to selection based on any degree of HLA mismatching (grades BX, C, or D). 3) Selection of donors based on HLA-cross-reactive groups (defined by in vitro serologic crossreactivity) was no more successful than that based on grade C and D mismatches and was no more successful than selection by crossmatching alone. 4) Lymphocytotoxic and platelet antibodies were not detected in many of the enrolled patients, even though patients demonstrating nonimmune factors were eliminated from the study. It can be concluded that HLA-compatible (grades A and BU) platelets provide optimal support for refractory patients, but that crossmatch-selected platelets are acceptable as an alternative component.     

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.     

Donor survey to assess facial flushing during automated red cell collections and medication use

Background: We conducted a donor survey to assess the occurrence of facial flushing and other symptoms during automated 2‐U red cell collections (2RBC) and plateletpheresis (PLT) procedures and evaluated the possible association of the reactions with angiotensin‐converting enzyme (ACE) inhibitors or with the collection technology. Methods: An online survey was developed using Zoomerang to capture details of the donors' experience and medication use after 2RBC or PLT donations in regional blood centers of the American Red Cross. Results: Between 12/16/09 and 4/19/10, 1,299 donors in five American Red Cross blood center regions completed an online survey (739 2RBC, 4.2% total registrations; 560 PLT, 2.3% total registrations). Facial flushing was reported by 29 donors, and was more likely associated with 2RBC than PLT procedures (3.0% vs. 1.3%, P = 0.03). Facial flushing with 2RBC donation was reported by eight of 72 (11%) donors on ACE inhibitors; and 14 of 667 (2%) donors who were not taking ACE inhibitors (P = 0.001). The incidence of facial flushing reactions with PLT donation was less than 2% whether donors reported ACEI inhibitor use or not. More than 95% of the donors reported their intent to donate again, regardless of symptoms. Conclusion: Facial flushing was more often reported by 2RBC donors taking ACE inhibitors than other donors [11% vs. 2%; P = 0.001]; and was uncommon among PLT donors, irrespective of ACE inhibitor use (<2%). All blood donors should be informed of the potential for common, minor side effects of the collection procedure and the possible but rare occurrence of more medically serious complications. J. Clin. Apheresis, 2011. © 2011 Wiley‐Liss, Inc.     

Very high users of platelet transfusions in the neonatal intensive care unit

BACKGROUND: In neonatal intensive care unit (NICU) practice, a small percentage of the patients receive a large proportion of the platelet (PLT) transfusions administered. This study sought to better define this very‐high‐user group. To accomplish this, records of all NICU patients in a multihospital health care system who, during a recent 5½‐year period, received 20 or more PLT transfusions were examined. STUDY DESIGN AND METHODS: Electronic medical record repositories of Intermountain Healthcare neonates with dates of birth from January 1, 2002, through June 30, 2007, who received 20 or more PLT transfusions were identified. The causes of the thrombocytopenia were sought, whether each transfusion given was a treatment for bleeding versus prophylaxis was determined, whether each transfusion was compliant with our transfusion guidelines was judged, and the outcomes were tabulated. RESULTS: During this period, 45 patients received 20 or more PLT transfusions (median, 29; range, 20‐79). Medical conditions could be categorized into six diagnoses: 1) extracorporeal membrane oxygenation (ECMO) for congenital diaphragmatic hernia (CDH; n = 13), 2) fungal sepsis (n = 8), 3) ECMO for reasons other than CDH (n = 8), 4) necrotizing enterocolitis (n = 7), 5) bacterial sepsis (n = 7), and 6) congenital hyporegenerative thrombocytopenia (n = 2). Nineteen percent of the transfusions were ordered for oozing, bruising, or bleeding and 81 percent for prophylaxis. Thirty‐six percent of transfusions were given in violation of our transfusion guidelines. Forty‐nine percent of the high users died, but no deaths were due to hemorrhage. All survivors developed chronic lung disease, and all survivors weighing less than 1250 g at birth developed retinopathy of prematurity. CONCLUSIONS: Almost all patients that received 20 or more PLT transfusions had an acquired, consumptive thrombocytopenia. All could have received fewer transfusions had the guidelines already in place been observed. Eighty‐one percent fewer PLT transfusions would have been administered had the paradigm been transfusing only if oozing, bruising, or bleeding was present.     

Platelet transfusion refractoriness caused by a mismatch in HLA-C antigens

BACKGROUND: HLA-C antigens have been thought to be of little significance in determining the efficacy of platelet transfusions. However, six alloimmunized patients were encountered who were refractory to platelet transfusions because of anti-HLA-Cw3, -Cw3, -Cw7, or -Cw8. STUDY DESIGN AND METHODS: Between 1995 and the present, 88 patients with hematologic malignancies became refractory to random-donor platelet transfusions due to HLA antibodies. HLA-A- and HLA-B-compatible platelet transfusions were successful in boosting platelet levels with 82 of the patients. This study concerns the remaining six HLA-immunized patients who were refractory to HLA-A- and HLA-B-compatible platelet transfusions. The response to the platelet transfusions was assessed by calculating both 1- and 24-hour posttransfusion CCIs for each transfusion. RESULTS: The average CCI(1 hour) and CCI(24 hours) in all patients were 20.0 and 12.8 for HLA-A-, HLA-B-, and HLA-C-compatible transfusions and were 1.4 and 1.2 for HLA-A- and HLA-B-compatible but HLA-C-incompatible transfusions, respectively (p < 0.001). CONCLUSION: These findings clearly indicate that matching of the HLA-C antigens is also required in some alloimmunized patients to obtain the effectiveness of platelet transfusions.