A multicentre study investigating vital sign changes occurring in complicated and uncomplicated transfusions.

BACKGROUND AND OBJECTIVES: Many hospitals require transfusions to be discontinued when vital signs stray from predetermined ranges, regardless of clinical symptoms. Variations in vital signs may be unrelated to transfusion, however, and needlessly stopping a transfusion may delay medical care while increasing donor exposures and healthcare costs. We hypothesized that a detailed study of vital sign changes associated with transfusion of blood product by component, including those associated with potential reactions (complicated) and those deemed to be uncomplicated, would establish a useful framework of reference for treating clinicians and transfusion services alike. MATERIALS AND METHODS: A retrospective electronic record review of transfusion service and transfusion recipient data was completed on 3852 inpatient transfusion episodes over a 6-month period at four academic tertiary care hospitals across the United States. Vital signs pre- and post-transfusion were recorded by trained clinical research nurses. Serious reactions were adjudicated by a panel of transfusion medicine experts. RESULTS: In both uncomplicated transfusions (n = 3765) and those including an adverse reaction (n = 87), vital sign fluctuations were generally modest. Compared to uncomplicated transfusions, transfusions complicated by febrile reactions were associated with higher pretransfusion temperature and higher pretransfusion pulse rates. Episodes of transfusion circulatory overload were associated with higher pretransfusion respiration rates compared to uncomplicated transfusions. CONCLUSION: Most transfusions are associated with only modest changes in vital signs. Pretransfusion vital signs may be an important yet previously understudied predictor of vital sign changes during transfusion. The optimal role of vital sign assessment during blood transfusion deserves further study.

Clinical and laboratory correlates of platelet alloimmunization and refractoriness in the PLADO trial.

BACKGROUND AND OBJECTIVES: Platelet alloimmunization and refractoriness to platelet transfusion are complications of platelet transfusion therapy. The platelet dose (PLADO) trial, as the largest prospective randomized trial of prophylactic platelet therapy to date, afforded an opportunity to analyse these two issues. MATERIALS AND METHODS: PLADO patient records were examined for evidence of platelet alloimmunization, defined as an increase in HLA Class I panel-reactive antibodies (PRA) to ≥20%, and clinical refractoriness, defined as two consecutive ≤4 h posttransfusion corrected platelet count increments (CCI) of <5000. Multivariate logistic regression, restricted to platelet-transfused subjects who received exclusively either in-process leucoreduction apheresis or whole blood-derived (WBD) leucocyte-reduced platelets, compared the frequency of these outcomes by platelet unit and patient characteristics. RESULTS: Forty of 816 evaluable platelet-transfused patients (5%) became alloimmunized during the trial. Prior pregnancy, chemotherapy only compared to progenitor cell transplant, and low platelet dose - all were associated with significantly higher rates of alloimmunization. Among 35 alloimmunized patients evaluated for refractoriness, 8 (23%) had two consecutive CCI < 5000/µl. Regardless of alloimmunization status, CCIs < 5000/µl were observed following 17% of platelet transfusions. Among 734 patients receiving at least two platelet transfusions, two consecutive CCIs of ≤5000 occurred in 102 (14%). CONCLUSIONS: The incidence of new platelet alloimmunization was low in the PLADO study, but follow-up was at most 30 days. Alloimmunization was present in only 8 of 102 (8%) of observed cases of refractoriness, suggesting that other causes of poor posttransfusion increments are frequent.

New granulocyte antigens demonstrated by microgranulocytotoxicity assay.

Although granulocyte transfusions and bone marrow transplantation are becoming common clinical modalities, our knowledge of surface nonerythroid, nonlymphoid, non-HLA hematopoetic antigens remains very incomplete. Accordingly, we have systematically screened sera from recipients of multiple granulocyte and whole blood transfusions, and immunoneutropenic patients for antibodies directed primarily at granulocytes. The initial screens demonstrated that >50% of the sera from the above sources contained non-HLA cytotoxic and/or agglutinating antibodies. Preliminary clustering indicated seven possible new specificities detected by microgranulocytotoxicity. Calculations for Hardy-Weinberg goodness of fit based on a study of 98 unrelated donors plus informative families established that 5 of these were alleles of a single new locus termed Human Granulocyte Antigen (HGA)-3a, b, c, d, and e. Absorptions indicated that these antigens were present on mature granulocytes but absent from platelets, lymphocytes, monocytes, and myeloid precursors. A single antigen of another separate locus, HGA-1, was also identified. Absorptions revealed a quite different distribution for HGA-1 than HGA-3, this antigen being detected on monocytes and myeloblasts as well as on mature granulocytes. Independent segregation of the three loci from HLA, from the NA-NB and the 5a-5b antigens, and from themselves was confirmed in informative families.Finally, it seems likely that other antigens will be identified because several other sera that react with both monocytes and granulocytes have been detected.

Randomized study of prophylactic platelet transfusion threshold during induction therapy for adult acute leukemia: 10,000/microL versus 20,000/microL.

PURPOSE: We designed and conducted a randomized single-institution trial comparing two common prophylactic platelet transfusion thresholds in patients undergoing induction therapy for acute leukemia. PATIENTS AND METHODS: Seventy-eight patients undergoing induction therapy for acute leukemia were randomized to receive prophylactic apheresis platelet concentrates when the platelet count was either < or = 10,000/microL or < or = 20,000/microL. RESULTS: There was no significant difference in the total number of bleeding episodes per patient with a median of four in the < or = 10,000/microL arm and two in the < or = 20,000/microL arm (25th to 75th percentiles of 2, 7 and 1, 5, respectively; P = .12). Patients randomized to the < or = 10,000/microL arm received more platelet transfusions for bleeding [one (0, 2) v zero (0, 0); P = .0003]. In contrast, patients on the < or = 20,000/microL arm received more platelet transfusions for prophylactic indications [10 (5, 14) v six (3, 8); P = 0.001], as would be expected, but less for bleeding. Nevertheless, the total number of platelet transfusions given to patients on the < or = 20,000/microL arm was higher and nearly significant [11 (6, 15) v seven (5, 11); P = .07]. There were no statistically significant differences between the groups with regard to RBC transfusion requirements, febrile days, days hospitalized, days thrombocytopenic, need for HLA-matched platelets, remission rate, or death during induction chemotherapy. No patient in either group died from hemorrhage or underwent major surgery for bleeding complications. CONCLUSION: Giving prophylactic platelets at a threshold of < or = 10,000/microL compared with < or = 20,000/microL can decrease the total utilization of platelets with only a small adverse effect on bleeding, and no statistically significant effect on morbidity.

Uptake of extracellular calcium by neonatal neutrophils.

Neutrophils from human neonates exhibit abnormalities of plasma membrane and cytoskeletal dependent functions such as chemotaxis, deformability, and lectin capping. The uptake of extracellular calcium by neutrophils is a key early event in neutrophil activation and in the optimal performance of these functions. We found that neonatal and control neutrophils acquire extracellular radioactive calcium comparably under most experimental conditions. No differences (P greater than 0.05) were seen between neonatal and control neutrophils following stimulation with soluble sodium fluoride, N-formyl-methionyl-L-leucyl-L-phenylalanine, dimethylsulfoxide, and opsonized zymosan particles. However, the uptake of calcium by resting (unstimulated) neutrophils was significantly less (P less than 0.0001) by neonatal cells. The kinetics of calcium uptake by neonatal and control neutrophils were similar both at rest and following stimulation for 15 min with sodium fluoride. Although additional studies will be necessary to completely define the ionic events involved in the chemotaxis of neonatal neutrophils, it seems unlikely that the abnormal mobility of these cells is due simply to an inability of neonatal neutrophils to acquire extracellular calcium in response to cellular stimulation.

Iron deficiency, infections, and immune function: a reassessment.

Many physicians believe that patients with iron deficiency have an increased susceptibility to infections. Data in the literature, however, are contradictory, and in many instances the reports are vulnerable to critical review. Literature available through 1976 was analyzed in an attempt to define possible relationships between infections, immune function, and states of iron imbalance, both iron deficiency and overload. Critical points that must be considered for an accurate interpretation were emphasized. It seems clear that the inflammatory response, when assessed by skin reactivity, is diminished in iron deficiency. The precise molecular defect remains undefined, but the abnormality is detected by several assays measuring cell-mediated immunity. Normal function is usually restored following iron repletion.

Prediction of early beneficial response to plasma exchange in Guillain-Barré syndrome.

We attempted to identify predictive factors of early beneficial response to plasmapheresis in Guillain-Barré syndrome (GBS). We reviewed 24 patients with typical severe GBS who underwent plasmapheresis and analyzed their outcome at one month. One group of 14 patients, designated as responders, improved dramatically, while ten patients showed little response. Age was the only important clinical predictor, with responders being younger. No other clinical variable (sex, preceding illness, severity, timing of plasmapheresis, cranial nerve involvement, or cerebrospinal fluid findings) reached significance. Among electrophysiologic parameters obtained before plasmapheresis, the amplitudes of compound muscle action potentials with distal stimulation of median and peroneal nerves were significantly reduced in non-responders. Plasmapheresis may improve only a subgroup of patients with GBS. Among patient characteristics, age and amplitudes of compound muscle action potentials are important predictors of early responsiveness.

Status epilepticus in pregnancy: effect of phenytoin malabsorption on seizure control.

In the second trimester of pregnancy in a 26-year-old woman, marked exacerbation of epileptic seizures occurred with somatomotor status epilepticus. The oral requirement of phenytoin varied, and up to 1,200 mg per day were needed to maintain a therapeutic plasma concentration during the second trimester. Intestinal malabsorption was shown to be a causal factor; 56 percent of the daily oral dose of phenytoin was found in the stool. Late in pregnancy and postpartum, therapeutic plasma concentrations of phenytoin were maintained with decreased daily oral doses. Intestinal absorption improved postpartum.

Therapeutic neutrophil transfusions: are controlled studies no longer appropriate?

The aim of this review is to determine whether sufficient data have been reported to completely define the role and/or efficacy of neutrophil transfusions in the treatment of specific types of infections in neutropenic patients. Data were collected from the literature pertaining to the use of therapeutic neutrophil transfusions. When only the controlled studies are analyzed, a significant therapeutic advantage for neutrophil transfusions plus antibiotics can be demonstrated when this treatment is compared to treatment with antibiotics alone. However, the controlled studies are vulnerable to critical analysis, and several points argue against applying data from these studies indiscriminately to all infected, neutropenic patients encountered in practice. Moreover, it is apparent when all of the data (controlled and uncontrolled studies) are tabulated, that information is insufficient to establish the efficacy of neutrophil transfusions as treatment for most types of specific bacterial infections. Several problems exist in the wholesale acceptance of liberal transfusion policies, and the benefits that justify continued controlled studies deserve emphasis.

National survey of neonatal transfusion practices: I. Red blood cell therapy.

Neonatal blood component transfusion practices during 1989 were surveyed via a questionnaire developed by the Pediatric Hemotherapy Committee of the American Association of Blood Banks. Of 1790 questionnaires mailed, 452 were selected to form the database for this analysis because they were from institutions in which neonates were transfused. Nearly all institutions contained intensive care units directed by neonatologists and were involved in the management of high-risk infants. Results from institutions serving as the primary pediatric teaching hospital of a medical school were compared with those with no medical school affiliation. Thirty-six percent of primary pediatric teaching hospitals and 52% of hospitals with no medical school affiliation performed pretransfusion testing in excess of that required, resulting in additional blood loss in neonates. Sixty-six percent of primary pediatric teaching hospitals used fresh frozen plasma to adjust the hematocrit of red blood cell concentrates prior to transfusion (a practice increasing donor exposure), compared with only 29% of hospitals with no medical school affiliation. The usual indication for small-volume red blood cell transfusions in severely ill neonates was to maintain a desired hematocrit level, whereas for stable infants, red blood cell transfusions were given to treat symptomatic anemia, rather than to maintain a predetermined hematocrit. As found in 1985, neonatal transfusion practices in 1989 were variable. However, improvements have occurred since 1985 to suggest that further research and educational efforts may serve to promote even better neonatal transfusion therapy.

National survey of neonatal transfusion practices: II. Blood component therapy.

Neonatal transfusion practices during 1989 of 452 institutions involved in transfusing infants were surveyed by questionnaire. Most respondents (77%) transfused fresh frozen plasma appropriately (ie, primarily to treat coagulation disorders). However, 11% stated that their most frequent use of fresh frozen plasma was solely to treat hypovolemia, a practice generally not recommended. Seventy-eight percent of respondents transfused platelets to treat bleeding infants with blood platelet counts of less than 50 x 10(9)/L; 84% gave platelets to sick, premature neonates with counts of less than 50 x 10(9)/L whether or not bleeding was evident. Only 35% of respondents transfused granulocytes for neonatal sepsis; most institutions used buffy coats isolated from units of blood--a product readily available, but of questionable efficacy when compared with leukapheresis granulocytes. Ninety-three percent of respondents provided blood components with low risk of transmitting cytomegalovirus: components from seronegative donors were used by 84%, leukocyte-reduced products by 6%, and a combination by 10%. Thirteen percent of respondents gave gamma-irradiated blood components to all and 46% gave them to some neonates to prevent graft vs host disease. Forty-one percent did not routinely irradiate. Ten percent of respondents used leukocyte reduction instead of gamma irradiation to prevent graft vs host disease, a practice currently not advocated. Thus, national transfusion practices for neonates are variable, controversial, and, occasionally, other than those usually recommended. Additional research and educational efforts are needed to ensure optimal transfusion therapy.

Prophylactic T cell infusion after T cell-depleted bone marrow transplantation in patients with refractory lymphoma.

Fifty-two patients with refractory lymphoma were prospectively treated with prophylactic T lymphocyte infusion after T cell-depleted allogeneic bone marrow transplantation, to induce graft-versus-lymphoma effect. Thirty-three patients had related donors; 19 had unrelated donors. After transplantation with marrow that had 0.8 +/- 0.4 x 10(5)CD3(+) cells/kg, T cells up to 1.75 x 10(6) CD3(+) cells/kg were given over 3 months provided > or = grade II acute graft-versus-host disease (GVHD) was not seen. The cumulative incidence of grades II-IV acute GVHD was 69%. Twenty of 32 evaluable patients (63%) developed chronic GVHD. Ten patients (19%) died of GVHD. The Kaplan-Meier 5-year overall survival of all patients was 34%. On multivariate analyses, chronic GVHD was significant for relapse (hazard ratio of 1.7, P < 0.05), and for overall survival (hazard ratio 1.4, P < 0.001). Chemosensitivity was significant for relapse only on univariate analysis. Patients who developed chronic GVHD had 4 years median survival, compared with 9 months in patients without chronic GVHD, P < 0.001. The study shows that patients with chronic GVHD have superior survivals, most probably related to a graft-versus-lymphoma effect, which could be modulated by prophylactic T cell infusion.

A dose escalation study for salvage chemotherapy in patients with refractory lymphoma prior to high-dose myeloablative therapy with stem cell transplantation.

Chemosensitive response prior to transplantation has been shown to be most significant for survival post transplant. To estimate toxicity of a dose-intensive regimen that was to improve chemosensitive response rate, 15 patients with primary refractory lymphoma were enrolled in dose escalation of pre-transplant salvage chemotherapy. The first cycle had a fixed dose of ifosfamide 6 g/m2 and mitoxantrone 12 mg/m2, with arabinosyl cytosine (Ara-C) 2 g/m2, and methylprednisolone 2.0 g. Each cycle of the second and third had cisplatin 90 mg/m2, Ara-C 6 g/m2, methylprednisolone 2.0 g, and escalated doses of ifosfamide from 7.5 g/m2 to 15 g/m2 and mitoxantrone from 16 to 28 mg/m2. Blood stem cells were collected before the second cycle and > or = 3 x 10(6) CD34 cells/kg were infused 2 days after the second and third cycles, respectively. The maximum tolerated doses of ifosfamide and mitoxantrone were 11.25 g/m2 and 16 mg/m2, respectively. Acute renal failure and bacterial infection occurred as non-hematologic dose limiting toxicities. Eleven patients completed therapy. Five patients achieved complete remission and five had partial remission. Nine patients received autologous and four received allogeneic transplants. Currently, six are alive without evidence of disease, with a 3-year survival of 40%. Although preliminary, the regimen suggests acceptable toxicity and significant activity that warrants further study.

Donor T-lymphocyte infusion for unrelated allogeneic bone marrow transplantation with CD3+ T-cell-depleted graft.

In T-cell-depleted allogeneic bone marrow transplantation (TCD-BMT) using unrelated donors, the role of donor lymphocyte infusion (DLI) for survival and disease control has not been defined. In a study of 116 patients (92 matched, 24 mismatched) who received CD3+ T-cell-depleted marrow graft, sequential infusions of escalated doses of donor T lymphocytes up to 1 x 10(6) CD3+ cells/kg were prospectively investigated. T cells were administered while patients were on cyclosporine, provided >or=grade II acute graft-versus-host-disease (GVHD) had not occurred. Acute GVHD of >or=grade II occurred in 27 of 110 (25%) patients before DLI and in 39 of 79 (49%) patients after DLI. In total, 12 of 27 (44%) patients without DLI and 44 of 72 (61%) patients who received DLI developed chronic GVHD. A total of 19 patients died of GVHD, with 17 of acute and two of chronic GVHD. Overall survival (OS) and event-free survival (EFS) at 5 years were 27 and 21%, respectively. The 2-year incidence of relapse was 14%. In multivariate analysis, only chronic GVHD was a good prognostic factor for both OS: hazard ratio (HR) 1.4, P=0.04, and EFS: HR 1.6, P=0.01. Both acute and chronic GVHD were favorable prognostic factors for relapse probability: HR 1.9 for both, P=0.02, 0.01, respectively. The 1-year cumulative incidence of transplant-related mortality (TRM), excluding cases of GVHD, was 42%. The two most common causes of 1-year non-GVHD death were viral infection (9%) and idiopathic pneumonia syndrome (12%). Although the incidence of relapse was low, the study suggests that the current scheme of DLI in unrelated TCD-BMT would not improve survival unless TRM decreases significantly.

The epidemiology of cytomegalovirus infection among patients with burns.

To determine the epidemiology of cytomegalovirus (CMV) infections among patients with burns, we prospectively studied 120 burn patients admitted to the University of Iowa Burn Center over a two-and-one-half year period. At the time of their admission, 44% of the patients had serologic evidence of prior CMV infection. Among 44 seropositive patients, 23 (52%) had four-fold or greater rises in CMV antibody titers. These patients had more severe burns (mean body surface area burn [BSAB] 26.8%) than those who did not exhibit titer rises (mean BSAB 16.2%, p = .04). Among 43 seronegative patients observed for at least 65 days after discharge from the center, eight (18.6%) seroconverted. Patients who seroconverted had longer hospital stays (p = .03), trends toward more severe burns (p = .08) and a younger age (p = .15) than patients who remained seronegative. Despite frequent serologic evidence of CMV infection, CMV did not contribute, either directly or indirectly, to the morbidity or mortality of burns in these patients.

Practical issues in neonatal transfusion practice.

Small premature infants frequently require transfusions of blood components, particularly red blood cells (RBCs), during the first weeks of life. Although great efforts have been made during the past few years to optimize the transfusion of blood components to these tiny patients, several questions have not been definitively answered. Accordingly, transfusion practices vary among neonatologists. The purpose of this article was to assess the available data critically. The findings indicated that stored RBCs can be transfused safely into premature infants to diminish donor exposures. It was also found that leukocyte-reduced blood components can be used to prevent the transmission of cytomegalovirus; thus, cellular components do not need to be obtained exclusively from donors negative for antibodies to cytomegalovirus. However, gamma-irradiation of cellular blood components cannot be justified for all neonatal transfusions. Obviously, as new information is reported, these findings may require revision.

Serum volumes should not be reduced when testing neonates for unexpected red cell antibodies.

Serum-to-red cell ratio (volume:volume) significantly affects the sensitivity of antibody detection. Obtaining sufficient serum quantity can be a problem when testing blood from transported neonates not accompanied by maternal samples. Reducing serum volumes used for testing might result in missed antibodies. The authors studied 1,177 sera for unexpected red cell antibodies by comparing one versus two drops of patient serum using a technique with LISS at 37 degrees C through the antiglobulin phase. The serum-to-red cell ratio using two drops was approximately 50: 1. Results of 60% (58/96) of samples containing antibody benefited by the use of increased serum. Eighteen percent; (17/96) had antibodies detected only with two drops that were missed entirely by one, and 43% (41/96) showed stronger positive reactions using two drops versus one. Importantly, antibodies detected only with or enhanced by two drops were clinically significant (anti-D, anti-K, anti-M, anti-c, anti-E). Thus, reducing serum-to-cell ratio is potentially dangerous, and blood banks should insist on adequate sample size to ensure patient safety.

Development of alloanti-Jka in a patient with hemolytic anemia due to autoanti-Jkb.

Autoanti-Jkb and a transient autoanti-E were identified in a patient with autoimmune hemolytic anemia, and red blood cells negative for Jkb and E antigens were transfused. Twelve weeks after transfusion, the autoantibody appeared to have developed broad specificity. However, autoadsorption studies revealed that the broad reactivity was due to the development of alloanti-Jka in addition to the autoanti-Jkb. Distinguishing this combination of alloanti-Jka plus autoanti-Jkb from an autoantibody with broad specificity will be important in selecting Jka antigen-negative red cells for subsequent transfusions. This case emphasizes the importance of additional serologic testing to detect alloantibodies in patients with broadly reactive warm autoantibodies.