Improved outcomes and cost savings for patients with bleeding disorders: a quality improvement project.

Background: Providing optimal care for patients with bleeding disorders according to national standards remains a challenge at designated Hemophilia Treatment Centers (HTCs). Improved care may reduce bleeds and costs. Objectives: To improve care and demonstrate cost savings by 1) reducing preventable hospitalizations and emergency room visits (PHER) for bleeding, 2) increasing use of prophylaxis in severe hemophilia, and 3) improving patient-HTC communication and primary care engagement. Methods: Prospective quality improvement project using the Define, Measure, Analyze, Improve, and Control methodology to implement uniform guideline-based bleeding disorder care at a rural HTC (N = 88). Intervention used a standardized physician checklist, improved communication, and reserved physician time for urgent management. Outcomes were determined by retrospective chart review; urgent management was tracked prospectively. Results: Intervention significantly reduced PHER by 85.4%. Use of prophylaxis in persons with severe hemophilia increased from 58.8% to 100%; attainment of a primary care physician and electronic portal enrollment met outcomes for intervention success. HTC clinic visit attendance was low at 55.2%. The majority of patients (71.6%) had at least 1 outpatient urgent episode (mean, 0.72 episode per year), and 93% had nonurgent management (mean, 9.3 episodes per year) occurring outside of a clinic visit. Hospital PHER factor cost in the group was reduced by 94.5%, from $11,800 to $640 per patient per year-a cost savings of $982,088 yearly. Conclusion: This collaborative study shows that implementation of a carefully designed quality improvement project, such as uniform guidelines with focus on strengthening ambulatory management, led to improved outcomes and cost savings.

Investigation and Validation of the TEG6s During Rotary Wing Aeromedical Flight.

INTRODUCTION: In order to improve rural and austere trauma care, hospital-based testing performed at the point of injury may shorten the time lapsed from injury to intervention. This study aimed to evaluate the use of the TEG6s® device in a rotary wing aircraft. Prior attempts suffered from limitation related to lack of vibration mitigation. METHODS: This was an investigator initiated, industry supported study. Haemonetics® provided a TEG6s® analyzer. The device underwent a standard validation. It was secured in place on the aircraft utilizing shipping foam for vibration mitigation. Donors provided 2 tubes of sample blood in one sitting. Paired studies were performed on the aircraft during level flight and in the hospital, using the Global Hemostasis with Lysis Cartridge. Both normal and presumed pathologic samples were tested in separate phases. Paired T-tests were performed. RESULTS: For normal donors, mean R (minutes) for laboratory compared to the aircraft was 6.2 vs. 7.2 (p = 0.025). Mean CRT MA (mm) was 59.3 and 55.9 ± 7.3 (p < 0.001) for lab and aircraft (p < 0.001). Among normal donors, R was within normal range for 17/18 laboratory and 18/18 aircraft tests (p > 0.99).During the testing of pathologic samples mean R time was 14.8 for lab samples and 12.6 minutes for aircraft (p = 0.02). Aircraft samples were classified as abnormal in 78% of samples, this was not significantly different than lab samples (p = 0.5). CONCLUSIONS: The use of the TEG6s® for inflight viscoelastic testing appears promising. While statistically significant differences are seen in some results, these values are not considered clinically significant. Classifying samples as normal or abnormal demonstrated a higher correlation. Future studies should focus on longer flight times to evaluate for LY30, takeoff and landing effects. Overall, this study suggests that TEG6s® can be utilized in a prehospital environment, and further study is warranted. LEVEL OF EVIDENCE: Level II, Diagnostic Tests or Criteria.

Rh immune globulin immunoprophylaxis after RhD-positive red cell exposure in RhD-negative patients via transfusion: A survey of practices.

BACKGROUND: Current Association for the Advancement of Blood & Biotherapies (AABB) standards require transfusion services to have a policy on Rh immune globulin (RhIG) immunoprophylaxis for when RhD-negative patients are exposed to RhD-positive red cells. This is a survey of AABB-accredited transfusion services in the United States (US) regarding institutional policies and practices on RhIG immunoprophylaxis after RhD-negative patients receive RhD-positive (i.e., RhD-incompatible) packed red blood cell (pRBC) and platelet transfusions. RESULTS: Approximately half of the respondents (50.4%, 116/230) have policies on RhIG administration after RhD-incompatible pRBC and platelet transfusions, while others had policies for only pRBC (13.5%, 31/230) or only platelet (17.8%, 41/230) transfusions, but not both. In contrast, 18.3% (42/230) report that their institution has no written policies on RhIG immunoprophylaxis after RhD-incompatible transfusions. Most institutions (70.2%, 99/141) do not have policies addressing safety parameters to mitigate the risk of hemolysis associated with the high dose of RhIG required to prevent RhD alloimmunization after RhD-incompatible pRBC transfusions. DISCUSSION: With approximately half of US AABB-accredited institutions report having policies on RhIG immunoprophylaxis after both RhD-incompatible pRBC and platelet transfusions, some institutions may not be in compliance with AABB standards. Further, most with policies on RhIG immunoprophylaxis after RhD-incompatible pRBC transfusion do not have written safeguards to mitigate the risk of hemolysis associated with the high dose of RhIG required. CONCLUSION: This survey underscores the diverse and inadequate institutional policies on RhIG immunoprophylaxis after RhD exposure in Rh-negative patients via transfusion. This observation identifies an opportunity to improve transfusion safety.

How to begin using social media for transfusion medicine education.

This article highlights fundamentals that are important for the transfusion medicine educator to understand about social media. Several examples of personal practical application are shared. Finally, the potential future state of social media will be discussed. In the spirit of a growth mindset, please suspend any previous judgements about social media and allow yourself to consider the possibility of using social media with your transfusion education.

The Use of Whole Blood in Rural Trauma Leads to Decreased Resource Utilization.

BACKGROUND: Nearly 40% of trauma deaths result from uncontrolled hemorrhage. Most of these deaths occur within 24 hours, highlighting the importance of early resuscitation. Balanced component resuscitation has been shown to improve outcomes in hemorrhagic shock. However, hemostatic properties may then be decreased, leading to inadequate coagulopathy treatment or higher transfusion requirements. Data comparing the efficacy of component vs. whole blood (WB) resuscitation in early trauma is poor, particularly in the rural population. This study investigates WB use and resource utilization at a rural Level 1 trauma center. METHODS: A prospective cohort study with historical controls (HC) was performed using patients over age 17 presenting as the highest priority trauma. Two units of WB were available to patients with signs of hemorrhagic shock, with subsequent transfusions via massive transfusion protocol or thromboelastography guidance. Component utilization, time to hemorrhage control, complications, and transfer times were examined. RESULTS: Forty patients received WB vs. 153 HC. WB patients had lower complication rates (35% vs. 55.6%; P = .02), and a significant reduction in pRBC utilization in the emergency department (0 vs. 2; P < .0001) and throughout admission (2.0 vs. 4.0; P = .0003). All patients had prolonged transport times given the rural setting (1.42 hours HC vs. 2.03 hours WB; P = .002). DISCUSSION: Unlike most urban WB studies, this study occurred in a rural area with extended transportation times, when WB is inaccessible for patients. Despite this delay, WB patients demonstrated lower component utilization and complication rates. Further research is needed to characterize the impact of early WB access.

Serial Convalescent Plasma Infusions for the Initial COVID-19 Infections in the Appalachian Region of West Virginia.

Purpose: The rapid spread of SARS-CoV-2, the virus that is responsible for causing COVID-19, has presented the medical community with another example of when convalescent plasma (CP) is still used today. The ability to standardize CP at the onset of a pandemic is unlikely to exist in a reliable and uniformly reproducible way. We hypothesized that CP of unknown strength given in a serial manner will promote health and reduce mortality in those inflicted with COVID-19. Methods: Participants were given up to 8 CP-units depending on their condition upon entry into the study and their response. Results: 102 out of 117 participants were given CP. The earlier a participant received CP corelated with survival (p = 0.0004). The number of CP-units given, throughout all the clinical severities, was not significant with outcomes, p = 0.3947. A higher number of CP-units given to the severe/critical participants (without biological immunosuppressants or restrictive lung disease) did correlate with survival p = 0.0116 (2.8 vs. 2 units). Lower platelets on admission corelated with mortality. Platelet levels increase correlated with CP infusions p < 0.0001. Conclusion: This study supports the serial use of CP of unknown strength based on clinical response for those infected with COVID-19. The use of 3-4 units of CP was found to be statistically significant for survival for severe and critical participants without restrictive lung disease and chronic biological immunosuppression. Increased platelet levels after CP infusions supports that CP is promoting overall health regardless of outcomes.

Impact of mobilization regimen on multiday collection of peripheral blood CD34+ cells by large volume leukapheresis.

BACKGROUND: The collection yield of hematopoietic progenitors cell (HPC) by leukapheresis is critical for a successful transplantation, which often requires multiday collections to achieve the collection goal. STUDY DESIGN AND METHODS: Collection procedures of 181 patients who underwent leukapheresis for more than 1 day were reviewed. Patients were separated into six groups based on the mobilization regimen: G-CSF on day 1 (D1) and day 2 (D2) (G-G); G-CSF on D1 and G-CSF and plerixafor on D2 (G-GP); G-CSF and plerixafor on day D1 and D2 (GP-GP); G-CSF and plerixafor on D1 and G-CSF on D2 (GP-G); chemotherapy and G-CSF on D1 and D2 (GC-GC); and chemotherapy, G-CSF, and plerixafor on D1 and D2 (GCP-GCP). Patient's pre-collection CD34 count (pre-CD34) on D1 and D2 were compared in the same individual and among groups. RESULTS: We found D2 pre-CD34 were significantly decreased in G-G, GP-G, and GP-GP groups and significantly increased in G-GP group (p < .001) using a repeated measures ANOVA analysis. D2 pre-CD34 remained at similar levels as D1 in GC-GC and GCP-GCP groups. A multiple regression analysis showed that the mobilization regimen was the only factor that significantly affected pre-CD34 D2/D1 ratio (p < .001). There was a significant difference in the pre-CD34 D2/D1 ratio (p < .001) among these six groups with the lowest in GP-G group (0.40 ± 0.45), and the highest in G-GP group (2.35 ± 0.36). DISCUSSION: Mobilization regimen has significant impact on pre-collection CD34 count. Apheresis facilities may change mobilizing drugs accordingly to achieve a specific HPC goal.

Hospital transfusion service operations during the SARS-CoV-2 pandemic: Lessons learned from the AABB hospital survey in preparation for the next infectious disease outbreak.

BACKGROUND: The SARS-CoV-2 pandemic disrupted hospital operations, affected the blood supply, and challenged the health care system to develop new therapeutic options, including convalescent plasma (CCP). The aim of this study is to describe and analyze blood supply fluctuations and the use of convalescent plasma in 2020. METHODS: AABB distributed a weekly and biweekly questionnaire through email to hospital-based members (HBM). RESULTS: The survey was sent to 887 HBM with 479 unique respondents, most of the hospitals served pediatric and adult patients, and all states of the country participated, except Idaho and Vermont. Fifty four percent of HBM reported increased wastage in the early phase of the pandemic (May), which decreased to 4% by the end of June and throughout the rest of the year. The majority of HBM reported receiving alerts from their blood suppliers reporting blood shortages throughout the year. During March and April, only 12% of HBM were performing elective surgical procedures. The top reasons to delay procedures were: bed availability (28%); COVID-19 caseload (23%; and blood availability (19%). By mid-April, 42% HBM had transfused CCP and reported >24 h delay in getting the units; the vast majority obtained CCP using the Expanded Access Protocol, and later, the Emergency Use Authorization. HBM consistently prioritized the most severe patients to receive CCP, but the proportion of severely ill recipients fell from 52% to 37% between May and October, with an increase from 5% to 21% of HBM providing CCP transfusion early in the course of the disease. DISCUSSION: Blood utilization and availability fluctuated during the pandemic. The fluctuations appeared to be related to the number of COVID-19 in the community. The use and regulatory landscape of CCP rapidly evolved over the first 8 months of the pandemic.

A Tertiary Academic Medical Center Blood Bank's Experience With Four-Factor Prothrombin Complex Concentrate.

OBJECTIVES: The role of transfusion medicine consultative services in prospectively auditing (PA) orders for four-factor prothrombin complex concentrate (4F-PCC) was evaluated at an academic medical center. METHODS: Data from 4 years of 4F-PCC orders were obtained from the laboratory information system, and electronic health records of patients receiving concentrate were reviewed. RESULTS: 4F-PCC was ordered for 427 patients with warfarin-, apixaban-, or rivaroxaban-associated hemorrhage. Turnaround time (TAT) to prepare 4F-PCC was longer when PA-recommended dose adjustments were needed (85 vs 66 minutes, P = .03). There was no difference in TAT between patients who died and those who were ultimately discharged (60 vs 70, P = .22). TAT was shortest for orders originating in the emergency department (ED) compared with other locations (64 vs 85, P < .001), and ED TAT was not associated with patient outcomes in ED patients. PA and dose adjustments reduced amounts of concentrate issued by 27 IU per dose (P = .01). Median international normalized ratio less than 1.3 after 4F-PCC transfusion was achieved for all anticoagulants after dose adjustments. PA did not affect order cancellation or product wastage rates. CONCLUSIONS: PA can ensure 4F-PCC is dosed appropriately without affecting patient outcomes.

Utilization of Thromboelastogram and Inflammatory Markers in the Management of Hypercoagulable State in Patients with COVID-19 Requiring ECMO Support.

The role of extracorporeal membrane oxygenation (ECMO) in the management of critically ill patients with COVID-19 is evolving. Extracorporeal support independently confers an increased predilection for thrombosis, which can be exacerbated by COVID-19-associated coagulopathy. We present the successful management of a hypercoagulable state in two patients who required venovenous ECMO for the treatment of COVID-19. This included monitoring inflammatory markers (D-dimer and fibrinogen), performing a series of therapeutic plasma exchange procedures, and administering high-intensity anticoagulation therapy and thromboelastography- (TEG-) guided antiplatelet therapy. TPE was performed to achieve goal D-dimer less than 3000 ng/mL D-dimer units (N ≤ 232 ng/mL D-dimer units) and goal fibrinogen less than 600 mg/dL (N = 200-400 mg/dL). These therapies resulted in improved TEG parameters and normalized inflammatory markers. Patients were decannulated after 37 days and 21 days, respectively. Post-ECMO duplex ultrasound of the upper and lower extremities and cannulation sites revealed a nonsignificant deep venous thrombosis at the site of femoral cannulation in patient 2 and no deep venous thrombosis in patient 1. The results of this case report show successful management of a hypercoagulable state among COVID-19 patients requiring ECMO support by utilization of inflammatory markers and TEG.

Educational Case: Warm Autoimmune Hemolytic Anemia.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.

Educational Case: Febrile Nonhemolytic Transfusion Reaction.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.

Inpatient management strategies in a severe case of heparin-induced thrombocytopenia.

We present important laboratory testing and clinical management strategies used to safely discharge home a 69-year old woman with heparin-induced thrombocytopenia (HIT) from the hospital. She was admitted for a coronary artery bypass graft procedure for which she was anticoagulated with heparin. Shortly after the procedure she developed thrombocytopenia and was diagnosed with HIT using the 4Ts scoring system, a latex-enhanced immunoassay (LEI) screen and confirmatory serotonin release assay. Her anticoagulation was switched from heparin to argatroban, and response to treatment was monitored in the laboratory using LEI. Unfortunately, she also received platelet transfusions and subsequently developed multifocal deep vein thrombosis with worsening platelet counts with nadir less than 10 x 10^3/µL. After five therapeutic plasma exchange procedures we noted an improvement in platelet counts, which plateaued into the 50s x 10^3/µL. Furthermore, the LEI remained positive. At this juncture we decided to transition from argatroban to fondaparinux so that she could leave the hospital in stable condition. Upon follow-up with hematology she exhibited no worsening clinical signs or symptoms of disease, and platelet counts markedly improved to within normal limits of detection. In this report we examine the utility of LEI in monitoring patients with HIT, therapeutic plasma exchange in the management of severe HIT (with thrombosis), and the use of subcutaneous fondaparinux in managing HIT in the outpatient setting.

Acute Hemolytic Transfusion Reaction Caused by a Red Cell Antibody That Was Missed by Pretransfusion Testing Using Tube Method.

Pretransfusion testing is very important to prevent transfusion of incompatible red cells, which might result in a hemolytic transfusion reaction. This includes the detection of antibodies in recipients' serum and compatibility testing between donor cells and recipient serum. The most commonly used methods include gel and tube techniques. We present a case in which an anti-E alloantibody was detected by gel method but not by tube testing. As a result, red cells that were retrospectively phenotyped as positive for E antigen were inadvertently selected and transfused after crossmatch using the same tube method. After transfusion, the patient developed signs of hemolytic transfusion reaction. This case highlights the potential risk of transfusion of incompatible red cells when alloantibody detection is solely relied on tube testing.

The tipping point: The critical role of therapeutic apheresis in a case of refractory acquired hemophilia.

Acquired hemophilia A (AHA) is a rare autoimmune disorder that leads to factor VIII (FVIII) deficiency via autoantibody formation. Standard treatment options include FVIII bypassing factors and immunosuppression. However, the role of therapeutic plasma exchange (TPE) is not clear in the treatment of AHA. We present a case of idiopathic AHA in a 66 year old female with severe bleeding and a FVIII inhibitor of 17.6 Bethesda units (BU). She failed to respond to standard treatment including maximum dose of recombinant FVIIa (rFVIIa), rituximab, and other immunosuppressive agents. Her FVIII inhibitor rapidly increased to 140 BU and FVIII was below 5%. TPE was initiated 3 weeks after admission and her bleeding stabilized after the first treatment and completely stopped after three treatments. Repeat testing revealed increased FVIII to 15% and FVIII inhibitor decreased to 2.0 BU. After an additional TPE treatment, her FVIII increased to 27% and FVIII inhibitor decreased to 0.6 BU and she was discharged without bleeding 40 days after admission. In this case, TPE played a critical role in reducing FVIII inhibitor, which resulted in a recovery of FVIII activity and hemostasis. Therefore, TPE should be initiated early in AHA patients with bleeding and high titer of FVIII inhibitor.

Determination of hemispheric language dominance in the surgical epilepsy patient: diagnostic properties of functional magnetic resonance imaging.

BACKGROUND: Presurgical evaluation for refractory epilepsy typically includes assessment of cognitive and language functions. The reference standard for determination of hemispheric language dominance has been the intracarotid amobarbital test (IAT) but functional magnetic resonance imaging (fMRI) is increasingly used. OBJECTIVE: To critically assess current evidence regarding the diagnostic properties of fMRI in comparison with the IAT for determination of hemispheric language dominance. METHODS: The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario, structured question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the fields of epilepsy and neurosurgery. RESULTS: A systematic review and meta-analysis that compared the sensitivity and specificity of fMRI to IAT-determined language lateralization was selected for critical appraisal. The review included data from 23 articles (n=442); study methodology varied widely. fMRI was 83.5% sensitive and 88.1% specific for detection of hemispheric language dominance. CONCLUSIONS: There are insufficient data to support routine use of fMRI for the purpose of determining hemispheric language dominance in patients with intractable epilepsy. Larger, well-designed studies of fMRI for language and other cognitive outcomes as part of the presurgical and postsurgical evaluation of epilepsy patients are necessary.