Differentiating patient characteristics between platelet refractory patients with and without antibodies to human leukocyte antigens.

BACKGROUND: Predicting whether a patient's platelet refractoriness (PR) is due to immune or nonimmune causes can be challenging. This study compared the demographics and clinical history of PR patients with human leukocyte antigen (HLA) antibodies (HLA-PR) versus PR patients without HLA antibodies. MATERIALS AND METHODS: A retrospective review of all patients with PR consults at a single institution over a 3-year period was performed. Patient charts were reviewed for all patients with confirmed PR, and demographic information (e.g., sex, race and ethnicity, preferred language) and clinical history (e.g., pregnancy, transfusion, primary diagnosis) were collected. Patient characteristics were compared among the HLA and non-HLA cohorts. RESULTS: A total of 295 patients with confirmed PR were identified, of whom approximately 70% did not have HLA antibodies and 30% did. Approximately 84% of the HLA-PR cohort was female. A history of transfusions was not associated with HLA-PR (p = .1). A history of pregnancy was strongly associated with the occurrence of HLA-PR (p < .001). Splenomegaly was associated with PR in the absence of HLA alloimmunization whereas infection, fever, bleeding, and disseminated intravascular coagulation were not. CONCLUSION: In this single-institution retrospective review, a history of pregnancy was strongly associated with HLA-PR, whereas a history of transfusion was not.

Transfusion medicine and blood banking education and training for blood establishment laboratory staff: A review of selected countries in Africa.

BACKGROUND: Avoidable human error is a significant cause of transfusion adverse events. Adequately trained, laboratory staff in blood establishments and blood banks, collectively blood facilities, are key in ensuring high-quality transfusion medicine (TM) services. Gaps in TM education and training of laboratory staff exist in most African countries. We assessed the status of the training and education of laboratory staff working in blood facilities in Africa. STUDY DESIGN AND METHODS: A cross-sectional study using a self-administered pilot-tested questionnaire was performed. The questionnaire comprised 26 questions targeting six themes. Blood facilities from 16 countries were invited to participate. Individually completed questionnaires were grouped by country and descriptive analysis performed. RESULTS: Ten blood establishments and two blood banks from eight African countries confirmed the availability of a host of training programs for laboratory staff; the majority of which were syllabus or curriculum-guided and focused on both theoretical and practical laboratory skills development. Training was usually preplanned, dependent on student and trainer availability and delivered through lecture-based classroom training as well as formal and informal on the job training. There were minimal online didactic and self-directed learning. Teaching of humanistic values appeared to be lacking. CONCLUSION: We confirmed the availability of diverse training programs across a variety of African countries. Incorporation of virtual learning platforms, rather than complete reliance on didactic, in-person training programs may improve the education reach of the existing programs. Digitalization driven by the coronavirus disease 2019 pandemic may provide an opportunity to narrow the knowledge gap in low- and middle-income countries (LMICs).

Global survey of transfusion medicine curricula in medical schools: Challenges and opportunities.

BACKGROUND: Physician's knowledge in transfusion medicine (TM) is critical for patient safety. Therefore, ensuring that medical schools provide adequate education in TM is important. The aim of this study was to assess the status of TM education at a global level. STUDY DESIGN AND METHODS: A comprehensive anonymous survey to assess TM education in existing medical school curricula was developed. The survey was distributed to deans and educational leads of medical schools in a range of low-, medium-, high-, and very high-human development index (HDI) countries. It included 20 questions designed to assess specific domains including structure of TM curriculum and teaching faculty. RESULTS: The response rate was 53%. The majority of responding schools from very-high-HDI countries offered a 6-year curriculum after high school or a 4-year curriculum after college education, whereas most schools from medium-HDI countries offered a 5-year medical curriculum. A formal teaching program was available in only 42% of these schools in contrast to 94% of medical schools from very high-HDI. Overall, 25% of all medical schools did not offer structured TM teaching. When offered, most TM teaching was mandatory (95%) and integrated within the third and fourth year of medical school. Formal assessment of TM knowledge was done in 72% of all responding medical schools. More than half of the deans considered the TM education in their medical schools as inadequate. CONCLUSION: Despite its limitations, the current survey highlights significant gaps and opportunities of TM education at a global scale.

Acute autoimmune hemolytic anemia due to anti-Ena autoantibody successfully treated with rituximab.

BACKGROUND: Autoimmune hemolytic anemia (AIHA) due to anti-Ena has been previously reported in association with massive intravascular hemolysis, disseminated intravascular coagulation, and fatal outcomes. Here we report a case of successfully treated AIHA due to anti-Ena . CASE REPORT: A 69-year-old male with a past medical history of cirrhosis due to nonalcoholic steatohepatitis status post-orthotopic liver transplant presented with 1-month history of progressive anemia. At presentation, his hemoglobin (Hb) was 5.6 g/dL, hematocrit (Hct) 16%, reticulocytes 0.3%, direct bilirubin (bili) 4 g/dL, lactate dehydrogenase 533 units/L (reference, 125-220 units/L), and haptoglobin 254 mg/dL (reference, 40-273 mg/dL). Blood bank testing revealed an autoantibody present in his plasma and a direct antiglobulin test positive for immunoglobulin G (IgC) but negative for complement. He received 1 unit of an incompatible blood group O phenotypically matched red blood cell unit. RESULTS: Over the course of the next 5 days, the Hb and Hct decreased to 4.1 g/dL and 12%, respectively, direct bili increased to 12.3 mg/day, reticulocytes slightly increased to 0.9%, and haptoglobin decreased to less than 8 mg/dL. Marrow study showed a hypercellular marrow with erythroid hyperplasia. Additional workup performed at a reference laboratory identified an anti-Ena autoantibody. He received prednisone and weekly rituximab infusions and was monitored weekly. At the 2-month visit, Hb and Hct were 10 g/dL and 32%, respectively. CONCLUSION: Unlike two of the previously reported fatal cases of AIHA with anti-Ena specificity, this 69-year-old male treated with weekly rituximab infusion underwent clinical recovery and significant anemia improvement.

How do we manage cardiopulmonary bypass coagulopathy?

BACKGROUND: Patients who undergo cardiopulmonary bypass (CPB) are at risk for coagulopathy. Suboptimal turnaround time (TAT) of laboratory coagulation testing results in empiric administration of blood products to treat massive bleeding. We describe our initiative in establishing the coagulation-based hemotherapy (CBH) service, a clinical pathology consultation service that uses rapid TAT coagulation testing and provides comprehensive assessment of bleeding in patients undergoing CPB. A transfusion algorithm that treats the underlying cause of coagulopathy was developed. STUDY DESIGN AND METHODS: The coagulation testing menu includes all aspects of coagulopathy with close proximity of the laboratory to the operating room to allow for rapid test results. The hemotherapy pathologist monitors laboratory results at several stages in surgery and uses a comprehensive algorithm to monitor a patient's hemostasis. The optimal number and type of blood products are selected when the patient is taken off CPB. RESULTS: The CBH service was consulted for 44 ventricular assist device implants, 30 heart transplants, and 31 other cardiovascular surgeries from May 2012 through November 2013. The TAT for laboratory tests was 15 minutes for complete blood count, antithrombin, and coagulation panel and 30 minutes for VerifyNow and thromboelastography, in comparison to 45 to 60 minutes in normal settings. The transfusion algorithms were used with optimal administration of blood components with preliminary data suggestive of reduced blood product usage and better patient outcomes. CONCLUSION: We described the successful introduction of a novel pathology consultation service that uses a rapid TAT coagulation testing menu with transfusion algorithms for improved management of CPB patients.

BBDash: An Electron-based tool for analyzing blood product utilization.

Blood transfusions can be associated with side effects ranging from occasional febrile reactions to extremely rare fatal reactions. Monitoring blood product orders and ensuring appropriate utilization is therefore an important strategy to ensure patient safety. However, data extracted from laboratory information systems can be difficult to interpret. We created BBDash, an Electron-based tool that reads Sunquest reports to create easy-to-interpret graphs related to blood product utilization.

A Single-Center Description of Pediatric Transfusion Reactions and Preventable Patient Harm.

BACKGROUND AND OBJECTIVES: In previous studies, researchers highlight that children have higher rates of transfusion reactions than adults. However, little is known about the pediatric populations that experience reactions, and there are no reports that consider appropriateness of pediatric transfusions in relation to preventable harm. With this study, we aim to describe pediatric transfusion reactions occurring at an academic institution and to quantify transfusion reactions that resulted from inappropriate transfusion indications, thereby identifying an area of potentially preventable patient harm (PPH). METHODS: This is a case series of acute transfusion reactions in pediatric patients at a single institution from January 2018 to December 2019. We reviewed patient data, clinical documentation, and transfusion reaction reports to determine the appropriateness of transfusions and calculate PPH. RESULTS: A total 155 acute transfusion reactions occurred in 106 pediatric patients, amounting to a total reaction rate of 544 of 100 000 transfusions. In 65% of reactions, the indication for transfusion was appropriate by institutional standards; 23% had questionable indication; and 12% were not indicated. The rate of potential PPH from inappropriate transfusions was 67 of 100 000 transfusions. CONCLUSIONS: Transfusion reactions that occur during inappropriately ordered blood transfusions represent PPH. Efforts should be made to develop transfusion guidelines, standardize practice, and educate physicians to prevent transfusion-related harm.

CRISPR/Cas9 for the Clinician: Current uses of gene editing and applications for new therapeutics in oncology.

Precise genomic editing has given rise to treatments in previously untreatable genetic diseases and has led to revolutions in treatment for cancer. In the past decade, the discovery and development of clustered regularly interspaced short palindromic repeats (CRISPR) technologies has led to advances across medicine and biotechnology. Specifically, the CRISPR/Cas9 system has improved translational discovery and therapeutics for oncology across tumor types. In this review, we briefly summarize the history and development of CRISPR, explain CRISPR-Cas systems and CRISPR gene editing tools, highlight the development and application of CRISPR technologies for translational and therapeutic purposes in different oncologic tumors, and review novel treatment paradigms using CRISPR in immuno-oncology, including checkpoint inhibitors and chimeric antigen receptor T cell therapy.

Overtransfusion of Autologous Blood Identifies Opportunities for Improving Patient Blood Management.

Background Preoperative autologous blood donation (PABD) has been declining in use nationally. A subset of patients scheduled for elective surgery, however, continue to be offered and choose this option. Our study aimed to understand the current impact of PABD before scheduled surgical procedures. Study design and methods A retrospective review was conducted in a single large academic center. Medical records associated with autologous units received in the transfusion service over a two-year period (1/1/2016-12/31/2017) were reviewed. Demographics, units donated, units transfused, wastage, pre-donation hemoglobin (Hb), pre-operative Hb, estimated blood loss (EBL), and clinical specialty were collected. Results During the study period, 118 patients underwent PABD, donating a total of 141 autologous red blood cell units. Patients who donated autologous units and were subsequently transfused had lower pre-donation Hb compared to patients who were not transfused (13.3 ± 1.4 g/dL vs. 14.3 ± 1.5 g/dL, p=0.004). Pre-operative Hb was lower than pre-donation Hb among both groups (12.1 ± 1.2 g/dL for patients receiving transfusion; 12.9 ± 1.5 g/dL, p=0.011 for patients who were not transfused). The majority of PABD patients (71%) had an estimated blood loss of less than 500 mL. Wastage rate of autologous units was 67%. PABD was disproportionately associated with a minority of surgeons and clinical services. Conclusion Within our institution, PABD is heavily used amongst a small subset of physicians across multiple surgical specialties and is associated with lower pre-operative Hb, tendency towards overtransfusion, and high rates of wastage of donated units. Our findings reinforce reports of inefficiencies in patient blood management and increased risks to patient health associated with PABD.

Quality Improvement in Transfusion Practice of Orthotopic Liver Transplantation Reduces Blood Utilization, Length of Hospital Stay, and Cost.

OBJECTIVES: Orthotopic liver transplantation (OLT) can require substantial usage of blood products. Higher rates of transfusion have been associated with increased length of hospital stay, higher rates of infection, graft failure, and mortality. This study was a retrospective analysis to assess the impact of quality improvement interventions in OLT. METHODS: Data collection included demographics, preoperative and intraoperative data, blood utilization, and cost data. Statistical analysis was performed using R software. RESULTS: Total blood product utilization was reduced by approximately 50%. Statistically significant decreases were noted in blood product usage in the intraoperative and first 48-hour postoperative utilization, the number of OLTs using fewer than five RBC units, length of hospital stay, and cost. CONCLUSIONS: This study showed successful implementation of quality improvement team interventions to reduce blood utilization during OLT. Reduced transfusion significantly correlated with decreased length of hospital stay and cost.

PIFA PLUSS P4 Assay for Screening of Heparin-Induced Thrombocytopenia.

BACKGROUND: The PIFA PLUSS PF4 Rapid Assay (PIFA) is a rapid screening test used for the diagnosis of heparin-induced thrombocytopenia (HIT). OBJECTIVE: To determine the usefulness of this assay as a screening method in our institution. METHODS: A total of 159 specimens from patients with suspected HIT were included in our study. We simultaneously performed PIFA assay and confirmatory polyspecific enzyme-linked immunosorbent assay (ELISA). We subjected most of the specimens with false-negative results to serotonin release assay (SRA). RESULTS: The initial sensitivity and specificity of the PIFA assay were calculated as 27.3% and 71.5%, respectively. A total of 12 of 16 false-negative results were further tested using the SRA method. The revised sensitivity and specificity were 50.0% and 73.5%, respectively. CONCLUSIONS: Despite its appealing feature of yielding rapid results, the PIFA assay is inadequate as a sole screening test for HIT because of its high probability of missing many true cases of HIT.

Exclusive use of acid citrate dextrose for anticoagulation during extracorporeal photopheresis in patients with contraindications to heparin: an effective protocol.

Extracorporeal photopheresis (ECP) routinely uses heparin for anticoagulation. For patients with contraindications to heparin, alternative anticoagulation using acid citrate dextrose (ACD-A) has been reported to be safe and effective. However, detailed ECP protocols that exclusively use ACD-A anticoagulation and minimize citrate toxicity have not yet been published. We report a protocol that completely replaces heparin with ACD-A for ECP, which was developed at the University of California, Los Angeles (UCLA), and our experience since its implementation. ECP was performed with the UVAR XTS photopheresis system using ACD-A and control of the rate of citrate infusion. Calcium gluconate solution was administered prophylactically and as needed for symptoms of citrate toxicity. The medical records of patients who underwent ECP using the ACD-A protocol between January 2003 and July 2006 were reviewed. The incidence and severity of citrate toxicity and the technical data for all procedures were analyzed. During this period, 94 ECP procedures were performed with ACD-A anticoagulation on five patients. All patients tolerated the procedures well without significant complications. Only minimal symptoms of citrate toxicity (grade 1) were observed in 24.5% of all procedures; symptoms resolved promptly following administration of additional calcium gluconate. In conclusion, an effective protocol for ECP using ACD-A anticoagulation exclusively in patients with contraindications to heparin employs continuous monitoring of flow rates and prophylactic administration of calcium gluconate to minimize citrate toxicity.

Standardized protocol to identify high-risk patients undergoing therapeutic apheresis procedures.

As the scope of therapeutic apheresis (TA) expands and more procedures are requested for critically ill patients, adverse reactions (AR) associated with TA become a major concern for physicians, nurses, patients and their families. To assess the risks for ARs associated with patients' underlying diseases, we developed a preprocedure assessment tool with a set of high-risk criteria which included: (1) unstable vital signs, (2) active nonphysiological bleeding, (3) evidence of severe bronchoconstriction, (4) severe anemia, (5) projected extracorporeal volume (ECV) >15% of total blood volume (TBV) in adults or >10% of TBV in pediatric patients, (6) pregnancy, and (7) conditions requiring continuous nursing support. A standard operating procedure with a "Request for Apheresis Procedure on High-Risk Patient" form and protocol were developed to identify patients as high-risk before initiation of a TA procedure. Here we report our experience in the 3-year period following the implementation of this protocol. During this period, a total of 3,254 TA procedures were performed, 44 of which were for patients identified as high-risk by the protocol. The incidence of overall ARs was 8% for all TA procedures and 45.5% for procedures performed for high-risk patients. The incidence of moderate-to-severe ARs was 3.7% for all TA procedures and 36.4% for procedures performed for high-risk patients. The protocol identified a group of patients with an increased risk for ARs, especially moderate-to-severe reactions during and/or immediately following TA.

Short-Term Experience with Off-Pump Versus On-Pump Implantation of the HeartWare Left Ventricular Assist Device.

Implantation of left ventricular assist devices while avoiding cardiopulmonary bypass (CPB) may decrease bleeding and improve postoperative recovery. To understand the effectiveness of this approach, we reviewed the charts of 26 patients who underwent HeartWare left ventricular assist device (HVAD) implantation without use of CPB (off-CPB group) and 22 patients who had HVAD implanted with CPB (CPB group) with an emphasis on the 30 day postoperative period. Preoperatively, both groups had similar demographic, functional, and hemodynamic characteristics. Off-CPB patients had significantly shorter surgery times than CPB patients, 188.5 (161.5-213.3) min versus 265.0 (247.5-299.5) min, respectively; p < 0.001. Blood transfusion requirements during surgery and within the postoperative 48 hour period were significantly lower in the off-CPB group than in the CPB group (odds ratio: 5.9; 95% confidence interval: 1.1-31.1, p = 0.042). Compared with the CPB group, the off-CPB group patients had a shorter intubation time, 21 (17.4-48.5) hours versus 41 (20.6-258.4) hours; p = 0.042. Intensive care unit stay was 7.0 (4.75-13.5) days for off-CPB versus 10.0 (6.0-19.0) days for CPB (p = 0.256). The off-CPB approach allows HVAD to be implanted quickly with significantly less perioperative bleeding and transfusion requirements and facilitates postoperative rehabilitation.

Bioinformatics Analysis to Determine Prognostic Mutations of 72 de novo Acute Myeloid Leukemia Cases from the Cancer Genome Atlas (TCGA) with 23 Most Common Mutations and no Abnormal Cytogenetics.

OBJECTIVES: Up to 40% of acute myeloid leukemia (AML) patients have normal cytogenetics (CN-AML) but they may have gene mutations. An important issue in the treatment of CN-AML is how gene mutation patterns may help with patient management. The Cancer Genome Atlas (TCGA) database has data from 200 cases of de novo AML including cytogenetics, gene mutations, and survival duration (prognosis). METHODS: Cases with the most common mutations and no cytogenetic abnormalities were selected from the TCGA. Unsupervised neural network analysis was performed to group them into clusters according to their pattern of mutations and survival. RESULTS: 72 cases of CN-AML with the 23 most common mutations were obtained from TCGA. Clustering was found to be based on 6 mutations, with the following prognostic groups: (a) good: NPM1, CEBPA, or TET2, (b) intermediate: NPM1/DNMT3A, or other mutations, (c) poor: RUNX1, FLT3-ITD, FLT3-ITD/NPM1, or FLT3-ITD/CEBPA. Some discrepancy between our results and those from previous studies is most likely due to inclusion of AML cases transformed from myeloproliferative neoplasms or myelodysplastic syndrome in previous studies. CONCLUSIONS: This study provides further molecular characterization and prognostic data most specific for the de novo subgroup of CN-AML patients.

Post-operative bleeding risk stratification in cardiac pulmonary bypass patients using artificial neural network.

The prediction of bleeding risk in cardiopulmonary bypass (CPB) patients plays a vital role in their postoperative management. Therefore, an artificial neural network (ANN) to analyze intra-operative laboratory data to predict postoperative bleeding was set up. The JustNN software (Neural Planner Software, Cheshire, England) was used. This ANN was trained using 15 intra-operative laboratory parameters paired with one output category - risk of bleeding, defined as units of blood components transfused in 48 hours. The ANN was trained with the first 39 CPB cases. The set of input parameters for this ANN was also determined, and the ANN was validated with the next 13 cases. The set of input parameters include five components: pro-thrombin time, platelet count, thromboelastograph-reaction time, D-Dimer, and thromboelastograph-coagulation index. The validation results show 9 cases (69.2%) with exact match, 3 cases (23.1%) with one-grading difference, and 1 case (7.7%) with two-grading difference between actual blood usage versus predicted blood usage. To the best of our knowledge, ours is the first ANN developed for post-operative bleeding risk stratification of CPB patients. With promising results, we have started using this ANN to risk-stratify our CPB patients, and it has assisted us in predicting post-operative bleeding risk.

Chimerism and tolerance post-in utero transplantation with embryonic stem cells.

BACKGROUND: Clinical application of in utero transplantation (IUT) in human fetuses with intact immune systems resulted in a very low level of donor chimerism. In this study, we examined whether the fetal immune system early in the second trimester of pregnancy (13.5 dpc) can initiate immune tolerance for major histocompatibility complex (MHC)-mismatched embryonic stem (ES) cells. We also examined whether immune tolerance mechanisms respond differently to ontogenetically different stem cells. METHODS: MHC-mismatched ES, fetal liver (FL), and bone-marrow (BM) cells (H-2kd) at 1 x 10(9) cells/kg fetal body weight were injected intraperitoneally into 13.5 dpc BALB/c fetuses (H-2Kd). Peripheral chimerism was determined in blood by flow cytometry (sensitivity< or =0.1%) at monthly intervals. Donor-specific immune responses were determined by cytotoxic lymphocyte (CTL) assay, mixed lymphocyte reaction, and T helper (Th)1 and Th2 cytokine assays. Chimeric mice at the age of 9 months received postnatal boosts (PB) with minimal conditioning of 200 cGy by intravenous injection of 1 x 10(9) of the corresponding cells/kg body weight. RESULTS: After IUT with ES, FL, or BM cells, the level of peripheral chimerism within the first 9 months of life was 0% to 0.4%. PB with 1 x 10(9)/kg of corresponding cells resulted in a decrease in the peripheral chimerism to 0% within 2 weeks of PB. CTL and cytokine assays before and after PB demonstrated a shift toward immunity. CONCLUSIONS: Immunologic tolerance was not achieved after IUT of murine fetuses at 13.5 dpc with MHC-mismatched ES cells, and only a low level chimerism was achieved.

Interpretation of coagulation test results using a web-based reporting system.

BACKGROUND: Web-based synoptic reporting has been successfully integrated into diverse fields of pathology, improving efficiency and reducing typographic errors. Coagulation is a challenging field for practicing pathologists and pathologists-in-training alike. OBJECTIVE: To develop a Web-based program that can expedite the generation of a individualized interpretive report for a variety of coagulation tests. METHODS: We developed a Web-based synoptic reporting system composed of 119 coagulation report templates and 38 thromboelastography (TEG) report templates covering a wide range of findings. RESULTS: Our institution implemented this reporting system in July 2011; it is currently used by pathology residents and attending pathologists. Feedback from the users of these reports have been overwhelmingly positive. Surveys note the time saved and reduced errors. CONCLUSION: Our easily accessible, user-friendly, Web-based synoptic reporting system for coagulation is a valuable asset to our laboratory services.