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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., (© 2015 The Authors Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.)

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., (© 2014 AABB.)

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., (© 2011 American Association of Blood Banks.)

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., (© 2011 American Association of Blood Banks.)

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.

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.

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.

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.

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.

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.

Background: Thrombotic thrombocytopenic purpura (TTP) was once a highly fatal disease with mortality reaching nearly 95 percent; however, application of therapeutic plasma exchange (TPE) has dramatically increased survival. Nevertheless, mortality remains substantial (10%-30% in many published reports), requiring the search for more efficacious treatments. Vincristine (VCR) has been generally reserved for refractory TTP. Despite its effectiveness in a salvage mode, VCR has not been widely advocated as first-line therapy in conjunction with TPE. We previously reported improved survival when VCR and TPE were administered at presentation in patients treated from 1979 to 1994. Utilizing this standardized approach, outcomes of an additional group of patients and the results of a literature review of VCR therapy for TTP are reported., Study Design and Methods: Medical records of all patients with a diagnosis of TTP treated between 1995 and 2002 at Cedars-Sinai Medical Center were reviewed. TPE was performed daily, exchanging 1.25 plasma volumes, until the platelet count normalized. Patients received VCR 1.4 mg/m2, (up to 2.0 mg total dose) after the first TPE. A literature review of all publications utilizing VCR in the management of TTP was performed with MEDLINE., Results: Twelve consecutive patients meeting the diagnostic criteria received treatment with VCR and TPE. All patients achieved durable remission. Patients tolerated VCR without significant complications., Conclusion: Our 100 percent survival rate, as well as evidence garnered from the literature review, suggests that combination therapy with VCR and TPE at presentation might be more effective than TPE alone and therefore warrants consideration as first-line therapy for TTP patients.

Background: This report describes the first year of a government-sponsored program that uses daily reports from 29 sentinel sites to monitor the capacity of the US blood supply to meet demand., Study Design and Methods: From August 15, 2001, to August 14, 2002, 29 sentinel sites provided daily reports of the number of units of RBCs in inventory, transfused, exported, and outdated by ABO and Rh, and platelets by random or apheresis donor. Days supply of each component category was calculated as the number of units in inventory reported on a day divided by the sum of units transfused, exported, and outdated on that day. Sites also provided daily responses to questions about threatened or actual shortages., Results: The median of the days supply of RBCs at the 26 hospital transfusion services was 7.2 days. However, median days supply varied substantially by site and by day of the week. A+, O+, and O- units accounted for 30, 35, and 12 percent of total inventory and were maintained at a median supply of 7.4, 6.4, and 9.5 days, respectively. Reports of threatened RBC shortages peaked in early January 2002 and again in early July 2002. The July 2002 peak was about twice the January 2002 peak. Inventories at community-based centers were similar to those at hospital transfusion services. Hospitals maintained only a 1-day supply of platelets. Eight percent of random and 4 percent of apheresis platelets were outdated. There were 20 reports that surgery had to be postponed or canceled because platelets were unavailable., Conclusions: Inventories of RBCs maintained at the participating sites were sufficient, with only one brief exception, to meet local demand during the first year of this monitoring program. The weekly rate of threatened shortage reports was more sensitive than days inventory as a predictor of actual shortages of RBCs. Unlike RBCs, platelet days supply, reports of threatened or actual platelet shortages, and platelet outdate rates did not vary seasonally.

Background: WBC reduction of blood components may reduce the incidence of transfusion reactions. The cost of this intervention might be offset by a reduction in the incidence of postoperative infection, thereby reducing the length of hospital stay and thus the cost of care for patients receiving transfusion. Cedars-Sinai Medical Center provided WBC-reduced blood components to all patients for a period of 2 years, creating an opportunity to compare the incidence of postoperative infection, length of hospital stay, and total hospital costs for patients undergoing coronary artery bypass graft surgery, before, during, and after WBC reduction., Study Design and Methods: Data were obtained by examining hospital records of patients who received transfusion and control patients who did not receive transfusion for the years 1991 (before WBC reduction), 1992 to 1993 (during WBC reduction), and 1994 (following discontinuation of WBC reduction). Comparisons were made by use of ANOVA following log or square root transformation of the data., Results: Length of hospital stay for patients who received transfusion decreased over time. Mean hospital stays were 15.9, 14.1, and 12.1 days before, during, and after WBC reduction, respectively. A similar trend was seen in the patients who did not receive transfusion. There was no indication that WBC reduction functioned as an independent variable that was responsible for the observed decrease. The rate of postoperative infection stayed constant during WBC reduction and only dropped when WBC reduction was stopped. Mean hospital cost showed no significant change over time for either the transfusion group or the nontransfusion group., Conclusion: The cost of providing a totally WBC-reduced blood supply may not be offset by immediate savings related to decreased postoperative infections, reduced length of hospital stay, and cost of hospital care.

Background: Alloimmune-mediated refractoriness to platelet transfusion is most commonly due to antibody to HLA antigens in multiply transfused or multiparous patients. Published reports of poor transfusion response due to antibodies to platelet-specific antigens are rare and often confounded by the presence of coexistent antibodies against HLA antigens., Case Report: A case is presented of a multiparous woman with acute myelogenous leukemia whose sole cause of transfusion refractoriness was antibody to platelet antigen HPA-1a. She responded dramatically to HPA-1a-negative platelet transfusion., Conclusion: This case provides strong serologic and clinical evidence that platelet transfusion refractoriness may result from antibodies to platelet-specific antigens.

Background: Autoantibody production by the fetus is thought to be extremely unlikely. Only one possible case of in utero autoantibody production against red cells by the fetus has previously been described., Study Design and Methods: A case of apparent red cell IgG autoantibody production in utero is reported., Results: This was established by a positive direct antiglobulin test in a newborn infant without evidence of maternal alloantibodies or autoantibodies. There was no evidence of clinically significant hemolysis at the infant's birth. After 6 weeks, his direct antiglobulin test remained strongly positive. The infant thrived without evidence of hemolysis, and after 6 months the direct antiglobulin test was negative., Conclusion: The production of autoantibodies to red cells in utero is possible, though rare. This did not result in apparent hemolysis in this patient.

Many patients are, perhaps inappropriately, denied the benefits of autologous blood transfusion, because they are thought to be too ill to donate blood safely. The safety and efficacy of autologous blood donation by selected patients with end-stage heart or lung disease who are awaiting organ transplantation were studied to determine if even these critically ill patients could be suitable candidates for autologous blood donation. Seventy-two adults awaiting heart or lung transplantation were evaluated for autologous blood donation in a hospital-based blood collection facility. Phlebotomy was performed if the patient met the required medical eligibility protocol, and if he or she consented to participate. Units of blood were separated into packed red cells and plasma and stored in a frozen state. Of 48 heart transplant candidates, 31 (65%) were each able to donate 1 to 8 units of blood. The median number of exposures to allogeneic components was 1 for patients who donated and 7 for nondonors (p = 0.0141). Among patients who donated, 54 percent required allogeneic components, as compared to 88 percent of nondonors (p = 0.0968). Of 24 lung transplant candidates, 15 (63%) made 1 to 6 donations each. The median number of exposures to allogeneic components was 0 for donors and 2 for nondonors (p = 0.1871), but only 45 percent of donors required allogeneic components, as compared to 100 percent of nondonors (p = 0.0418). No serious complications during or following phlebotomy were observed. It is concluded that autologous blood donation by patients with end-stage heart or lung disease may be safe.(ABSTRACT TRUNCATED AT 250 WORDS)

Several published reports have documented the variable survival of Yt(a+) red cells (RBC) in patients with anti-Yt(a) as measured by 51Chromium (Cr)-labeled RBC survival studies. Similar studies with anti-Yt(b) have not been reported. A 51Cr-labeled RBC survival study was performed using Yt(b+) RBCs and a monocyte monolayer assay in a young hemodialysis patient who required chronic transfusion therapy and who had developed anti-Yt(b). The survival of the transfused RBCs was 100 and 93 percent at 1 and 24 hours, respectively, with a half life of 21 days at termination of the study (normal, 28 to 32 days). These results showed no evidence of rapid destruction of the Yt(b+) RBCs, indicating that this patient could be transfused safely with blood from Yt(b+) donors. Long-term survival of the 51Cr-labeled Yt(b+) RBCs was shortened moderately, however, a finding that correlated with a slightly abnormal monocyte monolayer assay test.

We prospectively compared the incidence of complications following saline-washed versus packed red blood cell transfusions, to determine whether routine use of washed red blood cells could reduce significantly the incidence of transfusion reactions. Clinical reports of reactions were evaluated carefully to confirm whether the reaction was caused by transfusion. In 3,799 washed red blood cell transfusions, there were eight confirmed reactions (0.21%). Of 6,359 packed red blood cell transfusions, 31 reactions occurred (0.49%). The difference in incidence of confirmed complications was statistically significant (p less than 0.03). Administration of washed red blood cells to all patients requiring transfusions can thus be seen to reduce significantly the incidence of adverse reactions. This is likely the result of the removal of leukocytes and plasma achieved by the washing process. The increased safety of washed red blood cells must be weighed against their extra expense to determine their cost-effectiveness in transfusion therapy.

A review of our knowledge of acute hemolytic transfusion reactions indicates that we have learned much in recent years about the pathogenetic mechanisms involved. An approach to effective therapy for patients suffering such reactions should be based on our latest understanding of the pathophysiology of this syndrome. However, changes in our therapeutic approach have not kept abreast of our increased awareness of the etiologic factors, and the patient, therefore, is not getting the benefit of our increased knowledge in this area. The primary pathogenetic mechanisms involved in these reactions appear to be disseminated intravascular coagulation and a series of hemodynamic alterations leading to ischemic necrosis of tissues. Therapy would best be aimed at interfering with these primary pathophysiologic pathways.

Therapy for acute renal allograft rejection generally consists of administration of high doses of corticosteroids along with cytotoxic drugs. Failure of this treatment usually dictates removal of the graft. We describe a patient who was rejecting a renal transplant from his HLA-identical, mixed lymphocyte culture-compatible brother. This acute rejection episode was unresponsive to three days of therapy with high doses of steroids, azathioprine and coumadin. The patient rapidly improved following intensive exchange plasmapheresis and lymphocytapheresis. This therapy produced depletion of immunoglobulins, complement components, coagulation factors and circulating lymphocytes, and resulted in dramatic improvement in renal function and reversal of the rejection crisis. We suggest that intensive pheresis may represent an important adjunct to currently available therapy for the treatment of acute renal allograft rejection.

A nine-year-old boy had typical clinical, hematologic and blood group serologic findings of autoimmune hemolytic anemia except for one important exception; with most commercially available broad spectrum anti-human sera the direct antiglobulin tests were negative. With reagents prepared in the laboratory which were found to be relatively less potent in and anti-IgG and IgM activity but which utilize a short period of incubation after mixing with the washed cells, the tests were all clearly positive. If incubation were employed with the commercial reagents, the tests were positive. Further studies showed that the patient's cells were coated exclusively with IgA and that a commercial reagent, although potent in anti-IgG and anti-IgM, was relatively deficient in anti-IgA. It is proposed that incubation compensates for the latter and is cautioned that incubation, with reagents potent in anti-IgG, could lead to false negative reactions with weakly IgG sensitized cells due to antibody surplus prozones of inhibition. This case illustrates that the rare instances of "Coombs negative immune hemolytic anemias" may be based on mechanisms such as those reported here and, that to be ideal, a broad spectrum anti-human serum should have balanced anti-immunoglobulin activities in relation to its incubation time.

Although noncardiogenic pulmonary edema (NCPE) is a recognized complication of blood transfusion, the precise etiology is not well understood. NCPE may be secondary to complement-mediated pulmonary capillary injury initiated by either donor or recipient anti-leukocyte antibodies. It is not caused by simple volume overload. Recent blood banking texts and published case reports continue to suggest diuretics as part of the initial therapy for this complication. We report a case of transfusion-associated NCPE in which empirical diuretic therapy clearly was detrimental and suggest that the use of diuretics for treatment of this condition is not warranted. Reversal of progressive hypoxemia is the mainstay of therapy. Hemodynamic monitoring is important in differentiating NCPE from pulmonary edema secondary to cardiac failure or volume overload and should be used as a guide for further therapy.

A patient with warm autoimmune hemolytic anemia (AIHA) has been found to possess an autoantibody with Wrb specificity. While this is the first known description of Wrb specificity in this disease, additional studies on the Wrb status of En(a-) cells indicate that autoantibodies previously thought to be anti-Ena are in reality also anti-Wrb. Autoantibodies with Wrb specificity may thus be a rather common finding in patients with AIHA who have been thought to have "panagglutinins" on their red blood cells. Since anti-Wra alloantibodies are found frequently in patients with AIHA, it seems possible that the Wright system holds some clue to the pathogenesis of this disease.

Clinical studies have suggested that granulocyte transfusions may be of value in the treatment of septic neonatal patients who present with severe granulocytopenia. We have developed a protocol for the preparation of granulocyte concentrates from freshly collected units of whole blood, using an automated blood cell processor. The red cells were washed with saline. Then, the buffy coats were collected from the washed red cells and studied for their suitability as granulocyte concentrates for neonatal transfusion. The mean number of granulocytes per concentrate was 1.6 X 10(9) in a mean volume of 25 ml. Studies of granulocyte function, including viability, random mobility, chemotaxis, phagocytosis and nitro-blue tetrazolium reduction, demonstrated that the granulocytes were functionally unimpaired following preparation of the concentrates. These studies suggest that concentrates of functional granulocytes, suitable for transfusion to neonatal patients, can be prepared from fresh units of whole blood, using a cell processor. This procedure is more cost-effective than leukapheresis and allows for delivery of granulocytes for transfusion in a more timely fashion.

We used repeated leukapheresis in the long-term management of chronic lymphocytic leukemia. Twelve patients with far-advanced disease that was refractory to standard forms of therapy, were studied. Six patients completed a predefined course of therapy. Although a single patient responded favorably for a period of time, no other patient was benefited by this treatment. While circulating lymphocyte counts in these patients always could be reduced, generally, this was not associated with improvements in pancytopenia, hypogammagobulinemia, adenopathy, organomegaly, or constitutional symptoms of lethargy, fevers and night sweats. Mean survival was only ten months from onset of therapy. We conclude that long-term leukapheresis is ineffective in the management of far-advanced chronic lymphocytic leukemia.

Antibodies to cisplatin, an extensively used anticancer chemotherapeutic agent, have been implicated previously as a cause of immune hemolytic anemia. Investigation of a suspected case of cisplatin-induced hemolytic anemia in a 40-year-old man demonstrated that IgG could be adsorbed nonimmunologically by reagent red cells in vitro. This phenomenon was found to be a source of possible error in the interpretation of studies identifying specific cisplatin antibodies. Furthermore, cisplatin was found to be capable of producing a positive direct antiglobulin test (DAT), owing to the nonspecific adsorption of immunoglobulin and complement in vivo. Although this finding did not result in acute hemolysis, it may cause confusion in the investigation of DAT-positive hemolytic anemias. We question whether previous reports of cisplatin-induced hemolytic anemia are accurate in their assessment that such hemolysis was mediated immunologically. Future studies of suspected cases of hemolysis induced by this drug should include serologic investigation adequate to demonstrate the presence of specific cisplatin antibodies. A positive DAT in such patients should not be considered proof of drug-induced immune hemolytic anemia.

Autologous blood donation prior to elective surgery can protect patients from unnecessary exposure to allogeneic blood. However, the inappropriate use of autologous blood programs, which results in the collection of excessive quantities of blood or of the collection of any blood prior to low-risk surgical procedures, can be wasteful and potentially hazardous. All patients donating autologous blood at a large institution during a period of three months were studied in an effort to develop a schedule of optimal preoperative collection of autologous blood (SOPCAB), which is similar to a maximum surgical blood order schedule. Some 461 consecutive autologous donations from 264 patients were investigated. For certain surgical procedures, primarily the cardiac and orthopedic procedures, undercollection appeared to be the most common problem. For other procedures (laminectomies, nasal surgery), overcollection was more common. A model is presented for the careful scrutiny of autologous blood collection and use to allow for the creation of a SOPCAB for patients undergoing elective surgery.

We studied 342 potentially "high-risk" patients, including patients with severe heart disease, elderly patients, children, and pregnant women, to determine the incidence of complications related to phlebotomy. Our patients had an adverse reaction rate associated with blood donation of 4 percent, which is no greater than would be expected among normal volunteer blood donors. No patient experienced a dangerous complication associated with phlebotomy. We conclude that many patients currently denied the opportunity to donate blood preoperatively are actually suitable candidates for autologous blood transfusion programs.

In the course of investigating a patient with autoimmune hemolytic anemia in which the causative autoantibody had anti-Wrb specificity, it was demonstrated that an En(a-) red blood cell sample typed as Wr(a-b-). The only known example of Wr(a+b-) blood typed as En(a+) so that anti-Wrb and anti-Ena do not have the same specificity.

In 1975, we showed 18, 19 an En(a-) blood sample to be phenotypically Wr(a-b-). In the current report, we describe tests that show that three En(a-) members of a single family, not believed to be related to the family of the previously tested En(a-) person, are also Wr(a-b-). They have red blood cells that neither react with nor adsorb anti-Wra or anti-Wrb. In addition, we have shown that the red blood cells of six EnaEn heterozygotes, in the family tested, are Wr(a-b+) but carry only a single dose of Wrb antigen. Tests on anti-Ena have shown conclusively that one example is a mixture of separable anti-Ena and anti-Wrb and that a second example may well contain the same two antibodies. By various methods, we have demonstrated that the red blood cells of the only known Wr(a+b-) individual are En(a+) and do not display any of the physicochemical abberations of the En(a-) phenotype. It is further shown that neuraminidase and trypsin do not denature the Wra or Wrb antigens in vitro, but that the protease ficin does have a limited ability to denature Wrb. Additional observations on the first reported example of anti-Wrb are included. These various findings have been considered in the light of gene linkage of, or gene interaction between, the En and Wright system genes. It is concluded that the evidence does not exclude the possibility that En is a silent allele at the WraWrb locus so that the genotype EnEn (or WrWr) might result in the phenotype En(a-), Wr(a-b-). However, it is also pointed out that the evidence equally well supports the postulation that the Wra and Wrb genes are unable to function in the absence of an Ena gene. If this latter theory is proved correct, the interaction between Ena and the Wright genes can be thought of as similar to that between the H and ABO or X1r and CDE genes. It is pointed out that if En is a silent allele at the MN locus (current evidence on this point is not conclusive,) En and Wr cannot be synonymous for it is known that the Wra and M and N genes segregate independently. Location of En at the MN locus would not, however, refute the theory that Wra and Wrb cannot function in the absence of En. Finally, it is pointed out that the supposed anti-Wrb is probably just what its name implies but that even if this assumption is later disproved, the high incidence antigen defined by the antibody presently called anti-Wrb is unequivocally associated with Ena.

We attempted to control the platelet count of a patient with primary thrombocytosis utilizing long-term plateletpheresis therapy. The patient previously could not be controlled with chemotherapy, because of rapid development of leukopenia. Although intensive pheresis at the rate of four to five procedures per week produced rapid lowering of the patient's platelet count, continued therapy at the rate of two to three procedures a week failed to maintain these counts, and platelets gradually rose to pretreatment levels. We conclude that while plateletpheresis can produce acute lowering of elevated platelet counts, the rate of platelet production in primary thrombocytosis may be too rapid to allow for long-term control by pheresis alone, utilizing an acceptable treatment schedule of one of three procedures per week.

Exchange transfusion is a well-established procedure for the treatment of severe complications of sickle cell anemia. However, large-volume exchange is a difficult, time-consuming technique, and therefore rarely used. Exchange red blood cell pheresis, using automated equipment, can accomplish red blood cell exchange more rapidly and efficiently, and can be easily performed by a skilled team of nursing personnel. The recent introduction of a pediatric centrifuge bowl allows this technique to be applied to pediatric patients. This procedure was used in a 13-year-old male with sickle cell anemia, who presented with bilateral pulmonary infiltrates, respiratory distress, and hypoxemia, unresponsive to antibiotics and other means of conservative therapy. A one and one-half volume red blood cell exchange reduced the hemoglobin S concentration to 13 per cent. The patient experienced dramatic improvement within 24 hours, progressing to complete recovery within a few days.