Enhancement of t lymphocyte functions by Fc fragments of immunoglobulins. I. Augmentation of allogeneic mixed lymphocyte culture reactions requires I-A- or I-B-subregion differences between effector and stimulator cell populations

Fc fragments derived from human Ig were found to be capable of enhancing T cell-mediated, antigen-induced proliferative and mixed lymphocyte culture responses. Maximum enhancement occurred when suboptimal amounts of antigen or suboptimal numbers of stimulator cells were employed. Augmentation of the allogeneic mixed lymphocyte culture reaction requires an I-A and/or I-B subregion difference between effector and stimulator cell populations. Although a significant proliferative response was observed with K- or D- region differences, Fc fragments were unable to enhance the response. The T cell population acted upon by Fc fragments in the potentiation of these responses bears the Lyt-1(+)23(-) phenotype.     

Seroprevalence of human T-lymphotropic virus, hepatitis C virus, and human immunodeficiency virus in Asian American potential bone marrow donors

BACKGROUND: Asian Americans are generally underrepresented both as volunteer blood and bone marrow donors. STUDY DESIGN AND METHODS: To investigate the risk of transfusion transmission of viruses that is associated with increasing participation by Asian American donors, antibodies to human T-lymphotropic virus (HTLV), hepatitis C, and human immunodeficiency virus in Asian American volunteers recruited as potential bone marrow donors were measured. A total of 1354 Asian Americans were enrolled in the study, of whom 54 percent were Chinese, 26 percent Japanese, 9 percent Filipino, 4 percent Korean, 3 percent Indian, and 5 percent of other Asian or mixed Asian and other ethnicity. The majority of the study population was aged 20 through 49 and of high socioeconomic status, as indicated by education and income. Viral antibodies were measured with both screening enzyme-linked immunosorbent assays and supplemental testing, and polymerase chain reaction was used to resolve discrepant HTLV results. RESULTS: Confirmed seroprevalence rates for HTLV were 0.15 percent with one manufacturer's Western blot and 0.3 percent with the other; however, no sample was positive for HTLV types I or II in polymerase chain reaction. Confirmed seroprevalence to hepatitis C virus was 0.5 percent. No subject was seropositive for human immunodeficiency virus. CONCLUSION: On the basis of the moderate size and high education level of this study population, it is concluded that Asian American volunteer bone marrow donors do not pose a greater risk for transmission of HTLV type I or II, human immunodeficiency virus, or hepatitis C virus than does the average American blood donor.     

Fusion or Confusion on Holter Recording

Holter recording of a patient with an implanted dual chamber rate responsive pacemaker revealed an electrocardiogram, where ventricular depolarization seemed to be initiated by the atrial stimulus. In a second patient with a VVI pacemaker, Holter recording showed delay of the pacemaker impulse that was registered after the onset of ventricular depolarization. Misalignment in one of the recorder heads of the display system was responsible for this phenomenon, which in case of dual chamber pacing could have been easily misinterpreted as pacemaker malfunction.     

Cytokine generation in stored platelet concentrates

BACKGROUND: Cytokines, because of the nature of their immunoinflammatory actions, are potential mediators of the symptom complex of nonhemolytic transfusion reactions. One possible source of cytokines in the transfusion setting is the stored blood component itself. STUDY DESIGN AND METHODS: To test this possibility, the plasma portion of stored platelet concentrates (PCs) was assayed for the presence of interleukins 1 beta (IL-1 beta), 6 (IL-6), and 8 (IL-8) and tumor necrosis factor alpha (TNF-alpha). Samples were taken from PCs obtained from the inventory of a regional blood center (n = 120; 30 each of 2-, 3-, 4-, and 5-day-old units). RESULTS: Detectable levels of IL-8 were measured in 59 percent of the PCs sampled, ranging from 30 percent of the 2-day-old units to 83 percent of the 5-day-old units. The median IL-8 concentration ranged from undetectable levels in 2-day- old units up to 1100 pg per mL in 5-day-old units. The mean IL-8 concentration in 5-day-old units, 11,600 pg per mL, was 100 times the mean for 2-day-old units, which was 116 pg per mL (p < 0.0001). The highest levels of IL-8, 50,000 to 200,000 pg per mL, in general were found in units with the longest storage times and highest white cell counts. Sequential sampling of 17 individual PCs over 7 days of storage confirmed that IL-8 increases progressively with increasing storage time. Parallel, but smaller, increases in IL-1 beta were observed in those units with high IL-8 concentrations. TNF-alpha was detected in 3 (10%) of 30 five-day-old PCs, but never exceeded 55 pg per mL in any unit tested. IL-6 at levels of 740 and 508 pg per mL was detected in two 5-day-old units with high white cell counts of 9500 and 14,800 per microL, respectively, but not in 21 additional units tested with white cells < or = 9200 per microL or storage time of < or = 2 days. White cell reduction by third-generation filters on Day 1 of platelet storage prevented the generation of IL-8 and IL-1 beta to Day 5 of storage. CONCLUSION: Although IL-8 achieved levels in some units of PCs that appear capable of causing physiologic changes, the potential adverse effect on transfusion recipients of the infusion of cytokines in PCs remains to be investigated.     

The effect of solvent/detergent-treated plasma on red cells stored in vitro

BACKGROUND: The potential use of solvent/detergent-treated plasma (S/D plasma) in transfusion practice raises concerns about the cytolytic effects that any residual solvent and detergent in the virally inactivated blood component might have on units of red cells in vitro, if the two components are mixed during preparation. STUDY DESIGN AND METHODS: S/D plasma was mixed with variously processed units of stored red cells, in vitro, to evaluate the effect the residual solvent and detergent would have on cell membrane integrity. A paired protocol design was used in which half-units of red cells were exposed to S/D plasma (test), and the matched half-units were exposed to either the supernatant additive solution from the original red cell unit or standard fresh-frozen plasma (FFP) (control). After incubation for up to 5 days, the units were evaluated for evidence of hemolysis or changes in other red cell storage assays. RESULTS: This study showed that, for fresh additive solution red cells (AS-1), the 5-day storage plasma hemoglobin levels were comparable in the red cells exposed to S/D plasma (21 mg/dL) and in the paired half-units stored in the original AS-1 supernatant (31 mg/dL) (p > 0.05). Similar findings were recorded for stored AS-1 red cells (S/D plasma; 111 mg/dL vs. AS-1 supernatant, 147 mg/dL; p > 0.05); stored CPDA-1 red cells (S/D plasma, 133 mg/dL vs. FFP, 103 mg/dL; p > 0.05); frozen red cells (S/D plasma, 28 mg/dL vs. FFP, 18 mg/dL; p > 0.017); and stored irradiated AS-1 red cells (S/D plasma, 608 mg/dL vs. AS-1 supernatant, 726 mg/dL; p > 0.05). Comparable results were found for other assays, including levels of plasma potassium, osmotic fragility, and red cell antigen titer. CONCLUSION: These data show that S/D plasma does not induce red cell lysis even after 5 days of in vitro storage. These results are consistent with previous findings by this laboratory that platelets are not harmed by storage in S/D plasma. Red cells resuspended in S/D plasma and stored for up to 5 days maintain in vitro storage characteristics that are acceptable for the use of the cells in clinical transfusion practice.     

Long-Term Results of Hybrid Therapy in Patients with Atrial Fibrillation Who Develop Atrial Flutter During Flecainide Infusion

The flecainide infusion test has been proposed to screen candidates for hybrid pharmacological and ablation therapy. We report the long-term follow-up of 154 consecutive patients with paroxysmal or persistent atrial fibrillation (AF) who developed atrial flutter (AFL) during flecainide infusion (IC AFL), treated with inferior vena cava-tricuspid annulus isthmus catheter ablation and oral flecainide (hybrid therapy). Over a mean of 54.1 ± 13.1 months 82 patients (53%) remained free of AF and AFL. Flecainide was discontinued because of adverse effects in 6 patients (4%). A history of persistent AF, and the documentation of ≥1 spontaneous AFL episode before the flecainide test were independent predictors of successful hybrid therapy. In patients with paroxysmal AF without documented spontaneous AFL, the long-term efficacy of hybrid therapy was 38.5% (P = 0.03). The flecainide infusion test reliably detects candidates for hybrid therapy. The efficacy of this therapy is maintained over the long-term with a high patient compliance.     

In vitro changes in platelet function and metabolism following increasing doses of ultraviolet-B irradiation

Ultraviolet-B (UV-B) irradiation of platelet concentrates (PCs) may prevent the development of posttransfusion HLA alloimmunization. This study evaluated the effect of increasing doses of UV-B radiation on stored PCs. Pooled PCs were irradiated at UV-B doses of 600, 2400 or 10,000 mJ per cm2 and stored up to 96 hours under standard blood bank conditions. Compared to nonirradiated room-temperature and 37 degrees C controls, the irradiated units showed no significant changes in platelet count, white cell count, discharge of lactate dehydrogenase, release of beta-thromboglobulin, metabolism of ATP, ADP, ammonia, glutamine, glutamate, hypoxanthine, pCO2, or pO2 at any time of storage following any of the three UV-B doses. However, after a dose of 10,000 mJ per cm2, there were significant decreases in in vitro assays of platelet function-specifically, osmotic recovery and morphology score. Some metabolic systems were also affected by the 10,000 mJ per cm2 radiation dose, as shown by a decline in pH and bicarbonate and an increase in glucose consumption and lactate production (p < 0.05). The changes in these latter assays appeared only after 96 hours of postirradiation storage. Such changes were not seen in either the room- temperature or 37 degrees C control groups. Thus, heat generated during irradiation, per se, did not appear responsible for the observed in vitro changes in platelet function and metabolism. On the basis of the assays analyzed, it is concluded that UV-B irradiation of PCs at doses up to 10,000 mJ per cm2 does not induce significant metabolic or functional derangements following short-term storage (24-48 hours).(ABSTRACT TRUNCATED AT 250 WORDS)     

Collection and transfusion of blood and blood components in the United States, 1992

BACKGROUND: Studies were conducted to measure the state of the United States' national blood resource in 1992 and changes therein from 1989. STUDY DESIGN AND METHODS: With data supplied by the American Red Cross and the American Association of Blood Banks, as well as data from a stratified random-sample survey of 3350 non-American Association of Blood Banks hospitals, statistical methods were applied to estimate national blood activities in 1992. RESULTS: The total US blood supply in 1992 was 13,794,000 units, a decrease of 3.1 percent from 1989. Some 11,307,000 red cell units were transfused to 3,772,000 patients, an average of 3.0 units per transfused patient. Preoperative autologous blood deposits totaled 1,117,000 units, a 70-percent increase over 1989. Of this number, 566,000 units (50.7%) were transfused, 5,000 (4.4%) transferred to the allogeneic supply, and 546,000 (48.9%) discarded. Of 436,000 directed-donation units, 136,000 (31.2%) were transfused, 57,000 (13.1%) transferred to allogeneic supply, and 243,000 (55.7%) discarded. The total allogeneic blood supply, including imports, decreased by 7.4 percent from 1989, and allogeneic blood transfusions, including those to children, decreased by 8.6 percent. Over 8,300,000 platelet units were transfused; of these, some 3,600,000 were apheresis platelets. In addition, 2,255,000 units of plasma and 939,000 units of cryoprecipitate were transfused. CONCLUSION: While the US blood supply was adequate for transfusion needs in 1992, blood collections and red cell transfusions had decreased substantially since 1989.     

In vitro characteristics of volume-reduced platelet concentrate stored in syringes

For convenience, small volumes of platelet concentrate (PC) intended for neonatal patients are often dispensed in syringes. The PC, however, may remain in the syringe for up to several hours before the actual transfusion. As there are few data on the effect of such syringe storage on PCs, the in vitro syringe storage properties of small volumes of 1- and 5-day-old units, and volume-reduced units of PC were evaluated. In four separate experiments, PCs were stored in syringes in volumes of 10, 15, or 30 mL for up to 6 hours at 20 to 24 degrees C without agitation. Platelets were evaluated for pH, platelet count, and a variety of biochemical and in vitro functional assays. Results showed that even with the equivalent of a full unit of platelets stored in the syringe for up to 6 hours, the pH did not fall below 6.0. Although there was an increase in lactate production and consumption of glucose, which paralleled the decline in pH, the changes were not greater than those seen in platelets stored up to 5 days in gas-permeable blood bags. Similar results were seen for PCs stored in syringes for 6 hours at 37 degrees C. All of the pH levels recorded at the end of 6 hours of syringe storage were above the minimum required level of pH 6.0. Data from in vitro platelet assays imply that at any time during their shelf life, PCs can be stored in gas-impermeable polypropylene syringes for up to 6 hours and can maintain acceptable storage characteristics; in vivo data are needed to confirm these observations.