Use of emergency medical identification in the paediatric haemophilia population: a national study.

The use of emergency medical identification (EMI) such as MedicAlert(®) has been recommended for use in a variety of medical conditions; however, there is no consensus as to what form should be used and where they should be placed. There are also no uniform guidelines to direct first responders to where they should look for EMI in an emergency. The aim of this study was to identify current paediatric haemophilia nursing practice in educating families about EMI and their perceptions of patient/family adherence to using EMI. US haemophilia nurses listed on the Center for Disease Control's website received an email invitation to participate in a 30-item questionnaire posted on Survey-Monkey. Survey responses showed a wide variety of responses concerning recommendations about the form and location of EMI, particularly in the infant population. Nurses also reported that EMI was often not worn on the body and had low overall adherence. In the infant and preschool population, this was due to safety concerns, sizing, cost and parents not seeing the need for EMI. In school age and adolescents, the barrier to wearing EMI included stigma, cost and sizing. Collaboration is needed among nursing and medical staff, first responders, emergency room staff and manufacturers of EMI to develop standardized EMI which address these issues. Standard educational guidelines are needed to teach nurses and patient/families about the forms and location of EMI. Additionally, national guidelines are needed for the identification of paediatric EMI by first responders and emergency room staff.

Hepatitis B virus (HBV) DNA screening of blood donations in minipools with the COBAS AmpliScreen HBV test.

BACKGROUND: The risk of hepatitis B virus (HBV) transmission by blood transfusion (estimated at 1 in 63,000-1 in 205,000 units in the United States) exceeds that of hepatitis C virus (HCV) or human immunodeficiency virus (HIV). Reduction of window-period HBV transmissions through detection of HBV DNA-positive units by minipool nucleic acid testing (MP NAT) would be expected to decrease this risk. STUDY DESIGN AND METHODS: A large multicenter study of the COBAS AmpliScreen HBV test (Roche Molecular Systems) was conducted on minipools of 24 blood donation specimens. The yield of HBV DNA-positive, hepatitis B surface antigen (HBsAg)-negative window-period donations was determined relative to current and newly licensed HBsAg assays. Donors with selected HBV DNA, HBsAg, and anti-hepatitis B core antigen (HBc) results were further evaluated. RESULTS: The detection rate of window-period units was 1 in 352,451 (95% confidence interval, 1 in 2,941,176-1 in 97,561). Assay specificity was high (99.9964%). HBV DNA was detected in 84 percent of HBsAg-positive, anti-HBc-positive donations by MP NAT and in 94 percent when individual-donation (ID) NAT was added. HBV DNA was detected in 0.03 percent of HBsAg-negative, anti-HBc-positive donations by MP NAT and in 0.41 percent when ID NAT was added. CONCLUSIONS: Implementation of HBV MP NAT will provide an increment in safety relative to HBV serologic screening, similar to that for HCV and in excess of that for HIV. Our data indicate that the implementation of HBV MP NAT would likely interdict 39 HBV window-period units and prevent 56 cases of transfusion-transmitted HBV infection annually. The current data indicate that HBV MP NAT should not lead to discontinuation of anti-HBc testing but that discontinuation of HBsAg testing with retention of anti-HBc testing may be possible.

Rapid-sequence tandem transplant for children with high-risk neuroblastoma.

BACKGROUND: The majority of patients with high risk neuroblastoma (NB) still relapse. PROCEDURE: We designed a Phase II trial for children with advanced NB utilizing a program of induction chemotherapy followed by tandem high-dose chemoradiotherapy with stem cell rescue (HDC/SCR) in rapid sequence. Fifty-five patients were evaluable, ages 1-14 years, and 97 cycles of HDC/SCR have been completed to date. Pheresis was possible for every patient, despite their young age, with an average of 7.2 x 10(6) CD34+ cells/kg available to support each HDC/SCR cycle. RESULTS: Engraftment was rapid, with median time to neutrophil engraftment of 11 days. Five patients who completed the first HDC course did not complete the second and there were four toxic deaths. With a median follow-up of 24 months from diagnosis, 38 of 55 patients (3-year EFS 59%) remain event-free. A subset of the patients received stem cells purged by CD34 selection. The engraftment and EFS of these patients are similar to the overall group. CONCLUSION: This work demonstrates that a tandem transplant regimen for high-risk NB is a feasible treatment strategy in children and may improve disease-free survival.

Evaluation of an automated system for the collection of packed RBCs, platelets, and plasma.

BACKGROUND: This study evaluated the quality of WBC-reduced platelets, RBCs, and plasma collected on a new system (Trima, Gambro BCT) designed to automate the collection of all blood components. The study also evaluated donor safety and suitability of these components for transfusion. STUDY DESIGN AND METHODS: In Phase I, the quality of the components collected on the new system was evaluated by standard in vitro and in vivo testing methods. Results were compared to those from control components collected by currently approved standard methods. In Phase II, additional collections were performed to evaluate the acceptability of the new system and the safety of platelets collected. RESULTS: In vivo 24-hour RBC recovery was 76.8 +/- 3.1 percent for the test RBC units and 77.1 +/- 4.4 percent recovery for whole-blood (control) RBCs. The differences between test and control platelet results in the in vivo and in vitro assays were not clinically significant. Plasma clotting factors and fibrinogen levels met international standards. The system was well accepted by donors, and no major adverse donor reactions were reported for the 68 procedures performed. No problems were reported with transfusing the blood components collected. CONCLUSION: Blood components collected with the Trima are equivalent to currently available components, and they meet the applicable regulatory standards. This system provides consistent, standardized components with predictable yields. It provides the option of fully automating the collection of all blood components.

Tandem high-dose therapy in rapid sequence for children with high-risk neuroblastoma.

PURPOSE: Advances in chemotherapy and supportive care have slowly improved survival rates for patients with high-risk neuroblastoma. The focus of many of these chemotherapeutic advances has been dose intensification. In this phase II trial involving children with advanced neuroblastoma, we used a program of induction chemotherapy followed by tandem high-dose, myeloablative treatments (high-dose therapy) with stem-cell rescue (HDT/SCR) in rapid sequence. PATIENTS AND METHODS: Patients underwent induction chemotherapy during which peripheral-blood stem and progenitor cells were collected and local control measures undertaken. Patients then received tandem courses of HDT/SCR, 4 to 6 weeks apart. Thirty-nine patients (age 1 to 12 years) were assessable, and 70 cycles of HDT/SCR were completed. RESULTS: Pheresis was possible in the case of all patients, despite their young ages, with an average of 7.2 x 10(6) CD34(+) cells/kg available to support each cycle. Engraftment was rapid; median time to neutrophil engraftment was 11 days. Four patients who completed the first HDT course did not complete the second, and there were three deaths due to toxicity. With a median follow-up of 22 months (from diagnosis), 26 of 39 patients remained event-free. The 3-year event-free survival rate for these patients was 58%. CONCLUSION: A tandem HDT/SCR regimen for high-risk neuroblastoma is a feasible treatment strategy for children and may improve disease-free survival.

Therapeutic plasma exchange and cytapheresis in pediatric patients.

Pediatric therapeutic apheresis is reviewed including what it is, how it is performed and indications for its use. Pediatric patients are special, and the unique needs for replacement fluids and attention to access, anticoagulation, volume shifts and hypothermia are stressed. While all indications cannot be addressed, the procedures most commonly performed are reviewed. These include erythrocytapheresis, leukaphereses and plasma exchanges. A table details the strength of evidence supporting the use of apheresis procedures for many of these indications.

Identification of (CA/GT)n polymorphisms within the X-linked chronic granulomatous disease (X-CGD) gene: utility for prenatal diagnosis.

PURPOSE: The majority of known female carriers of X-linked chronic granulomatous disease (X-CGD), a deficiency of the gp91-phox (phagocyte oxidase) subunit and the most common genetic subtype of CGD, are not informative for the linked restriction fragment length polymorphisms (RFLPs) described to date. The isolation and characterization of two polymorphic (CA/GT)n repeats that lie within the X-CGD gene are reported, which are a useful linked marker for prenatal diagnosis. PATIENTS AND METHODS: cDNA for gp91-phox was used to probe a genomic library. Genomic clones were isolated and screened for (CA/GT)n repeats. The repeats were isolated and sequences surrounding the repeats were determined. Oligonucleotide primer pairs surrounding the repeats were chosen to facilitate polymerase chain reaction (PCR) across the repeat. RESULTS: Analysis of DNA derived from over 100 individuals shows both markers to be highly polymorphic with a resultant high proportion of heterozygosity in females. Several kindreds affected by X-CGD were studied and the (CA/GT)n length polymorphisms were shown to segregate with the clinical syndrome or biochemical carrier status. The technique was prospectively applied to several kindreds containing a carrier mother and an affected child. In a case where a male fetus was shown to carry the unaffected allele, the pregnancy was carried to term and the child was not affected. CONCLUSIONS: This approach is highly informative in a multiple allele system, can provide a technical analysis in just hours, requires only a ng of DNA, and permits the transport of diagnostic samples. Therefore, this method can be used early in pregnancy on a chorionic villus biopsy sample for prenatal diagnosis.

Liquid nitrogen freezers: a potential source of microbial contamination of hematopoietic stem cell components.

BACKGROUND: The recent report of hepatitis B transmission between hematopoietic progenitor and putative stem cell (HPC) components stored in liquid nitrogen led to the questioning of whether evidence existed for similar contamination by bacterial or fungal elements. STUDY DESIGN AND METHODS: Microbial contamination rates were reviewed for 704 HPC components from 255 patients over an 18-month period. Five liquid nitrogen freezers were surveyed for microbial contamination. The literature was reviewed to ascertain the published experience of other laboratories with HPC component contamination first documented on thawing. RESULTS: Seven (1.2%) of 583 thawed components were found to be contaminated with a variety of environmental or waterborne organisms, despite a meticulous protocol to prevent contamination during thawing. All of these components had been sterile on cryopreservation. Literature review revealed a similar incidence of post-thaw contamination from other centers. Microbial survey of liquid nitrogen freezers revealed low-level contamination in four of five. The organisms represented were similar to those cultured from thawed HPC components. One freezer was heavily contaminated by Aspergillus species. CONCLUSION: Liquid nitrogen freezers are not sterile, and both the liquid and vapor phases are potential sources of microbial contamination of HPC components. While low-level contamination by environmental organisms may be common, the occurrence of heavy contamination by potential pathogens such as Aspergillus species suggests that monitoring of liquid nitrogen sterility may be indicated. Strategies to assess and prevent microbial transmission from liquid nitrogen to HPC components need further development.

The efficacy of tranexamic acid versus placebo in decreasing blood loss in pediatric patients undergoing repeat cardiac surgery.

The antifibrinolytic drug, tranexamic acid, decreases blood loss in adult patients undergoing cardiac surgery. However, its efficacy has not been extensively studied in children. Using a prospective, randomized, double-blind study design, we examined 41 children undergoing repeat sternotomy for repair of congenital heart defects. After induction of anesthesia and prior to skin incision, patients received either tranexamic acid (100 mg/kg, followed by 10 mg.kg-1.h-1) or saline placebo. At the onset of cardiopulmonary bypass, a second bolus of tranexamic acid (100 mg/kg) or placebo was administered. Total blood loss and transfusion requirements during the period from protamine administration until 24 h after admission to the intensive care unit were recorded. Children who were treated with tranexamic acid had 24% less total blood loss (26 +/- 7 vs 34 +/- 17 mL/kg) compared with children who received placebo (univariate analysis P = 0.03 and multivariate analysis P < 0.01). Additionally, the total transfusion requirements, total donor unit exposure, and financial cost of blood components were less in the tranexamic acid group. In conclusion, tranexamic acid can reduce perioperative blood loss in children undergoing repeat cardiac surgery.

Large-volume leukapheresis in pediatric patients: processing more blood diminishes the apparent magnitude of intra-apheresis recruitment.

BACKGROUND: Recruitment of progenitors during a large-volume collection, as defined by increasing relative and absolute numbers of progenitors (colony-forming units-granulocyte-macrophage [CFU-GM] of CD34+ cells), has been reported previously. STUDY DESIGN AND METHODS: To ascertain whether intra-apheresis recruitment occurs in pediatric patients who have undergone mobilization with chemotherapy and granulocyte-colony-stimulating factor (G-CSF), each hour's portion of a 4-hour leukapheresis was collected into separate bags, and assessed by complete blood count, CFU-GM, and CD34+ cell assays. Seven pediatric patients (median age, 7; range, 2-19) were studied in connection with 2 to 4 collections each, for a total of 21 collections (with hourly samples). The collections lasted for 4 hours, at an inlet rate of 1 to 3 mL per kg per minute, for daily processing totals of 5 to 12 blood volumes. (One blood volume [mL] is estimated by the patient's weight in kg x 70 mL/kg.) Smaller (younger) patients had inlet rates exceeding 2 mL per kg per minute, and larger (older) patients had rates of 1 to 1.5 mL per kg per minute. CFU-GM and CD34+ cell counts obtained each hour of the collection and divided by the first hour's value were compared by nonparametric repeated-measures ANOVA. RESULTS: Second-, third- and fourth-hour CD34+ progenitor cell counts were arithmetically higher than first-hour counts, but the trend did not reach significance (p = 0.1561). Second-hour counts were higher than first-hour counts in the overall analysis (mean +/- standard error [SE], 1.00 and 1.39 +/- 0.1, respectively; p = 0.0525) and in children older than 5 years (1.00 vs. 1.70 +/- 0.30, respectively; p = 0.0259), but not in children younger than 5 years (p = 0.8125). CFU-GM counts did not differ among the 4 hours of collection (p = 0.1717) or between the first and second hour (p = 0.9587). CONCLUSION: In larger (older) patients, from whom fewer blood volumes were collected, there is a trend toward intra-apheresis recruitment, although less than reported previously. In the smaller (younger) patients, from whom more blood volumes were collected, no trend was observed. Lack of (or submaximal) prior mobilization in previously reported studies may have facilitated intracollection recruitment. Alternatively, the larger number of blood volumes collected from the smaller (younger) patients may have masked intra-apheresis recruitment. The study documents the feasibility of large-volume, 4-hour leukapheresis in pediatric patients.

Granulocyte transfusions. Time for a second look.

Among the available therapies to support neutropenic patients with infection, granulocyte transfusions have generated considerable controversy. Plagued by the inconvenience of harvesting cells, infusion-associated toxicity, and marginal efficacy, granulocyte transfusions, once in vogue in the 1980s, had been relegated to a secondary role. Several recent developments, however, have given new impetus to re-evaluating the role of granulocyte transfusions. The two most notable reasons include the ability to increase the number of circulating granulocytes in the donor by treatment with one or two doses of recombinant hematopoietic growth factors, such as granulocyte- and granulocyte-macrophage colony stimulating factor, and improvements in the efficiency of the collection process. Armed with these advances, it is an appropriate time to review the existing data and consider studies designed to determine the appropriate role of granulocyte transfusions in neutropenic hosts.

Pediatric large volume peripheral blood progenitor cell collections from patients under 25 kg: a primer.

Collection of peripheral blood progenitor cells from small pediatric patients provides many social and technical challenges not faced when collecting from adult patients. This paper provides a single institutions experience with 85 collections from 14 patients less than 25 kg of weight over a 2 year period. Specific challenges include obtaining venous access, anticoagulation, volume shifts, and obtaining patient cooperation. A systematic analysis of options for access, alternative modes of anticoagulation, and the effect of large ratios of extra-corporeal volume to patient's blood volume are discussed. Access uniformly required central venous catheters (CVC) ranging from 7-10 Fr. Anticoagulation included systemic heparinization titrating dose by activated clotting time in all cases and combined with citrate at a ratio of 1:25-1:30 in most cases. Collections were performed on a COBE Spectra, after priming with leukoreduced irradiated red cells and omitting both the initial 120cc diversion and rinse back of red cells at the end. Social challenges include issues of assent and ability to distract patients for the duration of a prolonged collection. Progenitor yields from collections from 14 patients were quantitated by CD34+ assay in all cases and CFU-GM in ten of 14 patients. A median of 4.5 x 10(6)/kg CD34+ cells were obtained for each collection. Complications, including those related to catheter access, are enumerated. In summary, large volume peripheral blood progenitor collection can be safely and efficaciously performed in small pediatric patients.