Clinical outcomes of ABO-incompatible RBC transfusions.

Factors that predict outcome after ABO-incompatible RBC transfusions are not well defined. We studied whether the volume of incompatible blood transfused would determine the signs and symptoms and survival outcome for ABO-incompatible RBC transfusions. We reviewed ABO-incompatible RBC transfusions from our institutions and our consultations for 35 years and from a survey of America's Blood Centers' members regarding causes, volume, signs, symptoms, and outcomes of ABO-incompatible RBC transfusions in their service areas from 1995 through 2005. All ABO-incompatible transfusions were due to error; 26 (62%) of 42 occurred at the patient's bedside. Of 36 patients who received more than 50 mL of incompatible blood, 23 (64%) manifested signs or symptoms related to the incompatible transfusion, and 6 (17)% died. Only 3 (25%) of 12 patients who received 50 mL or less of incompatible blood had associated signs or symptoms, and none died. Hypotension, hemoglobinuria, and/or hemoglobinemia were the most frequent findings in survivors and patients who died.ABO-incompatible RBC transfusion does not inevitably mean death or even occurrence of symptoms. Prompt recognition and discontinuation of the transfusion are critical because transfusing less ABO-incompatible blood may minimize signs and symptoms and may prevent death.

High-level long-term white blood cell microchimerism after transfusion of leukoreduced blood components to patients resuscitated after severe traumatic injury.

BACKGROUND: Long-term white blood cell (WBC) microchimerism (MC), of at least 2 years, has been reported in trauma patients receiving fresh nonleukoreduced (non-LR) blood. It is unknown, however, whether this occurs with LR blood products that are nearly devoid of WBCs. Twenty-seven patients transfused with LR and non-LR blood products were studied after severe traumatic injury. A secondary aim was to explore donor-recipient mixed lymphocyte reactivity in vitro. STUDY DESIGN AND METHODS: To quantify MC, allele-specific real-time polymerase chain reaction assays were developed targeting HLA Class II sequence polymorphisms. Extensive validation showed that these assays reliably detect a single copy of target sequence in a complex allogeneic background without false positivity. RESULTS: At a median follow-up of 26 months (range, 24-39 months), long-term MC was observed in 3 of 20 patients (15%) who received non-LR blood products and 2 of 7 (29%) who received LR blood products. The maximum MC ranged from 0.40 to 4.90 percent of circulating WBCs and appeared, by Class II genotype analysis, to be attributable to a single donor. CONCLUSION: It is concluded that robust levels of long-term MC, apparently traceable to a single donor, occur at similar frequency despite leukoreduction of transfused blood products. Exploratory analysis of donor-recipient mixed lymphocyte reactivity suggests that long-term MC may require a state of bidirectional tolerance before transfusion.

Microchimerism in transfused trauma patients is associated with diminished donor-specific lymphocyte response.

BACKGROUND: Blood transfusion can result in long-term survival of donor leukocyte subpopulations, or microchimerism, in the peripheral blood of injured patients. Neither injury severity nor the number of transfusions is associated with its occurrence. We sought to determine whether changes in general or antigen-specific lymphocyte activation may be associated with the subsequent development of microchimerism. METHODS: We evaluated 63 transfused trauma patients, which we compared with 10 non-transfused trauma patients and 10 healthy control subjects. Of the 63 transfused patients, 31 were known to have evidence of microchimerism at hospital discharge with real-time quantitative PCR for non-recipient HLA DR alleles. We assessed lymphocyte response to phytohemagglutinin (PHA) using blood sampled upon arrival to the hospital (before transfusion) and at discharge. We performed one-way mixed leukocyte cultures (MLC) with pre-transfusion recipient specimens to assess recipient lymphocyte response to mitomycin-C treated donor cells and vice versa. RESULTS: Lymphocyte response to PHA in microchimeric transfusion recipients was lower at admission (before transfusion) and discharge than in non-microchimeric recipients. Lymphocytes from microchimeric patients had less response to donor cells than did lymphocytes from non-microchimeric patients. Microchimeric patients also more frequently had diminished lymphocyte response to a single blood donor on MLC. CONCLUSIONS: Transfusion-associated microchimerism is correlated with diminished response to mitogen challenge as well as to specific alloantigenic challenges. This microchimerism is predated by diminished lymphocyte response to a specific blood donor in many instances. The blood donor associated with this diminished alloantigenic lymphocyte response may be the source of microchimeric cells present in the recipient.

Blood transfusion is associated with donor leukocyte microchimerism in trauma patients.

INTRODUCTION: Blood transfusion can result in survival of donor leukocyte subpopulations in the recipient. Persistence of donor leukocytes in the transfusion recipient is termed microchimerism. Microchimerism likely reflects engraftment of the recipient with donor hematopoietic stem cells and is very uncommon with transfusion for elective surgery, sickle cell anemia, thalassemia, and HIV. We have found, however, that microchimerism may be more common in trauma patients. OBJECTIVE: To determine how frequently transfusion after trauma is associated with microchimerism. METHODS: We prospectively enrolled 45 trauma patients who were transfused > or =2 units of PRBCs. We sampled blood before hospital discharge and determined microchimerism by polymerase chain reaction (PCR) analysis of specimens using quantitative allele-specific HLA DR assays to detect non-recipient alleles. Data are expressed as median with interquartile range. RESULTS: Patients had a median age of 38 (interquartile range 25, 58) years, ISS of 19 (13, 29), and mortality of 7%. Seventy-eight percent were men, and 84% had blunt trauma. Patients received a median of 6 (4, 16) (range 2, 87) units of PRBCs. Of the 45 patients, 24 (53%) had evidence of microchimerism. Compared with patients without evidence of microchimerism, these patients had no difference in mean age, gender, ISS, units of PRBCs transfused, time from transfusion to blood sampling, or proportion that underwent splenectomy. Twenty-one of the 24 patients with microchimerism had only 1 or 2 non-recipient DR alleles identified by PCR. CONCLUSIONS: Transfusion after trauma is associated with over half of recipients having evidence of microchimerism. Age, sex, ISS, and splenectomy of the recipient and the number of transfused units did not correlate with microchimerism. Because the median time from transfusion to sampling for PCR analysis was not longer in the group without microchimerism, it is unlikely microchimerism is due merely to failure of the recipient to clear transfused donor leukocytes.

TRALI: correlation of antigen-antibody and monocyte activation in donor-recipient pairs.

BACKGROUND: TRALI may be a severe reaction associated with transfusion of plasma-containing blood components. TRALI has usually been associated with antibodies against granulocytes and HLA class I antigens, but more recently with antibodies against HLA class II and monocytes. TRALI cases were investigated to determine correlation between antigen and antibody. Additionally, activation of monocytes by TRALI serums was studied. STUDY DESIGN AND METHODS: Sixteen cases of TRALI were investigated. All patients were typed for HLA antigens. Implicated donors were screened for HLA antigens and antibodies against granulocytes and monocytes. In 6 cases, recipient monocyte activation was measured in vitro after incubation with TRALI and control serums. In four cases, monocyte activation was measured after incubation of TRALI serums against a panel of monocytes of known HLA antigen type. RESULTS: In 14 of the 16 cases (87.5%), antigen-antibody correlation was identified. TRALI monocytes, incubated with implicated TRALI serum (n = 6), expressed significantly greater cytokine and tissue factor (p < 0.05, repeated-measures ANOVA) than controls. Panel monocytes incubated with TRALI serum showed increased expression of cytokine and/or tissue factor when corresponding antigen was present. CONCLUSION: In most cases of TRALI, a correlation between antigen and antibody can be identified. Activation of monocytes and their subsequent release of cytokines may play a role in the pathogenesis of TRALI.

Early diagnosis and successful treatment of a patient with transfusion-associated GVHD with autologous peripheral blood progenitor cell transplantation.

BACKGROUND: Transfusion-associated GVHD (TA-GVHD) is an uncommon complication of blood transfusion. Diagnosis of TA-GVHD is difficult, and it is usually rapidly fatal. There are few documented sur- vivors of TA-GVHD. CASE REPORT: A 61-year-old woman with chronic lymphocytic leukemia (CLL) was treated with fludarabine followed by combination chemotherapy and high-dose radioimmunotherapy and peripheral blood progenitor cell (PBPC) rescue. She was transfused with nonirradiated blood components at an outside hospital and presented 10 days later with rash, elevated liver enzymes, and progressive pancytopenia. Skin biopsy was consistent with GVHD, and HLA typing of lymphocytes from the patient demonstrated mixed chimerism. The patient was treated with solumedrol and cyclosporin A, followed by high-dose cyclophosphamide and antithymocyte globulin and autologous PBPC infusion. She had rapid engraftment, resolution of skin rash, and normalization of liver function abnormalities. She is in good health with normal blood counts and no evidence of CLL 34 months after transplantation. CONCLUSION: TA-GVHD occurs in the setting of an immunocompromised recipient receiving nonirradiated blood components. A typical presentation includes skin rash, liver function abnormalities, and pancytopenia. Demonstration of mixed chimerism by HLA typing facilitated diagnosis in this patient. High-dose immunosuppression, facilitated by the availability of autologous PBPCs, resulted in a successful outcome.

Comparative yield of HCV RNA testing in blood donors screened by 2.0 versus 3.0 antibody assays.

BACKGROUND: Two HCV antibody tests (EIA 2.0 [EIA2], Abbott; and the Version 3.0 ELISA [EIA3], Ortho) are currently licensed for screening of US blood donors. Testing of donors for HCV RNA allows comparison of the sensitivities of the two antibody-screening assays. STUDY DESIGN AND METHODS: All allogeneic blood donations at 13 US test sites were screened for HCV RNA by testing plasma minipools using an investigational assay (COBAS AmpliScreen HCV test, v2.0, Roche Molecular Systems). Some sites screened for HCV antibody by EIA2 and some used EIA3. The frequency of RNA-positive and antibody-negative (RNA-pos and Ab-neg) donations among donors screened by each antibody assay was compared. Antibody appearance was assessed in a donor follow-up study. RESULTS: A total of 5.51 x 10(6) donations were screened for HCV RNA. Of these, 2.27 million were screened for antibody by EIA2, and 3.24 million by EIA3. Twenty-three donations were HCV RNA-pos and Ab-neg. The frequency of RNA-pos and Ab-neg donations was higher among donations screened by EIA2 (1 in 134,000), compared to those screened by EIA3 (1 in 540,000) (p = 0.001). Of the 17 RNA-pos and Ab-neg donations identified by test sites that used EIA2, 14 were retested by EIA3 and 10 (71%) were reactive. Most RNA-pos and Ab-neg donors appear to be in the process of seroconversion. Donors that were initially EIA2-negative and EIA3-reactive showed a more prolonged pattern of seroconversion compared to those that were initially nonreactive by both antibody assays. Four donors were EIA2-negative, EIA3-reactive, and RIBA-indeterminate (c33c) for at least 90 days, 1 for more than 317 days. CONCLUSION: EIA3 would have detected the majority of RNA-positive donations missed by EIA2. Some RNA-positive donors are EIA2-negative and EIA3-reactive for a prolonged period of time.

Transfusion-related acute lung injury: report of a clinical look-back investigation.

CONTEXT: Transfusion-related acute lung injury (TRALI) is a syndrome that includes dyspnea, hypotension, bilateral pulmonary edema, and fever. TRALI is the third leading cause of transfusion-related mortality, but it is probably underdiagnosed and underreported. OBJECTIVE: To determine if blood products from a frequent plasma donor, whose blood product was implicated in a fatal case of TRALI, caused symptoms of TRALI in other recipients of her plasma. DESIGN, SETTING, AND PARTICIPANTS: Retrospective chart review (conducted from November 2000 through April 2001) of 50 patients who received blood components within 2 years (October 1998 through October 2000) from a donor linked to a transfusion-related fatality. MAIN OUTCOME MEASURE: Occurrence of mild/moderate (dyspnea with fever, chills, hypotension, and/or hypoxemia) or severe (acute pulmonary edema or need for mechanical ventilation) reaction associated with transfusion. RESULTS: Superimposed illness prevented assessment of TRALI in 14 patients. Of the 36 patient charts that could be reviewed, 7 mild/moderate reactions were reported in 6 patients (16.7%) and 8 severe reactions were reported in 8 patients (22.2%). Of 5 patients who received multiple transfusions from the same donor, 2 experienced 2 reactions: one had 2 mild/moderate reactions and the other had both a mild/moderate and a severe reaction. While 5 of the 7 mild/moderate reactions were reported to the hospital transfusion service, only 2 of the 8 severe reactions were reported. Only 2 reactions (1 mild/moderate and 1 severe) were reported to the regional blood collection facility. CONCLUSIONS: TRALI was frequently underdiagnosed and underreported in recipients of blood products from a donor whose blood products may have caused TRALI in several transfusion recipients. Clinical education and awareness of this often-overlooked diagnosis are imperative for appropriate prevention and treatment.

Distribution of hepatitis B virus genotypes among American blood donors determined with a PreS2 epitope enzyme-linked immunosorbent assay kit.

We genotyped 418 sera from volunteer blood donors from two large, regional blood centers in the United States who were HBsAg positive by an enzyme-linked immunosorbent assay (ELISA). The HBV genotypes were determined by a serological method using a preS2 epitope ELISA kit (Institute of Immunology, Tokyo, Japan) with monoclonal antibodies. Of the 418 samples, the genotypes of 320 could be determined (76.6%). One hundred forty-three (34.2%) were genotyped as A (preS2 subtype su), 31 (7.4%) were genotyped as B (subtype m), 59 (14.1%) were genotyped as C (subtype ks), 83 (19.9%) were genotyped as D or E (subtype ksu), and 4 (1.0%) were genotyped as F (subtype k). This kit cannot differentiate genotypes D and E. For 98 (23.4%) of the 418 samples, the genotype could not be determined; 11 of these 98 samples were positive for at least one of the preS2 genotype-specific epitopes (m, k, s, and u), but the combinations of positive epitopes were different from those of samples that could be genotyped; 45 had only the common epitope (b). In the group with a high signal-to-cutoff (S/C) ratio, the HBV genotype could be determined for 199 (84%) of 237 samples; in contrast, in the low-S/C-ratio group, only 10 (20%) of 51 samples could be genotyped (P < 0.001). These findings may indicate the limitation of genotyping samples with low S/C ratios for HBsAg by ELISA or the existence of genotype G or other new HBV genotypes in HBsAg-positive blood donors in the United States. Of the genotyped samples, 201 were assayed for HBeAg; only 9 (4.5%) were positive for HBeAg. The frequency of genotype C in HBeAg-positive donor samples (5 of 9 or 56%) was higher than that in HBeAg-negative donor samples (33 of 192, or 17%) (P = 0.022).

Noninfectious serious hazards of transfusion.

Serious, noninfectious transfusion complications include transfusion-related acute lung injury (TRALI), transfusion-associated graft-versus-host disease, anaphylaxis, hemolysis, and post-transfusion purpura. Prompt recognition and treatment are crucial, but prevention is preferable. Many transfusion reactions are not recognized as such, perhaps because signs and symptoms mimic other clinical conditions. However, any unexpected symptoms in a transfusion recipient should at least be considered as a possible transfusion reaction and be evaluated. Appropriate diagnosis is the key to treatment and may prevent additional reactions, not only in the patient, but possibly, as in the case of TRALI, in other patients.