Immunoglobulin G subclass responses to cytomegalovirus in seropositive patients after transfusion

The immunoglobulin G subclass responses to cytomegalovirus (CMV) after red cell (RBC) transfusion were studied in 26 seropositive surgery patients and 34 transfused seropositive oncology patients. Also included as controls were 18 surgical patients who received no RBCs during surgery. None of the 78 patients studied had IgG2 to CMV before or after transfusion. The absence of a total IgG response to CMV after transfusion could not be attributed to preexisting deficiencies in one or more subclasses, because all 78 patients had similar levels of IgG1, IgG3, and IgG4 to CMV before transfusion. Discriminant analysis was used for statistical evaluation of the combined CMV subclass responses in each patient and the individual subclass responses. Individual patients responded to CMV antigens with an increase in concentration in any of the three subclasses or any combination of the subclasses, excluding IgG2. IgG subclass analysis showed that 10 of 27 patients who did not respond with at least a fourfold total IgG titer rise had a significant increase in IgG subclass antibodies to CMV. Three of 33 patients with at least a fourfold total IgG titer rise lacked a subclass response. These results suggest that the measurement of IgG subclasses may be a sensitive indicator of immune response to CMV.     

Rapid clearance of transfused murine red blood cells is associated with recipient cytokine storm and enhanced alloimmunogenicity

BACKGROUND: Fourteen‐day stored red blood cells (RBCs) containing an RBC‐specific transgenic antigen (HOD) induce a recipient proinflammatory cytokine storm and are significantly more immunogenic compared to fresh RBCs. Given that recipient mice clear transfused stored RBCs more rapidly than fresh RBCs, we hypothesized that rapid RBC clearance was associated with adverse transfusion outcomes. STUDY DESIGN AND METHODS: HOD RBCs were treated by two distinct methods known to lead to rapid posttransfusion RBC clearance: phenylhydrazine or heat. HOD antigen expression was analyzed on the treated cells before transfusion, and RBC recovery, recipient cytokine response, and recipient anti‐HOD alloimmunization response were measured after transfusion. RESULTS: Phenylhydrazine and heat treatment each led to near complete RBC clearance in recipients by 24 hours posttransfusion, without significantly altering HOD antigen expression on the transfused RBCs. Recipients of phenylhydrazine‐ or heat‐treated RBCs had elevated circulating levels of keratinocyte‐derived chemokine/CXCL‐1, monocyte chemoattractant protein‐1, and interleukin‐6 after transfusion. Furthermore, phenylhydrazine‐ or heat‐treated RBCs were significantly more immunogenic than control RBCs, with a mean 25.1‐ and 10.3‐fold enhancement, respectively, of anti‐HOD alloimmunization magnitude by flow cytometric crossmatch. CONCLUSIONS: Three separate insults to RBCs (storage, phenylhydrazine, or heat treatment) result in rapid posttransfusion clearance, with a recipient proinflammatory cytokine storm and enhanced alloimmunogenicity. These data are consistent with the hypothesis that rapid clearance of RBCs is causally involved in these outcomes and suggest that human donor RBCs with favorable posttransfusion clearance profiles may be less immunogenic.     

Transfusion of fresh murine red blood cells reverses adverse effects of older stored red blood cells

BACKGROUND: Although a subset of recent studies have suggested that red blood cell (RBC) storage length is associated with adverse patient outcomes, others have shown no such relationship. Adults may be transfused with RBC units of different storage lengths, and existing studies do not take into consideration that fresh RBCs may alter responses to concurrently transfused stored RBCs. To test this possibility, we utilized a murine model and investigated transfusion outcomes of fresh, stored, or fresh‐plus‐stored RBCs. STUDY DESIGN AND METHODS: Fresh, 14‐day‐stored or fresh plus 14‐day‐stored leukoreduced RBCs from HOD‐transgenic donors (with RBC‐specific expression of hen egg lysozyme, ovalbumin, and human Duffy^b) were transfused into naïve C57BL/6 recipients. Serum cytokines and anti‐HOD alloimmunization were evaluated after transfusion. RESULTS: In six of six experiments (n = 90 mice total), a proinflammatory serum cytokine storm of interleukin‐6, keratinocyte‐derived chemokine/CXCL1, and monocyte chemoattractant protein‐1 was observed in transfusion recipients of stored but not fresh RBCs, along with high degrees of anti‐HOD alloimmunization. However, concurrent transfusion of fresh HOD RBCs along with stored HOD RBCs significantly decreased these adverse outcomes (p < 0.05). CONCLUSIONS: These results are consistent with fresh murine HOD RBCs losing protective properties during storage, and introduce a previously unrecognized variable in RBC storage studies. If translatable to humans, uniform “old blood” groups may be needed in future clinical studies to more accurately investigate the biologic effects of older RBC units.     

Alloimmunization to transfused HOD red blood cells is not increased in mice with sickle cell disease

BACKGROUND: Increased rates of red blood cell (RBC) alloimmunization in patients with sickle cell disease may be due to transfusion frequency, genetic predisposition, or immune dysregulation. To test the hypothesis that sickle cell pathophysiology influences RBC alloimmunization, we utilized two transgenic mouse models of sickle cell disease. STUDY DESIGN AND METHODS: Transgenic sickle mice, which express human α and β^S globin, were transfused with fresh or 14‐day‐stored RBCs containing the HOD (hen egg lysozyme, ovalbumin, and human Duffy^b) antigen; some recipients were inflamed with poly(I : C) before transfusion. Anti‐HOD alloantibody responses were subsequently measured by enzyme‐linked immunosorbent assay and flow crossmatch; a cohort of recipients had posttransfusion serum cytokines measured by bead array. RESULTS: Both Berkeley and Townes homozygous (SS) and heterozygous (AS) mice had similar rates and magnitude of anti‐HOD RBC alloimmunization after fresh HOD RBC transfusion compared with control animals; under no tested condition did homozygous SS recipients make higher levels of alloantibodies than control animals. Unexpectedly, homozygous SS recipients had blunted cytokine responses and lower levels of anti‐HOD alloantibodies after transfusion of 14‐day stored RBCs, compared with control animals. CONCLUSIONS: In sum, homozygous β^S expression and the ensuing disease state are not alone sufficient to enhance RBC alloimmunization to transfused HOD RBCs in two distinct humanized murine models of sickle cell disease under the conditions examined. These data suggest that other factors may contribute to the high rates of RBC alloimmunization observed in humans with sickle cell disease.     

Antigen copy number and antibody dose can determine the outcome of erythrocyte alloimmunization inducing either antibody-mediated immune suppression or enhancement in a murine model

Background

The administration of anti-D for the prevention of hemolytic disease of the fetus and newborn is one of the most successful clinical uses of the phenomenon of antibody-mediated immune suppression (AMIS). However, despite adequate prophylaxis, failures can still occur in the clinic and are poorly understood. Recently, the copy number of red blood cell (RBC) antigens has been shown to influence immunogenicity in the context of RBC alloimmunization; however, its influence on AMIS remains unexplored.

Study Design and Methods

RBCs expressing approximately 3,600 and approximately 12,400 copy numbers of surface-bound hen egg lysozyme (HEL), named respectively HEL^med-RBCs and HEL^hi-RBCs, and selected doses of a polyclonal HEL-specific IgG were transfused into mice. Recipient HEL-specific IgM, IgG, and IgG subclass responses were evaluated by ELISA.

Results

Antigen copy number affected the antibody dose required for AMIS induction with higher antigen copy numbers requiring larger doses of antibody. For instance, 5 μg of antibody caused AMIS for HEL^med-RBCs but not HEL^hi-RBCs, while 20 μg induced significant suppression for both HEL-RBCs. Overall, increasing amounts of the AMIS-inducing antibody were associated with a more complete AMIS effect. In contrast, the lowest tested doses of the AMIS-inducing IgG led to evidence of enhancement at the IgM and IgG levels.

Discussion

The results demonstrate that the relationship between antigen copy number and antibody dose can influence the outcome of AMIS. Further, this work suggests that the same antibody preparation can induce both AMIS and enhancement but that the outcome may depend on the quantitative interrelationship of antigen–antibody binding.     

The production of red blood cell alloantibodies in mice transfused with blood from transgenic Fyb-expressing mice

BACKGROUND: A murine model would be useful to identify which immune mechanisms could be manipulated to treat or prevent red blood cell (RBC) alloimmunization in patients who become sensitized to multiple or widely expressed antigens. STUDY DESIGN AND METHODS: Transgenic mice (B6CBAF1/J-Tg-Fy(b)) expressing the human Fy(b) antigen of the Duffy (Fy) blood group were donors. Recipient B6CBA-F1 mice received four weekly intravenous (IV) transfusions: either 0.3 mL of washed buffy coat-depleted RBCs or 0.3 mL of RBCs with spleen cells. Titers of immunoglobulin M (IgM) and immunoglobulin G (IgG) were measured in recipient serum samples by flow cytometry with RBCs from donor mice as target cells. Recipient serum samples were also tested against human RBCs of various Fy phenotypes. Additionally, RBC survival studies were performed in alloimmunized mice utilizing biotin-labeled Fy(b) transgenic mouse RBCs. RESULTS: B6CBA-F1 mice receiving washed buffy coat-depleted RBCs first made IgM, followed by IgG alloantibodies to transgenic mouse Fy(b)-positive RBCs. Recipients of Fy(b)-positive RBCs mixed with spleen cells also produced IgM and IgG alloantibodies, but at a slower rate than recipients of washed buffy coat-depleted RBCs. Serum samples showed specificity for Fy3, Fy(b), and Fy6. Decreased survival of transfused RBCs was evident at 24 hours after transfusion. CONCLUSIONS: It is possible to elicit the formation of anti-Fy alloantibodies by IV transfusion in mice that lack Fy antigens. The transfusion of RBCs alone was adequate to stimulate alloantibody production in B6CBA-F1 recipient mice. The survival of transfused Fy(b)-positive RBCs is diminished in sensitized mice. This model will be useful in further studies of RBC alloimmunization.     

Age of red blood cells and outcome in acute kidney injury

Introduction

Transfusion of red blood cells (RBCs) and, in particular, older RBCs has been associated with increased short-term mortality in critically ill patients. We evaluated the association between age of transfused RBCs and acute kidney injury (AKI), hospital, and 90-day mortality in critically ill patients.

Methods

We conducted a prospective, observational, predefined sub-study within the FINNish Acute Kidney Injury (FINNAKI) study. This study included all elective ICU admissions with expected ICU stay of more than 24 hours and all emergency admissions from September to November 2011. To study the age of RBCs, we classified transfused patients into quartiles according to the age of oldest transfused RBC unit in the ICU. AKI was defined according to KDIGO (Kidney Disease: Improving Global Outcomes) criteria.

Results

Out of 1798 patients, 652 received at least one RBC unit. The median [interquartile range] age of the oldest RBC unit transfused was 12 [11-13] days in the freshest quartile and 21 [17-27] days in the quartiles 2 to 4. On logistic regression, RBC age was not associated with the development of KDIGO stage 3 AKI. Patients in the quartile of freshest RBCs had lower crude hospital and 90-day mortality rates compared to those in the quartiles of older blood. After adjustments, older RBC age was associated with significantly increased risk for hospital mortality. Age, Simplified Acute Physiology Score II (SAPS II)-score without age points, maximum Sequental Organ Failure Assessment (SOFA) score and the total number of transfused RBC units were independently associated with 90-day mortality.

Conclusions

The age of transfused RBC units was independently associated with hospital mortality but not with 90-day mortality or KDIGO stage 3 AKI. The number of transfused RBC units was an independent risk factor for 90-day mortality.     

Mathematical calculation of lifespan of transfused RBCs in sickle cell disease patients

Background

Transfusion of donor red blood cells (RBCs) remains an important part of management of sickle cell disease (SCD). However, the survival characteristics of transfused donor RBCs in SCD patients have not been well studied. We sought to calculate survival kinetics of transfused RBCs in SCD patients since it is unclear whether transfused RBCs get destroyed at faster rate as innocent bystander or persist longer due to decreased destruction capacity such as functional splenectomy.

IMMUNOHEMATOLOGY: Storage of murine red blood cells enhances alloantibody responses to an erythroid‐specific model antigen

BACKGROUND: Red blood cell (RBC) alloimmunization can be a serious complication of blood transfusion, but factors influencing the development of alloantibodies are only partially understood. Within FDA‐approved time limits, RBCs are generally transfused without regard to length of storage. However, recent studies have raised concerns that RBCs stored for more than 14 days have altered biologic properties that may affect medical outcomes. To test the hypothesis that storage time alters RBC immunogenicity, we utilized a murine model of RBC storage and alloimmunization. STUDY DESIGN AND METHODS: Blood from transgenic HOD donor mice, which express a model antigen (hen egg lysozyme [HEL]) specifically on RBCs, was filter leukoreduced and stored for 14 days under conditions similar to those used for human RBCs. Fresh or 14‐day‐stored RBCs were transfused into wild‐type recipients. The stability of the HOD antigen and posttransfusion RBC survival were analyzed by flow cytometry. RBC alloimmunization was monitored by measuring circulating anti‐HEL immunoglobulin levels. RESULTS: Transfusion of 14‐day‐stored, leukoreduced HOD RBCs resulted in 10‐ to 100‐fold higher levels of anti‐HEL alloantibodies as detected by enzyme‐linked immunosorbent assay than transfusion of freshly collected, leukoreduced RBCs. RBC expression of the HOD antigen was stable during storage. CONCLUSIONS: These findings demonstrate that HOD murine RBCs become more immunogenic with storage and generate the rationale for clinical trials to test if the same phenomenon is observed in humans. Length of storage of RBCs may represent a previously unappreciated variable in whether or not a transfusion recipient becomes alloimmunized.     

A newly developed gel centrifugation test for quantification of RBC-bound IgG antibodies and their subclasses IgG1 and IgG3: comparison with flow cytometry

BACKGROUND: Novel gel centrifugation test (GCT) cards were evaluated with respect to their ability to estimate the quantity of IgG on RBCs and the determination of the IgG subclasses IgG1 and IgG3. STUDY DESIGN AND METHODS: In 65 patients with a positive DAT, the amount of IgG-gamma-, IgG1, and IgG3 on RBCs was examined by use of GCT cards and flow cytometry (FC) in parallel. The results were correlated with the presence or absence of hemolysis. In addition, D+ RBCs were studied after sensitization with anti-D sera from 22 alloimmunized pregnant women. RESULTS: The amount of IgG on the RBCs as determined by GCT dilution cards correlated with FC (r=0.70, p < 0.0001). IgG subclass results as determined by GCT IgG subclass cards were confirmed by FC in 14 cases with an anti-IgG-gamma-chain titer > or =300, whereas IgG subclass cards were not suitable in cases with anti-IgG-gamma-chain titers less than 300. In 44 patients with 2+ or 3+ DAT in the GCT and anti-IgG-gamma-chain titer < or =30, no hemolysis was observed, whereas hemolysis occurred in 13 of 14 patients with an anti-IgG-gamma-chain titer > or =300. GCT data obtained by IATs with anti-D sera were concordant with FC results. CONCLUSION: There is a correlation between the amount of RBC-bound IgG and immune hemolysis. The GCT cards that detect the anti-IgG-gamma-chain may be useful to predict hemolysis in patients with a 2+ or 3+ DAT in the GCT. The diagnostic value of GCT cards for IgG subclass testing should be investigated further.     

Red blood cell transfusion and increased length of storage are not associated with deep vein thrombosis in medical and surgical critically ill patients: a prospective observational cohort study

Introduction  

With prolonged storage times, cell membranes of red blood cells (RBCs) undergo morphologic and biochemical changes, termed 'RBC storage lesions'. Storage lesions may promote inflammation and thrombophilia when transfused. In trauma patients, RBC transfusion was an independent risk factor for deep vein thrombosis (DVT), specifically when RBC units were stored > 21 days or when 5 or more units were transfused. The objective of this study was to determine if RBC transfusions or RBC storage age predicts incident DVT in medical or surgical intensive care unit (ICU) patients.     

Duration of red blood cell storage is associated with increased incidence of deep vein thrombosis and in hospital mortality in patients with traumatic injuries

Introduction  

In critically ill patients the relationship between the storage age of red blood cells (RBCs) transfused and outcomes are controversial. To determine if duration of RBC storage is associated with adverse outcomes we studied critically ill trauma patients requiring transfusion.     

Timing of RhD-positive red blood cell administration is associated with D-alloimmunization in injured patients

Background

The D-alloimmunization rate in trauma patients does not appear to depend on the number of RhD-positive units transfused. The effect of the timing and pattern of RhD-positive transfusions has not been evaluated.

Methods

RhD-negative trauma patients who were transfused with RhD-positive red blood cells (RBC) or low titer group O whole blood (collectively called RBCs) on at least two separate calendar days and who had antibody detection tests performed at least 14 days after the second RhD-positive RBC transfusion without receiving RhIg were included in the analysis. Patients whose anti-D was detected within 14 days of the index RhD-positive RBC transfusion were excluded. Patient demographics and the dates of RhD-positive RBC transfusions and results of antibody detection tests performed after the index transfusion were collected on eligible patients.

Results

There were 44/61 (72.1%) patients in whom anti-D was not detected (non-alloimmunized) and 17/61 (27.9%) in whom anti-D was detected (alloimmunized). The patients had similar demographics with trends towards higher median admission heart rates and lower median admission Glasgow Coma Scale values in the alloimmunized group. Both groups received statistically identical median quantities of RhD-positive RBCs (non-alloimmunized 5 vs. alloimmunized 4 units, p = .53), however, the alloimmunized group received all their RhD-positive RBCs over a significantly shorter period of time compared to the non-alloimmunized (median 4 vs. 15 days, respectively, p = .01).

Conclusion

Receipt of all RhD-positive RBCs over a shorter period of time was associated with higher D-alloimmunization rates. These results need to be confirmed in larger studies.     

Some quantitative aspects of the human monocyte erythrophagocytosis and rosette assays

The sensitivity of peripheral blood mononuclear phagocytes (PBMPs) in the red cell (RBC) adherence and erythrophagocytosis assays were investigated using anti-D of subclasses IgG1 and IgG3. Particular emphasis was placed on identifying variability between PBMP preparations from different healthy donors. About 500 molecules of IgG1 type anti-D per RBC and about 100 molecules of IgG3 antibody per RBC were the lowest levels of sensitization which elicited a weak, positive test. Considerable variation between different preparations was seen, and it appeared that the capability of a PBMP preparation to react with weakly sensitized RBCs may not be closely related to its strength of reaction with strongly sensitized cells. PBMPs which were recovered after storage in liquid nitrogen were more reactive in both assays than freshly prepared PBMPs from the same donor. This study demonstrated the importance of weakly sensitized RBCs as part of the control system and indicated a need for caution when establishing a negative test result when the clinical significance of RBC antibody is being investigated.     

More efficient exchange of sickle red blood cells can be achieved by exchanging the densest red blood cells: An ex vivo proof of concept study

Background

In sickle cell disease (SCD), red blood cells (RBCs) containing hemoglobin S can be denser than RBCs containing wild-type hemoglobin, especially when dehydrated. We hypothesize that targeting denser RBCs during red blood cell (RBC) exchange for SCD could result in more efficient removal of dehydrated, sickled RBCs and preservation of non-sickled RBCs.

Black Hawk Down: The evolution of resuscitation strategies in massive traumatic hemorrhage

Citation

Borgman MA, Spinella PC, Perkins JG, Grathwohl KW, Repine T, Beekley AC, Sebesta J, Jenkins D, Wade CE, Holcomb JB: The ratio of blood products transfused affects mortality in patients receiving massive transfusions at a combat support hospital. J Trauma 2007, 63: 805–813 [1].

Background

Patients with severe traumatic injuries often present with coagulopathy and require massive transfusion. The risk of death from hemorrhagic shock increases in this population. To treat the coagulopathy of trauma, some have suggested early, aggressive correction using a 1:1 ratio of plasma to red blood cell (RBC) units.

Methods

Objective

To determine whether the ratio of plasma to RBCs transfused would affect survival by decreasing death from hemorrhage.

Design

Retrospective chart review.

Setting

United States Army combat support hospital in Iraq.

Subjects

246 patients who received a massive transfusion (≥10 units of RBCs in 24 hours) from November 2003 to September 2005. Three groups of patients were constructed according to the plasma to RBC ratio transfused during massive transfusion.

Intervention

None.

Outcome

Hospital mortality rates and the cause of death were compared among groups. Multivariable logistic regression was used to determine the independent association between plasma to RBC ratio and hospital mortality.

Results

For the low ratio group the plasma to RBC median ratio was 1:8 (interquartile range (IQR), 0:12–1:5), for the medium ratio group, 1:2.5 (IQR, 1:3.0–1:2.3), and for the high ratio group, 1:1.4 (IQR, 1:1.7–1:1.2) (p < 0.001). Median Injury Severity Score (ISS) was 18 for all groups (IQR, 14–25). For low, medium, and high plasma to RBC ratios, overall mortality rates were 65%, 34%, and 19%, (p < 0.001); and hemorrhage mortality rates were 92.5%, 78%, and 37%, respectively (p < 0.001). Upon logistic regression, plasma to RBC ratio was independently associated with survival (odds ratio 8.6, 95% confidence interval 2.1–35.2).

Conclusion

In patients with combat-related trauma requiring massive transfusion, a high 1:1.4 plasma to RBC ratio is independently associated with improved survival to hospital discharge, primarily by decreasing death from hemorrhage. For practical purposes, massive transfusion protocols should utilize a 1:1 ratio of plasma to RBCs for all patients who are hypocoagulable with traumatic injuries.     

Life and Death of Glucose-6-Phosphate Dehydrogenase (G6PD) Deficient Erythrocytes – Role of Redox Stress and Band 3 Modifications

Summary

G6PD catalyzes the first, pace-making reaction of pentosephosphate cycle (PPC) which produces NADPH. NADPH maintains glutathione and thiol groups of proteins and enzymes in the reduced state which is essential for protection against oxidative stress. Individuals affected by G6PD deficiency are unable to regenerate reduced glutathione (GSH) and are undefended against oxidative stress. G6PD deficiency accelerates normal senescence and enhances the precocious removal of chronologically young, yet biologically old cells. The term hemolytic anemia is misleading because RBCs do not lyse but are removed by phagocytosis. Acute hemolysis by fava bean ingestion in G6PD deficient individuals (favism) is described being the best-studied natural model of oxidant damage. It bears strong analogies to hemolysis by oxidant drugs or chemicals. Membrane alterations observed in vivo during favism are superimposable to changes in senescent RBCs. In summary, RBC membranes isolated from favic patients contained elevated amounts of complexes between IgG and the complement fragment C3b/C3c and were prone to vesiculation. Anti-band 3 IgG reacted to aggregated band 3-complement complexes. In favism extensive clustering of band 3 and membrane deposition of hemichromes were also observed. Severely damaged RBCs isolated from early crises had extensive membrane cross-bonding and very low GSH levels and were phagocytosed 10-fold more intensely compared to normal RBCs.KeyWords: G6PD, G6PD deficiency, Band 3, Hemolysis, Favism     

Cytomegalovirus infections in seropositive patients after transfusion. The effect of red cell storage and volume

Antibody responses to cytomegalovirus (CMV) after red cell (RBC) transfusion were studied in 84 seropositive surgery patients and 82 seropositive oncology patients. The surgery patients were randomized to receive RBCs stored either 3 to 8 or 20 to 42 days after donation. Of 38 patients receiving RBCs stored 8 days or less, 3 developed a rise in titer (4-fold increase) of IgG antibody to CMV 8 to 12 weeks after transfusion. This rate of response (8%) did not differ significantly (p = 0.23) from that (16%) in the 46 patients receiving RBCs stored 20 to 42 days. Seropositive oncology patients were randomized to receive RBCs from seronegative or random donors. Five (19%) of 27 oncology patients receiving seronegative RBCs and 13 (23%) of 55 patients receiving random RBCs (mean, 2 seropositive RBC units/patient) developed a rise in titer of antibody to CMV. No CMV morbidity occurred in either patient group. For both patient groups, a rise in titer of antibody to CMV was associated with the number of transfused RBC units. These results confirm that CMV-seronegative RBCs are unnecessary for infrequently transfused seropositive patients. They also suggest that multiple transfusions of stored RBCs are as immunosuppressive as multiple transfusions of RBCs used within a few days after donation.     

Transfusion of ABO-group identical red blood cells following uncrossmatched transfusion does not lead to higher mortality in civilian trauma patients

Background

Questions persist about the safety of switching non-group O recipients of group O uncrossmatched red blood cells (RBC) or low titer group O whole blood (LTOWB) to ABO-identical RBCs during their resuscitation.

Methods

The database of an earlier nine-center study of transfusing incompatible plasma to trauma patients was reanalyzed. The patients were divided into three groups based on 24-h RBC transfusion: (1) group O patients who received group O RBC/LTOWB units (control group, n = 1203), (2) non-group O recipients who received only group O units (n = 646), (3) non-group O recipients who received at least one unit of group O and non-group O units (n = 562). Fixed marginal effect of receipt of non-O RBC units on 6- and 24-h and 30-day mortality was calculated.

Results

The non-O patients who received only group O RBCs received fewer RBC/LTOWB units and had slightly but significantly lower injury severity score compared to control group; non-group O patients who received both group O and non-O units received significantly more RBC/LTOWB units and had a slightly but significantly higher injury severity score compared to control group. In the multivariate analysis, the non-O patients who received only group O RBCs had significantly higher mortality at 6-h compared to the controls; the non-group O recipients of O and non-O RBCs did not demonstrate higher mortality. At 24-h and 30-days, there were no differences in survival between the groups.

Conclusion

Providing non-group O RBCs to non-group O trauma patients who also received group O RBC units is not associated with higher mortality.     

Description of serologic features in autoimmune lymphoproliferative syndrome

BACKGROUND: Autoimmune lymphoproliferative syndrome (ALPS) is a recently recognized and rare disorder associated with inherited defects in the FAS: gene or other regulators of lymphocyte apoptosis. It is characterized by massive lymphadenopathy; splenomegaly; autoimmunity including episodes of immune hemolytic anemia, thrombocytopenia, and neutropenia.(1) The serologic basis for immune cytopenias associated with ALPS has not been previously characterized. STUDY DESIGN AND METHODS: RBC, granulocyte, and platelet serologies for ALPS patients and hepatitis C patients were assessed. Medical records were reviewed for clinical, immunologic, serologic, and transfusion history. Testing included: DAT; serum screening for antibodies to RBCs, granulocytes, platelets, cardiolipin, penicillin-coated RBCs, and human leukocyte antigens; antibody identification and IgG subclass; RBC phenotype. RESULTS: In a cohort of 11 patients with apoptosis defects (eight with heterozygous FAS: gene mutations); many had histories of hemolytic anemia (7), thrombocytopenia (4), and/or leukopenia (11); nine received steroid therapy, seven underwent splenectomy; five had been remotely transfused. On the basis of serologic testing even when they were clinically stable, nine had positive DATs; two had alloantibodies; 6 had IgG and/or IgM antibodies to cardiolipin; seven had platelet-directed antibodies; three had granulocyte-directed antibodies; none had HLA antibodies. CONCLUSIONS: Nearly all ALPS patients have antibodies directed against one or more hematopoietic cell lineages. Serologic testing is critical in the evaluation of these individuals and when transfusion is indicated, red cells that are matched for clinically significant C, E, and K antigens should be considered.