Cytophilic immunoglobulin G binding on neutrophils from a child with malignant osteopetrosis who developed fatal acute respiratory distress mimicking transfusion-related acute lung injury.

A 16-month-old boy, diagnosed at age 3 months with osteopetrosis, was treated since age 6 months with rhIFN-gamma in combination with rhM-CSF. The child developed acute respiratory distress within 1 hr of a paternal platelet transfusion. Both the child and the father were blood group type O, and platelets were collected the previous day from the father. Chest X-ray revealed right pulmonary consolidation and a complete "whiteout" on the left. By 24 hr, the lungs had the appearance of adult respiratory distress syndrome (ARDS). Over the course of the next 11 days, the child remained intubated and hypotensive, and died of respiratory insufficiency 11 days later. ARDS was confirmed at autopsy. Pre- and posttransfusion patient's sera, as well as paternal serum, were tested by granulocyte agglutination and flow cytometry against granulocytes (PMN) from the patient, father, mother, and routine cell-panel donors and lymphocytes for the presence of neutrophil-specific and lymphocyte (HLA) antibodies, to rule out classical transfusion-related acute lung injury (TRALI). Both the patient's and the paternal sera were devoid of antibodies, but the patient's neutrophils demonstrated strong binding of cytophilic IgG accompanied by extremely low serum IgG and IgG1 levels. Since rhIFN-gamma is known to upregulate Fc gamma receptor type I (Fc(gamma)RI) with high affinity for IgG1, the binding of cytophilic IgG suggests that the patient's neutrophils may have been activated in vivo. The case report of another child with osteopetrosis has also been described. Although the blood specimen was not available for serological studies, this 4 1/2-year-old child treated with rhIFN-gamma and rhM-CSF also died of adult respiratory distress syndrome, with similar clinical presentations.

Noninfectious complications of blood transfusion.

The noninfectious complications of blood transfusion consist of a diverse group of immune-mediated transfusion reactions that range from immediate life-threatening to subclinical reactions. Each reaction involves the recognition and interaction of the both the humoral and cellular immune systems. In the past, many of the noninfectious complications of transfusion were attributed solely to antigen-antibody interactions. Today, an emerging body of evidence suggests that cytokines and cytokine inhibitors play a central role in the pathophysiology of immune-mediated transfusion reactions and account for the broad diversity of clinical presentations.

Cost analysis of immunomagnetic marrow purging for neuroblastoma: in-house purging versus submission to purging centers.

High-dose chemoradiotherapy in conjunction with autologous bone marrow transplantation has been used in the treatment of advanced stage neuroblastoma. Because of frequent marrow involvement, marrow purging methods, such as the immunomagnetic technique, have been developed. Current cost constraints force institutions to consider in-house purging versus submission of marrow to purging centers. Our analysis demonstrates that 15 procedures per year are needed to justify an up-front investment in equipment and supplies with a break-even period of 5 years. This number is also required to keep technical proficiency current without frequent retraining of personnel. The analysis includes start-up costs for institutions without a bone marrow processing laboratory, as well as for institutions already processing marrow or peripheral blood stem cells. For institutions performing fewer procedures per year, submission of marrow to purging centers is more cost effective than in-housing purging.

A uniform labeling system for bone marrow and peripheral blood stem cells.

The separation of bone marrow (BM) constituents, BM cell purging, and cryopreservation of BM and peripheral blood stem cells (PBSC) are frequently performed in the clinical laboratories. In 1991, recognizing the increasing involvement of transfusion services in BM and PBSC processing, the American Association of Blood Banks (AABB) established standards that, in general, held BM and PBSC processing to the same standards as applied to blood components. In 1993, the AABB defined the information that was required on the container label, but did not establish a uniform system of labeling for BM/PBSC preparations. We present a system of labeling for definitive identification of allogeneic BM and autologous BM/PBSC collections that identifies all components derived from the original product from the time of collection to final infusion or disposal. This system avoids the risk of component misidentification, particularly when multiple collections are processed simultaneously. Our transfusion service computer system was adapted with BM/PBSC component names and abbreviated codes to provide a singular validated mechanism for labeling, tracking, and final disposition of these products. We propose the adaptation of a "universal system" for BM/PBSC labeling for AABB accredited transfusion services utilizing the existing guidelines for labeling of blood and blood components.

Predictive factors for the rate of engraftment of neuroblastoma patients autotransplanted with purged marrow.

Predictive values for patient engraftment in neuroblastoma have not been defined. By analyzing the parameters available to us at the time of harvest and post-harvest, we found that the MNC/kg after purging demonstrated significant correlation with patient engraftment as measured by the patient's time to reach a WBC count of 1,000/microL and an ANC count of 500/microL. Platelet and red cell independence was difficult to measure as some of these patients remain platelet- and red cell-dependent for extended periods of time. Platelet refractoriness, alloimmunization, infection and many other factors can delay platelet and red cell recovery following transplantation. A larger number of patients is needed to assess a correlation between the parameters analyzed and platelet and red cell recovery, as well as to validate our observation with myeloid recovery.

Postfiltration factor VIII and fibrinogen levels in cryoprecipitate stored at room temperature and at 1 to 6 degrees C.

The 13th edition of the standards of the American Association of Blood Banks specified storage at 1 to 6 degrees C for cryoprecipitated anti-hemophilic factor (Cryo) administered up to 6 hours after thawing if the Cryo is used for factor VIII (FVIII) content (Standard J4.210). Previous editions specified room-temperature (RT) storage for up to 6 hours. Currently, the temperature specification has been deleted. There are few data addressing the optimal storage temperature and maximum storage time for FVIII and fibrinogen in thawed Cryo. Thirty bags of Cryo were assayed for FVIII and fibrinogen. Each bag was divided into two aliquots; one was stored at RT and the other at 1 to 6 degrees C. Assays were performed immediately after thawing (Base) and 6 and 24 hours after thawing, respectively. All samples were filtered through 200-mu blood component infusion sets before assay. Three hundred analyses were performed, 150 each for FVIII and fibrinogen by conventional clotting technique. Data were analyzed by using a paired t test. Cryo stored at 1 to 6 degrees C for 6 and 24 hours showed an FVIII loss of 35 percent (p less than 0.0001) and 63 percent (p less than 0.0001), respectively. Cryo stored at RT for 6 and 24 hours had an FVIII loss of 8 percent (p greater than 0.05) and 20 percent (p less than 0.0001). Cryo stored at 1 to 6 degrees C for 6 and 24 hours had a fibrinogen loss of 20 percent (p less than 0.0001) and 43 percent (p less than 0.0001). Cryo stored at RT for 6 hours had no fibrinogen loss and a 2 percent loss at 24 hours (p greater than 0.05). These preliminary data show a significant loss of FVIII and fibrinogen activity in Cryo stored at 1 to 6 degrees C and filtered before assay. The FVIII and fibrinogen activity at RT is clearly maintained up to 6 hours after thawing.

Open reduction and internal fixation of proximal interphalangeal joint fracture-subluxations.

Proximal interphalangeal (PIP) joint fracture-subluxations represent a small component of hyperextension injuries to the finger. Six unstable PIP fracture-subluxations that were not amenable to nonoperative treatment underwent open reduction and internal fixation. Among the patients, the technique of open reduction and internal fixation with temporary transarticular K-wire fixation and early protected range of motion has been found to result in a good range of motion with minimal complaints on follow-up.

Irradiation effect on aging red blood cells.

Irradiation of stored red blood cells (RBC) is increasingly utilized for patients who are immunosuppressed or on chemotherapeutic regimens. With the growing demand for irradiated cellular blood products, there has been an increasing need for transfusion services to store previously irradiated blood until needed for transfusion. The effect of irradiation on aging stored RBC has not been studied to date. Five units each of group A, RBC collected in CPD-Adsol (AS-1) with a prior shelf-life of 10, 20, 30, and 40 days, respectively, were divided equally utilizing a sterile docking device and stored at 1 to 6 degrees C. Baseline samples from each bag were obtained for the measurement of extracellular potassium (K+), plasma free hemoglobin (PFH), total lactate dehydrogenase (LD), and erythrocyte 2,3-DPG activity. One of each pair received 2,000 rads of gamma irradiation. Samples were obtained at 3 and 7 days post-irradiation, and multiples of 7 days until expiration. All irradiated units reached a state of K+ equilibrium at 60 to 70 mmol per L irrespective of the length of previous storage with an inverse relationship of RBC age at irradiation and the time required to reach the state of equilibrium. Increased K+ leakage from irradiated aging RBC suggests the need for including in vivo studies of cell survival to establish a post-irradiation storage life. Length of storage prior to irradiation had no effect on PFH, LD activity, and 2,3-diphosphoglycerate (2,3-DPG) activity compared to paired controls.

Effects of irradiation on red cells stored in CPDA-1 and CPD-ADSOL (AS-1).

Red blood cells (pRBC) collected in citrate, phosphate, dextrose, adenine-formula 1 (CPDA-1) and citrate, phosphate, dextrose-adenine, manitol saline solution (CPD-ADSOL [AS-1]) anticoagulants are increasingly being stored for variable periods in transfusion service inventories following irradiation. While anecdotal reports of increased K+ following irradiation and storage have recently appeared in the literature, concomitant in vitro biochemical changes resulting from differences in anticoagulants have not been reported. Utilizing two venipunctures, two units each of 225 mL of blood from five volunteers were collected in anticoagulant-adjusted CPDA-1 and AS-1 bags. Within two hours of collection, each unit was equally divided. One of each pair was irradiated (2000 rads). Samples were analyzed on Days 0, 1, 3, 7, and every seven days to expiration. Irradiation resulted in a 2.3 fold increase in K+ during the first seven days of storage for both anticoagulants, although significantly greater K+ levels were observed in the CPDA-1 pairs compared to the AS-1 pairs. Comparison of glucose utilization, plasma free hemoglobin, 2,3-diphosphoglycerate (2,3-DPG) and lactate dehydrogenase between control and irradiated CPDA-1 and AS-1 pairs and between anticoagulants were documented.

Impaired platelet function associated with parenteral nafcillin.

A 44-year-old Caucasian female was admitted with a subarachnoid hemorrhage owing to a multilobular tubular anterior communicating artery aneurysm. Eleven days after the original craniotomy, an epidural hematoma was evacuated. The patient was placed on empiric nafcillin antimicrobial coverage (two g every six hours). Within 24 hours, the onset of epistaxis and oozing of blood from the endotracheal tube and craniotomy site was noted. Recurrent subdural and epidural hematomas necessitated a third emergent craniotomy. The development of an acquired qualitative platelet defect was suggested by the findings of a prolonged template bleeding time and markedly abnormal platelet aggregation/ATP release studies despite a normal platelet count. Nafcillin therapy was immediately discontinued. Clinical bleeding resolved. Subsequent bleeding times and platelet aggregation studies confirmed the nafcillin-induced platelet dysfunction.