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Background: Human herpesvirus-8 (HHV-8) causes Kaposi's sarcoma and can be detected and induced in peripheral blood mononuclear cells (PBMCs) from infected individuals. The prevalence of viral genomes in induced/cultured PBMCs from healthy blood donors has not been systematically studied., Materials and Methods: PBMCs from 164 donors were purified and stored as two equal aliquots in liquid nitrogen. One aliquot was used for CD19+ B-cell purification with a fraction reserved for DNA extraction. The second aliquot was cultured for 2 or 4 days in culture media containing n-butyrate and tetradecanoyl phorbol acetate. DNA was extracted from all four cell sources: PBMCs, purified B cells, induced PBMCs harvested at days 2 and 4 of culture. A sensitive real-time PCR with a DNA equivalent of 3×10(5) cells per reaction was run in duplicate for all samples along with a quantitative HHV-8 DNA standard ranging from 1.6 to 200 copies., Results: For all 164 donors, HHV-8 genomes were not detected in the DNA equivalent of 3-6×10(5) of PBMCs and induced/cultured PBMCs with a real-time PCR assay (95% CI: 0-3.5/164). HHV-8 DNA was not detected from DNA equivalent of 1.5 (0.5-5.6)×10(5) CD19+ B cells from 139/164 donors. HHV-8 antibodies were detected in 7 of the 164 donors (4.3%)., Conclusions: HHV-8 genomes were not detected from PBMCs, induced/cultured PBMCs and CD19+ B cells from 164 blood donors. The level of detectable HHV-8 genomes in blood donors seems to be extremely low, if they exist., (© 2010 The Author(s). Vox Sanguinis © 2010 International Society of Blood Transfusion.)

Background: Transfusion-related acute lung injury (TRALI) has been associated with both human leukocyte antigen (HLA) and human neutrophil antigen (HNA) antibodies. HNA antibody frequency, specificity, and demographic associations have not been well defined in the blood donor population., Study Design and Methods: A subset of 1171 donors (388 nontransfused males, 390 HLA antibody-negative females with three or more pregnancies, and 393 HLA antibody-positive females with three or more pregnancies) from a larger Leukocyte Antibody Prevalence Study was tested for immunoglobulin (Ig)G and IgM HNA antibody using a granulocyte immunofluorescence flow cytometry assay. Additional testing on selected samples included monoclonal antibody immobilization of granulocyte antigen-flow cytometry and granulocyte genotyping., Results: Eight samples were HNA antibody positive (prevalence, 0.7%; 95% confidence interval [CI], 0.3%-1.3%]). Three HNA antibodies (one IgG and two IgM) were found in nontransfused males (prevalence, 0.8%; 95% CI, 0.2%-2.2%); all were panreactive or nonspecific. One HLA antibody-negative previously pregnant female had an IgG HNA antibody with HNA-1a specificity (prevalence, 0.3%; 95% CI, 0.01%-1.4%). Four HLA antibody-positive previously pregnant females demonstrated HNA antibodies, three IgG and one IgM (prevalence, 1%; 95% CI, 0.3%-2.6%). Two of these were HNA-1a specific, one HNA-4a specific, and one nonspecific., Conclusions: HNA antibodies occur with low frequency in the donor population and are present in both male and female donors. Despite the implementation of TRALI reduction strategies, HNA antibodies are still present in donor blood products. Although our data do not create a case for urgent implementation of donor HNA antibody testing, future new developments for high-throughput HNA antibody screening, including for HNA-3a, may warrant reconsideration., (© 2010 American Association of Blood Banks.)

The Transfusion Medicine Service (TMS) covers diverse clinical and laboratory-based services that must be delivered with accuracy, efficiency and reliability. TMS oversight is shared by multiple regulatory agencies that cover product manufacturing and validation standards geared toward patient safety. These demands present significant informatics challenges. Over the past few decades, TMS information systems have improved to better handle blood product manufacturing, inventory, delivery, tracking and documentation. Audit trails and access to electronic databases have greatly facilitated product traceability and biovigilance efforts. Modern blood bank computing has enabled novel applications such as the electronic crossmatch, kiosk-based blood product delivery systems, and self-administered computerized blood donor interview and eligibility determination. With increasing use of barcoding technology, there has been a marked improvement in patient and specimen identification. Moreover, the emergence of national and international labeling standards such as ISBT 128 have facilitated the availability, movement and tracking of blood products across national and international boundaries. TMS has only recently begun to leverage the electronic medical record to address quality issues in transfusion practice and promote standardized documentation within institutions. With improved technology, future growth is expected in blood bank automation and product labeling with applications such as radio frequency identification devices. This article reviews several of these key informatics issues relevant to the contemporary practice of TMS.

The effect of the age of RBCs on anti-RBC alloimmunization has not been investigated in previous studies of the RBC storage lesion. D-negative recipients of at least 1 D-positive RBC unit were identified. Responders produced an anti-D, while nonresponders had not made anti-D when the database was searched. The 2 groups were matched for age, sex, length of serologic follow-up, and hospital location. There were 29 responders and 58 nonresponders. The median number of all RBCs transfused to the responders was 6, vs 10 for the nonresponders (P < .01); the median age of the RBCs was 15 vs 14 days, respectively (P = .70). Responders received a median of 3 D-positive RBC units vs 4 D-positive RBCs for nonresponders (P = .02); median ages of the D-positive RBCs were 16 vs 14 days, respectively (P = .21). There was no association between the age of transfused RBCs and the likelihood of anti-D alloimmunization.

It is indisputable that there are numerous biochemical, structural, inflammatory, and physiologic changes in stored red cells, sometimes referred to collectively as the "red cell storage lesion". It remains controversial however whether any of these changes have clinical relevance and actually impact the clinical outcomes in transfused patients. More than 25 published clinical studies have evaluated the effects of red blood cell storage on patient outcomes. The majority of studies are non-randomized observational studies with methodologic limitations described in this review. These studies do however provide equipoise to support the ethical conduct of the large, definitive randomized clinical trials which are now underway., ((c) 2010. Published by Elsevier Ltd.)

Background: HLA antibody testing of previously transfused or pregnant donors may help reduce the risk of transfusion-related acute lung injury (TRALI). However, the prevalence of HLA antibodies in transfused donors has not been well characterized., Study Design and Methods: Transfusion and pregnancy history was obtained from consenting donors. HLA Class I and II antibody testing was performed by multiantigen bead Luminex platform. Cutoff values for Class I and II antibodies used normalized background ratios of 10.8 and 6.9, respectively. Linear probability models were used to evaluate potential associations between HLA alloimmunization and donor characteristics., Results: A total of 7920 donors (2086 males and 5834 females) were tested. HLA antibody prevalence did not significantly differ between 895 transfused (1.7%) and 1138 nontransfused males (1.0%; odds ratio [OR], 1.75; 95% confidence interval [CI], 0.80-3.82]. Prevalence in 45 transfused nulliparous females (4.4%; 95% CI, 0.1%-11.8%) was not different from the 1.6% prevalence in 1732 nontransfused nulliparous females (OR, 2.94; 95% CI, 0.68-12.74). Transfused parous females had higher prevalence than nontransfused counterparts (p = 0.004; OR, 1.39; 95% CI, 1.07-1.80). In a linear probability model, the estimated additive risk of transfusion-induced alloimmunization was only 0.8% (95% CI, -0.2% to 1.8%; p = 0.10). Donor transfusion history showed that 58% of transfusions occurred more than 10 years previously., Conclusion: Transfused volunteer blood donors do not appear to have a significantly higher prevalence of HLA antibodies than their nontransfused counterparts. Thus, in an effort to reduce TRALI risk, ascertaining past history of transfusion and testing these donors for HLA antibodies is not necessary.

Background: As blood centers prepare fewer plasma products from female donors to avoid HLA antibodies, the standard starting material for cryoprecipitate (cryo), fresh-frozen plasma (FFP), might become increasingly scarce. A unit of cryo must contain at a minimum 80 IU of VIIIC and 150 mg of fibrinogen. Plasma frozen within 24 hours after phlebotomy (FP24) contains nearly equivalent levels of clotting factors as FFP at the time of thawing and, although not AABB/FDA approved for this purpose, might be a suitable starting material for cryo (cryo24) manufacture., Study Design and Methods: FP24 was collected from 20 male donors and cryo24 was subsequently prepared according to standard blood center protocols. The cryo24 was then thawed and VIIIC, von Willebrand factor (VWF) antigen, and fibrinogen levels were measured in these cryo24 units and compared to the corresponding levels in 20 randomly selected units of standard cryo (prepared from FFP)., Results: The mean (+/-SD) levels in cryo and cryo24 at the time of thawing were as follows: fibrinogen (mg/unit) 455.8 (+/-172.6) and 575.8 (+/-185.9; p = 0.04), VIIIC (IU/unit) 216.1 (+/-52.3) and 252.4 (+/-70.1; p = 0.07), and VWF (IU/unit) 448.1 (+/-118.9) and 505.9 (+/-135.1; p = 0.16), respectively. All units of standard cryo and cryo24 met the current minimum content standards., Conclusion: All units of cryo24 in this pilot study met the current minimum content standards for cryo. While clinical studies of its efficacy are warranted, cryo24's in vitro characteristics are at least equivalent to that of standard cryo.

Background: Human herpesvirus 8 (HHV-8) is a gamma-herpesvirus that causes Kaposi's sarcoma. The prevalence of HHV-8 genomes in US blood donors has not been systemically studied., Study Design and Methods: A sensitive and quantitative real-time polymerase chain reaction (PCR) assay was used to detect HHV-8 DNA from purified CD19+ B lymphocytes from randomly selected US whole blood donors. Cellular target for the GAPDH gene was used to quantify cell-equivalent DNA. HHV-8 PCR was run in duplicate for each donor specimen along with an HHV-8 genomic copy standard. HHV-8 antibodies were detected by an indirect immunofluorescence assay., Results: Specimens were obtained from 962 blood donors. DNA from more than 3 x 10(5) B-cell equivalents were obtained from 684 donors. No HHV-8 DNA was detected from any of the blood donor specimens. For the 684 donors, HHV-8 genomes were not detected in the DNA equivalent of 3 x 10(5) to 6 x 10(5) CD19+ B cells with real-time PCR, which has a detection limit of eight copies (95% confidence interval, 0-3/684). Negative results from the remaining 220 donors were potentially confounded by insufficient input DNA into the PCR procedures. Antibodies to HHV-8 were detected in 7.3% (70/962) of the donors. HHV-8 genomes were not detected from 40 of 70 HHV-8-seropositive donor B-cell DNA samples., Conclusion: The results indicate that the prevalence of detectable HHV-8 genomes in healthy blood donors is very low.

We compare our experience using a new rapid qualitative immunoassay (RQI) test (platelet Pan Genera Detection, Verax, Worcester, MA) for bacterial screening of whole blood platelet (WBP) pools with our previous WBP bacterial screen, pH testing. All WBP pools were RQI tested at the time of issue. All RQI+ pools were cultured in an automated culture system, with subsequent bacterial identification if the culture was positive. During approximately 5.5 months, 7,733 WBP pools were RQI tested. There were 14 positive RQI tests; 12 WBP pools were sterile when cultured and considered false-positive RQI tests. One pool was positive for coagulase-negative Staphylococcus, while another was positive for group B Streptococcus. The specificity and positive predictive value of the RQI test were 99.85% and 14.3%, respectively. The specificity and positive predictive value of the RQI test were higher than pH testing, leading to less waste of sterile WBP pools.

Background: We conducted a trial of prophylactic platelet transfusions to evaluate the effect of platelet dose on bleeding in patients with hypoproliferative thrombocytopenia., Methods: We randomly assigned hospitalized patients undergoing hematopoietic stem-cell transplantation or chemotherapy for hematologic cancers or solid tumors to receive prophylactic platelet transfusions at a low dose, a medium dose, or a high dose (1.1x10(11), 2.2x10(11), or 4.4x10(11) platelets per square meter of body-surface area, respectively), when morning platelet counts were 10,000 per cubic millimeter or lower. Clinical signs of bleeding were assessed daily. The primary end point was bleeding of grade 2 or higher (as defined on the basis of World Health Organization criteria)., Results: In the 1272 patients who received at least one platelet transfusion, the primary end point was observed in 71%, 69%, and 70% of the patients in the low-dose group, the medium-dose group, and the high-dose group, respectively (differences were not significant). The incidences of higher grades of bleeding, and other adverse events, were similar among the three groups. The median number of platelets transfused was significantly lower in the low-dose group (9.25x10(11)) than in the medium-dose group (11.25x10(11)) or the high-dose group (19.63x10(11)) (P=0.002 for low vs. medium, P<0.001 for high vs. low and high vs. medium), but the median number of platelet transfusions given was significantly higher in the low-dose group (five, vs. three in the medium-dose and three in the high-dose group; P<0.001 for low vs. medium and low vs. high). Bleeding occurred on 25% of the study days on which morning platelet counts were 5000 per cubic millimeter or lower, as compared with 17% of study days on which platelet counts were 6000 to 80,000 per cubic millimeter (P<0.001)., Conclusions: Low doses of platelets administered as a prophylactic transfusion led to a decreased number of platelets transfused per patient but an increased number of transfusions given. At doses between 1.1x10(11) and 4.4x10(11) platelets per square meter, the number of platelets in the prophylactic transfusion had no effect on the incidence of bleeding. (ClinicalTrials.gov number, NCT00128713.), (2010 Massachusetts Medical Society)

Background: The direct antiglobulin test (DAT) commonly detects immunoglobulin G (IgG) molecules or complement fragments on the red blood cell (RBC) surface. If IgG antibodies are present then elution procedures can be performed to identify the specificity of these antibodies. Our reference laboratory performs elutions on the RBCs of those patients who have received cellular blood products in the past 30 days and have either a newly identified positive DAT with anti-IgG or the agglutination strength is increased over a previous DAT and if ordered by a clinician regardless of transfusion history. This study questioned how frequently elutions contributed novel serologic information under our reference laboratory's current policy or whether elutions should be performed in more selective serologic conditions., Study Design and Methods: Recipients whose RBCs underwent eluate testing were identified from the blood bank's database and information about the antecedent DAT and antibody detection test and eluate was recorded., Results: In total 648 eluates were evaluated and 82 of 648 (12.7%) revealed a novel antibody not present in the serum (an informative eluate). In 2 of 82 informative eluates non-anti-A/B alloantibodies that were not present in the serum were detected: one example each of anti-D and anti-E. Both were associated with a microscopically positive antecedent DAT. The rate of an informative eluate was higher when the antibody detection test was negative., Conclusion: The strength of the DAT does not indicate the likelihood of an informative eluate. Performing an eluate when the antibody detection test is positive has limited value.

Background: Antibodies to human leukocyte antigens (HLA) in donated blood have been implicated as a cause of transfusion-related acute lung injury (TRALI). A potential measure to reduce the risk of TRALI includes screening plateletpheresis donors for HLA antibodies. The prevalence of HLA antibodies and their relationship to previous transfusion or pregnancy in blood donors was determined., Study Design and Methods: A total of 8171 volunteer blood donors were prospectively recruited by six US blood centers from December 2006 to May 2007. Donors provided a detailed history of pregnancy and transfusion and a sample for HLA Class I and II antibody testing by multiantigen bead flow analysis., Results: A total of 8171 donors were enrolled; 7920 (96.9%) had valid HLA antibody test results and 7841 (99%) of those had complete pregnancy and transfusion information. The prevalence of any HLA antibody was similar in nontransfused (n = 1138) and transfused (n = 895) men, 1.0% versus 1.7% (p = 0.16). HLA antibodies were detected in 17.3% of all female donors (n = 5834) and in 24.4% of those with a history of previous pregnancy (n = 3992). The prevalence of HLA antibodies increased in women with greater numbers of pregnancy: 1.7% (zero), 11.2% (one), 22.5% (two), 27.5% (three), and 32.2% (four or more pregnancies; p < 0.0001)., Conclusion: HLA Class I and Class II antibodies are detectable at low prevalence in male donors regardless of transfusion and in female donors without known immunizing events. The prevalence of HLA antibodies increases significantly with more pregnancies. These data will allow blood centers to estimate the impact of HLA antibody testing as a potential TRALI risk reduction measure.

Purpose: The clinical outcomes, safety, and use of resources associated with the administration of factor VIIa (recombinant) to nonhemophilic patients requiring neurosurgery were evaluated., Methods: An interdisciplinary group created guidelines for the pharmacy and therapeutics committee for the unlabeled use of factor VIIa (recombinant). Nonhemophilic patients were eligible to receive the agent without approval from the hematology-coagulation service if they had an intracranial hemorrhage (ICH), were undergoing an emergency neurosurgical procedure, and had coagulopathy. A standard single dose of 40 microg/kg was recommended for these patients. Data were prospectively collected between March 2004 and March 2006 for all neurological surgery patients receiving factor VIIa (recombinant)., Results: A total of 92 nonhemophilic patients received single doses of factor VIIa (recombinant) under the guidelines during the two-year study period. The majority of patients had a baseline International Normalized Ratio (INR) of >2, underwent emergency neurosurgical procedures, and had an intracranial hemorrhage. All guideline criteria for indication and approval were followed for 48 patients. Eighty-seven patients received concomitant treatment for reversal of anticoagulation. A significant correction in the baseline INR after administration of factor VIIa (recombinant) was noted (p < 0.0001). Five patients experienced adverse events. Implementation of the guidelines decreased the annual cost of factor VIIa (recombinant) by 46%., Conclusion: A protocol calling for administration of factor VIIa (recombinant) 40 microg/kg in nonhemophilic patients with coagulopathy and ICH led to a rapid and significant decrease in the INR, allowing for emergency surgical intervention. Few adverse events were detected in these patients, and none were deemed to be directly related to factor VIIa (recombinant).

Background: Epstein-Barr virus (EBV) persists in infected B lymphocytes in blood donors. Lymphocytes are viable during platelet (PLT) storage. The effects of storage and leukoreduction on lymphocytes and EBV genomes are evaluated., Study Design and Methods: Forty nonleukoreduced PLT concentrates were stored at 20 to 24°C for up to 7 days. EBV genomes in B cells were quantified on Days 1 and 5. Viable white blood cells (WBCs) and T and B cells were quantified in 10 of 40 units on Days 1, 3, 5, and 7 of storage. For the leukoreduction study, four pools of PLTs were leukoreduced within 24 hours of collection. B cells from before leukoreduction and all peripheral blood mononuclear cells from after leukoreduction were assayed for EBV., Results: Viable WBCs and T cells were stable whereas viable B cells were reduced to 71% of the Day 1 level by Day 5. A total of 31 of 37 (83.8%) units were EBV positive. Although EBV genomes remained stable in most units, 12 of 37 units demonstrated a median of 5.1 (range 2- to 134)-fold increase in EBV genomes per 105 B cells on Day 5. For the leukoreduction study, EBV genomes were detected in four of four pools before leukoreduction with a median of 3.8 (range, 0.2-93.6) EBV genomes per 105 B cells. EBV genomes were not detected in any of the postleukoreduction specimens., Conclusions: Seventy percent of B lymphocytes are viable on Day 5 of PLT storage. Although the mean number of EBV genomes remained stable, a subset of units had increased EBV genomes during storage. Leukoreduction removed polymerase chain reaction-detectable EBV genomes from PLT pools.

Background: A variable effect of inflammation on alloimmunization to transfused red blood cells (RBCs) in mice has been recently reported. We investigated whether RBC alloimmunization in humans was affected by transfusion of blood products in temporal proximity to experiencing a febrile transfusion reaction (FTR) to platelets (PLTs), an event predominantly mediated by inflammatory cytokines., Study Design and Methods: Blood bank databases were used to identify patients who experienced an FTR or possible FTR to PLTs from August 2000 to March 2008 (FTR group). The control group of patients received a PLT transfusion on randomly selected dates without experiencing an FTR. The "event" was defined as the PLT transfusion that caused the FTR in the FTR group or the index PLT transfusion in the control group. The number of transfused blood products and their proximity to the event were recorded along with other recipient data. The primary endpoint was the rate of RBC alloimmunization between the two groups., Results: There were 190 recipients in the FTR group and 245 in the control group. Overall, the recipients in the control group were younger and received more blood products on the day of their event and over the subsequent 10 days. The alloimmunization rate among recipients in the FTR group was higher than in the control group (8% vs. 3%, respectively; p = 0.026)., Conclusions: These preliminary data support our hypothesis that recipient inflammation may affect RBC alloimmunization in humans; however, a more detailed understanding of the pathophysiologic association between inflammation and alloimmunization is required before definitive conclusions can be reached.

The leading cause of transfusion-related morbidity and mortality in the United States is transfusion-related acute lung injury (TRALI). Diagnostic criteria for TRALI have recently been developed and primarily consist of hypoxia and bilateral pulmonary edema occurring during or within 6 h of a transfusion in the absence of cardiac failure or intravascular volume overload. The primary differential diagnosis is transfusion-associated circulatory overload and differentiation can be difficult. Treatment is supportive with oxygen and mechanical ventilation. Diuresis is not indicated and the role of steroids is unproven. Patients typically recover within a few days. All types of blood products have been associated with TRALI, however, the plasma-rich components, such as fresh frozen plasma and apheresis platelets, have been most frequently implicated. The pathogenesis of TRALI is not completely understood. Leukocyte antibodies in donor plasma have been implicated in most cases with antibodies directed at human leukocyte antigen (HLA) class I, HLA class II or neutrophil-specific antigens, particularly HNA-3a. Activation of pulmonary endothelium is important in the development of TRALI and may account for most cases being observed in surgical or intensive care unit patients. Transfused leukoagglutinating antibodies bind to recipients' neutrophils localized to pulmonary endothelium resulting in activation and release of oxidases and other damaging biologic response modifiers that cause capillary leak. In a minority of TRALI cases, no antibodies are identified and it is postulated that neutrophil priming factors in the transfused component can mediate TRALI in a patient with pulmonary endothelial activation, the so called "two hit" mechanism. Recognition of the role of anti-leukocyte antibodies has led to new strategies to reduce the risk of TRALI. Female blood donors with a previous pregnancy frequently have HLA antibodies with an overall prevalence of 24% and increasing prevalence related to the number of previous pregnancies. Since HLA antibodies have been implicated in TRALI, blood centers have adopted policies to produce plasma components primarily from male donors. Strategies to reduce the risk from apheresis platelets are problematic and are likely to involve testing female apheresis platelet donors for HLA antibodies. Much more research is needed to understand the blood component and patient risk factors for TRALI so that novel strategies for treatment and additional measures to reduce the risk of TRALI can be developed.

Background: Patients with neutropenia are at increased risk for infections. Granulocyte transfusions (GT) have had mixed success in treatment of neutropenic infections in adult patients with hematologic malignancy. This study examined the outcomes of GT therapy in neutropenic solid organ transplant recipients, a novel population for this therapy., Methods: We performed a retrospective examination of the transfusion and medical records of all 14 solid organ-transplant recipients without hematologic malignancy who experienced neutropenia and received GT therapy from 2004 to 2006., Results: Twelve patients received GT therapy for an active infection and two patients for infection prophylaxis. The mean absolute neutrophil count (ANC) one day increment per GT in these patients was 526/microl (median 215/microl). The mean ANC one day increment per dose of 10(10) granulocytes was 246/microl (median 86/microl). Of the 12 infected patients, four patients (33%) showed a clinical response to GT with improvement or resolution of the infection, 7 (58%) patients had no clinical response and one additional patient had a clinical response to a course of GT but died during a second GT course. Neither patient receiving GT for prophylaxis developed an infection., Conclusions: We observed temporal increases in ANC to levels above 1,000/microl in 15/18 (83.3%) courses of GT. We observed a clinical response to infection in 5/12 (42%) patients, the remaining infected patients had no clinical response. Our results suggest that GT therapy in neutropenic solid organ transplant recipients can boost peripheral blood neutrophil counts. Additional studies are needed to document an independent clinical benefit for GT in this patient population.

Background: Pittsburgh's Centralized Transfusion Service (CTS) provides transfusion support to 16 hospitals and features an electronic database that contains patient transfusion and serologic histories. This database can be accessed from any hospital in the system. A major cause of ABO-incompatible transfusions is the "wrong blood in tube" (WBIT) phenomenon, that is, the sample is not from the recipient identified on the label. We hypothesized that having access to patient historical ABO types from anywhere in the CTS system can identify WBIT errors and prevent mistransfusions., Study Design and Methods: The transfusion committee records of the 16 CTS hospitals from March 2005 to September 2007 were reviewed for major collection errors, that is, the current ABO type differed from the historical type in the database. The patient's historical ABO type, the discrepant type, and the hospital(s) where these samples were collected were recorded., Results: In 6 of 16 major collection errors for which complete information was available, the current and historical ABO types were obtained from different hospitals within the CTS system. In 3 cases, selection of ABO type-specific blood based on the current sample would have led to an ABO-compatible transfusion (e.g., correct type A, current type O). In the other 3 cases, an ABO-incompatible transfusion would have resulted (e.g., correct type O, current type A)., Conclusions: Access to a centralized patient database detected 38 percent more ABO typing errors and prevented six mistransfusions, which would not have been prevented at a single institution. Centralization of patient transfusion data should be encouraged.

Background: The D antigen is highly immunogenic, requiring only a small quantity of transfused red blood cells (RBCs) to cause alloimmunization in D- immunocompetent recipients. The relatively low sensitization rate in oncology patients transfused with D+ platelets is well documented. A study of the alloimmunization rate of primarily nononcology D- recipients transfused with D+ RBCs was undertaken., Study Design and Methods: Transfusion service records were examined to identify D- recipients who were not alloimmunized to the D antigen and who had a follow-up antibody screen performed at least 10 days after the initial D+ RBC transfusion(s). The age and sex of the recipients, date and number of D+ RBC transfusion(s) and their leukoreduction status, all subsequent serologic investigations, and the hospital ward where the units were issued were recorded., Results: There were 98 study-eligible recipients identified who received a total of 445 D+ RBC units. The mean follow-up length was 182 days. Most recipients (87%) had antibody screens performed more than 21 days after the initial D+ RBC transfusion. In total, 24 recipients made 44 new alloantibodies: 22 anti-D (22%), 11 anti-E, 5 anti-C, 2 anti-K, and 1 each of anti-Kp(a), anti-Jk(a), anti-Bg, and anti-Fy(b). The rate of anti-D alloimmunization among recipients of entirely leukoreduced D+ units was 13 percent (1/8). Reexposure to D+ RBCs after the initial bleeding episode did not increase the rate of alloimmunization., Conclusions: The 22 percent rate of anti-D alloimmunization in patients requiring urgent RBC transfusion was intermediate between the rates previously reported for D- oncology patients transfused with D+ RBCs and that in immunocompetent volunteer recipients.

Purpose of Review: Limitations in donor availability for stem cell or organ transplantation require that ABO-incompatible donors be used. Crossing ABO lines can have immune consequences characterized by immediate or delayed hemolysis., Recent Findings: The use of peripheral blood as a stem cell source has essentially eliminated the risk for ABO-mediated hemolysis during infusion. Delayed red cell engraftment is expected after a major ABO-incompatible transplant and may be associated with pure red cell aplasia. The incidence of hemolysis associated with minor ABO incompatibility, the passenger lymphocyte syndrome, is waning because anti-B-cell immunosuppressive therapy is increasingly a component of graft versus host disease prophylaxis. The impact of ABO mismatching on stem cell recipient survival remains an area of active investigation. Although major ABO-incompatible organs are not used routinely for transplantation, minor ABO-incompatible organs are frequently used to meet the demand for organs. Passenger lymphocyte syndrome in this setting is a common complication, and has now been observed with every organ type and increasingly with non-ABO antibodies. Hemolysis can occur, but it is uncommonly severe., Summary: ABO-mismatched donors are commonly used for transplantation, and immune hemolysis remains the main complication. Clinicians must be vigilant in order to recognize hemolysis and implement appropriate therapy.

Background: The Epstein-Barr virus (EBV) establishes and maintains latent infection in B lymphocytes of the healthy adults. Lymphocytes remain viable during red blood cell (RBC) storage. The effect of RBC storage on the stability of EBV-infected B lymphocytes and EBV genome is not known., Study Design and Methods: Eight randomly selected non-leukoreduced AS-5 RBC units were stored for 42 days under standard blood bank refrigerated at 1-6 degrees C. Cell count and EBV genomes in CD19+ B lymphocytes were measured in fresh products and weekly for 6 weeks. Total white blood cells (CD45+), T lymphocyte (CD3+), and B lymphocyte (CD19+) were quantified by a single platform flow cytometric assay. EBV genomes were quantified by real-time polymerase chain reaction using DNA purified from CD19+ B cells., Results: Viable white blood cell, T and B lymphocytes followed a biphasic decline curve during RBC storage consisting of a steep steady decline during the first 3 weeks followed by a plateau for the remainder of the storage. At the end of the RBC shelf-life, 19% of the original T and B cells remained viable. EBV genomes per 10(5) CD19+ B lymphocytes remained constant during RBC storage. However, the total EBV genomes in the RBC units decline by more than 80% of their original value at the end of RBC storage due to loss of viable B lymphocytes., Conclusions: The results indicate that lymphocytes and EBV latently infected B cells can survive the normal storage conditions for RBC.

Background: A reduction in postoperative length of stay (PLOS) was recently demonstrated with the use of leukoreduced (LR) blood in cardiac surgery patients compared to a historical cohort who received non-LR blood. Follow-up data are now presented in a similar population after a 12-month period in which LR blood was no longer routinely used., Study Design and Methods: This is an extension of a study in which all patients admitted over a 12-month period for open heart surgery were given LR blood (Group 2) and were compared against a historical cohort given non-LR blood (Group 1). This study measures the outcomes of a new cohort of patients admitted during a 12-month period where LR blood was no longer routinely used (Group 3)., Results: PLOS increased in patients who received transfusions with non-LR blood (Group 3, n = 595) versus patients with LR blood (Group 2, n = 645; p = 0.045 by nonparametric rank U test). Mean PLOS increased from 9.5 days (95% confidence interval [CI], 8.9-10.0) to 10.8 days (95% CI, 10.0-11.6). In comparison, an earlier cohort who received non-LR blood (Group 1, n = 501) had a mean PLOS of 10.1 days (95% CI, 9.4-10.7). With the exception of decreased red blood cell (RBC) usage in Group 3, there were no significant differences in non-RBC blood usage, estimated blood loss, bypass time, mediastinitis rates, operative mortality rate, or overall mix of cases., Conclusions: The use of non-LR blood for cardiac surgery was associated with an increased PLOS compared to the use of LR blood and supports our previous demonstration of the benefits of LR blood in cardiac surgery.

Transfusion-associated acute lung injury (TRALI) has emerged as a leading cause of transfusion-related morbidity and mortality. TRALI is characterized by acute non-cardiogenic pulmonary edema and respiratory compromise in the setting of transfusion. The study of TRALI has been hampered by inadequate case definitions and an incomplete understanding of the pathologic mechanisms. Recent consensus conferences took an important first step by providing a framework for case definition. Recent advances in the understanding of the pathogenesis of TRALI have also occurred. TRALI has been primarily attributed to donor leukocyte antibodies that are thought to interact with recipient neutrophils, resulting in activation and aggregation in pulmonary capillaries, release of local biologic response modifiers causing capillary leak, and lung injury. An alternate mechanism termed the "two hit" or "neutrophil priming" hypothesis postulates that a pathway to neutrophil activation and aggregation can occur without leukocyte antibodies. A first event such as sepsis or trauma can induce pulmonary endothelial activation, release of cytokines, and priming of neutrophils. A subsequent second event such as exposure to lipids, cytokines or antibodies in a blood component would then cause activation of adherent neutrophils and a release of bioreactive molecules leading to lung injury. There are limited clinical and animal studies to support the "two hit" model. These proposed mechanisms are not mutually exclusive in that donor leukocyte antibody can be pathogenic in both models and have implications for new strategies to prevent TRALI.

Background: Bacterial contamination of blood products is a leading cause of transfusion-related morbidity and mortality. Transfusion services are now compelled to employ methods of detecting bacteria in platelet (PLT) components. The use of pH screening of whole-blood PLTs (WBPs) was evaluated with a pH meter at the time of issue as a surrogate test for bacterial contamination., Study Design and Methods: All WBPs selected for transfusion in May through September 2004 were tested individually for pH at time of issue. Those with a pH value of less than 7.0 were cultured in an automated culture system for 5 days. The white blood cell (WBC) and PLT counts in 56 representative WBP units that failed pH screening were compared to WBP units with acceptable pH values., Results: Of the 37,060 WBP units that underwent pH screening, 405 had a pH value of less than 7.0 (1.1%). Four of those units were culture positive (1.0%) for Staphylococcus aureus, Bacillus subtilis, diphtheroids, and coagulase-negative Staphylococcus. Only one cocomponent red blood cell (RBC) unit was culture-positive and grew the same bacteria (S. aureus) as the WBP unit. The rate of pH failure increased with WBP storage length with the greatest rate of pH failures occurring in 5-day-old WBPs. The units that failed pH screening had significantly more WBCs and PLTs than units with acceptable pH values., Conclusion: pH screening of WBPs at issue prevented transfusion of bacterially contaminated WBPs and RBCs. This method, however, results in significant PLT wastage. Higher WBC and PLT content likely explains pH failures not due to bacterial contamination.

Background: An ongoing issue in transfusion medicine is whether newly identified or emerging pathogens can be transmitted by transfusion. One method to study this question is through the use of a contemporary linked donor-recipient repository., Study Design and Methods: The Retrovirus Epidemiology Donor Study Allogeneic Donor and Recipient (RADAR) repository was established between 2000 and 2003 by seven blood centers and eight collaborating hospitals. Specimens from consented donors were collected, components from their donations were routed to participating hospitals, and recipients of these units gave enrollment and follow-up specimens for long-term storage. The repository was designed to show that zero transmissions to enrolled recipients would indicate with 95 percent confidence that the transfusion transmission rate of an agent with prevalence of 0.05 to 1 percent was lower than 25 percent., Results: The repository contains pre- and posttransfusion specimens from 3,575 cardiac, vascular, and orthopedic surgery patients, linked to 13,201 donation specimens. The mean number of RADAR donation exposures per recipient is 3.85. The distribution of components transfused is 77 percent red cells, 13 percent whole blood-derived platelet concentrates, and 10 percent fresh frozen plasma. A supplementary unlinked donation repository containing 99,906 specimens from 84,339 donors was also established and can be used to evaluate the prevalence of an agent and validate assay(s) performance before accessing the donor-recipient-linked repository. Recipient testing conducted during the establishment of RADAR revealed no transmissions of human immunodeficiency virus, hepatitis C virus, or human T-lymphotropic virus., Conclusions: RADAR is a contemporary donor-recipient repository that can be accessed to study the transfusion transmissibility of emerging agents.

As liver transplantation becomes increasingly common and complex, the demands on the transfusion service grow. Liver transplant recipients present unique challenges not only in terms of blood supply, but requirements for specialized blood components, serologic problems, and immunologic effects of transfusion on both the allograft and the recipient. As a result of immunosuppression, liver transplant recipients are more susceptible to some transfusion complications such as cytomegalovirus (CMV) infection but not to transfusion associated graft versus host disease. The transfusion specialist must recommend the optimal approach to reducing the risk of these complications in liver transplant recipients.

Background: Proven clinical benefits of leukoreduced blood components include reduced febrile nonhemolytic transfusion reactions, alloimmunization against HLA antigens, and CMV transmission. Immunomodulatory effects of leukoreduction have also been postulated to play a significant role in the clinical outcome of open heart surgery., Study Design and Methods: A prospective case control study was implemented in which all patients admitted over a 1-year period for open heart surgery at a single hospital were given leukoreduced blood products. Clinical outcomes were prospectively measured and compared to a historical cohort of patients from the previous year when leukoreduced blood products were not routinely used., Results: A significant improvement in the mean postoperative length of stay was seen in the study group (N = 645) versus control group (N = 501; 10.1 vs. 9.5 days; p = 0.005). No significant changes were seen in the rate of mediastinitis, operative mortality, or stay in the intensive care unit. There was no difference in the postoperative length of stay among study patients who did not receive transfusion (N = 308) versus control patients who did not receive transfusion (N = 296; 6.2 vs. 6.4 days; p = 0.104)., Conclusions: The use of leukoreduced blood was associated with a decrease in the postoperative length of stay in the setting of open heart surgery. The mechanisms through which these changes in clinical outcomes are generated remain unknown.

As solid organ transplantation becomes increasingly common and complex, the demands on the transfusion service expand. Transplant recipients present unique challenges not only because of product availability but also because of specialized blood components, serologic problems, and immunologic effects of transfusion on the allograft and the recipient. Solid organ transplant recipients receive immunosuppressive agents that make them more susceptible to infectious or immunologic complications of transfusion such as cytomegalovirus infection and graft-versus-host disease. Other immunologic consequences of transfusion such as alloimmunization may also be severe, resulting in acute or chronic graft rejection. The transfusion specialist must recommend the optimal approach to reducing the risk of these complications in organ transplant recipients.

Background: It is known that the use of filtration to reduce WBCs in RBC units is associated with a 6- to 15-percent loss of RBCs. It is not known if the use of such WBC-reduced RBCs results in an increased need for RBC units or in the transfusion of more units per year to patients with anemia., Study Design and Methods: In the multicenter Viral Activation Transfusion Study (VATS), anemic HIV-positive patients were randomly assigned to receive either WBC-reduced or non-WBC-reduced RBCs. The number of RBC units transfused per patient and the rate of RBC use were studied. All RBC units given after the enrollment transfusion were counted, until the end of follow-up or the occurrence of bleeding (receiving >5 RBCs within 2 consecutive days)., Results: As expected, the WBC-reduced RBC units in VATS were lighter in weight than the non-WBC-reduced units (median weight: WBC-reduced, 300 g; non-WBC-reduced, 330 g; p<0.0001). After the enrollment transfusion, 258 WBC-reduced arm patients received 1279 units of RBCs (average, 5.0 units/patient, median, 2 units) while 262 patients in the non-WBC-reduced arm received 1111 RBCs (4.2 units/patient; median, 2 units). The number of units transfused for anemia was slightly greater in the WBC-reduced arm, but the difference was not significant (p = 0.41). Similarly, the rate of RBC use was somewhat higher in the WBC-reduced arm, but the difference was not significant (p = 0.14). The median was 2.3 units per patient per year of follow-up in the WBC-reduced arm; the median in the non-WBC-reduced arm was 1.2 units., Conclusion: This study confirms that WBC-reduced RBC units are significantly lighter in weight than non-WBC-reduced RBCs. However, in the setting of a large, randomized, blinded study of transfusion for anemia, the smaller size of the WBC-reduced RBC units had no significant effect on the number of RBC units transfused or on the rate at which RBC units were used. In this study, the frequency of blood transfusion may have had a greater relationship to the frequency of routine, scheduled appointments or transfusion orders for a specified Hb trigger than to the actual Hb content of the unit.

The phenomenon of microchimerism and its relationship to long-term graft tolerance is an area of active study. The ability to establish a tolerant state has been enhanced with current immunosuppressive drugs and emerging therapies such as donor HPC infusions. An undesirable outcome of host-donor WBC interaction is GVHD. GVHD is a rare complication reported most frequently in liver transplantation. Two cases of GVHD reported in recipients of organs from donors homozygous for a shared HLA haplotype would support a policy of avoiding the use of these donors. TA-GVHD is very rare in solid organ transplant recipients, with only four published cases; only two had convincing supportive evidence and one of these had an underlying hematologic abnormality. These few cases do not support a policy of routine irradiation of cellular blood components for all solid organ transplant recipients. The use of donor HPC infusions to enhance chimerism and graft tolerance has increased the number of GVHD cases observed (usually mild) and decreased the severity and number of rejection episodes. The long-term effects of donor HPC infusions on graft survival is under investigation.

Background: WBC-reduced platelet components may be prepared by filtration or apheresis processing. Both methods have previously been shown to result in a residual total WBC content <5 x 10(6) per component. However, there may be differences in the efficacy of these techniques for removing certain WBC subsets., Study Design and Methods: Two multiparameter flow cytometric assays were developed and validated to perform WBC analysis on WBC-reduced platelets collected with two apheresis instruments (Amicus and COBE Spectra) and on 6 units of filtered pooled random-donor platelet concentrates., Results: All components contained <1 x 10(5) WBCs. The COBE Spectra and Amicus apheresis platelet components contained more WBCs than did filtered pooled platelets (p<0.05). Lymphocytes (T and B), monocytes, and granulocytes were identified in all components. Granulocyte content was lowest in the Amicus components and filtered pools. Monocytes were lowest in filtered pools. Amicus platelet components had fewer granulocytes and monocytes than the COBE Spectra platelets. Amicus and COBE Spectra components contained more lymphocytes than the filtered pools., Conclusion: Multiparameter flow cytometry can be used to quantify and characterize WBCs in WBC-reduced platelet components. WBC reduction by filtration or apheresis was highly effective. WBCs from each subset were identified in all components. Although filtered pools had the lowest numbers of WBCs, the very low numbers observed in all components suggests that the absolute quantitative differences in WBC subset content are of questionable clinical significance.

Background: Single-donor platelets (SDPs) are frequently preferred over pooled random-donor platelets (RDPs) to reduce donor exposures and the risk for virus transmission or HLA alloimmunization. Transfusion-associated virus-transmission risks have significantly decreased, which suggests that white cell reduction by filtration eliminates any difference in the risk of alloimmunization in transfused leukemic patients. Health care reform pressures of make it appropriate to examine the cost-effectiveness of SDPs versus RDPs in reducing donor exposures., Study Design and Methods: A decision analysis model was developed and sensitivity analyses were used to assess the incremental cost (dollars/quality-adjusted life-year) associated with the use of SDPs versus RDPs for adult patients undergoing hematopoietic progenitor cell transplantation or primary coronary artery bypass grafting (CABG)., Results: Among transplant patients, the incremental cost of choosing SDPs as opposed to RDPs ranged from $168,700 to $519,822 per quality-adjusted life-year. For patients undergoing primary CABG, the incremental cost was $192,415 (females) and $216,280 (males). Variations in the cost differential between SDPs and RDPs, the number of random-donor platelets in the RDP, and the risk of bacterial sepsis markedly influenced cost-effectiveness. The model was minimally affected by variations in the risks of transmission of HIV and hepatitis B and C, and human T-lymphotropic viruses., Conclusion: In comparison with other accepted medical interventions, the use of SDPs as opposed to RDPs may not be a cost-effective method of reducing donor exposures in the adult patient populations studied. SDPs were more cost-effective in patients undergoing primary CABG than in leukemia patients undergoing hematopoietic progenitor cell transplantation. Regardless of diagnosis, decreasing the acquisition cost differential would have the greatest impact on improving the cost-effectiveness of SDPs, as opposed to RDPs, to decrease donor exposures.

Pressures to reduce costs are forcing hospitals to examine alternative delivery systems for transfusion services. An outsourcing arrangement for the transfusion service can be an attractive option, providing benefits not only in terms of economics, but also in terms of quality and medical support. Successful centralized testing models in Pittsburgh and Seattle have demonstrated the feasibility of this approach. When properly implemented, an outsourcing arrangement for transfusion services can improve patient care and reduce costs.

Objectives: Transfusion-related acute lung injury (TRALI) following random donor platelet (RDP) transfusion is a rare complication of transfusion without any well-documented case reported in the English language literature. We describe 2 patients in whom TRALI occurred following RDP transfusion., Methods: Conventional clinical and laboratory methods., Results: Both patients developed acute shortness of breath 30-60 min after completion of RDP transfusion and required mechanical ventilatory support. Chest X-ray (CXR) in both cases revealed bilateral pulmonary infiltrates. Patient 1 required vasopressors for hypotension. Right heart catheterization ruled out fluid overload. Patient 2 remained hemodynamically stable. Both patients improved rapidly with continued respiratory support and were extubated within 48 h. CXR at this time showed clearing of infiltrates. In both cases a granulocyte antibody was identified in the plasma of a platelet donor supporting the diagnosis of TRALI., Conclusions: In suspected cases of TRALI. HLA and granulocyte antibody testing is indicated for the recipients and for donors of implicated components. Implicated donors need not be excluded from the donor pool, but can be used for fractionated plasma and plasma-free components.

The Reference Laboratory Alliance (RLA) in Pittsburgh is an example of multiple hospital laboratories integrated for the purpose of delivering competitive outpatient laboratory services in a managed-care environment. Developed in 1994, the RLA model includes a "virtual" core laboratory (comprising four tertiary care centers of excellence) and a distributed network of more than 30 community hospitals. Linked through information systems, logistics, and an extensive committee structure, the RLA is capable of delivering a "seamless" service to the region's managed-care organizations. In its first full year of operation, the RLA is expected to shift between $12 and $15 million worth of laboratory activity back into the community's hospitals. Through its pathology component, the RLA is now actively engaged in redefining the role of the clinical laboratory in the managed-care environment.

Background: Transfusing fresh autologous blood during cardiac surgery may improve hemostasis and decrease the need for transfusion., Study Design and Methods: A prospective randomized study was performed with fresh whole blood (WB) obtained by intraoperative hemodilution (IH) and with platelet-rich plasma (PRP) obtained by perioperative apheresis from adult cardiac surgery patients., Results: Seventy patients were randomly assigned to three arms: 24 to the PRP arm, 18 to the IH arm, and 28 to serve as controls. A mean of 924 +/- 130 mL of WB was collected from the IH group, and a mean of 650 +/- 124 mL of PRP was collected from the PRP group (mean, 1.42 +/- 0.74 x 10(11) platelets); these components were transfused after bypass. Preoperative measures were similar among groups. Intraoperatively, the groups did not differ in bypass time, estimated blood loss, number of transfusions, or proportion receiving transfusion(s). Postoperatively, control patients had more mediastinal drainage (736 mL vs. 476 mL [IH] and 463 mL [PRP]; p = 0.014), but there was no difference in the proportion of patients requiring red cell transfusion (p = 0.87), the hemoglobin at discharge (p = 0.20), or the length of hospitalization (p = 0.57)., Conclusion: Although a hemostatic benefit manifested as reduced postoperative bleeding was observed, this study does not support the use of fresh blood components obtained by IH or PRP collection during low-risk cardiac surgery. Additional studies are needed to assess whether more aggressive component collection or the use of these techniques in high-risk cases may have a greater impact on clinical outcome variables, including transfusion.

The role of preformed xenoreactive antibodies in xenograft recipients is unknown. Humans and baboons possess red cell agglutinating activity associated with isohemagglutinins and heteroagglutinins (HA). We examined the role of HA in two patients who received ABO-identical baboon livers. Human antibaboon HA were assessed by correlating serial titers with studies for rejection. Serial direct antiglobulin testing (DAT) was used to detect baboon antihuman HA, potentially produced by transplanted passenger lymphocytes. Patient 1 survived 70 days. The human antibaboon HA titers remained essentially unchanged from preoperative values. Although hyperacute rejection did not occur, and there was only mild cellular rejection, liver function was suboptimal. Postreperfusion immunoglobulin and complement deposition and histologic changes suggested complement-mediated injury. DAT testing was negative except for passively acquired anti-A from transfusion. At autopsy there was marked bile stasis, but no rejection. Patient 2 survived 26 days with essentially unchanged HA titers until preterminal. Although there was no hyperacute rejection and only mild humoral rejection (without cellular rejection), suboptimal liver function and bile stasis were again noted. Postreperfusion immunoglobulin and complement deposition again suggested complement-mediated injury. DAT testing was negative. At autopsy there was no rejection. Human antibaboon HA do not appear to be associated with hyperacute or cellular rejection, but their role in the complement-mediated injury, suspected in both cases, cannot be definitively excluded. Baboon antihuman HA were not detected in either patient.

The development and expansion of the CTS in Pittsburgh shows the feasibility of this transfusion medicine delivery system. Few of the changes driven by health care reform both improve patient care and reduce costs. When properly implemented, a CTS achieves these objectives, benefits the community as a whole, and enhances the role of transfusion medicine specialists and the blood center in the region.

Intraoperative hemodilution (IH) and autologous platelet rich plasma (APRP) collection are two techniques used to obtain autologous blood in the operating room. They have been used to reduce allogeneic blood exposure in patients undergoing both cardiac and non-cardiac surgery. Both components have the advantage of providing fresh blood not subject to the storage lesion. Whole blood (IH) or platelet rich plasma is removed from the patient as anesthesia is induced and replaced with acellular fluid. The blood is transfused back after bypass or major bleeding has ceased. Although used commonly, the data supporting the use of either technique are controversial. Methodologic problems which have confounded studies evaluating their utility include: poorly defined transfusion criteria, concommitant use of other blood conservation techniques (i.e. cell salvage, pharmacologic agents, hypothermia, controlled hypotension) and changing transfusion practices with greater tolerance of normovolemic anemia. Randomized controlled studies with well defined up to date transfusion criteria are needed to identify patients likely to benefit from these techniques.

Transplantation of ABO-unmatched livers has been associated with the development of donor-derived antibody (DDAb) and hemolysis. Nine (22%) of 41 consecutive patients undergoing liver transplantation at our institution received 10 ABO-unmatched livers. Five (56%) of nine patients developed DDAbs and hemolysis. All five patients were group A1 and received group O livers. DDAbs appeared a mean of 9.2 +/- 2.8 (1 SD) days after surgery and persisted for 15.2 +/- 10.3 days. All patients with DDAbs developed hemolysis. During the period when DDAbs were demonstrable, the hemoglobin dropped by a mean of 4.8 g per dL (48 g/L), and the patients were transfused with a mean of 7.8 +/- 2.3 units of group O red cells. One patient with hemolysis underwent exchange transfusion for acute renal failure. Patients with hemolysis required significantly more red cells postoperatively (15.0 vs. 6.9 units, p = 0.04) than did ABO-matched patients. None of the parameters examined (age, recipient or donor gender, secretor status, rejection, or donor isoagglutinin titers) were predictive of DDAb or hemolysis, although hemolysis occurred in three of four cases in which donor serum IgG anti-A titers were > or = 128, as opposed to one of four cases in which titers were < 128. Because recipients of ABO-unmatched livers are at high risk for transiently developing DDAb and hemolysis with associated morbidity, the prophylactic use of donor-type red cells for surgery and after operation is justified.

Activation of platelets may be measured by using the monoclonal antibody S12 to detect alpha granule membrane protein 140 (GMP-140) antigen expressed only on activated platelets. S12 was used to measure activation of apheresis platelet concentrates by flow cytometry. Eleven platelet concentrates obtained by one method and nine obtained by another were analyzed 4 hours after collection. Means +/- 1SD of 25.3 +/- 14.8 percent and 28.9 +/- 11.6 percent, respectively, of platelets were found to be activated (range, 4.8-53.1%). Six of the platelet concentrates obtained by the second method were filtered. There was a drop of 17.8 percent (range, 10-25%) in the mean total number of platelets recovered after filtration, but there was no difference in the proportion of activated platelets measured immediately before and after filtration. The 1-hour posttransfusion platelet count increment was obtained after 12 of these apheresis platelet concentrates were transfused to eight patients who were not refractory from either a clinical or alloimmune standpoint. There was a significant inverse correlation between the platelet count increment and the proportion of activated platelets in the component (p less than 0.05, r = -.58). These data suggest that apheresis platelet concentrates with more activated platelets have a reduced 1-hour recovery. Filtration did not enhance activation or selectively remove activated platelets. Expression of GMP-140 may serve as a useful quality control measurement.

The bulk of experimental and clinical data support the theory that homologous transfusion causes significant down-regulation of immunologic functions in a number of settings. These changes in immune function may account for the beneficial associations of transfusion with increased renal allograft survival, and decreased recurrence in Crohn's disease. Conversely, these transfusion-induced effects may be responsible in part for the deleterious association of homologous transfusion with increased cancer recurrence, and increased posttransfusion bacterial and viral infection rates. Host defenses against malignancy and infection may in some instances be severely compromised by transfusions of homologous blood, but the circumstances under which this occurs need to be better defined. Likewise, the hypothesis that modification of blood components to contain fewer leukocytes or less plasma might ameliorate these effects is attractive, but little or no data exist to support or refute it. Future clinical studies will no doubt address these issues.

Cryoprecipitate is frequently administered as treatment for hemostatic defects in patients with uremia. The only published data supporting this approach however, involves seven patients described by Janson and colleagues in whom bleeding times were shortened and bleeding complications reduced after cryoprecipitate infusion. We retrospectively reviewed our institution's experience with cryoprecipitate in this setting. Five patients had sufficiently complete data for evaluation of the efficacy of therapy with cryoprecipitate, including pretreatment bleeding time greater than 15 minutes, normal coagulation studies, and platelet count greater than 100,000/microliters. Two patients had normalization of their bleeding time and a favorable clinical outcome after cryoprecipitate infusion. Three patients failed to shorten their bleeding time after cryoprecipitate infusion or, in one case, multiple infusions. One of these latter patients had correction of his abnormal bleeding time after subsequent administration of deamino-8-D-arginine vasopressin (DDAVP). We conclude that the hemostatic response to cryoprecipitate therapy is variable, and that cryoprecipitate therapy does not achieve restoration of normal hemostasis in some patients with uremic bleeding.

Homologous blood transfusion has been implicated as a modulator of the host immune system in a number of clinical settings. Improved renal allograft survival is observed in patients receiving pretransplant transfusions. Decreased recurrence of active inflammatory bowel disease has been recently reported in transfused patients with Crohn's disease. Conversely, deleterious immunomodulatory effects of transfusion may explain the association between transfusion and increased susceptibility to cancer recurrence and bacterial and viral infection. Clinical studies regarding cancer recurrence and transfusion are retrospective and conflicting. There is epidemiologic evidence for more rapid progression of HIV-1 infection in heavily transfused patients. Studies on transfused surgical patients have shown transfusion to be associated with an increased frequency of postoperative bacterial infections. Some studies have come to different conclusions. These investigators have suggested that transfusion may represent a surrogate marker for other risk factors for infection. Animal models designed to control for confounding factors have supported an association between transfusion and bacterial infection severity in most, but not all, reports. Attempts to define the immunologic alterations associated with transfusion have revealed a generalized impairment of cellular immunity in both humans and animals. Although the preponderance of data supports an association between perioperative transfusion and increased susceptibility to postoperative bacterial infection, it is not certain to what extent this relationship constitutes cause and effect.