Novel In-Line Hemolysis Detection on a Blood Gas Analyzer and Impact on Whole Blood Potassium Results.

BACKGROUND: Preanalytical error due to hemolyzed blood samples is a common challenge in laboratory and point-of-care (POC) settings. Whole blood potassium (K+) measurements routinely measured on blood gas analyzers are particularly susceptible to hemolysis, which poses a risk for incorrect K+ results. The GEM Premier 7000 with IQM3 (GEM 7000) blood gas analyzer provides novel integrated hemolysis detection within the sample measurement process. Therefore, the GEM 7000 can detect and flag hemolyzed whole blood samples at the POC, warning the operator of potentially erroneous results. METHODS: Heparinized venous or arterial whole blood samples were used for K+ interference studies and assessed for hemolysis agreement utilizing either a traditional volumetric method or chemistry analyzer serum index measurements with the Roche cobas c311 or Abbott Alinity c. RESULTS: Hemolysis interference studies performed at 2 different K+ concentrations (3.8 and 5.3 mmol/L) identified that a plasma free hemoglobin ≥116 mg/dL can impact K+ results on the GEM 7000. Hemolysis agreement studies demonstrated an excellent agreement of >99% with the volumetric method, 98.8% with cobas H index, and 96.4% with Alinity H index. GEM 7000 K+ results were correctly flagged for both native and spiked samples. CONCLUSION: GEM 7000 hemolysis detection provides a novel technology to detect hemolysis in whole blood samples. Moreover, the GEM 7000 demonstrates excellent agreement with traditional laboratory hemolysis detection methods and offers an integrated technological solution for assuring the quality of whole blood K+ results in POC settings.

Characterization of Ebola convalescent plasma donor immune response and psoralen treated plasma in the United States.

BACKGROUND: In 2014, passive immunization by transfusion of Ebola convalescent plasma (ECP) was considered for treating patients with acute Ebola virus disease (EVD). Early Ebola virus (EBOV) seroconversion confers a survival advantage in natural infection, hence transfusion of ECP plasma with high levels of neutralizing EBOV antibodies is a potential passive immune therapy. Techniques to reduce the risk of other transfusion-transmitted infections (TTIs) are warranted as recent ECP survivors are ineligible as routine blood donors. As part of an ongoing clinical trial to evaluate the safety and effectiveness of ECP, the impact of amotosalen/UVA pathogen reduction technology (PRT) on EBOV antibody characteristics was examined. STUDY DESIGN AND METHODS: Serum and plasma samples were collected from EVD-recovered subjects at multiple timepoints and evaluated by ELISA for antibodies to recombinant EBOV glycoprotein (GP) and irradiated whole EBOV antigen, as well as for EBOV microneutralization, classic plaque reduction neutralization test (PRNT) and EBOV pseudovirion neutralization assay (PsVNA) activity. RESULTS: Six subjects donated 40 individual ECP units. Substantial antibody titers and neutralizing activity results were demonstrated but were generally lower for the ACD plasma samples compared to the serum samples. Anti-EBOV titers by all assays remained essentially unchanged after PRT. CONCLUSION: Treatment of ECP with PRT to reduce the risk of TTI did not significantly reduce EBOV IgG antibody titers or neutralizing activity. Although ECP was used in the treatment of repatriated patients, no PRT units from this study were transfused to EVD patients. This inventory of PRT-treated ECP is currently available for future clinical evaluation.

Electronic charting of transfusion medicine consults: implementation, challenges and opportunities.

BACKGROUND: The Joint Commission lists improving staff communication (handoffs) as part of several National Safety Goals. In this study, we developed an electronic web-based charting system for clinical pathology handoffs, which primarily consist of transfusion medicine calls, and evaluated the advantages over a paper-based handwritten call log. MATERIALS AND METHODS: A secure online web browser application using Research Electronic Data Capture (REDCap) was designed to document on-call pathology resident consults. A year after implementation, an online survey was administered to our pathology residents in order to evaluate and compare the usability of the electronic application (e-consults) to the previous handwritten call log, which was a notebook where trainees hand wrote different components of the consult. RESULTS: The REDCap web-based application includes discrete fields for patients' information, requesting physician contact, type of consult, action items for follow-up and faculty responses, as well as other information. These components have eventually progressed to be an online consult call catalog. With approximately 1079 consults per year, transfusion medicine-related calls account for ~90% of the encounters, while clinical chemistry, microbiology and immunology calls constitute the remainder. The overall response rate of the survey was 96% (29 of 30 participants). Of the 16 respondents who experienced both call log systems, 100% responded that REDCap was an improvement over the handwritten call log (P < 0·0001). CONCLUSION: E-consult documentation entered into a web-based application was a user-friendly, secure clinical information access and effective handoff system as compared to a paper-based handwritten call log.

Blood product transfusion and mortality in neonatal extracorporeal membrane oxygenation.

BACKGROUND: Neonates receiving extracorporeal membrane oxygenation (ECMO) support are transfused large volumes of red blood cells (RBCs) and platelets (PLTs). Transfusions are often administered in response to specific, but largely unstudied thresholds. The aim of this study is to examine the relationship between RBC and PLT transfusion rates and mortality in neonates receiving ECMO support. STUDY DESIGN AND METHODS: We retrospectively examined outcomes of neonates receiving ECMO support in the neonatal intensive care unit (NICU) for respiratory failure between 2010 and 2016 at a single quaternary-referral NICU. We examined the association between RBC and PLT transfusion rate (mL per kg per day) and in-hospital mortality, adjusting for confounding by using a validated composite baseline risk score (Neo-RESCUERS). RESULTS: Among the 110 neonates receiving ECMO support, in-hospital mortality was 28%. The median RBC transfusion rate (mL/kg/d) after cannulation was greater among non-survivors, compared to survivors: 12.4 (IQR 9.3-16.2) versus 7.3 (IQR 5.1-10.3), p < 0.001. Similarly, PLT transfusion rate was greater among non-survivors: 22.9 (9.3-16.2) versus 12.1 (8.4-20.1), p = 0.02. After adjusting for baseline mortality risk, both RBC transfusion (adjusted relative risk per 5 mL/kg/d increase: 1.33; 95% CI 1.05-1.69, p = 0.02) and PLT transfusion (adjusted relative risk per 5 mL/kg/d increase: 1.12; 95% CI 1.02-1.23, p = 0.02) were both associated with in-hospital mortality. CONCLUSIONS: RBC and PLT transfusion rates are associated with in-hospital mortality among neonates receiving ECMO. These data provide a basis for future studies evaluating more restrictive transfusion practices for neonates receiving ECMO support.

Predicting mortality in patients with disseminated intravascular coagulation after cardiopulmonary bypass surgery by utilizing two scoring systems.

: We evaluated clinical and laboratory biomarkers of disseminated intravascular coagulation (DIC) following cardiac surgery in the cardiothoracic surgical ICU (CTICU) to predict mortality. We retrospectively analyzed CTICU patients with suspected DIC identified from the hospital laboratory database, and calculated International Society on Thrombosis and Haemostasis (ISTH) and the Japanese Association for Acute Medicine (JAAM) DIC scores to predict DIC-related mortality. The predictive accuracy of the JAAM and ISTH DIC scoring system were then assessed by logistic regression analysis and receiver operative characteristics analysis, and compared to other potential predictors of mortality (e.g., Acute Physiology and Chronic Health Evaluation II, systemic inflammatory response syndrome criteria, laboratory variables). Our study showed a 30-day mortality rate of 71% in CTICU patients with DIC. The JAAM DIC score offered the best predictive accuracy [area under the curve (AUC): 0.723, 95% % confidence interval (CI): 0.638-0.947, P = 0.021], when compared with ISTH DIC score (AUC: 0.707, 95% CI: 0.491-0.923, P = 0.066) and Acute Physiology and Chronic Health Evaluation II (AUC: 0.687, 95% CI: 0.483-0.891, P = 0.110). A JAAM DIC score at least 6 was reported in 89% of the nonsurvivors and 46% of survivors (P = 0.010), and predicted mortality [odds ratio: 9.33 (1.50-58.20)] with a 73% sensitivity and a 78% specificity. Our results also show a strong relationship between acid-base derangement and mortality. This initial evaluation of DIC-related mortality in the CTICU found the standardized JAAM DIC scoring system in combination with acid-base laboratory values were most useful to predict mortality in postcardiac surgery patients with DIC. Additional prospective studies are needed to further validate our findings.

Hemoglobin A clearance in children with sickle cell anemia on chronic transfusion therapy.

BACKGROUND: Chronic transfusion therapy for sickle cell anemia reduces disease complications by diluting sickle-erythrocytes with hemoglobin A (HbA)-containing erythrocytes and suppressing erythropoiesis. Minor antigen mismatches may result in alloimmunization, but it is unknown if antigen mismatches or recipient characteristics influence HbA clearance posttransfusion. STUDY DESIGN AND METHODS: Children with sickle cell anemia on chronic transfusion therapy were followed prospectively for 12 months. All patients received units serologically matched for C/c, E/e, and K; patients with prior red blood cell (RBC) antibodies had additional matching for Fya , Jkb , and any previous alloantibodies. Patients' RBC antigen genotypes, determined by multiplexed molecular assays (PreciseType Human Erythrocyte Antigen, and RHCE and RHD BeadChip, Immucor) were compared to genotypes of transfused RBC units to assess for antigen mismatches. Decline in hbA (ΔHbA) from posttransfusion to the next transfusion was calculated for each transfusion episode. RESULTS: Sixty patients received 789 transfusions, 740 with ΔHbA estimations, and 630 with donor Human Erythrocyte Antigen genotyping. In univariate mixed-model analysis, ΔHbA was higher in patients with past RBC antibodies or splenomegaly and lower in patients with splenectomy. RBC antigen mismatches were not associated with ΔHbA. In multivariate linear mixed-effects modeling, ΔHbA was associated with RBC antibodies (2.70 vs. 2.45 g/dL/28 d, p = 0.0028), splenomegaly (2.87 vs. 2.28 g/dL/28 d, p = 0.019), and negatively associated with splenectomy (2.46 vs. 2.70 g/dL/28 d, p = 0.011). CONCLUSIONS: HbA decline was increased among patients with sickle cell anemia with prior immunologic response to RBC antigens and decreased among those with prior splenectomy, demonstrating that recipient immunologic characteristics influenced the clearance of transfused RBCs.

Red blood cell minor antigen mismatches during chronic transfusion therapy for sickle cell anemia.

BACKGROUND: Red blood cell (RBC) alloimmunization occurs at a high frequency in sickle cell anemia (SCA) despite serologic matching for Rh (C/c, E/e) and K antigens. RBC minor antigen genotyping allows for prediction of antigens and RH variants that may lead to alloimmunization. STUDY DESIGN AND METHODS: RBC antigen genotyping was performed on chronically transfused pediatric SCA patients, using PreciseType human erythrocyte antigen (HEA), RHCE, and RHD BeadChip arrays. All patients received C/c, E/e, and K serologically matched units (Category 1); patients with prior RBC antibodies were also matched for Fya , Jkb , and any antibodies (Category 2). The RBC genotypes of all leukoreduced (LR) units transfused over a 12-month period were determined by the prototype HEA-LR BeadChip assay. RESULTS: There were 2320 RBC units transfused to 90 patients in 1135 transfusion episodes. Thirty-five (38.9%) patients had homozygous or compound heterozygous RH variants. Seven new alloantibodies were detected, with alloantibody incidence of 0.706 in 100 units for Category 2 transfusions and 0.068 in 100 units for Category 1 (p = 0.02). Three patients on Category 2 transfusions formed new anti-Jsa and had a higher rate of exposure to Jsa than those who did not form anti-Jsa (20.4 vs. 8.33 exposures/100 units, p = 0.02). The most frequent mismatches were S (43.9%), Doa (43.9%), Fya (29.2%), M (28.4%), and Jkb (28.1%). CONCLUSIONS: Alloimmunization incidence was higher in those with prior RBC antibodies, suggesting that past immunologic responders are at higher risk for future alloimmunization and therefore may benefit from more extensive antigen matching beyond C/c, E/e, K, Fya , and Jkb .

Technology: Is There Sufficient Evidence to Change Practice in Point-of-Care Management of Coagulopathy?

Currently, hemostasis is one of the most widely researched topics in perioperative medicine. As investigators learn more about the complexity of coagulation, developing tests with the ability to rapidly monitor coagulation and guide targeted therapy is the key to optimizing hemostasis management. There is mounting evidence that algorithmic transfusion using point-of-care (POC) testing can reduce red cell and platelet transfusions and major bleeding after cardiac surgery. Integrating these tests during cardiac surgery and trauma management is especially important because these groups use the most blood products within a health system and the risks of transfusion are well documented. Currently, numerous POC tests are available for evaluating hemostasis. The purpose of this review is to provide a comprehensive evaluation of the current evidence surrounding the most common POC testing devices in practice for managing coagulation.

Managing the Precarious Hemostatic Balance during Extracorporeal Life Support: Implications for Coagulation Laboratories.

For the past four decades, extracorporeal life support (ECLS) has been used to treat critically ill adult and pediatric patients with cardiac and/or respiratory failure unresponsive to medical management, and there are increasing numbers of centers performing ECLS for numerous indications worldwide. Despite the progress with advancing technology, hemorrhagic and thrombotic complications occur frequently and are associated with worse outcomes, but the exact cause is often elusive or multifactorial. As a result of the interaction between blood and a nonendothelialized circuit, there is activation of coagulation, fibrinolysis, as well as an increased inflammatory response; thus, anticoagulation of the patient and circuit is necessary. While unfractionated heparin (UFH) remains the mainstay anticoagulant used during ECLS, there is a paucity of published data to develop a universal anticoagulation guideline and centers are forced to create individualized protocols to guide anticoagulation management, frequently while lacking expertise. From an international survey, centers often use a combination of tests to guide management, which in turn can lead to discordant results and confused management. Studies are urgently needed to investigate optimization of current anticoagulation strategies with UFH, as well as use of alternative anticoagulants and nonthrombogenic biomaterials.

Observational study of haemostatic dysfunction and bleeding in neonates with hypoxic-ischaemic encephalopathy.

OBJECTIVE: Evaluate the relationship between initial haemostatic parameters and the frequency and severity of bleeding in neonates with hypoxic-ischaemic encephalopathy (HIE). DESIGN: Retrospective observational cohort study. SETTING: 2 academically affiliated level III neonatal intensive care units in Atlanta, Georgia. PARTICIPANTS: 98 neonates with moderate-to-severe HIE who underwent haemostatic testing within 12 hours of birth and were born from 1 January 2008 to 31 December 2013. PRIMARY AND SECONDARY OUTCOME MEASURES: Initial haemostatic dysfunction was defined as one or more of the following: prothrombin time (PT) ≥18 s, platelet count <100×103/µL or fibrinogen <150 mg/dL. Bleeding assessed using the Neonatal Bleeding Assessment Tool and graded according to the WHO bleeding scale. The robust Poisson regression was used to evaluate the independent association between components of initial haemostatic dysfunction and bleeding. RESULTS: Among the 98 neonates evaluated, the prevalence of initial haemostatic dysfunction was 69% (95% CI 59% to 78%). 27 neonates (28%; 95% CI 19% to 38%) had abnormal bleeding events and 56 (57%) received at least 1 blood product transfusion. 3 neonates died from bleeding complications. The most common products transfused were fresh-frozen plasma (71%), followed by packed red blood cells (24%) and platelets (21%). In multivariable analysis, fibrinogen <150 mg/dL (adjusted relative risk 2.41, 95% CI 1.09 to 5.36) and platelet count <100×103/µL (adjusted relative risk 2.59, 95% CI 1.30 to 5.16), but not initial PT, were associated with an increased risk of bleeding. The most severe bleeding occurred in neonates with a fibrinogen <150 mg/dL. CONCLUSIONS: Among neonates with moderate-to-severe HIE, haemostatic dysfunction is prevalent and associated with an increased risk of bleeding and high transfusion burden. Further studies are needed to determine the appropriate transfusion approaches in this population to prevent bleeding.

The Role of the Laboratory and Transfusion Service in the Management of Ebola Virus Disease.

The Ebola outbreak that began in 2013 infected and killed record numbers of individuals and created unprecedented challenges, including containment and treatment of the virus in resource-strained West Africa as well as the repatriation and treatment for patients in the United States and Europe. Valuable lessons were learned, especially the important role that the laboratory and transfusion service plays in the treatment for patients with Ebola virus disease (EVD) by providing data for supportive care and fluid resuscitation as well as the generation of investigational therapies such as convalescent plasma (CP). To provide treatment support, laboratories had to evaluate and update procedures to ensure the safety of laboratory personnel. Because there is no licensed EVD-specific treatment, CP was used in more than 99 patients with only 1 possible severe adverse event reported. However, given the biologic variability inherent in CP as well as the small number of patient treated in a nonrandomized fashion, the efficacy of CP in the treatment of EVD remains unknown.

Challenges with Navigating the Precarious Hemostatic Balance during Extracorporeal Life Support: Implications for Coagulation and Transfusion Management.

For the past four decades, extracorporeal life support (ECLS) has been used to treat critically ill adult and pediatric patients with cardiac and/or respiratory failure, and there are increasingly numbers of centers worldwide performing ECLS for numerous indications. Despite the progress with advancing the technology, hemorrhagic and thrombotic complications are frequently reported and associated with worse outcomes, but the exact cause is often elusive or multifactorial. As a result of the interaction between blood and an artificial circuit, anticoagulation is necessary and there is resultant activation of coagulation, fibrinolysis, as well as, an increased inflammatory response. While unfractionated heparin (UFH) remains the mainstay anticoagulant used during ECLS, there is a paucity of published data to develop a universal anticoagulation guideline and centers are forced to create individualized protocols to guide anticoagulation management while lacking expertise. From an international survey, centers often use a combination of tests, which in turn result in discordant results and confused management. Studies are urgently needed to investigate optimization of current anticoagulation strategies with UFH, as well as, use of alternative anticoagulants and non-thrombogenic biomaterials. Blood transfusion during extracorporeal support typically occurs for several reasons, which includes circuit priming, restoration of oxygen carrying capacity, maintenance of a hemostatic balance, and treatment of hemorrhagic complications. As a result, the majority of patients will have been exposed to at least one blood product during extracorporeal support and transfusion utilization is high. ECLS Centers have adopted transfusion thresholds based upon practice rather than evidence as there have been no prospective studies investigating the efficacy of red cell (RBC) transfusion in patients receiving extracorporeal support. In addition, RBC transfusion has been associated with increased mortality in ECLS in several retrospective studies. Additional studies are needed to establish evidence based thresholds for transfusion support and diagnostics to guide transfusion therapy to assess efficacy of transfusion in this population, as well as, exploration of alternatives to transfusion.

Leukoreduced red blood cell transfusions do not induce platelet glycoprotein antibodies in patients with sickle cell disease.

BACKGROUND: Alloimmunization to red blood cell (RBC) antigens after transfusion is well described in patients with sickle cell disease (SCD). We recently demonstrated that leukocyte-reduced RBC transfusions appeared to induce human leukocyte antigen (HLA) antibodies in some children with SCD; now, we hypothesize that residual platelets contained in transfused RBC products may lead to platelet glycoprotein antibody formation. STUDY DESIGN AND METHODS: A cross-sectional study was conducted among never pregnant pediatric patients with SCD who either had received many RBC transfusions or had never received any transfusions. Serum was tested for antibodies to platelet-specific glycoproteins using a commercial enzyme immunoassay. RESULTS: Platelet-specific glycoprotein antibodies were found in 12 of 90 patients (13%) in the transfused group versus 5 of 24 patients (21%) in the never transfused group (p = 0.35). The prevalence of antibodies as well as the median standardized optical density for these two groups was not significantly different for any of the studied platelet glycoprotein antigens. There was no association with the presence of platelet-specific glycoprotein antibodies with either RBC or HLA antibodies. CONCLUSIONS: Leukocyte-reduced RBC transfusions do not appear to induce platelet-specific glycoprotein antibodies. The positive platelet-specific glycoprotein antibody results from this study may represent platelet autoantibodies, platelet alloantibodies, or false-positive reactions. A better understanding of the immunobiology of patients with SCD at baseline and after blood product exposure may help improve future transfusion and transplantation.

Impact of red blood cell alloimmunization on sickle cell disease mortality: a case series.

BACKGROUND: Although red blood cell (RBC) transfusion represents an integral component of sickle cell disease (SCD) care, transfusion support for some patients can result in alloimmunization to RBC antigens. Alloimmunized patients with SCD appear to experience worse survival compared to nonalloimmunized patients. While this difference in mortality may in part be due to underlying immunologic differences related to disease severity, it may also reflect direct clinical consequences of RBC alloimmunization. Alloimmunized patients have an increased risk of serious hemolytic transfusion reactions (HTRs) and may not receive adequate RBC transfusion support due to lack of compatible RBC units. CASE REPORT: This study reports on five RBC alloimmunized patients with SCD who died, to illustrate the concept that RBC alloimmunization itself contributes to premature death. RESULTS: The clinical course for each of the reported patients provides insight into the direct and indirect consequences of RBC alloimmunization, where patients experienced delayed HTRs or did not receive needed RBC transfusions. CONCLUSION: Future work examining the clinical impact of RBC alloimmunization should not only consider HTRs but should also address the potential consequences associated with difficulties in obtaining compatible blood.

Effect of antiplatelet therapy and platelet function testing on hemorrhagic and thrombotic complications in patients with cerebral aneurysms treated with the pipeline embolization device: a review and meta-analysis.

PURPOSE: The pipeline embolization device (PED) necessitates dual antiplatelet therapy (APT) to decrease thrombotic complications while possibly increasing bleeding risks. The role of APT dose, duration, and response in patients with hemorrhagic and thromboembolic events warrants further analysis. METHODS: A PubMed and Google Scholar search from 2009 to 2014 was performed using the following search terms individually or in combination: pipeline embolization device, aneurysm(s), and flow diversion, excluding other flow diverters. Review of the bibliographies of the retrieved articles yielded 19 single and multicenter studies. A statistical meta-analysis between aspirin (ASA) dose (low dose ≤160 mg, high dose ≥300 mg), loading doses of APT agents, post-PED APT regimens, and platelet function testing (PFT) with hemorrhagic or thrombotic complications was performed. RESULTS: ASA therapy for ≤6 months post-PED was associated with increased hemorrhagic events. High dose ASA ≤6 months post-PED was associated with fewer thrombotic events compared with low dose ASA. Post-PED clopidogrel for ≤6 months demonstrated an increased incidence of symptomatic thrombotic events. Loading doses of ASA plus clopidogrel demonstrated a decreased incidence of permanent symptomatic hemorrhagic events. PFT did not show a statistically significant relationship with symptomatic hemorrhagic or thrombotic complications. CONCLUSIONS: High dose ASA >6 months is associated with fewer permanent thrombotic and hemorrhagic events. Clopidogrel therapy ≤6 months is associated with higher rates of thrombotic events. Loading doses of ASA and clopidogrel were associated with a decreased incidence of hemorrhagic events. PFT did not have any significant association with symptomatic events.

The use of convalescent plasma to treat emerging infectious diseases: focus on Ebola virus disease.

PURPOSE OF REVIEW: The purpose of this review is to discuss the use of convalescent plasma for the treatment of emerging infectious diseases, focusing on the recent use for the treatment of Ebola virus disease (EVD). RECENT FINDINGS: Ebola convalescent plasma has been used as a therapy for treatment of EVD during the 2014 West Africa epidemic. Several cases from the United States and Europe have been recently published, in addition to multiple ongoing clinical trials in the United States and West Africa. Even more recently, convalescent plasma has been used for treatment of individuals with Middle East respiratory syndrome coronavirus (MERS-CoV) infection. SUMMARY: Although the first reports of successful treatment with passive immune therapy date back to the early 1900s, convalescent plasma has materialized as a possible therapy for patients who develop infection from one of the emerging infectious diseases such as EVD or MERS-CoV, although the efficacy of such therapy has yet to be proven in clinical trials.

Immunophenotypic parameters and RBC alloimmunization in children with sickle cell disease on chronic transfusion.

Alloimmunization against red blood cell (RBC) antigens is a cause of morbidity and mortality in transfused patients with sickle cell disease (SCD). To investigate distinguishing characteristics of patients who develop RBC alloantibodies after transfusion (responders) versus those who do not (non-responders), a cross-sectional study of 90 children with SCD on chronic RBC transfusion therapy at a single institution was conducted in which 18 immune parameters (including T and B cell subsets) were tested via flow cytometry, and medical records were reviewed. RBC alloimmunization was present in 26/90 (29%) patients, with anti-E, K, and C among the most commonly detected alloantibodies despite prophylactic matching for these antigens at the study institution. In addition, RBC autoantibodies had been detected in 18/26 (69%) of alloimmunized versus 7/64 (11%) of non-alloimmunized patients (P < 0.0001). Alloimmunized patients were significantly older (median 13.0 years vs. 10.7 years, P = 0.010) and had more RBC unit exposures (median 148 U vs. 82 U, P = 0.020) than non-alloimmunized patients. Sex, age at initiation of chronic transfusion, splenectomy, stroke, and transfusion outside of the study institution were not significantly associated with RBC alloimmunization. Alloimmunized patients had a significantly increased percentage of CD4+ T memory cells compared to non-alloimmunized patients (57% vs. 49%, P = 0.0047), with no other significant differences in immune cell subsets or laboratory values detected between these groups. Additional research of RBC alloimmunization is needed to optimize transfusion therapy and to develop strategies to prevent alloimmunization.

The Use of TKM-100802 and Convalescent Plasma in 2 Patients With Ebola Virus Disease in the United States.

BACKGROUND: The current West Africa Ebola virus disease (EVD) outbreak has resulted in multiple individuals being medically evacuated to other countries for clinical management. METHODS: We report two patients who were transported from West Africa to the United States for treatment of EVD. Both patients received aggressive supportive care measures, as well as an investigational therapeutic (TKM-100802) and convalescent plasma. RESULTS: While one patient experienced critical illness with multi-organ failure requiring mechanical ventilation and renal replacement therapy, both patients recovered without serious long-term sequelae to date. CONCLUSIONS: It is unclear what role the experimental drug and convalescent plasma had in the recovery of these patients. Prospective clinical trials are needed to delineate the role of investigational therapies in the care of patients with EVD.

Building capacity in laboratory medicine in Africa by increasing physician involvement: a laboratory medicine course for clinicians.

OBJECTIVES: To describe a 4-day laboratory medicine course for clinicians given at Addis Ababa University, Ethiopia, designed to improve the use of laboratory-based diagnoses. METHODS: Each day was dedicated to one of the following topics: hematology, blood bank/transfusion medicine and coagulation, chemistry, and microbiology. The course included lectures, case-based learning, laboratory tours, and interactive computer case-based homework. The same 12-question knowledge quiz was given before and after the course. RESULTS: Twenty-eight participants took the quiz before and 21 after completing the course. The average score was 5.28 (range, 2-10) for the initial quiz and 8.09 (range, 4-11) for the second quiz (P = .0001). Two of 12 and 8 of 12 questions were answered correctly by more than 60% of trainees on the initial and second quiz, respectively. CONCLUSIONS: Knowledge and awareness of the role of the laboratory increased after participation in the course. Understanding of laboratory medicine principles by clinicians will likely improve use of laboratory services and build capacity in Africa.