Cost implications of implementation of pathogen-inactivated platelets.

BACKGROUND: Pathogen inactivation (PI) is a new approach to blood safety that may introduce additional costs. This study identifies costs that could be eliminated, thereby mitigating the financial impact. STUDY DESIGN AND METHODS: Cost information was obtained from five institutions on tests and procedures (e.g., irradiation) currently performed, that could be eliminated. The impact of increased platelet (PLT) availability due to fewer testing losses, earlier entry into inventory, and fewer outdates with a 7-day shelf life were also estimated. Additional estimates include costs associated with managing (1) special requests and (2) test results, (3) quality control and proficiency testing, (4) equipment acquisition and maintenance, (5) replacement of units lost to positive tests, (6) seasonal or geographic testing, and (7) health department interactions. RESULTS: All costs are mean values per apheresis PLT unit in USD ($/unit). The estimated test costs that could be eliminated are $71.76/unit and a decrease in transfusion reactions corresponds to $2.70/unit. Avoiding new tests (e.g., Babesia and dengue) amounts to $41.80/unit. Elimination of irradiation saves $8.50/unit, while decreased outdating with 7-day storage can be amortized to $16.89/unit. Total potential costs saved with PI is $141.65/unit. Costs are influenced by a variety of factors specific to institutions such as testing practices and the location in which such costs are incurred and careful analysis should be performed. Additional benefits, not quantified, include retention of some currently deferred donors and scheduling flexibility due to 7-day storage. CONCLUSIONS: While PI implementation will result in additional costs, there are also potential offsetting cost reductions, especially after 7-day storage licensing.

Measuring trade-offs that matter: assessing the impact of a new electronic cross-match policy on the turnaround time and the cross-match workload efficiency.

BACKGROUND: Our traditional cross-match (XM) policy generated a significant number of XM units that were never issued. To minimize the unnecessary XM workload, we proposed a new policy where orders eligible for the electronic XM (EXM) are pended until orders to issue red blood cells (RBCs) are received. To address concerns that this new policy might unduly delay blood availability, we conducted a study to assess whether the new policy was noninferior to the traditional policy with regard to the turnaround time (TAT). STUDY DESIGN AND METHODS: We monitored the TAT and XM workload efficiency (XM-to-issue [C : I] ratio) for a total of 8 weeks split between the two policies' periods. The primary outcome was the proportion of RBC issue requests that was turned around in less than 12 minutes. RESULTS: Fifty percent (1133 of 2265) of issue requests were turned around in 12 minutes or less under the traditional policy compared to 43.9% (975 of 2223) under the new policy (absolute difference of 6.1%; 95% confidence interval [CI], 3.2%-9.1%; p < 0.001). The adjusted overall median TAT was slower by 1 minute (13 min vs. 14 min, p < 0.001) but the adjusted C : I ratio was better (1.00 vs. 1.15; p < 0.001) under the new policy. CONCLUSION: Our study showed that the impact of the new policy on the TAT was not inferior to the traditional policy. Since the median TAT of 14 minutes under the new policy met the published benchmarks, the trade-off between delays in the TAT and efficiency gains in the XM workload remained acceptable for patient care.

Anti-Ge2: further evidence for lack of clinical significance.

Anti-Ge2 may be immune or naturally occurring, and it reacts with an antigen on glycophorin D. Ge2 is encoded by a gene, GYPC, which is located on the long arm of chromosome 2. Anti-Ge2 is usually an immunoblobulin G (IgG) antibody. In the available literature, we have not been able to find any reported cases of proven acute hemolytic transfusion reactions caused by Anti-Ge2. We present the case of a 67-year-old man with metastatic pancreatic carcinoma who had symptomatic anemia and a hemoglobin concentration of 6.3 g/dL. During pretransfusion testing, Anti-Ge2 was identified in his serum. Only a single unit of compatible, Ge:-2 frozen red blood cells (RBCs) could be provided by the blood supplier. A second unit of crossmatched, least-incompatible, leukocyte-reduced RBCs, presumably Ge:-2, was also transfused. The transfusion was completed without incident, and the patient's hemoglobin concentration rose appropriately. Posttransfusion values for haptoglobin, lactate dehydrogenase, and urine hemoglobin were within normal limits. A monocyte monolayer assay performed on this anti-Ge2 supports the data that antibodies of this specificity do not cause hemolysis. The clinical and laboratory data obtained in our patient clearly indicated that no hemolysis of transformed RBCs occurred during and for 24 hours after transfusion. We believe that this report adds to a limited experience with anti-Ge2 and provides further evidence for concluding that, to all likelihood, this is not a clinically important RBC antibody. The risk of transfusing apparently "incompatible" (Ge:2) RBCs seems remote and should allow for timely administration of RBCs when treating patients with serious anemia.

Autoimmune hemolytic anemia in pediatric liver or combined liver and small bowel transplant patients: a case series and review of the literature.

BACKGROUND: Autoimmune hemolytic anemia (AIHA) occurring after solid organ transplantation is an infrequently reported entity. We describe in this report six cases of AIHA in pediatric liver or combined liver and small bowel transplant patients. STUDY DESIGN AND METHODS: We retrospectively identified and reviewed the records of pediatric liver or combined liver and small bowel transplant patients with both serologic and clinical evidence of AIHA. We also performed an English language literature review for prior publications of AIHA occurring after solid organ transplantation. RESULTS: We identified six patients presenting with severe hemolysis 9 months to 14 years after transplantation. All six developed warm AIHA, and two had concomitant cold agglutinins. All except one patient received various therapeutic combinations including steroids, intravenous immune globulin, rituximab, plasmapheresis, splenectomy, and vincristine. Five patients achieved remission 2 weeks to 3 months after presentation. Although tacrolimus has been speculated to play a causative role in the development of AIHA after organ transplantation, our case series demonstrated slightly better outcomes despite continuing tacrolimus compared to published cases where most patients either received significantly reduced doses of tacrolimus or were switched to a different immunosuppressant (83% vs. 76% cumulative literature remission rate). CONCLUSION: AIHA may occur in solid organ transplant patients at a much higher frequency than previously believed. Hemolysis is often severe and resistant to steroid treatment alone. Thus early diagnosis and institution of aggressive multimodality treatment, including the use of rituximab, may be needed to achieve remission.

Motivating factors and deterrents for blood donation among donors at a university campus-based collection center.

BACKGROUND: Insight into motivating factors and barriers for blood donation, especially for young people and underrepresented minorities, is important to donor recruitment and retention. We surveyed donors at a new blood collection facility based on a large, ethnically diverse university campus. STUDY DESIGN AND METHODS: Individuals who had donated or attempted to donate at the facility during the first 17 months of its operation were invited by e-mail to respond to an anonymous, Web-based questionnaire. Respondents were asked to provide demographic characteristics, rate the importance of various motivating and deterring factors for blood donation, and indicate how they prefer to be contacted by the blood center. RESULTS: More than 30% of the 1619 invitees responded, 95.6% (n = 479) of whom gave complete responses. The respondents were ethnically diverse, and 79.1% were between 18 and 28 years of age. Altruism was by far the most important motivating factor for donation. However, incentives were also rated as important or very important by 72.2% of the respondents. Inconvenience due to time or location constraints was the most important deterrent. E-mailing was the most preferred contact method and chosen by 80.3% of those surveyed. Some differences were noted in the responses from members of different age, sex, and ethnic groups. CONCLUSION: Although overall altruism and inconvenience were the major motivating factor and deterrent for blood, some demographic differences existed in donor attitude toward incentive programs and preference for the method of contact used by blood centers for recruitment purposes.

ABO blood type-incompatible kidney transplantation and access to organs.

OBJECTIVE: To determine whether ABO-incompatible (ABOi) kidney transplantation can be performed safely and result in acceptable posttransplantation outcomes. DESIGN: Prospective study. SETTING: Transplantation center. PATIENTS: In the 1½ years of a new program, 18 patients with renal failure and an ABOi living kidney donor were included in the study. All donors and recipients were of incompatible blood types and underwent transplantation beginning in June 2008. INTERVENTIONS: Patients received immunomodulation (anti-CD20 antibody, intravenous immunoglobulin, and plasmapheresis) until an acceptable isoagglutinin titer was obtained on the date of transplantation. All the kidneys were transplanted heterotopically, and all the patients received induction immunosuppression followed by a combination of prednisone, mycophenolate mofetil, and tacrolimus. Isoagglutinin titers were monitored, and postoperative plasmapheresis was initiated if titers increased. MAIN OUTCOME MEASURES: Patient and allograft survival; length of stay; 1-, 3-, and 6-month and 1-year renal function; and incidence of rejection. RESULTS: Patient survival was 100%, with allograft survival of 94.4%. Mean (SD) length of stay was 6.9 (1.9) days. Donor to recipient transplantation was A to O in 11 cases, A2 to B in 1, B to A in 3, B to O in 1, and AB to B in 2. Mean (SD) creatinine levels, a measure of graft function, were 1.2 (0.5) mg/dL at discharge, 1.4 (0.4) mg/dL at 1 month, 1.3 (0.45) mg/dL at 3 months, 1.1 (0.3) mg/dL at 6 months, and 1.2 (0.2) mg/dL at 1 year. One episode of cellular rejection occurred. CONCLUSIONS: These short-term results suggest that with a straightforward regimen, ABOi kidney transplantation is possible, acceptable results and graft function are obtainable, and access to kidney transplantation for those with a blood type-incompatible donor can be expanded.

Immunoglobulin M red blood cell alloantibodies are frequently adsorbed by rabbit erythrocyte stroma.

BACKGROUND: Rabbit erythrocyte stroma (RESt, Immucor) adsorption is often used to remove cold autoantibodies from patient samples to facilitate detection of underlying alloantibodies. However, reports in the literature show that adsorption of clinically significant alloantibodies can occur. A 2006 study by Storry and colleagues suggested that immunoglobulin (Ig)M antibodies are adsorbed by RESt regardless of antigen specificity. In our study, we further investigated the adsorption of IgM red blood cell alloantibodies by RESt. STUDY DESIGN AND METHODS: A total of 12 sera containing monoclonal IgM antibodies of various specificities (anti- D, -C, -c, -E, -e, -K, -Jk(b), and -S) and titers, which were all shown to exhibit only IgM reactivity after dithiothreitol treatment, and two sera with polyclonal IgG (anti-Fy(a) and -K) were all adsorbed by RESt. Titers of unadsorbed, once-adsorbed, and twice-adsorbed IgM and IgG antibodies were determined in parallel. RESULTS: Ten of the 12 monoclonal IgM samples showed significant (more than fourfold) reduction in titer after RESt adsorptions. Both of the polyclonal IgG samples tested showed insignificant (fourfold or less) reduction in titer. CONCLUSIONS: RESt is known to effectively remove IgM cold autoantibodies. Our results show that monoclonal IgM alloantibodies are also frequently adsorbed by RESt with significant reduction in titer. Adsorption is variable and some IgM alloantibodies are not adsorbed. Further studies may elucidate the effect of RESt adsorption on IgG alloantibodies. Caution is needed when RESt is employed to remove interferences by cold autoantibodies in pretransfusion testing, and the risk of missed IgM alloantibodies must be considered.

Moderate and severe adverse events associated with apheresis donations: incidences and risk factors.

BACKGROUND: The goal of this observational retrospective study was to evaluate various donor and procedural variables as potential risk factors for different types of moderate to severe adverse events (AEs) during apheresis collections. STUDY DESIGN AND METHODS: Data on all apheresis collections performed on Trima Accel (TA; CaridianBCT) instruments over a 28-month period were extracted from a donor database (Vista Information System, CaridianBCT) and reviewed along with AE reports from the same period. Donor and procedural variables were compared among uneventful procedures and those that resulted in various types of moderate to severe AEs, including presyncopal or syncopal (PS) episodes, citrate reactions (CR), reactions with both components (PS + CR), and self-reported incidents of significant venipuncture-related vascular injuries (VIs). RESULTS: A total of 59 moderate to severe AEs occurred among 15,763 procedures (0.37%), including 19 PS, 4 CR, 17 PS + CR, 12 VI, and 7 miscellaneous reactions. Greater blood loss and lower net fluid balance were associated with PS; female sex, older age, and smaller total blood volume (TBV) were associated with CR; and development of VI may be associated with female sex and smaller TBV. Younger age was not a risk factor for AEs. CONCLUSIONS: Apheresis collections performed by TA instruments are safe with a low incidence of significant AEs. Various types of AEs have different predisposing factors. Apheresis may be a safer option for donors with risk factors for PS reactions associated with whole blood collections, such as younger age, female sex, and small TBV.

A severe case of atypical hemolytic uremic syndrome associated with pneumococcal infection and T activation treated successfully with plasma exchange.

BACKGROUND: A severe nondiarrheal form of hemolytic uremic syndrome in children is associated with pneumococcal infection (pHUS). Neuraminidase released by the pneumococci may cleave N-acetylneuraminic acid residues on red blood cells (RBCs), leading to the exposure of the T cryptantigen and polyagglutinability of RBCs, a process known as T activation. Data suggest a pathogenic role of exposed T antigens on glomeruli interacting with naturally occurring anti-T in the development of renal dysfunction in pHUS. By reducing the levels of anti-T and neuraminidase, plasma exchange (PE) may have a role in the treatment of severe cases of pHUS. CASE REPORT: A previously healthy 2-year-old boy presented with acute renal failure, thrombocytopenia, microangiopathic hemolytic anemia, pneumococcal infection, and T activation of RBCs. A diagnosis of pHUS was made. Due to rapid clinical decline, daily single-volume PE with 5 percent albumin replacement was initiated. Infusion of additional plasma was avoided by using only saline-washed RBCs for transfusion. He made a full recovery after 13 PEs and remained well at follow-up 7 months later. RESULTS: Polyagglutinability of RBCs was shown by mixing patient RBCs with five normal donor sera. The agglutination assays with a panel of lectins confirmed the specificity of exposed T antigen as the cause of polyagglutinability. CONCLUSION: The dramatic response seen in this patient suggests that PE utilizing albumin replacement may benefit patients with severe pHUS.

Platelet transfusions in heparin-induced thrombocytopenia: a report of four cases and review of the literature.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a complication of heparin therapy associated with thrombocytopenia and thrombosis. The diagnosis of HIT is based on clinical criteria and laboratory tests, including the serotonin release assay (SRA). Because HIT patients are thrombocytopenic, platelet (PLT) transfusions may be contemplated; however, many published reviews have concluded that PLT transfusions are contraindicated in HIT because they may precipitate thrombotic events. This study reports four patients with clinically suspected HIT who received PLT transfusions without complications, and the literature regarding this subject has been reviewed. STUDY DESIGN AND METHODS: Patients with a SRA ordered for suspected HIT were retrospectively identified. Charts of patients with positive SRAs who received a PLT transfusion when HIT was clinically suspected were reviewed for evidence of PLT transfusion safety and efficacy. A comprehensive search of the published literature regarding PLT transfusions in patients with HIT was conducted. RESULTS: A SRA was performed on 189 patients with suspected HIT. Thirteen patients tested positive and 4 of these received a PLT transfusion. No patient developed a thrombotic complication. All 4 patients had adequate posttransfusion PLT increments. Two of the 3 patients with active bleeding had cessation of bleeding after transfusion. Review of the literature revealed no case of a complication clearly attributable to PLT transfusion. CONCLUSION: Four patients with clinically suspected HIT and a positive SRA were transfused PLTs both efficaciously and safely. These outcomes, combined with the results of the literature review, suggest that PLT transfusions should not be withheld when clinically indicated in patients with HIT.

Vaccination elicits correlated immune and clinical responses in glioblastoma multiforme patients.

Cancer vaccine trials have failed to yield robust immune-correlated clinical improvements as observed in animal models, fueling controversy over the utility of human cancer vaccines. Therapeutic vaccination represents an intriguing additional therapy for glioblastoma multiforme (GBM; grade 4 glioma), which has a dismal prognosis and treatment response, but only early phase I vaccine trial results have been reported. Immune and clinical responses from a phase II GBM vaccine trial are reported here. IFN-gamma responsiveness was quantified in peripheral blood of 32 GBM patients given therapeutic dendritic cell vaccines. Posttreatment times to tumor progression (TTP) and survival (TTS) were compared in vaccine responders and nonresponders and were correlated with immune response magnitudes. GBM patients (53%) exhibited >or=1.5-fold vaccine-enhanced cytokine responses. Endogenous antitumor responses of similar magnitude occurred in 22% of GBM patients before vaccination. Vaccine responders exhibited significantly longer TTS and TTP relative to nonresponders. Immune enhancement in vaccine responders correlated logarithmically with TTS and TTP spanning postvaccine chemotherapy, but not with initial TTP spanning vaccination alone. This is the first report of a progressive correlation between cancer clinical outcome and T-cell responsiveness after therapeutic vaccination in humans and the first tracing of such correlation to therapeutically exploitable tumor alteration. As such, our findings offer unique opportunities to identify cellular and molecular components of clinically meaningful antitumor immunity in humans.

Risk factors for acute, moderate to severe donor reactions associated with multicomponent apheresis collections.

BACKGROUND: Legitimate concerns exist over the safety of donors during multicomponent apheresis collections (MACs), when large volumes of red blood cells (RBCs) and plasma are removed. This study evaluates the predictive value of various donor- and procedure-related variables for moderate to severe donor acute adverse events (AAEs). STUDY DESIGN AND METHODS: Data on all apheresis donation procedures performed at a large university hospital-based donor center over a 2-year period were obtained by a review of adverse event forms and procedure logs (Trima Accel 5.1, Gambro BCT). Various donor- and procedure-related variables were compared between procedures that resulted in moderate to severe AAEs and those that did not. RESULTS: Moderate to severe AAEs occurred in 53 (0.47%) of 11,333 apheresis donation procedures. The majority of events (96.2%) had predominantly features of vasovagal reactions (VVRs). Females were at significantly higher risk (odds ratio [OR] = 2.8, p < 0.0003) compared to males. Donors who experienced AAEs had significantly lower predonation total blood volume (TBV) and hematocrit (Hct) and higher total RBC loss and net fluid loss at the end of the procedures. Total plasma loss alone was not significantly different between the two groups. Total blood loss was significantly higher among donors who experienced AAEs as a percentage of the donor's TBV. CONCLUSION: Apheresis collections are well tolerated even when multiple components are collected, with a very low overall incidence of moderate to severe AAEs (0.47%). Small, female donors with lower predonation Hct are at higher risk, especially when RBCs are collected.

Rituximab as successful therapy in a patient with refractory paroxysmal cold hemoglobinuria.

BACKGROUND: Paroxysmal cold hemoglobinuria (PCH) is a rare autoimmune hemolytic anemia (AIHA) attributed to a biphasic hemolysin known as the Donath-Landsteiner (DL) antibody. It is most commonly encountered as an acute transient AIHA after a viral infection in children; the disease resolves after cessation of the infection. The rarest form of PCH is a chronic form in adults that is not (nowadays) associated with infection and is not responsive to conventional therapies. Rituximab has been found to be effective therapy in other forms of AIHA, such as cold agglutinin syndrome, that are refractory to conventional therapies. We describe a case of PCH refractory to steroids that responded to rituximab therapy on two separate occasions. CASE REPORT: A 64-year-old woman with fatigue was found to be profoundly anemic with laboratory findings consistent with AIHA. She was admitted for the workup and management of her disease after she failed to respond to a course of oral steroids. Laboratory evaluation demonstrated a positive DL test suggesting PCH. She was given a course of rituximab that resulted in normalization of her hemoglobin concentration. She presented 9 months later with recurrent hemolysis. She was given another course of rituximab that again resulted in termination of hemolysis. The patient remained in remission since her last dose of rituximab 19 months previously. CONCLUSION: To our knowledge, this is the first report of an adult case of refractory PCH successfully treated with rituximab.