HLA and RBC immunization after filtered and buffy coat-depleted blood transfusion in cardiac surgery: a randomized controlled trial

BACKGROUND: WBC reduction of all blood components is being introduced in many countries. Prevention of immunologic side effects of transfusions is part of the motivation. To compare the immunogenicity of before- or after-storage WBC-reduced RBCs with RBCs without buffy coat, a randomized clinical trial was performed. STUDY DESIGN AND METHODS: Cardiac surgery patients were randomly assigned to receive either RBCs without buffy coat (PCs), WBC-reduced RBCs that were filtered before storage (FFs), or WBC-reduced RBCs that were filtered after storage (SFs). Serum samples for antibody analyses were collected before and after surgery. RESULTS: Sera of 404 patients were tested. Of the 317 patients with negative preoperative screening, 12.6 percent developed anti-WBC antibodies (PC, 14.5%; FF, 9.6%; SF, 13.3%). Of the 87 patients with preoperative anti-WBC antibodies, 28.7 percent showed a marked increase in panel reactivity (PC, 31.3%; FF, 29.0%; SF, 25.0%). ELISA showed the newly formed antibodies to be of IgG class and directed against HLA class I in more than 90 percent of the samples tested. Newly formed anti-RBC antibodies appeared in 5.3 percent (PC, 7.1%; FF, 3.4%; SF 5.4%). Alloimmunization against WBCs and RBCs was strongly correlated (p < 0.01). The differences in newly formed anti-WBC antibodies and anti-RBC antibodies between the trial arms did not show significance. CONCLUSION: Buffy coat removal, and additional WBC reduction by filtration, either before or after storage, result in similar posttransfusion alloimmunization frequencies after a single transfusion event with multiple RBCs.     

Safety and efficacy of unmodified whole blood vs. buffy coat-depleted red cell concentrates in autologous transfusion of elective orthopaedic surgery patients

Storing autologous blood as whole blood (WB) has been proposed for increasing the cost-effectiveness of preoperative autologous blood donation programmes. However, experimental data suggest that autologous leucocytes might lead to immunomodulation similar to the effect attributed to allogeneic leucocytes. In a retrospective analysis, the postoperative outcome of 120 patients undergoing elective orthopaedic surgery and having donated up to two units of autologous WB (AWB) was compared with that of a control group of 52 patients, whose autologous donation had been processed into buffy coat-depleted red cell concentrates (RCC). At least one autologous unit, but no allogeneic units, had been transfused in all analysed patients. Donation schemes were equally efficacious in both groups. There was no significant difference in postoperative infection rates between the two groups. Overall rates were 7.7% in the RCC group and 8.3% in the WB group. Surgical, thromboembolic and other recorded complications, length of postoperative hospital stay and days of the use of antibiotics were also not significantly different between the two groups. The results of this study suggest that transfusion of up to two units of unmodified AWB is as efficacious as the transfusion of autologous RCC and does not negatively influence the postoperative outcome in elective orthopaedic surgery.     

Transfusion of buffy coat-depleted blood components and risk of postoperative infection in orthopedic patients

BACKGROUND: Allogeneic blood transfusions have been reported to increase susceptibility to postoperative infection, but the findings were inconclusive. This study was designed to investigate the effect of buffy coat-depleted allogeneic and autologous transfusion on postoperative infection in patients undergoing orthopedic surgery. STUDY DESIGN AND METHODS: Patients (n = 385) undergoing elective orthopedic surgery (primary and revision joint replacement, spinal, or pelvic surgery) were included in a prospective observational study of the incidence of postoperative infection between April and December 1996. Infection rates in patients who received allogeneic buffy coat-depleted blood transfusions were compared with those in patients who received no transfusion or only autologous (buffy coat-depleted) blood. RESULTS: Patients without exposure to allogeneic blood (no blood or only autologous blood) had an infection rate of 3.9 percent, as compared to a rate of 12.2 percent for those with exposure to allogeneic blood (allogeneic blood, autologous plus allogeneic blood) (odds ratio 3.442; 95% CI, 1.349-10.40; p = 0.006). Of the 385 study patients, 309 underwent primary hip or knee replacement surgery. In this homogeneous subgroup, the postoperative infection rate was 4.6 percent after no transfusion or autologous transfusion and 11.9 percent after allogeneic transfusion (odds ratio 2.827; 95% CI 1.059-8.799; p = 0.036). Multivariate regression analysis confirmed buffy coat-depleted allogeneic blood transfusion as an independent variable associated with high risk for postoperative infection. CONCLUSION: Buffy coat-depleted allogeneic blood transfusion increases the incidence of postoperative infection in patients undergoing uncontaminated orthopedic surgery.     

Review of evidence for a connection between Chlamydia pneumoniae and atherosclerotic disease

BACKGROUND: Established risk factors account for no more than 50% of coronary artery disease cases; therefore, the search continues for other modifiable risk factors. In recent years, there has been renewed interest in the infectious theory of atherosclerosis. Chlamydia pneumoniae has been implicated as a potential cause of atherosclerotic disease. OBJECTIVE: This review discusses possible mechanisms of C pneumoniae involvement in atherosclerosis, summarizes the case-control studies and antibiotic trials completed, and identifies remaining questions about future therapy. METHODS: Published data were identified by a MEDLINE search of the English-language literature from 1966 through 2001 using the terms Chlamydia, atherosclerosis, and coronary artery disease. Relevant conference presentations and book chapters were also included. RESULTS: C pneumoniae antibodies are found in approximately 50% of middle-aged adults world-wide. These antibodies have been detected in atherosclerotic tissue by various methods, including microimmunofluorescence, and several studies have linked high antibody titers with increased risk of cardiovascular events. A few possible mechanisms for this perceived increase in risk have been proposed, such as induction of atheroma through damage to the endothelium, expression of procoagulant factor leading to thrombus formation, and production of cytokines resulting in increased inflammatory response. Results of animal studies suggest that early antibiotic treatment may reduce cardiovascular risk, but the first human studies have not produced conclusive results. CONCLUSIONS: Although a connection has been suggested, the precise mechanism by which C pneumoniae affects atherosclerosis has not yet been identified. Large-scale trials are needed to determine whether eradication of C pneumoniae reduces the incidence of cardiovascular events in humans.     

A case of splenic abscess due to Chlamydia pneumoniae

In this report, a case of chlamydial disease with splenic abscess associated with Chlamydia pneumoniae antigen and antibody was described. On spleen biopsy of the patient, an antigen specific to C.pneumoniae was detected by immunofluorescence staining with a monoclonal antibody. Serologic studies revealed a high antibody titer to C.pneumoniae in sera collected from the patient and her husband. Treatment with the antibiotic minocycline improved her condition.     

Immunological impact of the CD71+ RBCs: A potential immune mediator in transfusion

Donor - recipient sex - mismatched transfusion is associated with increased mortality. The mechanisms for this are not clear, but it may relate to transfusion-related immunomodulation. Recently, CD71⁺ erythroid cells (CECs), including reticulocytes (CD71⁺ RBCs) and erythroblasts, have been identified as potent immunoregulatory cells. The proportion of CD71⁺ RBCs in the peripheral blood is sufficient to play a potential immunomodulatory role. Differences in the quantity of CD71⁺ RBCs are dependent on blood donor sex. The total number of CD71⁺ RBCs in red cell concentrates is also affected by blood manufacturing methods, and storage duration. As a component of the total CECs, CD71⁺ RBCs can affect innate and adaptive immune cells. Phagocytosed CECs directly reduce TNF-α production from macrophages. CECs can also suppress the production of TNF-α production from antigen presenting cells. Moreover, CECs can suppress T cell proliferation thorough immune mediation and / or direct cell-to-cell interactions. Different in their biophysical features compared to mature RBCs, blood donor CD71⁺ RBCs may be preferential targets for the macrophages. This report summarizes the currently literature supporting an important role for CD71⁺ RBCs in adverse transfusion reactions including immune mediation and sepsis.     

Role of Chlamydia pneumoniae in atherosclerosis

Cardiovascular disease, resulting from atherosclerosis, is a leading cause of global morbidity and mortality. Genetic predisposition and classical environmental risk factors explain much of the attributable risk for cardiovascular events in populations, but other risk factors for the development and progression of atherosclerosis, which can be identified and modified, may be important therapeutic targets. Infectious agents, such as Chlamydia pneumoniae, have been proposed as contributory factors in the pathogenesis of atherosclerosis. In the present review, we consider the experimental evidence that has accumulated over the last 20 years evaluating the role of C. pneumoniae in atherosclerosis and suggest areas for future research in this field.     

In-vitro activity of gatifloxacin against Chlamydia trachomatis and Chlamydia pneumoniae

We compared the activity of gatifloxacin, a new quinolone, ofloxacin and erythromycin against five isolates of Chlamydia trachomatis and 20 isolates of Chlamydia pneumoniae, including TW183 and clinical isolates from the USA and Japan. Testing was done in cycloheximide-treated HEp-2 cells. Gatifloxacin was slightly less active against C. trachomatis and slightly more active against C. pneumoniae than ofloxacin, with MICs at which 90% of the isolates had no inclusions and minimal chlamydicidal concentrations at which 90% of the isolates had no inclusions after passage of 0.25 mg/L. Gatifloxacin was less active than erythromycin for both species.     

亚洲地区肺炎支原体和肺炎衣原体在成人社区获得性肺炎中的流行病学研究

目的由Malaya大学医学中心牵头进行的非典型病原在亚洲社区获得性肺炎（CAP）患者中的流行病学研究。结果显示，肺炎支原体和肺炎衣原体分别占成人病原的11．4％和5．8％。本研究将对这2种病原所致感染的临床和实验室资料进一步总结分析。方法亚洲7个国家12个研究中心采用统一的检测方法（DNA检测及血清学方法）和判断标准，对16岁以上的CAP患者进行肺炎支原体和肺炎衣原体的检测。结果在急性肺部感染者中，肺炎支原体和肺炎衣原体肺炎的临床表现与其他病原所致者非常相似，并无特征性。肺炎支原体和肺炎衣原体在男性和女性中检出率相仿，但肺炎支原体感染在16至44岁患者中更为多见（22．2％），而肺炎衣原体感染者重症患者相对较多。88例在病程中血清抗体显著增高的肺炎支原体感染者中，48例（54．5%）患者急性期抗体阴性，如果未检测恢复期血清抗体，上述患者则会漏诊；51例肺炎衣原体感染者中急性期血清抗体阴性则较为少见（21．6％）。肺炎支原体和肺炎衣原体既往感染和（或）病原携带率分别为5．7％和7．9%。结论肺炎支原体肺炎和肺炎衣原体肺炎发病率高，诊断困难，因此在亚洲成人CAP抗感染经验治疗时宜选用对这2种病原亦有效的药物。     

PCR detection and differentiation of Chlamydia pneumoniae, Chlamydia psittaci and Chlamydia trachomatis.

A PCR-based system was developed for the detection and differentiation of Chlamydia trachomatis, Chlamydia psittaci and Chlamydia pneumoniae. A conserved 145 bp fragment of the chlamydial omp1 gene was amplified from all three species. The three species were then differentiated from each other by digestion of this PCR product with restriction enzymes Eco RI and either Hind III or Pst I. The system was shown to work for two strains of C. pneumoniae, 11 strains of C. psittaci and 10 serovars of C. trachomatis, and had a sensitivity of less than 10 chlamydial elementary bodies. This method was also applicable to the detection of C. trachomatis in conjunctival and nasopharyngeal swabs.     

Universal leukoreduction decreases the incidence of febrile nonhemolytic transfusion reactions to RBCs

BACKGROUND: Febrile nonhemolytic transfusion reactions (FNHTR) is a relatively common complication associated with allogeneic transfusion. Because WBCs have been implicated in the mechanism of FNHTRs, it has been proposed that the transfusion of leukoreduced RBCs should be associated with a decreased incidence of FNHTRs. These reactions are generally not life threatening, but they are expensive in their management, evaluation, and associated blood‐product wastage. Over the past several years, the proportion of leukoreduced RBCs has increased at Johns Hopkins Hospital in an effort to move toward complete leuko‐reduction. A retrospective analysis is reported here of FNHTRs in RBC recipients as the inventory increased in percentage of leukoreduced RBC units. STUDY DESIGN AND METHODS: Between July 1994 and December 2001, all transfusion reactions (TRs) associated with the transfusion of allogeneic RBCs were retrospectively analyzed. Both computerized data and individual TR reports were reviewed. Patients who had both allergic and febrile features were included as part of both categories. TRs were reported as a percentage of total units transfused. Two time periods were selected for direct comparison. July to December 1994 represents the time period before the initiation of an increase in leuko‐reduction. July to December 2001 represents a time period when almost complete leukoreduction (99.5%) had been achieved. The TR data were compared between these two time periods, comparing a time before leuko‐reduction to a time period after leukoreduction had been achieved. The trends in TRs over the entire 7.5‐year period of July 1994 to December 2001 were also assessed. RESULTS: In the initial period before the initiative to move toward leukoreduction, 96 percent of our RBC inventory was non‐leukoreduced. In the study period after leukoreduction, 99.5 percent of our RBC inventory was leukoreduced. When comparing these two time periods, the incidence of FNHTRs decreased from 0.37 percent to 0.19 percent (p = 0.0008). The trend over the entire 7.5‐year study period confirms the decrease in FNHTRs as the percentage of leukoreduced RBCs increased. The incidence of allergic TRs has remained unchanged over this time period. CONCLUSIONS: As our institution has increased its inventory of leukoreduced RBCs to approximately 100 percent, selective leukoreduced protocols have been discontinued. The incidence of FNHTRs has decreased significantly and the rate of allergic reactions has essentially remained unchanged. Leukoreduction is effective in decreasing FNHTRs associated with the transfusion of allogeneic RBCs.     

Lack of evidence of transfusion transmission of Creutzfeldt-Jakob disease in a US surveillance study

BACKGROUND: Since 2004, several reported transfusion transmissions of variant Creutzfeldt-Jakob disease (vCJD) in the United Kingdom have reawakened concerns about the possible risk of similar transmissions of nonvariant or classic forms of CJD.
STUDY DESIGN AND METHODS: Patients with a CJD diagnosis and a history of donating blood were reported to the study coordinator. Through review of blood distribution and hospital records, the recipients of blood components from these donors were identified. We then determined each recipient's vital status and, if deceased, the cause(s) of death identified by matching the recipient's personal identifiers with the Centers for Disease Control and Prevention's National Death Index database. We conducted such searches after recipients were enrolled in this study and annually thereafter for those who remained alive.
RESULTS: The study included a total of 36 blood donors who subsequently developed CJD and 436 recipients. Through 2006, 91 of these recipients were still alive, 329 were deceased, and 16 were lost to follow-up. After transfusion, these three groups had survived a total of 2096.0 person-years. A total of 144 recipients survived 5 years or longer after transfusion and 68 of them had received blood donated 60 or fewer months before the onset of CJD in the donor. We identified no recipient with CJD.
CONCLUSIONS: The current results of this large, ongoing lookback study show no evidence of transfusion transmission of CJD. They reinforce the conclusion that the risk, if any, of transfusion transmission of prion disease by CJD donors is significantly lower than the comparable risk of such transmission by vCJD donors.     

The in-vitro antibiotic susceptibility of Chlamydia pneumoniae

A cell culture technique was used to test the in-vitro susceptibility of the type strain of Chlamydia pneumoniae to 23 antibiotics including macrolides, tetracyclines and quinolones. The activity of the antibiotics tested was similar to previous findings with C. trachomatis. Clarythromycin had the lowest MIC overall (0.007 mg/l). Other macrolides were found to have similar MICs to erythromycin (0.06 mg/l). Both the macrolides and the tetracyclines were more active than the quinolones. It is proposed that the tetracyclines and erythromycin should be the drugs of choice for treating infections with C. pneumoniae; however several other antibiotics need to be evaluated.     

Cord blood as a source of autologous RBCs for transfusion to preterm infants

BACKGROUND: This prospective study was conducted to gain experience as to whether it is technically possible to produce autologous RBCs in additive solution from cord blood (CB), to optimize the blood supply for preterm infants. STUDY DESIGN AND METHODS: CB was collected from 47 infants with a mean (+/- SD) birth weight of 1717 (+/- 699) g. Whenever possible, RBC components were prepared by standard centrifugation using a six-bag system. All samples were put in sterility testing quarantine for 5 days, and a maximum storage of 14 days from collection to transfusion was specified. The babies were given either the autologous RBCs or standard allogeneic RBC concentrates, if autologous blood was not available. RESULTS: In 81 percent of the samples, autologous RBC components could be processed (vol, 7-87 mL; Hct, 31-82%). But within the group of extremely low birth weight infants (body weight <1000 g), a mean CB net volume of only 37 mL was collected, and the RBC preparation was successful only in exceptional cases. Three CB samples (8.6%) tested positive in sterility testing. Of the 47 infants, 21 were treated with a total of 62 allogeneic and 4 autologous RBC transfusions. Most infants with a body weight over 1400 g did not need any RBC transfusion. CONCLUSION: The preparation of autologous RBCs from the CB of preterm infants is technically possible in principle. However, major concerns must be raised as to whether such preparations are of benefit in ensuring safe care of neonates with blood components, with respect to the high rate of bacterial contamination and the limited availability in babies with low birth weight.