The comparative safety of bacterial risk control strategies for platelet components: a simulation study.

BACKGROUND: Bacterial contamination of platelets is a problem that can lead to harmful septic transfusion reactions. The US Food and Drug Administration published a guidance in September 2019 detailing several permissible risk control strategies. Our objective was to compare the safety of each bacterial testing strategy for apheresis platelets. STUDY DESIGN AND METHODS: We used simulation to compare safety of the nine risk control strategies involving apheresis platelet testing. The primary outcome was the risk of exposure. An exposure event occurred if a patient received platelets exceeding a specific contamination threshold (>0, 103 , and 105 colony-forming units (CFU/mL). We generated a range of bacterial contamination scenarios (inoculum size, doubling time, lag time) and compared risk of exposure for each policy in each contamination scenario. We then computed the average risk difference over all scenarios. RESULTS: At the 0 CFU/mL exposure threshold, two-step policies that used secondary culture ranked best (all top three), while single-step 24-hour culture with 3-day expiration ranked last (ninth). This latter policy performed well (median rank of 1) at both the 103 and 105 CFU/mL thresholds, but 48-hour culture with 7-day expiration performed relatively poorly. At these higher thresholds, median ranks of two-step policies that used secondary culture were again top three. Two-step policies that used rapid testing improved at the higher (105 CFU/mL) harm threshold, with median rankings between 1 and 5. CONCLUSION: Two-step policies that used secondary culture were generally safer than single-step policies. Performance of two-step policies that used rapid testing depended on the CFU per milliter threshold of exposure used.

The association of inpatient blood utilization and diagnosis-related group weight: implications for risk-adjusted benchmarking.

BACKGROUND: Risk-adjusted benchmarking could be useful to compare blood utilization between hospitals or individual groups, such as physicians, while accounting for differences in patient complexity. The aim of this study was to analyze the association of red blood cell (RBC) use and diagnosis-related group (DRG) weights across all inpatient hospital stays to determine the suitability of using DRGs for between-hospital risk-adjusted benchmarking. Specific hierarchical organizational units (surgical vs. nonsurgical patients, departments, and physicians) were also evaluated. STUDY DESIGN AND METHODS: We studied blood use among all adult inpatients, and within organizational units, over 4 years (May 2014 to March 2018) at an academic center. Number of RBCs transfused, all patient refined (APR)-DRGs, and other variables were captured over entire hospital stays. We used multilevel generalized linear modeling (zero-inflated negative binomial) to study the relationship between RBC utilization and APR-DRG. RESULTS: A total of 97,955 hospital stays were evaluated and the median APR-DRG weight was 1.2. The association of RBCs transfused and APR-DRG weight was statistically significant at all hierarchical levels (incidence rate ratio = 1.22; p < 0.001). The impact of APR-DRG on blood use, measured by the incidence rate ratio, demonstrated an association at the all-patient and surgical levels, at several department and physician levels, but not at the medical patient level. The relationship between RBCs transfused and APR-DRG varied across organizational units. CONCLUSION: Number of RBCs transfused was associated with APR-DRG weight at multiple hierarchical levels and could be used for risk-adjusted benchmarking in those contexts. The relationship between RBC use and APR-DRG varied across organizational units.

Bacteria differentially induce degradation of Bcl-xL, a survival protein, by human platelets.

Bacteria can enter the bloodstream in response to infectious insults. Bacteremia elicits several immune and clinical complications, including thrombocytopenia. A primary cause of thrombocytopenia is shortened survival of platelets. We demonstrate that pathogenic bacteria induce apoptotic events in platelets that include calpain-mediated degradation of Bcl-x(L), an essential regulator of platelet survival. Specifically, bloodstream bacterial isolates from patients with sepsis induce lateral condensation of actin, impair mitochondrial membrane potential, and degrade Bcl-x(L) protein in platelets. Bcl-x(L) protein degradation is enhanced when platelets are exposed to pathogenic Escherichia coli that produce the pore-forming toxin α-hemolysin, a response that is markedly attenuated when the gene is deleted from E coli. We also found that nonpathogenic E coli gain degrading activity when they are forced to express α-hemolysin. Like α-hemolysin, purified α-toxin readily degrades Bcl-x(L) protein in platelets, as do clinical Staphylococcus aureus isolates that produce α-toxin. Inhibition of calpain activity, but not the proteasome, rescues Bcl-x(L) protein degradation in platelets coincubated with pathogenic E coli including α-hemolysin producing strains. This is the first evidence that pathogenic bacteria can trigger activation of the platelet intrinsic apoptosis program and our results suggest a new mechanism by which bacterial pathogens might cause thrombocytopenia in patients with bloodstream infections.

Intravenous immune globulin therapy for Stevens-Johnson syndrome/toxic epidermal necrolysis complicated by hemolysis leading to pigment nephropathy and hemodialysis.

BACKGROUND: Intravenous immune globulin (IVIG) is generally thought to be of relatively low risk for adverse events and some experts consider this to be the best treatment for Stevens-Johnson syndrome/toxic epidermal necrolysis. OBJECTIVE: We evaluated the underlying cause of anemia and renal failure in 2 consecutive patients being treated with IVIG for Stevens-Johnson syndrome/toxic epidermal necrolysis. METHODS: This is a retrospective chart review. RESULTS: We present 2 patients with Stevens-Johnson syndrome/toxic epidermal necrolysis and severe hemolysis requiring blood transfusion who subsequently developed pigment nephropathy necessitating hemodialysis after treatment with IVIG. Both patients had antibodies to their ABO blood type detected in the eluate from their red blood cell membrane. LIMITATIONS: This is a retrospective review with only 2 cases. CONCLUSIONS: We propose that IVIG-associated hemolysis is an adverse reaction that may not be as rare as once thought, presenting as a mild decrease in hemoglobin and hematocrit. Antibodies to blood type A and B are given as part of pooled immune globulin and are considered to be the cause of hemolysis. More severe anemia requiring transfusion is less common, and the breakdown products produced by hemolysis can lead to pigment nephropathy and renal failure. We present methods by which this severe complication can be anticipated and managed more effectively.

Anucleate platelets generate progeny.

Platelets are classified as terminally differentiated cells that are incapable of cellular division. However, we observe that anucleate human platelets, either maintained in suspension culture or captured in microdrops, give rise to new cell bodies packed with respiring mitochondria and alpha-granules. Platelet progeny formation also occurs in whole blood cultures. Newly formed platelets are structurally indistinguishable from normal platelets, are able to adhere and spread on extracellular matrix, and display normal signal-dependent expression of surface P-selectin and annexin V. Platelet progeny formation is accompanied by increases in biomass, cellular protein levels, and protein synthesis in expanding populations. Platelet numbers also increase during ex vivo storage. These observations indicate that platelets have a previously unrecognized capacity for producing functional progeny, which involves a form of cell division that does not require a nucleus. Because this new function of platelets occurs outside of the bone marrow milieu, it raises the possibility that thrombopoiesis continues in the bloodstream.

The utility of patient characteristics in predicting severe ADAMTS13 deficiency and response to plasma exchange.

BACKGROUND: Idiopathic thrombotic thrombocytopenic purpura (TTP) is a rare form of thrombotic microangiopathy (TMA) characterized by extreme deficiency of ADAMTS13, an enzyme responsible for cleavage of von Willebrand factor. Plasma exchange therapy is the cornerstone of current treatment and is ineffective for most other forms of TMA. The availability of ADAMTS13 testing has improved diagnostic accuracy and appropriate selection of patients who are most likely to respond to plasma exchange. STUDY DESIGN AND METHODS: We performed a retrospective chart review of 110 cases of clinically suspected TTP with ADAMTS13 test results from 2005 to the present. The primary goal was to identify presenting clinical and/or laboratory features of patients with ADAMTS13 deficiency that would prove useful in increasing the likelihood of, or excluding the possibility of, TTP. In addition, patient outcomes including alternative diagnoses and response to plasma exchange were reviewed. RESULTS: Significant correlations for severe ADAMTS13 deficiency were seen for four of the observed variables: indirect bilirubin, reticulocyte percentage, creatinine, and platelet count; a fifth variable, D-dimer, just missed significance but performed well in subsequent analysis. Receiver operator characteristics curves for individual variables had area under the curve (AUC) values ranging from 0.75 to 0.85; a combined model had an AUC of 0.98. In addition, we constructed tree models both for clinical use as a diagnostic algorithm and for recursive partitioning to help establish cutoff points for categorical variables in developing an easy-to-use clinical prediction score. CONCLUSION: These results may enable the rapid exclusion and accurate diagnosis of TTP using readily available laboratory data.

Quality Improvement After Multiple Fatal Transfusion-Transmitted Bacterial Infections.

OBJECTIVES: Transfusion-transmitted bacterial infection (TTBI) from platelet components is likely underrecognized and can be fatal. Twenty-four-hour prospective culture was felt to be insufficiently preventive after multiple TTBIs occurred and strategies to improve safety were sought. METHODS: Two fatal and one severe TTBIs occurred from a split-apheresis platelet donation contaminated with Klebsiella pneumoniae. Improvement opportunities were identified and corrective and preventive action (CAPA) followed. RESULTS: To mitigate bacterial contamination and improve detection sensitivity, additional prospective culture 48 hours postcollection was implemented. Since implementation, secondary cultures have caught two true positives (0.01%) missed by 24-hour culture. Bacterial testing at issue and pathogen reduction were later implemented as an added layer of safety. CONCLUSION: While rare, TTBI is a prominent cause of morbidity and mortality from contaminated platelets. The approach to CAPA presented here may lower the risk of future transfusion-transmitted infections but must be weighed against potential added costs.

Managing transfusion service quality.

CONTEXT: Providing blood products for transfusions is a complex process subject to errors both within and outside the transfusion service. Transfusion-related errors can have grave consequences for the patient undergoing transfusion. As with many processes performed within health care systems, there is an expectation of error-free practice. Although this is an unobtainable goal, a focused quality-management plan, employing a medical event reporting system in a just working environment, can effect measurable system-quality improvement. OBJECTIVE: To illustrate the intrinsic value of quality-improvement activities through discussion of examples of quality misadventures from our transfusion service during the past 20 years. DATA SOURCES: Examples of quality-improvement activities were extracted from our quality-system archives. The published literature on transfusion quality was reviewed. CONCLUSIONS: Active reporting, structured investigation, and systematic resolution of transfusion-related errors are effective methods for improving and maintaining transfusion quality.

Teaching pediatric laboratory medicine to pathology residents.

CONTEXT: Laboratory data are essential to the medical care of fetuses, infants, children, and adolescents. However, the performance and interpretation of laboratory tests on specimens from these patients, which may constitute a significant component of the workload in general hospitals and integrated health care systems as well as specialized perinatal or pediatric centers, present unique challenges to the clinical pathologist and the laboratory. Therefore, pathology residents should receive training in pediatric laboratory medicine. OBJECTIVE: Children's Health Improvement through Laboratory Diagnostics, a group of pathologists and laboratory scientists with interest and expertise in pediatric laboratory medicine, convened a task force to develop a list of curriculum topics, key resources, and training experiences in pediatric laboratory medicine for trainees in anatomic and clinical pathology or straight clinical pathology residency programs and in pediatric pathology fellowship programs. DATA SOURCES: Based on the experiences of 11 training programs, we have compiled a comprehensive list of pediatric topics in the areas of clinical chemistry, endocrinology, hematology, urinalysis, coagulation medicine, transfusion medicine, immunology, microbiology and virology, biochemical genetics, cytogenetics and molecular diagnostics, point of care testing, and laboratory management. This report also includes recommendations for training experiences and a list of key texts and other resources in pediatric laboratory medicine. CONCLUSIONS: Clinical pathologists should be trained to meet the laboratory medicine needs of pediatric patients and to assist the clinicians caring for these patients with the selection and interpretation of laboratory studies. This review helps program directors tailor their curricula to more effectively provide this training.

Plasmapheresis for the treatment of intrahepatic cholestasis of pregnancy refractory to medical treatment.

Pruritus associated with intrahepatic cholestasis of pregnancy (ICP) is usually mild but some cases are refractory to medical treatment. We report a case of intractable ICP that was successfully treated with plasmapheresis. Plasmapheresis should be considered for ICP that is refractory to traditional therapies.