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.

Red blood cell concentrates treated with the amustaline (S-303) pathogen reduction system and stored for 35 days retain post-transfusion viability: results of a two-centre study.

BACKGROUND AND OBJECTIVES: Pathogen reduction technology using amustaline (S-303) was developed to reduce the risk of transfusion-transmitted infection and adverse effects of residual leucocytes. In this study, the viability of red blood cells (RBCs) prepared with a second-generation process and stored for 35 days was evaluated in two different blood centres. MATERIALS AND METHODS: In a single-blind, randomized, controlled, two-period crossover study (n = 42 healthy subjects), amustaline-treated (Test) or Control RBCs were prepared in random sequence and stored for 35 days. On day 35, an aliquot of 51 Cr/99m Tc radiolabeled RBCs was transfused. In a subgroup of 26 evaluable subjects, 24-h RBC post-transfusion recovery, mean life span, median life span (T50 ) and life span area under the curve (AUC) were analysed. RESULTS: The mean 24-h post-transfusion recovery of Test and Control RBCs was comparable (83·2 ± 5·2 and 84·9 ± 5·9%, respectively; P = 0·06) and consistent with the US Food and Drug Administration (FDA) criteria for acceptable RBC viability. There were differences in the T50 between Test and Control RBCs (33·5 and 39·7 days, respectively; P < 0·001), however, these were within published reference ranges of 28-35 days. The AUC (per cent surviving × days) for Test and Control RBCs was similar (22·6 and 23·1 per cent surviving cells × days, respectively; P > 0·05). Following infusion of Test RBCs, there were no clinically relevant abnormal laboratory values or adverse events. CONCLUSION: RBCs prepared using amustaline pathogen reduction meet the FDA criteria for post-transfusion recovery and are metabolically and physiologically appropriate for transfusion following 35 days of storage.

Incidence and clinical characteristics of transfusion-associated circulatory overload using an active surveillance algorithm.

BACKGROUND: The concordance of haemovigilance criteria developed for surveillance of transfusion-associated circulatory overload (TACO) with its clinical diagnosis has not been assessed. In a pilot study to evaluate an electronic screening algorithm, we sought to examine TACO incidence and application of haemovigilance criteria in patients with post-transfusion pulmonary oedema. STUDY DESIGN AND METHODS: From June to September 2014, all transfused adult inpatients at four academic hospitals were screened with an algorithm identifying chest radiographs ordered within 12 h of blood component release. Patients with post-transfusion pulmonary oedema underwent case adjudication by an expert panel. TACO incidence was calculated, and clinical characteristics were compared with other causes of post-transfusion pulmonary oedema. RESULTS: Among 4932 transfused patients, there were 3412 algorithm alerts, 50 cases of TACO and 47 other causes of pulmonary oedema. TACO incidence was 1 case per 100 patients transfused. TACO classification based on two sets of haemovigilance criteria (National Healthcare Safety Network and proposed revised International Society for Blood Transfusion) was concordant with expert panel diagnosis in 57% and 54% of reviewed cases, respectively. Although the majority of clinical parameters did not differentiate expert panel adjudicated TACO from other cases, improved oxygenation within 24 h of transfusion did (P = 0·01). CONCLUSIONS: The incidence of TACO was similar to that observed in prior studies utilizing active surveillance. Case classification by haemovigilance criteria was frequently discordant with clinical diagnoses of TACO in patients with post-transfusion pulmonary oedema. Improvements in oxygenation within 24 h of transfusion merit further evaluation in the diagnosis of TACO.

Incidence of weak D in blood donors typed as D positive by the Olympus PK 7200.

The incidence of weak D has been reported to be between 0.23 and 0.5 percent in Europe and 3.0 percent in the United States. All studies were performed before the introduction of monoclonal anti-D reagents. Using current commercial reagents, this study evaluated D+ samples for the presence of weak D. D+ donors, typed by the Olympus PK 7200, using diluted monoclonal blend anti-D and diluted polyclonal anti-D, were selected by sampling batches of 100 to 200 samples from the previous day's collection. Anti-D reagents used on the Olympus PK 7200 are required to detect RBCs with the weak D phenotype which do not agglutinate at immediate spin (IS) when tested with polyclonal anti-D by manual tube methods. More than 95 percent of donors tested were Caucasian. Using tube tests with two different monoclonal blend anti-D reagents and one polyclonal anti-D typing reagent, the presence or absence of the D antigen was evaluated after the IS reading. Donors found negative or weakly positive (< 2+) at IS were further typed for weak D by the IAT. The weak D samples were RHD genotyped by allele-specific PCR. Of 1,005 donors tested, 4 (0.4%) were classified as weak D by one or more anti-D reagents. Polyclonal anti-D reagent demonstrated weaker reactions when compared with the monoclonal blends. All weak D samples were found positive for exon 4, intron 4, and exon 10, a finding consistent with most D+ samples. The incidence of weak D found in this study is not significantly different from that found in earlier studies using polyclonal anti-D reagents.

Autoimmune thyroid phenomena are not evidence for human lymphocyte antigen-genetic heterogeneity in insulin-dependent diabetes.

It is well established that there is genetic heterogeneity between a human lymphocyte antigen (HLA)-DR3-associated allele and an HLA-DR4-associated allele in insulin-dependent diabetes mellitus (IDDM). Equally well established are the association of DR3 with Graves' disease and other autoimmune disorders in nondiabetics and the increased prevalence of autoimmune thyroid disease in IDDM. Perhaps in large part because of these facts, it has been postulated that there are two major forms of classical IDDM--one form characterized by coexistent autoimmune disease, such as autoimmune thyroid disease which is associated with DR3, and another form not associated with additional autoimmune disorders, which is associated with DR4. Several studies have repudiated the idea of specific clinical findings in IDDM being associated exclusively with DR4. However, the DR3-thyroid association in IDDM has not been investigated carefully. Therefore, in order to study this putative association, we divided a group of diabetic children into overlapping subgroups based on thyroid enlargement, antithyroid microsomal antibodies, acquired hypothyroidism, and no evidence of thyroid disease. The distributions of HLA-DR3 and -DR4 among these subgroups did not differ from each other; nor did the distribution of the HLA alleles differ from those of randomly selected IDDM individuals. These results suggest that thyroid autoimmunity in IDDM is part of the IDDM "syndrome" and is associated with DR3 and DR4 to the same extent that IDDM without thyroid disease is associated with these two antigens. Thus, although genetic studies are consistent with the heterogeneity between DR3 and DR4 in IDDM, there is no HLA-thyroid disease association to support this heterogeneity.

Autoimmune hemolytic anemia following T cell-depleted allogeneic bone marrow transplantation.

The development of immune-mediated hemolytic anemia is a well-recognized complication after allogeneic bone marrow transplantation (BMT). The majority of reported cases, however, have been alloimmune in origin due to ABO or minor red blood cell antigen incompatibilities between the donor and recipient. In this study, we report seven adult patients who developed autoimmune hemolytic anemia (AIHA) between June 1985 and January 1993. These patients were identified from a total of 236 adult patients who received T cell-depleted (TCD) grafts as graft-versus-host disease (GVHD) prophylaxis. The onset of AIHA was at a median of 10 months (range 7-25 months) post-transplant and occurred in 5% of all patients transplanted with TCD grafts who survived at least 6 months. Six patients had a warm reacting autoantibody, while one patient had a cold-reacting antibody with a thermal amplitude up to 30 degrees C. All were receiving immunosuppressive treatment for GVHD at the time of diagnosis. Initial treatment in all patients consisted of steroids. Three of the seven had a partial response while the four remaining patients failed to respond to corticosteroids. Splenectomy was performed in three patients with two partial responses. Four patients were treated with additional therapeutic interventions, including plasmapheresis, immunoglobulin infusions, staphylococcus protein A column, or other immunosuppressive agents. In five cases, erythropoietin was administered as adjunctive treatment to maintain adequate hematocrit levels. Two patients are presently in complete remission after prolonged courses of steroids, while a third patient has compensated hemolysis requiring low-dose steroids. Four patients died due to either infectious complications or disseminated intravascular coagulation secondary to cold agglutinin disease. These data indicate that AIHA is a clinically significant and not infrequent complication in allogeneic marrow transplant recipients. The response to conventional treatment is generally unsatisfactory as even patients who ultimately remit require prolonged courses of immunosuppressive therapy.

Molecular remission occurring after donor leukocyte infusions for the treatment of relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation.

Donor leukocyte infusions were administered to a patient who had relapsed with chronic myelogenous leukemia after having failed two successive HLA-matched allogeneic bone marrow transplants. Serial cytogenetic, restriction fragment length polymorphism, and polymerase chain reaction studies of the patient's marrow and blood after receiving donor leukocyte infusions revealed disappearance of the leukemic clone and the establishment of complete donor chimerism. An antileukemic response in this patient occurred initially in the absence of clinically evident graft-versus-host disease (GVHD), but complete eradication of the leukemic clone did not occur until after the onset of GVHD. The patient is now 48 weeks post infusion and remains in complete remission. This case demonstrates that leukocyte infusions are an effective form of adoptive immunotherapy which can result in a sustained molecular remission.

Effect of hemolysis on apparent values of platelet-associated IgG.

Addition of red blood cells hemolyzed in the presence of dilute plasma in quantities equivalent to as little as 0.2% hemolysis of red blood cells in whole blood caused significant elevation in the apparent value of IgG associated with platelets (PAIgG) isolated from the preparation. Addition of hemolysate to plasma containing low concentrations of platelets, simulating that obtained from thrombocytopenic patients, caused more striking elevations in apparent PAIgG. Centrifugation of platelet-rich plasma containing hemolysate through a 30% solution of Percoll restored the value of PAIgG essentially to normal. Additional studies using simulated patient whole blood samples anticoagulated with EDTA yielded similar results. The apparent elevation of PAIgG in these preparations appears to result from IgG-bearing membranous material and microspherocytes that co-isolate with platelets separated from blood by conventional methods. Caution should be used in interpreting the results of PAIgG measurements on platelets isolated from blood samples in which even minimal in vitro hemolysis has occurred.

Evaluation of cerebrospinal fluid mononuclear cells obtained from children with acute lymphocytic leukemia: advantages of combining cytomorphology and terminal deoxynucleotidyl transferase.

Sixty cerebrospinal fluid (CSF) samples were obtained from 28 children with terminal deoxynucleotidyl transferase (TdT) positive acute lymphocytic leukemia (ALL). Cell morphology was evaluated using Wright's stained cytocentrifugation prepared slides. The presence of nuclear TdT was detected by an immunofluorescent (IF) assay. Evaluation of CSF mononuclear cells using these two methods simultaneously allowed us to differentiate between leukemic and nonleukemic pleocytosis. Agreement between cytomorphology and TdT in identifying CNS lymphoblasts was found in 55 of 60 samples. Seventy-two per cent of the TdT-positive samples were obtained from children with CSF cell counts less than 10 WBC/mm3. We recommend that these two methods be used in conjunction when evaluating CSF mononuclear cells from children with TdT positive ALL.

A platelet aggregating factor in thrombotic thrombocytopenic purpura: initial activity, fluctuations, and removal by plasma exchange.

A factor capable of aggregating normal platelets was found in the plasma of six consecutive patients with thrombotic thrombocytopenic purpura (TTP). The activity of the aggregating factor in whole plasma, the cold protein fraction from plasma and the residual supernatant was monitored during each patient's course of therapeutic plasma exchange. Although two patients demonstrated the highest level of aggregating activity at the time of diagnosis, the level fluctuated in five of six patients. Increasing levels of activity were usually accompanied by signs of clinical deterioration. Activity repeatedly within the normal range was not seen until remission of the syndrome. Neutralization of the aggregating activity in vivo through removal of patient plasma and replacement with fresh frozen plasma (plasma exchange) was accomplished less readily and less predictably than by mixing patient plasma and normal plasma in vitro. Use of the aggregating factor level in evaluating the need of plasma exchange is discussed.

Comparing the transfusion medicine content of the NBME's examinations in 1984-1985 and 1989-1990.

Recognition of the seriousness of transfusion-transmitted diseases has been demonstrated by U.S. medical schools through the integration of transfusion medicine (TM) content into their curricula. To evaluate the degree to which these changes in curricula have been reflected in the National Board of Medical Examiners' (NBME) examinations, a study conducted in 1991 evaluated the proportions of TM-related items on Parts I and II of the NBME examinations for 1984-1985 versus 1989-1990. Both Part I (basic sciences) and Part II (clinical sciences) demonstrated significant gains in TM items between the comparison periods (p less than .001), with Part II having the higher gain. An analysis of students' knowledge revealed that students in 1989-1990 tended to perform better on TM items than on examination items generally. The increases in TM content and student performance on TM items on the 1989-1990 examinations suggest that the national effort to expand and improve teaching of TM in U.S. medical schools has been effective.

Use of deoxyribonucleic acid (DNA) fingerprints for identity determination: comparison with traditional paternity testing methods--Part II.

Six red blood cell (RBC) antigen systems, coupled with human lymphocyte antigen (HLA) phenotyping, were used to establish paternity on 28 mother/child/alleged-father trios. Samples were subsequently examined using the deoxyribonucleic acid (DNA) fingerprinting test with the multilocus Jeffreys DNA probes 33.6 and 33.15. In 27 of 28 paternity cases, the DNA fingerprinting test results supported and enhanced the results of RBC and HLA typing by resolving disputed paternity cases conclusively. One discrepancy between conventional serological methods and DNA analysis is discussed.

Clinical features of thrombotic thrombocytopenic purpura.

1. Thrombotic thrombocytopenic purpura (TTP) is a serious acute disorder, characterized by hemolytic anemia with fragmented RBC, thrombocytopenic purpura, progressive neurologic disturbances, but no significant impairment in renal function. 2. The natural course of TTP is rapidly progressive and, if untreated, will result in the death of the patient shortly after its onset.

Complete remission of paraneoplastic sensorimotor neuropathy: a case associated with small-cell lung cancer responsive to chemotherapy, plasma exchange, and radiotherapy.

A 61-year-old man was found to have small-cell lung cancer following a 1-year history of a progressive peripheral sensorimotor neuropathy. The neuropathy initially improved following chemotherapy, but subsequently progressed to the point of respiratory failure. Treatment with plasma exchange, additional chemotherapy, and radiotherapy resulted in a sustained complete tumor remission and neurologic recovery. The role of plasma exchange is unclear, but its use should be considered in cases of severe sensorimotor neuropathy unresponsive to antineoplastic treatment.

The morphologic changes of the rat type II pneumocytes induced by oxytetracycline.

Ultrastructural changes in pulmonary alveoli of adult Sprague-Dawley rats administered oxytetracycline (1 mg. per ml.) in their drinking water were compared with those of control rats whose drinking water contained no antibiotics. Groups of rats were sacrificed after 4 and 8 weeks of oxytetracycline treatment. Type II pneumocytes of oxytetracycline-treated rats showed an increase in size and number of lamellar bodies, as well as in their cell volume, when compared with controls. Electron microscopic morphometry confirmed these findings; the lamellar inclusion bodies increased 6 and 10 per cent and the cell volume increased 3 and 5 per cent at 4 and 8 weeks, respectively. The type I pneumocyte and alveolar macrophage showed engulfed myelin figures, and the Clara cells appeared quiescent. These findings suggest that the type II pneumocyte hypertrophy can be induced independently from the diffuse alveolar damage. The oxytetracycline treatment may provide a model system in which the pathologic morphology and function of the type II pneumocyte can be studied independently.

Studies of the minimum temperature at which human platelets can be stored with full maintenance of viability.

Platelet concentrates from normal donors were stored for 3 days under identical conditions except for the temperature of storage, which was maintained at 21 +/- 0.5, 19.5 +/- 0.5, or 18 +/- 0.5 degrees C. Immediate posttransfusion recovery of the stored platelets determined by 51Cr labeling averaged 47, 47, and 48 percent after storage at 21, 19.5, and 18 degrees C, respectively (differences not significant). Mean life span of the transfused platelets, however, was 8.12, 5.21, and 1.85 days at 21, 19.5, and 18 degrees C, respectively. The difference between mean life span following storage at 21 degrees C was significantly different from that after storage at 18 degrees C (p less than 0.03). Reduction in viability after storage at the lower temperature correlated with the reduction in the number of discoid platelets. These findings indicate that platelet viability is compromised after storage for 3 days at 18 degrees C and, possibly, at 19.5 degrees C, and illustrate the need for quality control of temperature in short-term platelet storage.

Why is fresh-frozen plasma transfused?

A three-part study to determine the reasons for fresh-frozen plasma (FFP) transfusions at hospitals in southeastern Wisconsin was conducted. During a 1-month period, hospital transfusion services reported that patients undergoing open-heart surgery received 42 percent, medical patients 26 percent, noncardiac surgery patients 23 percent, neonatal patients 1 percent, and other patients 7 percent of the FFP transfused. In the second phase of the study, the records of 102 patients receiving FFP during a 1-month period at two teaching hospitals were reviewed. Justification for the FFP transfusion was provided in the hospital chart for only 11 percent of the transfusion episodes, although abnormal results of coagulation studies or signs of hypovolemia were recorded for an additional 51 percent. Frequently, FFP and red cell (RBC) transfusions were given during the same transfusion episode. In the third phase of the study, clinicians completed a questionnaire specifying their "trigger" for prescribing FFP: bleeding (43% of episodes), abnormal coagulation studies (26%), signs/symptoms of hypovolemia (16%), and "other" (15%). They judged that the FFP transfusion was effective in 47 percent of transfusion episodes and ineffective in only 6 percent. These findings indicate that FFP is used mainly as a source of coagulation factor replacement in hospitals served by The Blood Center of Southeastern Wisconsin, that justification for FFP use rarely is provided in patient records, that both FFP and RBCs are frequently transfused together, and that clinicians believe FFP is beneficial for their patients. Educational efforts addressing appropriate use of FFP should be initiated.

Minimal evidence of platelet and endothelial cell reactive antibodies in thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is a syndrome characterized by microvascular thrombosis with thrombocytopenia and end-organ injury. Evidence suggests that platelet or endothelial cell injury may be initial pathological events in TTP. A number of factors in patient plasma, including immunoglobulins, have been proposed to mediate cellular injury in TTP. However, systematic analyses of TTP patient plasma for the presence of platelet or endothelial cell antibodies are lacking. We, therefore, analyzed 48 TTP patient plasma samples for the presence of platelet and endothelial cell antibodies by using enzyme-linked immunosorbent assay, flow cytometry, and microlymphocytotoxicity. Twelve of 48 TTP patient samples (25%) reacted against purified platelet glycoproteins. Nine (19%) also contained antibodies that bound to allogeneic target platelets in flow-cytometric assays. Nine of 48 samples (19%) contained antibodies to human umbilical vein endothelial cells in flow-cytometric assays, and seven of 48 patient samples (15%) bound to human dermal microvascular endothelial cells. Six of 48 (13%) patient plasma samples contained antibodies that bound to human umbilical vein endothelial cells activated with gamma-interferon and tumor necrosis factor-alpha. Of twenty samples that were reactive in one or more platelet or endothelial cell assay, eight contained human leukocyte antigen antibodies reactive in microlymphocytotoxicity. These studies demonstrate that antibodies reactive against platelet or endothelial cell antigens are not prevalent in TTP, and that more than a third of antibodies detected are human leukocyte antigen alloantibodies. Our findings suggest that autoantibodies against platelets or endothelial cells are not important in the pathogenesis of this syndrome.

Patterns of red blood cell use in southeastern Wisconsin.

We conducted a retrospective study of red blood cell use in southeastern Wisconsin to characterize transfusion practices and provide data for designing educational programs. Charts of 533 patients who received 3,006 units of blood at ten hospitals were reviewed. Demographic, diagnostic, surgical, and laboratory data and indications for transfusion were obtained. Mean blood use per patient (U/pt) was 5.6, 7.2, and 4.1 units for all patients, surgical and non-surgical, respectively. Fifty percent of the patients underwent surgery, used 64% of the blood, and required more postoperatively (4.2 U/pt) than intraoperatively (2.8 U/pt). Open-heart surgeries required 32% of all blood. Eighty-two percent of postoperative transfusions occurred when the hematocrit was less than or equal to 30%. Only 2.8% of eligible elective surgery patients made pre-deposit autologous donations and contributed 1% of the total blood used.