Ronald G. Strauss

Donation reactions among autologous donors

Studies of risk factors associated with reactions among autologous blood donors have been limited. Therefore, 2091 autologous and 4737 homologous donations were examined. Donors at greatest risk for reaction were autologous donors who had reactions at first donation; among 45 who made repeat donations for the same surgery, 17 (38%) had repeat reactions. The group least likely to experience reactions were the autologous donors ≥66 years old; they experienced a 1.9≥ percent (6/310) incidence of reactions. More reactions were seen in both autologous and homologous donors in the categories of first‐time donor, female gender, decreasing age, and lower weight. Multiple logistic regression analysis showed that all of these variables were independent predictors of donor reaction, with first‐time donation (odds ratio, 2.4) and female gender (odds ratio, 1.9) being the strongest predictors of reaction. Donor room personnel should be alerted that autologous donors who react at first donation are very likely to react at subsequent donations. Contrary to common concern, elderly autologous donors are least likely to have reactions.

Multiple transfusions fail to provoke antibodies against blood cell antigens in human infants

We conducted studies of both red cell (RBC) and leukocyte (WBC) antibody formation in infants following multiple transfusions given during the first weeks of life. Fifty‐three infants received 683 RBC transfusions from 503 different donors, plus 62 platelet, 4 granulocyte, and 53 fresh‐frozen plasma units during the first 4 months of life. Three hundred fifty serum samples were obtained before, during, and after the transfusions. None of the infants formed unexpected RBC antibodies when tested at 37°C by a two‐cell low‐ionic‐strength solution antibody screen that included an anti‐globulin phase. Twenty posttransfusion serums were negative when tested at room temperature. Lymphocytotoxic and granulocytotoxic WBC antibodies were measured in posttransfusion serums from 13 infants, and none were found. Despite exposure to many RBC and WBC antigens, no infants produced alloantibodies against blood cell antigens. Thus, immunologically mediated transfusion reactions should be quite rare in young infants, and this study supports recommendations of the American Association of Blood Banks Standards to omit repeat RBC compatibility testing during the first 4 months of life in infants whose initial RBC antibody screens reveal no unexpected antibodies.

Current Issues in Neonatal Transfusions

Abstract. Two controversial issues of neonatal transfusion practices, erythrocyte ‘booster’ transfusions and granulocyte transfusions, are critically reviewed, and current recommendations for transfusion practices are made. Infants should receive erythrocyte transfusions to treat congestive heart failure caused primarily by anemia. It is customary to maintain the hematocrit at > 40% in neonates with severe respiratory disease, although the efficacy of this practice has not been firmly established. Erythrocyte transfusions seem to be indicated for infants with anemia plus recurrent apnea, poor weight gain or the syndrome of tachycardia, tachypnea, dyspnea and poor feeding for which no other cause can be found. Granulocyte transfusions are likely to benefit seriously ill neonates exhibiting all three of the following: strong evidence of bacterial sepsis, neutropenia (compared to age‐related normal values) and a diminished marrow neutrophil storage pool. Granulocyte transfusions for septic infants expressing only one or two of these features should be considered to be experimental therapy.

A near-fatal reaction during granulocyte transfusion of a neonate.

Although reactions to granulocyte transfusions in neonates are rarely reported, we observed a near‐fatal pulmonary reaction, presumably due to white cell antibodies, in a neonate with Rh hemolytic disease. The hemolytic disease was being treated with exchange transfusions, and at 2 days after the infants birth, bacterial sepsis was suspected and granulocyte transfusions were begun. The first granulocyte transfusion (Day 3) was uneventful. Five minutes after the beginning of the second granulocyte transfusion (Day 4), severe respiratory distress, hypotension, bradycardia, cyanosis, and acidosis suddenly occurred. The infants serum obtained after the reaction contained granulocytotoxic and B‐lymphocytotoxic antibodies that reacted with leukocytes from the second granulocyte donor. Antibodies could not be detected either in the initial infant serum or in maternal serum. However, an antileukocyte antibody was present in the serum of a parous woman donor. We used plasma from this woman to prepare reconstituted whole blood for the exchange transfusion that we performed immediately preceding the second granulocyte transfusion. Despite the sequence of events, an irrefutable cause‐and‐effect mechanism could not be established because the properties of the donor and neonatal antibodies were similar, but not identical. However, this catastrophic event emphasizes both the potential for adverse effects of granulocyte transfusions in neonates and the need for caution when transfusing blood from parous women.

Routinely washing irradiated red cells before transfusion seems unwarranted

The practice of irradiating cellular blood components to prevent graft-versus-host disease (GVHD) in immunodeficient patients’ and in recipients of blood transfusions from first-degree relativesZ is growing rapidly. Thus, interest is high regarding all aspects of this practiceparticularly the potential for adverse effects. The weight of reported evidence suggests that gamma-radiation of blood components, in doses usually used to prevent GVHD, does not cause clinically significant cellular damage. l s 3 However, blood components are usually irradiated shortly before transfusion, and only limited information is available regarding the effects of irradiation followed by extended storage before transfusion. Several concerns have been raised in letters published in TRANSFUSION, and the emerging controversy has created a number of practical problems. At present, clear answers do not exist, and the purpose of this editorial is to offer an approach for dealing with this issue until definitive information becomes available. To place the saga into perspective, a critical analysis of each of the six letters published in TRANSFUSION4-9 will be presented in chronological order. Readers of this analysis should keep several factors in mind. First, “Letters to the Editor,” although reviewed by expert referees, may not be critiqued as closely as are original manuscripts. Accordingly, I have reassessed each letter in detail; as a consequence, my criticisms may appear to be excessively harsh. They are not intended to be disparaging, however, but merely to judge realistically the validity of the information reported. Second, milliequivalents (mEq) and millimoles (mmol) of potassium (K+) are identical. Thus, comparison of units among the letters reviewed should be easy, and values will be reported as per the original authors without an attempt to convert all data to a uniform style. Third, most attention has been focused on neonatal red cell (RBC) transfusions because it is believed that the relatively high K+ concentrations present in the extracellular fluid of irradiated RBCs will be detrimental to neonatal patients, with their small blood volumes. However, the vast majority of neonatal transfusions are given as packed RBCs (hematocrit = 80%) at a dose of about 10 mL per kg transfused in about 3 hours. Thus, most RBC transfusions contain very small volumes of plasma that are transfused slowly. In the first letterY4 5 units each of packed RBCs and whole blood were divided into two equal aliquots, one of which was irradiated with the relatively high dose of 3000 cGy (rads), and then stored for 14 days. Within 2 days, plasma K+ in irradiated aliquots was approximately threefold that in unirradiated aliquots; after 14 days, plasma K+ in irradiated aliquots was twofold that in unirradiated aliquots. The highest level was in RBC units stored 14 days (68 mmol/L). Only a single value was given for K+ at each observation point. Values were not defined; that is , it was not stated whether they represented the mean, median, highest, or lowest values observed. In addition, no measure of variability (e.g., standard deviation, standard error, range) was provided. Finally, no statistical analysis was reported. In the second letter,5 an unspecified number of RBC units was irradiated with 2000 rads (cGy) and stored for 4 days. Within 1 day, plasma K+ was increased about twofold in irradiated units as compared with unirradiated units. This relationship remained fairly constant throughout storage, and, after 4 days, the peak K+ concentration was 26.2 mmol per L. Plasma K+ could be lowered by washing and resuspending the RBCs in fresh-frozen plasma, and this was recommended for neonatal RBC transfusions. The number of units studied was not specified, and, again, the K+ values were not defined. Neither an indication of variability (e.g., standard deviation, standard error, range) nor results of statistical analysis was reported. In the third letter,6 the need for washing irradiated RBCs to reduce high K+ values, as recommended by the second letterY5 was questioned. Calculations were presented to document (quite correctly, I believe) that the actual quantity (0.09 mmol) of K+ transfused during a small-volume transfusion (10 mL of RBCs with hematocrit 70%) is negligible-despite the alarmingly high plasma K+ concentration of 30 mmol per L. The fourth letter7 was in reply to the third6 and argued that the actual K+ dose (0.09 mmol) delivered with the small-volume transfusion was, in fact, a very substantial K+ load for a tiny, premature neonatal patient with a plasma volume of approximately 50 mL. Calculations were presented to demonstrate (quite incorrectly, I believe) that transfused K+ would be confined to the plasma volume and would increase the infant’s total K+ by more than 50 percent. The final two letters8B9 appear in this issue of TRANSFUSION. Avoy8 addressed the debate raised by the third and fourth letter^.^.^ Calculations and assumptions regarding the distribution of K+ throughout the total body water were presented to support the conclusions of the third letter.6 Although one might quibble with the fine points of the arguments presented, it seems clear that the quantity of K+ transfused in a small-volume RBC

Neonatal Anemia: Pathophysiology and Treatment

All neonates experience a decline in circulating red blood cell (RBC) mass due to diminished erythropoietin (EPO) levels. This effect is more pronounced in small, premature infants and can lead to severe anemia and need for RBC transfusions--particularly, if repeated phlebotomy is required to monitor acutely-ill neonates. Although optimal RBC transfusion therapy has been a long-term challenge for neonatologists, the emergence of recombinant EPO as promising therapy for neonatal anemia is the major issue for 1994. Accordingly, this report for the 12th International Convocation on Immunology (Transfusion Immunology and Medicine) will focus on this aspect of neonatal transfusion medicine. Although several controlled trials to evaluate EPO as therapy have been completed, definitive answers to all questions regarding efficacy and possible toxicity have not been provided. However, therapy with EPO plus iron and adequate nutrition is likely to be proven effective for the relatively late anemia of stable prematures. To date, EPO has not been shown, convincingly, to alleviate the anemia present early in the life of acutely-ill, premature infants.

Mechanisms of adverse effects during hemapheresis

For over 20 years blood components have been collected from normal donors by automated hemapheresis. Cell separators have become increasingly sophisticated, and relatively pure component “concentrates” can be obtained quite safely. Cytapheresis donors are monitored carefully, and serious reactions are very rare. In contrast, therapeutic apheresis procedures may be technically demanding and frequently are performed on very sick patients. Large volumes of blood are rapidly removed from the patient, anticoagulated, and separated into components by the automated cell separator. The blood component containing the pathogenetic factor (e.g., plasma containing an antibody) is retained outside of the body, and the remaining components (e.g., red cells, white cells, and platelets) plus the replacement fluid are reinfused. Complications can occur in normal cytapheresis donors because of the technical challenges of the procedure (e.g., extracorporeal circuit to be filled, use of citrate anticoagulant, need for large bore intravascular access, and rapid blood flow rates). All of these factors apply also to therapeutic patients plus the additional requirement for replacement fluids, and the clinical features of the underlying illness for which each patient is being treated. Fortunately, even with therapeutic patients, most complications are of modest severity and are easily managed with only temporary slowing or interruption of the hemapheresis procedure.

Neutrophil (granulocyte) transfusions in the new millennium

he advent of recombinant granulocyte-colonystimulating factor (GCSF) as a means of markedly increasing the blood neutrophil (polymorT phonuclear leukocyte, PMN) count in normal blood donors and, consequently, to collect large numbers of PMNs for transfusion has rekindled interest in PMN (granulocyte) transfusion therapy for patients with severe neutropenia (<500 PMNslpL blood) or PMN dysfunction. Stimulation of donors with GCSF has culminated a series of technological advances (corticosteroid donor stimulation, hydroxyethyl starch plus concentrated citrate “anticoagulant” solutions, and rapid centrifugal leukapheresis of large volumes of donor blood) enabling the collection and transfusion of doses of PMNs (6-8 x l0I0/transfusion) much larger than the previously acceptable-but acknowledged to be marginal-doses of 1 to 2 x 1O1O PMNs. Although the transfusion of granulocytes obtained from GCSF-stimulated donors has great theoretical potential, the efficacy and possible toxicity have not been defined by randomized clinical trials, and several questions-which can be only partially answered at present-must be addressed. Question 1: As a transfusion medicine professional, what kind of PMN concentrates can I expect to collect from GCSF-stimulated donors? Historically, donors stimulated with properly timed corticosteroids (4 hours before leukapheresis) yielded about 2 x 10’O PMNs per unit.’ Stimulation with GCSF alone or in combination with corticosteroids will produce higher, but variable PMN yields (48 x 10I0PMNs/unit), dependingon the doses of GCSF and steroid and the schedule of administration. In this issue of TRANSFUSION, Dale et a1.* report on the collection of a mean of 7.7 x loio PMNs from donors given G-CSF (600 mg, subcutaneously) and dexamethasone (8 mg, by mouth) 12 hours before leukapheresis (hetastarch:blood = 1:13; 10 L donor blood processed). Both G-CSF and corticosteroids are known to alter PMN functions, but they exert relatively minor effects at the doses administered to donors for PMN c~llection.~-~When overall cellular functions are studied, the properties of PMNs collected from donors stimulated with a single dose

A survey of Canadian neonatal blood transfusion practices.

In 1990, the Pediatric Hemotherapy Committee of the American Association of Blood Banks developed and distributed a questionnaire addressing neonatal blood transfusion practices. The same questionnaire was subsequently sent to Canadian university-affiliated hospitals (n = 92). This report describes the results of the Canadian survey. Seventy-two percent (n = 66) of institutions contacted responded. Of these 42% (n = 28) had sufficient experience with neonatal transfusions and provided sufficient data for analysis. Although the majority of stated practices did follow published guidelines, several areas of variability and/or suboptimal practices were identified. With respect to component selection and preparation, suboptimal practices included excessive pretransfusion testing, unnecessary routine washing of RBC concentrates for small-volume transfusions, routine volume reduction of platelet concentrates and the use of suboptimal granulocyte preparations. With respect to transfusion practices, a disturbingly high percentage of respondents indicated that frozen plasma would be given in situations generally considered inappropriate. There was a great deal of variability in the provision of blood components at low risk for CMV, in the use of gamma irradiation and in the platelet count used for prophylactic platelet transfusions. The data collected in this survey provide information concerning practices that require improvement, identify areas where further research is desirable and provide a basis for comparison with current and future neonatal blood transfusion practices.

Concurrent comparison of the safety of paid cytapheresis and volunteer whole-blood donors.

Background: Historically, paid blood donors were found to transmit hepatitis at higher rates than volunteers. In those older studies, paid donors frequently were recruited from prisons or slum areas–a finding consistent with the belief that monetary payment in itself did not necessarily lead to the high‐risk status of commercial blood. Instead, it was the population base from which the donors were recruited that was important.