Unusual serological findings associated with ceftriaxone-induced immune hemolytic anemia in a child with disseminated low-grade glioma.

Ceftriaxone-induced immune hemolytic anemia (CIHA) is the second most common cause of drug-induced hemolytic anemia. Prompt recognition of this drug reaction is essential because brisk hemolysis can be deadly. The extent to which ceftriaxone antibodies persist after CIHA is unknown; rechallenging patients who have experienced CIHA is not recommended. We report a case of CIHA in a neurooncology patient, which is the first to show anticeftriaxone antibodies with Rh specificity and persisted for 8 months after the drug reaction. These findings have implications for understanding the mechanism of CIHA.

Predicting risk of peripartum blood transfusion during vaginal and cesarean delivery: A risk prediction model.

OBJECTIVE: The objective of this study is to develop a model that will help predict the risk of blood transfusion using information available prior to delivery. STUDY DESIGN: The study is a secondary analysis of the Consortium on Safe Labor registry. Women who had a delivery from 2002 to 2008 were included. Pre-delivery variables that had significant associations with transfusion were included in a multivariable logistic regression model predicting transfusion. The prediction model was internally validated using randomly selected samples from the same population of women. RESULTS: Of 156,572 deliveries, 5,463 deliveries (3.5%) required transfusion. Women who had deliveries requiring transfusion were more likely to have a number of comorbidities such as preeclampsia (6.3% versus 4.1%, OR 1.21, 95% CI 1.08-1.36), placenta previa (1.8% versus 0.4%, OR 4.11, 95% CI 3.25-5.21) and anemia (10.6% versus 5.4%, OR 1.30, 95% CI 1.21-1.41). Transfusion was least likely to occur in university teaching hospitals compared to community hospitals. The c statistic was 0.71 (95% CI 0.70-0.72) in the derivation sample. The most salient predictors of transfusion included type of hospital, placenta previa, multiple gestations, diabetes mellitus, anemia, asthma, previous births, preeclampsia, type of insurance, age, gestational age, and vertex presentation. The model was well-calibrated and showed strong internal validation. CONCLUSION: The model identified independent risk factors that can help predict the risk of transfusion prior to delivery. If externally validated in another dataset, this model can assist health care professionals counsel patients and prepare facilities/resources to reduce maternal morbidity.

Serum inhibitors to granulopoiesis in thalassemia major.

Peripheral blood (pb) and bone marrow CFU-C were evaluated in patients with thalassemia major. A decrease in both pb and marrow CFU-C was noted when compared to normal donors and individuals with hemolytic anemia requiring transfusion therapy. Experiments suggested that a nondialyzable serum factor was resonsible for the depressed pb CFU-C in 6 and of 6 children with thalassemia. Serum lipoprotein electrophoresis revealed type IV pattern in 9 out of 18 children with elevation of the pre-beta fraction. These experiments suggest (1) decreased stem cell CFU-C, (2) decreased pb CFU-C, and (3) a serum inhibitor that may be contributing to the depressed pb CFU-C.

Protease inhibitor and triple-drug therapy: cellular immune parameters are not restored in pediatric AIDS patients after 6 months of treatment.

OBJECTIVE: To assess whether treatment of HIV-positive children by antiretroviral drugs for a 6-month period would improve immune function significantly. DESIGN AND METHODS: Immunological assessment of 89 HIV-positive children who received protease inhibitor monotherapy for 12-16 weeks as part of phase I/II studies, followed by triple antiretroviral therapy for an additional 12 weeks, was conducted. Immunological parameters were assessed in vitro at four time points (at enrollment, at weeks 2-4, at weeks 12-16, and at weeks 24-28). Assessments included: cytokine production by monocytes, T-cell proliferation to mitogen or recall antigens (including an HIV antigen) and apoptotic cell death. Plasma levels of tumor necrosis factor (TNF)-alpha and soluble TNF receptor (sTNF-R) were also measured, in addition to CD4+ T-lymphocyte counts and viral load. In addition, limited analyses were performed on samples from 17 children after 120 weeks of therapy, including 104 weeks of triple therapy. RESULTS: At enrollment, the 89 children exhibited severe immune defects. Antiretroviral therapy raised CD4+ T-lymphocyte counts significantly and decreased viral loads. In contrast, the in vitro immune parameters studied were not improved, except for plasma levels of sTNF-RII which decreased in parallel with the decrease in viral load. In addition, there was a trend towards increased skin test reactivity for the ritonavir-treated children. No differences were seen in the immune parameters whether the patients were treated with mono- or triple therapy. Results obtained after 120 weeks of therapy demonstrated that defective interleukin-12 production was not restored by long-term therapy. CONCLUSIONS: After 6 months of therapy, with the exception of decreased sTNF-RII levels, and a trend towards increased skin test reactivity, restoration of several defective cellular immune responses did not occur despite significantly decreased viral loads and increased CD4+ T-lymphocyte counts.

Review of neonatal red cell transfusion practices.

In the United States in 1991, 290,000 or 7.1% of the 4,110,907 live births were premature infants; 53,299 or 1.3% were infants with birth weights of less than 1500 grams. Many if not all of these very low birth weight infants will require red blood cell transfusions for one of several reasons. These include exchange transfusions for hyperbilirubinemia, but most often transfusions are simple small volume transfusion also called 'topper' transfusions. Most of these small volume transfusions are given for iatrogenic blood loss or 'bleeding into the laboratory.' Studies have demonstrated that the sicker the infant, the more blood sampling is needed and the greater the exposure to red blood cell (RBC), platelet and plasma products. Simple RBC transfusions may also be given for specific clinical indications or to maintain a predetermined hemoglobin concentration. This manuscript will review the criteria for RBC transfusion in neonates and selection of product as regards anticoagulant and specialized processing. In addition, the results of recombinant erythropoietin (r-EPO) clinical trials in neonates will be discussed.

Prevention of transfusion-associated graft-versus-host disease by inactivation of T cells in platelet components.

Patients with hematological malignancies and infants with congenital immunodeficiencies who received blood are two of many populations at risk for transfusion-associated graft-versus-host disease (TA-GVHD). Of the methodologies (eg, photoinactivation, peglyation, ultraviolet light, and irradiation) that can be used to prevent TA-GVHD, only irradiation of whole blood and cellular components is currently accepted practice of the US Food and Drug Administration (FDA). Among the newer methods that have been developed to reduce the risks of bacterial and viral contaminants of platelet transfusions, photochemical treatment (PCT) using psoralens and long-wavelength ultraviolet (UVA) irradiation modifies bacterial and viral genomes sufficiently to inhibit replication. Among a broad group of compounds, the synthetic psoralen compound amotosalen hydrochloride (HCl) (S-59) has been shown to be particularly effective in inactivating bacteria and viruses, without adversely affecting in vitro and in vivo platelet function.

Accelerated recovery from immune-mediated thrombocytopenia with plasmapheresis.

Autoimmune thrombocytopenia unresponsive to corticosteroid therapy developed in a 16-year-old female with long-standing Sjögren's syndrome. Serial plasma exchange caused a linear decrease in platelet antibody titer associated with a concomitant rise in platelet count. Statistical analysis of sequential platelet counts revealed an increase with plasmapheresis and immunosuppression that was significantly greater than that achieved with immunosuppression alone (p less than 0.005).

Human immunodeficiency virus infection in urban adolescents: can we predict who is at risk?

Few studies have evaluated the extent of human immunodeficiency virus (HIV) in the adolescent population. However, there has been growing concern that sexual and drug experimentation common in this age group may increase their risks of transmitting the virus. Between October 1, 1987, and January 31, 1989, a blinded, unlinked HIV seroprevalence study was conducted among all adolescents aged 13 through 19 receiving ambulatory care at Children's National Medical Center and having blood drawn for other routine medical indications. Overall, seroprevalence in this group of patients was 0.37% (3.7/1000), with the highest prevalence in females (4.7/1000) and patients 18 through 19 years of age (5.6/1000). Of adolescents considered at high risk who were offered and accepted voluntary HIV testing during the same time period, 4.1% (41/1000) were positive. Inasmuch as this represents only 38% of all of the positive tests obtained in the blinded testing phase of the study, it may indicate that a substantial proportion of HIV-positive adolescent patients may be missed by using standard criteria and methods of identifying risk and/or that those most at risk may be reluctant to be tested for HIV infection. The results suggest that HIV infection is present in this population of urban adolescents and that the seroprevalence rate is higher than in other nonselect groups. Moreover, using traditional risk factors as screening criteria may not identify the majority of those infected. Trends need to be followed and further studies conducted in an attempt to define which adolescents are at highest risk for HIV infection.

Clinical heterogeneity in mitochondrial DNA deletion disorders: a diagnostic challenge of Pearson syndrome.

The clinical presentation of mitochondrial DNA (mtDNA) disorders is quite diverse. Very often, the initial symptoms do not fit a specific disease, and diagnosis is difficult to make. We describe a patient who presented with macrocytic anemia. Extensive biochemical and clinical work-up failed to provide an etiology for the macrocytic anemia. The patient over the course of 6 years developed gait problems, exercise intolerance, episodic vomiting, short stature, dermatological problems, and recurrent infection. At age 8 years she had encephalopathy with ataxia and dysphagia. The presence of elevated lactate, bilateral basal ganglia calcification, and ragged red fibers led to mtDNA mutational analysis. A novel 4.4-kb deletion from nucleotide position 10,560 to nucleotide position 14, 980 was identified in muscle biopsy. The same heteroplasmic mtDNA deletion was present in blood, buccal cells, and hair follicles, but not in mother's blood, consistent with sporadic mutation in the patient. This case emphasizes the importance of considering mtDNA disorder in patients with multisystemic symptoms that cannot be explained by a specific diagnosis.

Escherichia coli virulence factors and 99mTc-dimercaptosuccinic acid renal scan in children with febrile urinary tract infection.

Correlation of virulence factors of Escherichia coli with renal inflammation documented by 99mTc-dimercaptosuccinic acid renal scan was undertaken in 59 children with febrile urinary tract infections to identify more accurately the role of bacterial virulence factors in the development of pyelonephritis. P fimbriae were present in 63% of isolates from the positive scan group and 83% of those from the negative scan group (P = 0.126). Multivariate regression analysis showed no significant role for established E. coli virulence factors in the development of pyelonephritis. The pap genome was independently associated with negative scan (P less than 0.007) and with the absence of reflux (P = 0.031). E. coli pyelonephritogenic clone O16:K1:H6 was isolated from negative scan patients and did not produce hemolysin. We conclude that P fimbriae are important in the development of febrile urinary tract infection regardless of the level of infection. Virulent E. coli clones described in prior Scandinavian urinary tract infection studies were not common causes of pyelonephritis in our patient population.

The high rate of blood donor exposure for critically ill neonates.

The purpose of this study was to determine the number and volume of red blood cell (RBC) transfusions and the number of donors a newborn is exposed to during his or her newborn intensive care unit (NICU) stay. On one day at the Medical University of South Carolina (MUSC) and two days at the University of Virginia Hospital (UVH) all babies who had or were receiving RBCs comprised the study group. Patient records were reviewed at discharge. Fifty-two (70%) of the 75 NICU babies had or were receiving RBCs and were enrolled. The average number of RBC transfusions was nine (range 1 to 28, median 7) and the average transfusion volume was 16.5 ml (range 5 to 60) for a total volume of 148 ml transfused during a NICU stay. Each baby was exposed to an average of 6.9 donors (range 1 to 25, median 6.5). The practice of splitting RBC packs to share among different infants and of giving multiple small volume transfusions maximizes donor exposure and transfusion-related infectious risks in this population.

Massive transfusion in the neonate.

The neonate who undergoes massive transfusion is at risk for transfusion-associated complications similar to the adult, but also faces some that are unique to the infant. By understanding the mechanics of the procedures that result in single or multiple blood volume exchange, the transfusion medicine physician can better assist his/her colleagues in the support of these patients.

The irradiation of blood and blood components to prevent graft-versus-host disease: technical issues and guidelines.

In recent years, there have been several advances in blood irradiation practice. These include a better definition of the most appropriate dose level that should be used when irradiating blood components. Commercial innovation has provided the tools for a quality assurance program to assess the dose that is delivered throughout the canister in a free-standing irradiator, and, through the use of radiation-sensitive indicator labels, to confirm that the irradiation process has taken place. With the apparent increased use of linear-accelerators to irradiate blood components, appropriate quality assurance measures need to be developed. The maximum storage period for irradiated red cells should be shorter than for nonirradiated red cells if the treatment is performed early during the storage period because irradiation reduces the in vivo 24-hour red cell recovery parameter. The storage period for irradiated platelets does not need to be modified. Some questions are being raised regarding whether fresh-frozen plasma should be irradiated to inactivate a small number of immunocompetent progenitor cells that may be present. Table 4 summarizes the practices that should be followed in connection with the technical issues that have been addressed in this article. These guidelines follow the recommendations issued in July 1993 by the FDA in the United States. This article and Tables 1 and 2 contain additional guidelines.

The precision of duplicate prothrombin time and partial thromboplastin time assays in neonates.

An evaluation of duplicate prothrombin time (PT) and activated partial thromboplastin time (PTT) assays was performed in 277 neonatal samples. Performance criteria were analyzed to determine whether single vs duplicate procedures could be utilized reliably without exposing the neonates to the risk of erroneous PT and PTT results. In addition, we evaluated whether this approach might decrease phlebotomy and hence reduce the number of blood transfusions administered. For PT assays, 97.5% (270/277) of the duplicate results were different by 1 second or less. Only 2.5% (7/277) differed by 3 seconds. For PTT duplicates, 75.0% (207/277) of the values were different by 2 seconds or less and 13.0% (36/277) by 2 to 4 seconds. An additional 12.3% (34/277) were discrepant by as many as 4 seconds. The largest discrepancies occurred in specimens with markedly elevated PT and PTT results, indicative of a significant coagulopathy. In addition, heparin neutralization was performed successfully in 22 neonatal blood specimens showing either partial or full correction of PTT values due to heparin specimen contamination. This study indicates that single PT and PTT assays as well as heparin neutralization tests can be accurately performed and may be able to reduce blood donor exposure by as many as one blood transfusion every 2 to 3 days of hospitalization.

Benign hepatocellular tumors in the young. A clinicopathologic spectrum.

Hepatic tumors unassociated with cirrhosis were encountered in seven patients aged 10 to 19 years. Four patients had received androgens for aplastic anemia. Two patients had transfusional hemosiderosis. One patient had had a renal transplant 2 1/2 years ago. Two patients are alive at 2 3/4 and 2 1/2 years after surgical resections. Nodules were found at autopsy in the others. The tumors were well differentiated and, in the androgen-related cases, differed from the others in the following features: canalicular bile retention, mild nuclear atypia, and acinar formation. No mitoses, vascular invasion, or metastatic tumor were evident. The clinical setting was variable; different factors, including iron overload and androgen therapy, played a role in the development of tumor. Although the androgen-related cases showed mild cellular atypia, biologic evidence of malignancy was lacking as in most previous reports.

Autologous blood transfusion in the pediatric patient.

The use of autologous blood has been encouraged by blood banks and transfusion services for the past 10 years, mainly because of public concern over the safety of blood. The virtues include reduced likelihood of reactions to transfused blood and reduction or elimination of the risk of alloimmunization and transfusion transmitted diseases such as hepatitis C and the human immunodeficiency virus. The pediatric patient population has been largely excluded from published series on autologous blood usage. In this article, the literature on the use of autologous blood in pediatric patients is reviewed, and some considerations for collecting autologous blood from smaller patients are addressed, including the volume of blood to collect from smaller patients. Based on the experience reported in the literature, patients as young as 6 years of age may be candidates for autologous blood donation before a scheduled surgical procedure. Other methods to provide autologous blood for pediatric patients are discussed, including intraoperative hemodilution and intraoperative and postoperative blood salvage. By considering all the potential options available to pediatric patients, the likelihood of requiring transfusion of allogeneic blood can be reduced, along with the associated risks.

Sickle cell anemia and hearing.

The present investigation examined the effects of sickle cell anemia on threshold hearing. The study included 43 homozygous sickle cell anemia patients, ages 7-18 years, and 23 age-matched controls with documented normal hemoglobin. Both the study and control groups received otologic and audiologic examinations. Bilaterally normal hearing was found in 88% of the sickle cell subjects. Unilateral or bilateral mild high frequency sensorineural hearing loss was demonstrated in 12% (5 of 43). The control subjects revealed no hearing loss. The sickle cell group, therefore, exhibited a higher than usual incidence of hearing loss. Further, three of the five subjects with hearing loss evidenced central nervous system involvement, resulting in a probability of < 0.025 that this relation might occur by chance. Periodic hearing evaluations of children with sickle cell anemia should be performed to identify those with auditory complications and those who possibly may have CNS involvement.