Controversies in transfusion medicine. Prophylactic platelet transfusion revisited after 25 years: con.
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Biomedical subjects
Publications and source records attributed to E Patten.
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Delayed hemolytic transfusion reactions (DHTRs) are generally attributed to an anamnestic immune response. Case reports of DHTRs due to a primary immune response are rare. Transfusion reactions occurring in patients on the pediatric burn unit from 1981 to September 1988 were reviewed, and additional information was obtained for patients for whom a DHTR was documented. Of 62 transfusion reactions, 11 were classified as a primary immune response (DHTR), with either a positive antibody screen, a positive direct antiglobulin test (DAT), or both. None of the 11 patients included in the study had been previously tranfused or pregnant. The average number of units transfused prior to antibody identification was 19. The average time elapsed between the first transfusion and antibody identification was 3.6 weeks. Anti-K and anti-E were the most frequently identified. Three patients had a decrease in hemoglobin (average 1.5 g/dL) and hematocrit at the time that a positive DAT was detected. Such changes could not be demonstrated for the remaining eight patients. The conclusion was that a DHTR may he caused by a primary immune response in burned children more often than expected, but DHTR signs and symptoms are often not apparent due to the complications of burn trauma.
Sick neonates often require periodic small volume transfusions (10 mL/kg) to replace blood drawn for laboratory monitoring during their hospital stay. We use red blood cells (RBCs), stored as CPDA-1 whole blood, up to their expiration date, and are unaware of any clinical problems with this practice. We proceeded to confirm our clinical impression by reviewing the hospital records of 22 transfused neonates who received a median of 2.5 RBC transfusions (range 1 to 11) with a volume of 16 mL (range 5 to 38) each, and total volume of 60 mL (range 16 to 152). The RBCs were stored a median of 7 days (range 2 to 27). Following transfusion, there was an increase (P less than .05) in hemoglobin (mean 2.8 +/- 1.6 gm/dL [SD]) and hematocrit (9.0% +/- 4.7%). The bilirubin also rose (0.6 +/- 1.5 mg/dL, P less than .05), but this was not considered clinically significant. No significant change occurred in pH or bicarbonate. Paradoxically, RBCs over 10 days of age resulted in a fall in potassium (-0.9 +/- 0.8 mEq/L, P less than .01), but not below 3.4 mEq/L. We could find no evidence by clinical observation or laboratory indexes that small volume transfusion of RBCs more than 5 days old was deleterious to the newborns studied. By using RBCs up to their expiration date, the number of donor exposures and the potential risk of transfusion-transmitted diseases can be decreased.
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Three new lymphocyte activation antigens are described whose kinetics of appearance place them very early in the activation pathway. The 78,000 dalton early antigen (Ea) 1 is present at low levels on resting lymphocytes, and its expression is enhanced twofold to threefold within 3 hr of stimulation. Ea2, a nondisulfide-bonded 86,000 and 73,000 dalton heterodimer, is first detectable 3 hr after activation and peaks by 9 hr. Its presence on all but a few cell lines, plus the variable association with a lower m.w. (28,000) structure, suggest that it may serve as a receptor for a growth factor. Neither Ea1 nor Ea2 are restricted to lymphocytes. The 31,000 dalton Ea3 antigen is induced only by PHA but not by other means of activation, and may pre-exist within the cell. The Ea3 antibody blocks PHA-induced but not OKT3-induced mitogenesis, suggesting differences in the pathways of activation by these two stimuli. These reagents, and OKT3, were used to define the cyclosporine A (CSA)-sensitive stage of lymphocyte activation. CSA blocks at a point before the biosynthesis of Ea1 and after that of T3/T cell receptor loss from the cell surface, at a point close to Ea2 biosynthesis.
Plasma exchange is a process in which large volumes of plasma, usually equivalent to one plasma volume, are exchanged with donor plasma or a plasma substitute. This permits the removal of antibody, immune complexes, inflammatory mediators, paraproteins, drugs, toxins, and other plasma constituents. Plasma exchange may also have an effect on the immune system by enhancing the function of the reticuloendothelial system, removing blocking antibody, increasing clearance of tumor cells, and making lymphocytes more vulnerable to immunosuppressive drugs. Over 100 diseases have been treated with plasma exchange with variable success. Results of controlled studies are less dramatic than those of earlier uncontrolled case reports. Reports of complications and even death have tempered initial enthusiasm. Now, over a decade since the initial promising reports began to appear in the literature, the role of plasma exchange remains undefined.
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In September, 1979, the Transfusion Committee at the University of Texas Medical Branch in Galveston implemented a preoperative blood ordering policy of type and screen (TS) for selected surgical procedures. During the first year in which this policy was in force, 2,301 TS requests were received, most of them for patients in the Department of Obstetrics and Gynecology. During this time, requests for cross matching declined by 12% (28,863 to 25,283) despite a 3% increase in packed red blood cell and whole blood transfusions (11,282 to 11,629). The cross match/transfusion ratio fell from 2.55 to 2.17, and outdating of blood dropped 42% (446 to 260). In the 20 months since this policy was introduced, 4,334 TS requests have been processed. Of these, 211 were changed to cross matching by the patient's physician, but only 100 patients (2.3%) actually received transfusions. No untoward reactions were observed by transfusing blood before the results of the cross matching were known. We estimate a savings to patients of $164, 920, and conclude that TS is safe and effective.
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Autoimmune hemolytic anemia (hemoglobin 5.2 g, reticulocyte count 31.0 per cent) developed in a 53-year-old hypertensive woman who was taking Aldomet. Both the patient's serum and the eluate prepared from her red blood cells contained an antibody with anti-Jka specificity. Rapid sustained improvement in the anemia occurred after cessation of Aldomet and a two week course of prednisone therapy. Eight months later, anti-Jka was no longer detectable in the patient's serum and the direct antiglobulin test was nonreactive.
Because of previous reports of benefit of plasma exchange in immunologic disorders, we plasmapheresed a 45-year-old woman with immune thrombocytopenia and autoimmune hemolytic anemia (Evans' syndrome) who appeared to be dying despite splenectomy, prednisone, immunosuppressives and transfusions. Nine liters of plasma were removed over a 12-day period. Prior to plasma exchange, the patient's hematocrit remained below 16 per cent despite six units of red blood cells over a three-day period. Following plasma exchange, the hematocrit rose to 29 per cent; the platelet count gradually rose from 14,500/microliter to 272,000/microliter; and the transfusion requirements declined to only two units of red blood cells over the next 37 days. We conclude that plasmapheresis should be considered in the management of patients with refractory immune thrombocytopenia and autoimmune hemolytic anemia.
Delayed hemolytic transfusion reactions usually occur as a result of a secondary immune response with maximal hemolysis occurring seven days posttransfusion. We report a delayed hemolytic transfusion reaction in which hemoglobinuria, anemia, and reticulocytosis developed four weeks after transfusion. The incriminated antibody, anti-C, was first detected eight weeks posttransfusion using enzyme-treated red blood cells. We conclude, that in all likelihood, this hemolytic transfusion reaction was due to a primary immune response, this case illustrates the importance of sequential testing in cases of suspected transfusion reactions.