A machine learning approach to predict mortality due to immune-mediated thrombotic thrombocytopenic purpura.

Background: Mortality due to immune-mediated thrombotic thrombocytopenic purpura (iTTP) remains significant. Predicting mortality risk may potentially help individualize treatment. The French Thrombotic Microangiopathy (TMA) Reference Score has not been externally validated in the United States. Recent advances in machine learning technology can help analyze large numbers of variables with complex interactions for the development of prediction models. Objectives: To validate the French TMA Reference Score in the United States Thrombotic Microangiopathy (USTMA) iTTP database and subsequently develop a novel mortality prediction tool, the USTMA TTP Mortality Index. Methods: We analyzed variables available at the time of initial presentation, including demographics, symptoms, and laboratory findings. We developed our model using gradient boosting machine, a machine learning ensemble method based on classification trees, implemented in the R package gbm. Results: In our cohort (n = 419), the French score predicted mortality with an area under the receiver operating characteristic curve of 0.63 (95% CI: 0.50-0.77), sensitivity of 0.35, and specificity of 0.84. Our gradient boosting machine model selected 8 variables to predict acute mortality with a cross-validated area under the receiver operating characteristic curve of 0.77 (95% CI: 0.71-0.82). The 2 cutoffs corresponded to sensitivities of 0.64 and 0.50 and specificities of 0.76 and 0.87, respectively. Conclusion: The USTMA Mortality Index was acceptable for predicting mortality due to acute iTTP in the USTMA registry, but not sensitive enough to rule out death. Identifying patients at high risk of iTTP-related mortality may help individualize care and ultimately improve iTTP survival outcomes. Further studies are needed to provide external validation. Our model is one of many recent examples where machine learning models may show promise in clinical prediction tools in healthcare.

How do I reduce variation in red blood cell transfusion practices in a large integrated health care system?

BACKGROUND: Reducing variation in transfusion practices can prevent unwarranted transfusions, an outcome that improves quality of care and patient safety, while lowering costs and eliminating waste of blood. We developed and assessed a system-wide initiative to reduce variation in red blood cell (RBC) transfusion in terms of both transfusion utilization and the number of units transfused. INTERVENTION DESIGN AND METHODS: Our initiative combined a single-unit default order for RBC transfusion in hemodynamically stable, non-bleeding patients with a "Why Give 2 When 1 Will Do?" Choosing Wisely campaign, while also promoting a restrictive hemoglobin threshold (Hb <7 g/dl). This multimodal intervention was implemented across an academic medical center (AMC) with over 950 beds and 10 community hospitals. RESULTS: Between our baseline (CY 2020) and intervention period (CY 2021), single-unit orders increased from 57% to 70% of all RBC transfusion orders (p < .001). The greatest change in ordering practices was at community hospitals, where single-unit orders increased from 46% to 65% (p < .001). Over the same time period, the system-wide mean (SD) Hb result prior to transfusion fell from 7.3 (0.05) to 7.2 g/dl (0.04) (p < .05). We estimate this effort saved over 4000 units of blood and over $4 million in direct and indirect costs in its first year. DISCUSSION: By combining a single-unit default setting in the RBC order with a restrictive hemoglobin threshold, we significantly reduced variation in ordering practices. This effort demonstrates the value of single-unit policies and "nudges" in system-wide patient blood management initiatives.

Efficacy of a Dual-Epitope Dendritic Cell Vaccine as Part of Combined Immunotherapy for HER2-Expressing Breast Tumors.

Previous work from our group and others has shown that patients with breast cancer can generate a T cell response against specific human epidermal growth factor 2 (HER2) epitopes. In addition, preclinical work has shown that this T cell response can be augmented by Ag-directed mAb therapy. This study evaluated the activity and safety of a combination of dendritic cell (DC) vaccination given with mAb and cytotoxic therapy. We performed a phase I/II study using autologous DCs pulsed with two different HER2 peptides given with trastuzumab and vinorelbine to a study cohort of patients with HER2-overexpressing and a second with HER2 nonoverexpressing metastatic breast cancer. Seventeen patients with HER2-overexpressing and seven with nonoverexpressing disease were treated. Treatment was well tolerated, with one patient removed from therapy because of toxicity and no deaths. Forty-six percent of patients had stable disease after therapy, with 4% achieving a partial response and no complete responses. Immune responses were generated in the majority of patients but did not correlate with clinical response. However, in one patient, who has survived >14 y since treatment in the trial, a robust immune response was demonstrated, with 25% of her T cells specific to one of the peptides in the vaccine at the peak of her response. These data suggest that autologous DC vaccination when given with anti-HER2-directed mAb therapy and vinorelbine is safe and can induce immune responses, including significant T cell clonal expansion, in a subset of patients.

Antibody Titers in Transfusion Medicine: A Critical Reevaluation of Testing Accuracy, Reliability, and Clinical Use.

CONTEXT.­: Substantial variability between different antibody titration methods has been identified since the development and introduction of the uniform procedure in 2008. OBJECTIVE.­: To determine whether more recent methods or techniques decrease interlaboratory and intralaboratory variation measured using proficiency testing. DESIGN.­: Proficiency test data for antibody titration between 2014 and 2018 were obtained from the College of American Pathologists. Interlaboratory and intralaboratory variations were compared by analyzing the distribution of titer results by method and phase, comparing the results against the supplier's quality control titer, and by evaluating the distribution of paired titer results when each laboratory received a sample with the same titer twice. RESULTS.­: A total of 1337 laboratories participated in the antibody titer proficiency test during the study period. Only 54.1% (5874 of 10 852) of anti-D and 63.4% (3603 of 5680) of anti-A reported responses were within 1 titer of the supplier's intended result. Review of the agreement between laboratories of the same methodology found that 78.4% (3139 of 4004) for anti-A and 89.0% (9655 of 10 852) of laboratory responses for anti-D fell within 1 titer of the mode response. When provided with 2 consecutive samples of the same titer (anti-D titer: 16), 85% (367 of 434) of laboratories using the uniform procedure and 80% (458 of 576) using the other method reported a titer difference of 1 or less. CONCLUSIONS.­: Despite advances, interlaboratory and intralaboratory variance for this assay remains high in comparison with the strong reliance on titer results in clinical practice. There needs to be a reevaluation of the role of this test in clinical decision-making.

Obstetric and Newborn Weak D-Phenotype RBC Testing and Rh Immune Globulin Management Recommendations: Lessons From a Blinded Specimen-Testing Survey of 81 Transfusion Services.

CONTEXT.­: Modern RHD genotyping can be used to determine when patients with serologic weak D phenotypes have RHD gene variants at risk for anti-D alloimmunization. However, serologic testing, RhD interpretations, and laboratory management of these patients are quite variable. OBJECTIVE.­: To obtain interlaboratory comparisons of serologic testing, RhD interpretations, Rh immune globulin (RhIG) management, fetomaternal hemorrhage testing, and RHD genotyping for weak D-reactive specimens. DESIGN.­: We devised an educational exercise in which 81 transfusion services supporting obstetrics performed tube-method RhD typing on 2 unknown red blood cell challenge specimens identified as (1) maternal and (2) newborn. Both specimens were from the same weak D-reactive donor. The exercise revealed how participants responded to these different clinical situations. RESULTS.­: Of reporting laboratories, 14% (11 of 80) obtained discrepant immediate-spin reactions on the 2 specimens. Nine different reporting terms were used to interpret weak D-reactive maternal RhD types to obstetricians. In laboratories obtaining negative maternal immediate-spin reactions, 28% (16 of 57) performed unwarranted antiglobulin testing, sometimes leading to recommendations against giving RhIG. To screen for excess fetomaternal hemorrhage after a weak D-reactive newborn, 47% (34 of 73) of reporting laboratories would have employed a contraindicated fetal rosette test, risking false-negative results and inadequate RhIG coverage. Sixty percent (44 of 73) of laboratories would obtain RHD genotyping in some or all cases. CONCLUSIONS.­: For obstetric and neonatal patients with serologic weak D phenotypes, we found several critical problems in transfusion service laboratory practices. We provide recommendations for appropriate testing, consistent immunohematologic terminology, and RHD genotype-guided management of Rh immune globulin therapy and RBC transfusions.

Evaluation of a COVID-19 convalescent plasma program at a U.S. academic medical center.

Amidst the therapeutic void at the onset of the COVID-19 pandemic, a critical mass of scientific and clinical interest coalesced around COVID-19 convalescent plasma (CCP). To date, the CCP literature has focused largely on safety and efficacy outcomes, but little on implementation outcomes or experience. Expert opinion suggests that if CCP has a role in COVID-19 treatment, it is early in the disease course, and it must deliver a sufficiently high titer of neutralizing antibodies (nAb). Missing in the literature are comprehensive evaluations of how local CCP programs were implemented as part of pandemic preparedness and response, including considerations of the core components and personnel required to meet demand with adequately qualified CCP in a timely and sustained manner. To address this gap, we conducted an evaluation of a local CCP program at a large U.S. academic medical center, the University of North Carolina Medical Center (UNCMC), and patterned our evaluation around the dimensions of the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework to systematically describe key implementation-relevant metrics. We aligned our evaluation with program goals of reaching the target population with severe or critical COVID-19, integrating into the structure of the hospital-wide pandemic response, adapting to shifting landscapes, and sustaining the program over time during a compassionate use expanded access program (EAP) era and a randomized controlled trial (RCT) era. During the EAP era, the UNCMC CCP program was associated with faster CCP infusion after admission compared with contemporaneous affiliate hospitals without a local program: median 29.6 hours (interquartile range, IQR: 21.2-48.1) for the UNCMC CCP program versus 47.6 hours (IQR 32.6-71.6) for affiliate hospitals; (P<0.0001). Sixty-eight of 87 CCP recipients in the EAP (78.2%) received CCP containing the FDA recommended minimum nAb titer of ≥1:160. CCP delivery to hospitalized patients operated with equal efficiency regardless of receiving treatment via a RCT or a compassionate-use mechanism. It was found that in a highly resourced academic medical center, rapid implementation of a local CCP collection, treatment, and clinical trial program could be achieved through re-deployment of highly trained laboratory and clinical personnel. These data provide important pragmatic considerations critical for health systems considering the use of CCP as part of an integrated pandemic response.

Blood conservation strategies at United States hospitals during the COVID-19 pandemic: Findings from a multi-institutional analysis - International Society of Blood Transfusion survey.

BACKGROUND: Due to the coronavirus disease 2019 (COVID-19) pandemic, the transfusion medicine community has experienced unprecedented blood supply shortages since March 2020. As such, numerous changes to everyday practice have occurred with a specific emphasis on blood conservation. We sought to determine the strategies used to mitigate blood shortages and promote blood conservation during the pandemic. METHODS: An anonymous, 37-question survey was developed using Research Electronic Data Capture and distributed via e-mail to transfusion medicine specialists across the US obtained via publicly available databases. RESULTS: Amongst surveyed [41.1% response rate (51/124 institutions)], 98.0% experienced a product shortage, with the greatest number reporting red blood cell (RBC) shortages (92.0%). This led to 35.3% of institutions altering the composition and/or number of blood product suppliers, including a 100% increase in the number of institutions acquiring blood from organizations that connect hospital transfusion services with blood collection centers (e.g., Blood Buy) compared to before March 2020. Prospective triaging of blood products was the most common blood conservation strategy (68.1%), though 35.4% altered their RBC exchange or transfusion program for patients receiving chronic RBC transfusion/exchange. As a result of these changes, 78.6% of institutions reported that these changes resulted in a reduction in blood product usage, and 38.1% reported a decrease in product wastage. CONCLUSIONS: Most hospitals experienced the effects of the supply shortage, and many of them implemented blood conserving measures. Conservation strategies were associated with decreased blood utilization and waste, and future studies could evaluate whether these changes persist.

Race, rituximab, and relapse in TTP.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is characterized by recurring episodes of thrombotic microangiopathy, causing ischemic organ impairment. Black patients are overrepresented in iTTP cohorts in the United States, but racial disparities in iTTP outcome and response to therapy have not been studied. Using the United States Thrombotic Microangiopathies Consortium iTTP Registry, we evaluated the impact of race on mortality and relapse-free survival (RFS) in confirmed iTTP in the United States from 1995 to 2020. We separately examined the impact of rituximab therapy and presentation with newly diagnosed (de novo) or relapsed iTTP on RFS by race. A total of 645 participants with 1308 iTTP episodes were available for analysis. Acute iTTP mortality did not differ by race. When all episodes of iTTP were included, Black race was associated with shorter RFS (hazard ratio [HR], 1.60; 95% CI, 1.16-2.21); the addition of rituximab to corticosteroids improved RFS in White (HR, 0.37; 95% CI, 0.18-0.73) but not Black patients (HR, 0.96; 95% CI, 0.71-1.31). In de novo iTTP, rituximab delayed relapse, but Black patients had shorter RFS than White patients, regardless of treatment. In relapsed iTTP, rituximab significantly improved RFS in White but not Black patients. Race affects overall relapse risk and response to rituximab in iTTP. Black patients may require closer monitoring, earlier retreatment, and alternative immunosuppression after rituximab treatment. How race, racism, and social determinants of health contribute to the disparity in relapse risk in iTTP deserves further study.

Considerations for immune effector cell therapy collections: a white paper from the American Society for Apheresis.

BACKGROUND AIMS: This white paper was developed to provide leukapheresis guidance for the collection of mononuclear cells from adult and pediatric patients who are destined for immune effector cell (IEC) therapies for commercial and research applications. Currently, there is considerable variability in leukapheresis processes and limited published information regarding best practices relevant to new cellular therapies, especially IECs. Herein the authors address critical leukapheresis questions in five domains to help guide consistent collection processes and ensure high-quality products. The first four domains are onboarding, pre-collection, collection and post-collection, with protocol feasibility, preparation, care and follow-up of the patient/donor at each step, respectively, and technical considerations during collection. The fifth domain of quality assurance focuses on ensuring product potency, purity, safety and auditing. METHODS: The American Society for Apheresis (ASFA) Clinical Applications Committee (IEC Therapy Subcommittee) was charged by the society's board of directors with working collaboratively with other ASFA committees and organizations, including the Foundation for the Accreditation of Cellular Therapy, Association for the Advancement of Blood and Biotherapies, American Society for Transplantation and Cellular Therapy, National Marrow Donor Program and International Society for Cell & Gene Therapy, to develop guidelines regarding leukapheresis collection of cells destined for the manufacture of IEC therapies. After a review of the literature and discussion with members of the involved committees and various institutions, a draft guidance was created and circulated for comment and revision. RESULTS: Critical aspects of apheresis that could affect the quality and quantity of the leukapheresis product were identified. These areas were then discussed and reviewed. After consensus, the best practice guidelines were proposed and accepted. CONCLUSIONS: In the current era of rapid growth of IEC therapies, it is important to address critical leukapheresis steps to provide high-quality products and more consistent practices and to eliminate redundant efforts.

Lack of defined apheresis collection criteria in publicly available CAR-T cell clinical trial descriptions: Comprehensive review of over 600 studies.

BACKGROUND: Chimeric antigen receptor T (CAR-T) cell successes have encouraged continued clinical study. Apheresis collection of starting material for CAR-T cell therapy product manufacturing is critical but described approaches suggest variability and clinical guidelines are currently lacking. The goal of this study was to gather and assess variability in apheresis collection descriptions in publicly available CAR T-cell therapy clinical trials. STUDY DESIGN: We searched clinicaltrials.gov (a publicly available clinical trial database) for "chimeric antigen receptor T cells" on July 01, 2020 and studies accessed July 30, 2020-August 15, 2020. Data collected included date posted, study characteristics, apheresis mentions (number, location, and context), laboratory parameters and transfusion allowances. Apheresis context was analyzed using a qualitative inductive approach of grounded theory method with open coding. Text was classified into 37 context codes, grouped into 12 categories, and then consolidated into patient, procedure, product, and miscellaneous themes. RESULTS: Apheresis was mentioned 1044 times in 322 (51.9%) of 621 total studies. Laboratory parameters mentioned included white blood cells (100 studies), absolute neutrophil count (220 studies), absolute lymphocyte count (102 studies), CD3+ cell (38 studies), hemoglobin (233 studies, 54 studies specified transfusion allowance), and platelet (269 studies, 48 studies specified transfusion allowance). CONCLUSIONS: Apheresis collection of CAR-T cell products is not well-defined in clinical study descriptions and the context is inconsistent. Laboratory parameters useful for apheresis collection are variably present and do not consistently align with current practices. Further exploration, and clinical guideline development will encourage alignment of apheresis collections for CAR-T cell products.

Heterogeneity in Approaches for Switching From Universal to Patient ABO Type-Specific Blood Components During Massive Hemorrhage.

CONTEXT.­: ABO mistransfusions are rare and potentially fatal events. Protocols are required by regulatory agencies to minimize this risk to patients, but how these are applied in the context of massive transfusion protocols (MTPs) is not specifically defined. OBJECTIVE.­: To evaluate the approaches used by transfusion services for switching from universally compatible to patient ABO type-specific blood components during massive hemorrhage. DESIGN.­: We added 1 supplemental multiple-choice question to address the study objective to the 2019 College of American Pathologists proficiency test J-survey (J-A 2019). We also reviewed the available literature regarding this topic. RESULTS.­: A total of 881 laboratories responded to the supplemental question. Approximately 80% (704 of 881) reported a policy for ABO-type switching during an MTP. Policies varied considerably between responding laboratories, but most (384 of 704, 55%) required 2 ABO types to match before switching from universal to recipient-specific blood components. Additional safety measures used in a minority of these protocols included reaction strength criteria (103 of 704, 15%), on-call medical director approval (41 0f 704, 5.8%), universal red cell unit number limits (12 of 704, 1.7%), or the presence of a mixed field (3 of 704, 0.4%). CONCLUSIONS.­: This survey reveals that significant heterogeneity exists regarding the available approaches for ABO-type switching during an MTP. Specific expert guidance regarding this issue is very limited, and best practices have not yet been established or rigorously investigated.

Mathematical modeling of the impact of recirculation on exchange kinetics in tandem extracorporeal membrane oxygenation and therapeutic plasma exchange.

Vascular access connection configurations during tandem extracorporeal membrane oxygenation (ECMO) and therapeutic plasma exchange (TPE) may impact exchange kinetics. In these tandem procedures, typically the TPE inlet line is proximal to the TPE return line with respect to blood flow in the ECMO device, maximizing the opportunity for replacement fluid homogenization within the ECMO circuit. However, if TPE inlet and return line connections are switched, recirculation-a phenomenon in which replacement fluid leaving the TPE return line is prematurely drawn into the TPE inlet line prior to satisfactory homogenization within the ECMO circuit-will occur. Such recirculation could diminish TPE efficacy in patients on ECMO and mitigate therapeutic benefits. Using a mathematical model of recirculation in tandem ECMO and TPE, we demonstrate that the predicted impact of recirculation is negligible and vascular access connection positioning does not appear to be a point of clinical concern with regard to TPE kinetics.

Convalescent Plasma Therapy in Four Critically Ill Pediatric Patients With Coronavirus Disease 2019: A Case Series.

Coronavirus disease 2019 is a pandemic with no specific therapeutic agents or vaccination. Small published case series on critically ill adults suggest improvements in clinical status with minimal adverse events when patients receive coronavirus disease 2019 convalescent plasma, but data on critically ill pediatric patients are lacking. We report a series of four critically ill pediatric patients with acute respiratory failure who received coronavirus disease 2019 convalescent plasma as a treatment strategy for severe disease. CASE SUMMARY: Patients ranged in age from 5 to 16 years old. All patients received coronavirus disease 2019 convalescent plasma within the first 26 hours of hospitalization. Additional disease modifying agents were also used. All patients made a full recovery and were discharged home off of oxygen support. No adverse events occurred from the coronavirus disease 2019 convalescent plasma transfusions. CONCLUSION: Coronavirus disease 2019 convalescent plasma is a feasible therapy for critically ill pediatric patients infected with severe acute respiratory syndrome coronavirus 2. Well-designed clinical trials are necessary to determine overall safety and efficacy of coronavirus disease 2019 convalescent plasma and additional treatment modalities in pediatric patients.

Therapeutic plasma exchange taper does not decrease exacerbations in immune thrombotic thrombocytopenic purpura patients.

BACKGROUND: Despite rapid and intensive treatments with therapeutic plasma exchange (TPE) and immunosuppression, immune thrombotic thrombocytopenic purpura (TTP) patients are at risk of disease exacerbation, i.e., early recurrence of TTP within 30 days of achieving treatment response. TPE taper, a practice of performing additional TPE procedures after achieving treatment response, is commonly performed for decreasing exacerbations, although no evidence supports this practice. STUDY DESIGN AND METHODS: In this prospective observational investigation over four years, our center switched its standard of care for treating all TTP patients from not performing TPE taper after achieving treatment response (i.e., no-taper cohort) to performance of TPE taper (i.e., yes-taper cohort) to characterize impacts on exacerbations. Continuous and categorical data were analyzed by Mann-Whitney, Fisher's exact, and log-rank tests; significance was defined as p < 0.05. RESULTS: The two cohorts were well matched and had no significant differences in demographics, presentation laboratory values, or TTP history (p > 0.05 for all). The yes-taper cohort of 26 patients with 29 consecutive episodes did not have a significantly different exacerbation rate from the no-taper cohort of 24 patients with 27 consecutive episodes (exacerbation rates of 37.9% vs. 33.3%, respectively; p = 0.78); however, treatment-related complications directly attributed to the TPE procedures, blood products, or central venous catheters were significantly greater in the yes-taper cohort (nine vs. one events, respectively; p = 0.01). CONCLUSION: Since TPE taper did not reduce exacerbations in our TTP patients, we no longer advocate for TPE taper and have reverted to our original standard of care.

Evaluation of mobilization efficacy with an extended interval following plerixafor administration.

Plerixafor is a hematopoietic stem cell mobilizing agent used in combination with granulocyte-colony stimulating factor to improve collection for autologous stem cell transplantation. Despite a recommendation for administration 11 h prior to apheresis per package labeling, logistical challenges lead many institutions to administer plerixafor at an extended interval. The purpose of this study was to determine if plerixafor effectively and efficiently mobilizes CD34+ cells when given at an extended interval prior to apheresis. This was a retrospective evaluation of adult patients who received plerixafor based on an algorithm reserving daily plerixafor only for patients with a pre-apheresis CD34+ count of < 20 cells/µL (pre-apheresis plerixafor) or with a low CD34+ yield after the first apheresis session (rescue plerixafor). The primary outcome was achievement of a disease-specific collection goal of ≥ 6 ×106 CD34+ cells/kg for multiple myeloma and ≥ 4 ×106 CD34+ cells/kg for lymphoma. The mean interval between plerixafor administration and apheresis was 17 h in this study. Despite this extended interval, 64% of patients met their disease-specific collection goal. A minimum collection goal of ≥ 2 ×106 CD34+ cells/kg was achieved by 95% of patients. Mobilization remained efficient with a median of two days to complete collection. Based on this data, plerixafor effectively and efficiently mobilizes CD34+ cells when given at an extended interval prior to apheresis.

The Impact of an Undergraduate Biology Class on Donor Recruitment at a Hospital-Based Blood Donor Center.

OBJECTIVES: A biology class, BIOL 294H, taught undergraduates about platelet donation while partnering with the University of North Carolina's (UNC's) hospital-based Blood Donation Center to recruit apheresis platelet donors. We identified our platelet donors' demographics and learned how BIOL 294H affected recruitment. METHODS: Every platelet donor presenting to the UNC Blood Donation Center from February 7, 2017, to March 10, 2017, was asked to complete an electronic 10-question survey. RESULTS: A total of 159 unique donors completed the survey; 64% were female and 75% were between ages 18 and 25 years. Overall, 70% were UNC undergraduate students. Over half (56%) reported first learning about platelet donation through word of mouth, and 22% cited specific efforts associated with BIOL 294H. CONCLUSIONS: Recruitment of undergraduate platelet donors primarily included BIOL 294H peer interactions and deliverables from the class, such as social media updates and events on campus. The sustained recruiting efforts of our students over many years contributed to recruitment of a majority of our platelet donors.

Heparin-induced thrombocytopenia associated with collection of hematopoietic progenitor cells by apheresis.

Heparin-induced thrombocytopenia (HIT) can occur following exposure to heparin and is characterized by thrombocytopenia with increased risk for thrombosis. This condition is mediated by formation of immunoglobulin G antibodies against platelet factor 4/heparin complexes that can subsequently lead to platelet activation. Herein, we detail the clinical and laboratory findings, treatments, and outcomes of two patients who developed HIT and thrombosis after undergoing collection of hematopoietic progenitor cells by apheresis (HPC-A) for autologous HPC transplant. Given that heparin may be used during HPC-A collections, these cases emphasize the importance of prompt consideration of HIT in patients that develop thrombocytopenia and thrombosis following HPC-A collection with heparin anticoagulation.