5041 Background: Chronic exposure to androgen receptor (AR) targeted therapies can drive lineage plasticity, promoting the emergence of neuroendocrine (NE) prostate cancer (NEPC) and treatment resistance. NEPC is characterized by a phenotypic shift, with loss of AR expression and emergence of markers (e.g., synaptophysin, SYP). To definitively diagnose NEPC, a metastatic biopsy is typically required; however, there are numerous barriers to obtaining a timely tissue diagnosis. As such, there is an unmet need for blood-based assays that can accurately identify treatment-emergent NEPC. In this study, we evaluate concordance between circulating tumor cell (CTC) SYP and AR expression patterns in patients with and without evidence of NE differentiation on tissue histology. Methods: Blood for CTC analysis was prospectively collected from patients with advanced prostate cancer. Patients were retrospectively assigned to either an adenocarcinoma (AR-positive) or NE differentiated (SYP-positive) group based on clinical and patho-genomic factors. Amphicrine PC was included in NE differentiated cohort. The RareCyte system was used to generate slides for CTC-based immunofluorescent (IF) analysis for SYP and AR. Associations between CTC SYP and AR expression, PSA at time of CTC collection, and overall survival (OS) were assessed for patients with ≥ 5 CTCs using Wilcoxon rank-sum test, Fisher’s exact test, and Kaplan-Meier analyses. Results: We enrolled 52 patients with metastatic castration-resistant prostate cancer (mCRPC); 26 were classified as NE differentiated and 26 as AR-positive adenocarcinoma. Median time between biopsy and CTC collection was 10.6 months (IQR 4.1–34.3) and 19.4 months (IQR 3.5–66.4) for the NE differentiated and AR-positive adenocarcinoma cohorts respectively. NE differentiated patients had a significantly higher fraction of SYP-positive CTCs (median 28.6 % vs 0%, p = 0.0084), whereas patients in the adenocarcinoma cohort had a higher fraction of AR-positive CTCs (median 96.7% vs 0.0%, p = 0.0004). Phenotype classification based on high AR or SYP expression ( > 80% of CTCs positive) significantly differentiated cohorts and was strongly associated with tissue histology (p = 0.0048). PSA level at the time of CTC collection was significantly lower in the NE differentiated cohort (median 3.8 vs 486.9 ng/mL, p = 0.0001). There was no difference in OS from time of diagnosis or time of metastasis between groups. Conclusions: SYP and AR CTC expression demonstrated strong concordance with tissue histology and established clinical features of NEPC and AR-positive adenocarcinoma. These early findings support the feasibility of CTC expression profiling to identify NE biomarker expression. However, results are only hypothesis-generating and prospective validation with matched tissue biopsy in a larger cohort with adequate follow up is warranted.

Cutaneous lymphomas remain notoriously difficult to diagnose despite integration of multiple ancillary studies, including PCR analysis of the gamma chain of the T cell receptor (TRG) for clonality. Although widely available, flow cytometry on skin samples is infrequently used in the evaluation of possible cutaneous lymphoma, in part due to high rates of non-diagnostic laboratory results reported in small studies. Systematic evaluation of this in large cohorts is lacking, however, and the role of paucicellularity–which represents an analytic challenge for any flow cytometry sample–is poorly understood in skin. This study aims to assess the performance of flow cytometry in analyzing skin biopsies with a focus on paucicellularity. Records of flow cytometry studies of the skin from a single institution were categorized by diagnosis (negative, suspicious, abnormal, or non-diagnostic), and, if abnormal/suspicious, by the population involved (T cell, B cell, plasma cell, or myeloid). The percentages of records including disclaimers related to a paucicellular specimen, possible blood contamination, and/or non-specific background staining were then calculated. For a subset of samples, flow cytometry diagnosis was compared to concurrent TRG PCR and final clinical diagnosis. We identified 424 flow cytometry samples from 379 patients analyzed between May 2000 and September 2024. No abnormal populations were identified in 198 (46.7%) samples, while populations of abnormal T cells were identified in 102 (24.1%) samples, abnormal B cells in 64 (15.1%) samples, and abnormal myeloid cells in 20 (4.7%) samples. Twenty (4.7%) samples were non-diagnostic. The remaining diagnoses each comprised <2%. Overall, 26.7% of samples had one or more disclaimers in the comment; 21.7% were paucicellular (including the 4.7% non-diagnostic samples), 4.7% had possible blood contamination, and 4.3% had high non-specific staining. Paucicellularity was more often reported in suspicious samples (46.7%) compared to negative (28.3%) and abnormal (4.7%) samples. The language used to report cellularity was highly variable. In a subset of 38 samples that had concurrent flow cytometry and TRG analyses, 25 (66%) had concordant results, despite 20% of these flow samples being paucicellular. The remaining 13 (34%) had discordant results. Flow cytometry studies agreed with the final clinical diagnosis in 7 (78%) of the 9 discordant samples for which there was clinical follow up, and the remaining 2 were paucicellular. The vast majority (>90%) of flow cytometry studies of skin provides diagnostic information that complements existing ancillary studies (e.g. molecular clonality), and its use should be considered more frequently in the evaluation of cutaneous lymphomas. Given that a substantial number of samples included disclaimers for paucicellularity, skin is an under-recognized paucicellular specimen type for flow cytometry that should be included in ongoing efforts for standardization of paucicellular specimen analysis and reporting.

Masses are commonly detected in the kidneys either as incidental findings or upon workup of urinary symptoms on an initial presentation. We describe a large series of rare cases in which individuals presented with symptoms or imaging findings of kidney masses concerning for primary carcinoma of renal cell or urothelial origin but were found on pathological analysis to be lymphomas or atypical lymphoid proliferations, with or without an accompanying renal malignancy. These mass lesions, including some unique mimics of renal carcinomas such as reactive follicular hyperplasia and IgG4-related disease primary to the kidney, are all lymphoid kidney proliferations from a single institution. Herein, we demonstrate the need for consideration of lymphoid abnormalities in the diagnosis of renal masses, which can affect further workup and management. We also review the differential diagnosis of primary renal masses originating from neoplastic and non-neoplastic lymphoid disorders.

Abstract Von Willibrand disease (VWD) is the most common inherited bleeding disorder. The 2021 Guidelines on VWD diagnosis recommend newer assays measuring the platelet-binding activity of von Willebrand factor (VWF), such as VWF: GPIbM and VWF: GPIbR, over the traditional ristocetin cofactor assay (VWF: RCo). Among these newer assays, the GP1bM INNOVANCE VWF Ac assay obtained de novo FDA approval in October 2022. Its ristocetin-independent activity distinguishes it from other assays. Our laboratory conducted a comprehensive validation on the Stago StaR-Max platform, utilizing Siemens Standard Plasma for calibration. The VWF activity measured by the GP1bM assay was compared with the existing VWF: Ab assay (IL, HemosIL® von Willebrand Factor Activity). The validation studies revealed a good correlation between the two assays. Since implementing the GP1bM assay in October 2023, our attention has been drawn to at least four cases exhibiting unexpectedly high activity levels compared to VWF antigen levels. On average, the activity-to-antigen ratio was 1.9. Notably, all these cases showed the presence of all multimers (low, intermediate, and high). Despite extensive investigation, encompassing considerations like heterophile antibody interference using scantibodies, retesting with different lot numbers of Innovance VWF Ac reagent, and rerunning tests at an outside laboratory, the cause of this anomaly remains elusive. A notable variable lies in the platform disparity between Siemens and Stago. Given the recent introduction of this assay, it has yet to gain widespread adoption in laboratories, resulting in a limited understanding of its practical variations. While recent studies affirm the overall superior performance of newer assays compared to the ristocetin cofactor assay, intricate details of each assay remain less explored. The novelty of the GP1bM assay and its limited usage in laboratories underscore the potential emergence of stable outliers as it becomes more widely adopted. The peculiar cases in our study pose an enigma as to why the reported activity is approximately double the antigen level. As laboratories increasingly embrace and integrate the GP1bM assay, a more complete understanding of its potential variations is expected to unfold. This may elucidate the mysteries surrounding these peculiar cases and ensure the assay’s robust interpretation in clinical settings.

Sickle cell disease (SCD) is a genetic disorder where red blood cells sickle, causing anemia and pain. Historically linked to marginalized groups, SCD saw little progress in treatment strategies for decades. Addressing these requires holistic strategies including dedicated centers, education, patient inclusion, and tackling implicit bias. Efforts must ensure treatments are accessible and stigma-free. Progress depends on collaboration and advocacy, aiming for an equitable, patient-focused health care system responsive to the unique needs of those with SCD. This review illustrates the actionable steps that the medical community can take to improve care for patients with SCD.

Primary T-cell lymphoma (TCL) of the central nervous system (CNS) is a rare and potentially aggressive entity. We describe a case of TCL presenting in the basal ganglia with γδ receptor expression and a remarkably aggressive clinical course. To the best of our knowledge, this is the fifth reported case of γδ TCL presenting in the CNS. We review existing literature, including the previously reported cases of γδ TCL of the CNS. In our case, a 69-year-old male presented with acute onset dysarthria and right-sided weakness, with initial imaging concerning for stroke. Repeat imaging demonstrated a 2.6-cm mass in the left basal ganglia-corona radiata. Pathologic examination of a stereotactic biopsy revealed TCL with γδ receptor phenotype. The patient suffered rapid clinical decline and passed away within 6 weeks of initial diagnosis. This represents an important differential diagnosis and sheds light on the potentially poor prognosis conferred by γδ TCL of the CNS.

In the current WHO classification, a T-cell prolymphocytic leukemia (T-PLL) diagnosis requires lymphocytosis of >5 × 109/L, evidence of monoclonality, and TCL1A or MTCP1 rearrangement. However, the 2019 consensus document suggested that in the absence of rearrangement of TCL1-family, the presence of abnormalities involving chromosome 11 (11q22.3; ATM), chromosome 8 (idic(8)(p11), t(8;8), trisomy 8q), 5, 12, 13, 22, or a complex karyotype, as well as involvement specific sites (e.g., splenomegaly, effusions) would suffice for a diagnosis of T-PLL. We present a patient diagnosed with T-PLL with MTCP1 rearrangement who was successfully treated with alemtuzumab followed by consolidative allogeneic unrelated donor stem cell transplantation. Eight years later, the patient presented with inguinal lymphadenopathy with features more akin to peripheral T-cell lymphoma, NOS (PTCL, NOS) of the GATA3 subtype, and there was no evidence of peripheral blood involvement. However, the lymphoma cells were clonally related to those at presentation. Currently, literature on T-PLL-like cases lacking the rearrangement of TCL1A is limited, and the possibility of whether a proportion of such cases could represent PTCL, NOS (with leukemic involvement) needs consideration.

Lindsey K. Durowoju, Rida A. Hasan, Daniel E. Sabath, Andrew Bryan, and Monica B. Pagano have no conflicts of interest related to the matters described in this manuscript. Hamilton C. Tsang holds stock in Pfizer, Roche, and Johnson & Johnson. John R. Hess is a paid consultant to Hemerus, LLC and UpToDate and a stockholder for Medcura Inc.

Sickle cell disease (SCD) is marked by red blood cells that deform into a sickle shape, causing severe health complications. Historic neglect and slow therapeutic progress have left many, especially African descendants, vulnerable. Recent treatment strides include novel drugs and gene therapy, promising improved management. Nonetheless, challenges persist with treatment adoption because of cost, adverse effects, and accessibility. Advancements hold hope for enhanced life quality and longevity for SCD patients.

BACKGROUND:Administering platelets through a rapid infuser is proven to be safe. However, the clinical significance of infusing ABO-incompatible platelets with red blood cells (RBCs) in a rapid infuser remains unclear. There is a theoretical risk that isoagglutinin in the plasma of a platelet unit can interact with RBCs and induce hemolysis. MATERIALS AND METHODS:Seven in vitro studies were performed including five cases (type A RBCs and type O platelets) and two controls (type A RBCs and platelets). Anti-A titers were measured in platelet units. An RBC unit and a platelet unit were mixed in the rapid infuser reservoir and incubated for 30 min. The primary outcome was the presence of hemolysis based on the following parameters: free hemoglobin concentration, hemolysis check, direct antiglobulin test (DAT), and direct agglutination. RESULTS:The post-mix DAT was positive for IgG in all test samples (5/5), and weakly positive for complement in 3/5. The changes in free Hb in test cases between measured and calculated post-mix spanned -2.2 to +3.4 mg/dL. Post-mix hemolysis check was negative in 3/5 and slightly positive in 2/5 cases, with no significant differences compared to the control case. Anti-A titers ranged from 16 to 512 and were not associated with hemolysis. All samples were negative for direct agglutination. CONCLUSION:Our study suggested that mixing ABO-incompatible platelets with RBCs in a rapid infuser does not induce in vitro hemolysis. These findings support the use of rapid infusers regardless of platelet compatibility in support of hemostatic resuscitation.

AIMS:It is unclear whether activated partial thromboplastin time (aPTT) or anti-Xa is more accurate for monitoring heparin anticoagulation in mechanical circulatory support (MCS) patients. This study investigates the relationship between aPTT and anti-Xa in MCS patients and identifies predictors of discordance. METHODS AND RESULTS:aPTT and anti-Xa were simultaneously measured in a prospective cohort of MCS patients receiving unfractionated heparin at a tertiary academic medical centre. Therapeutic aPTT and anti-Xa levels were 60-100 s and 0.3-0.7 IU/mL, respectively, and concordance was defined as both levels being subtherapeutic, therapeutic, or supratherapeutic. To identify predictors of discordance, both a machine learning random forest model and a multivariate regression model were applied to patient demographics, device type, and 14 laboratory variables; 23 001 pairs of simultaneously measured aPTT/anti-Xa were collected from 699 MCS patients. aPTT and anti-Xa were concordant in 35.5% of paired observations and discordant in 64.5% (aPTT > antiXa 61.5%; aPTT < antiXa 3.0%). Discordance with a high aPTT relative to anti-Xa (aPTT > antiXa) was associated with high INR, eGFR, and total bilirubin, as well as low platelets, haemoglobin, pre-albumin, white blood cell count, and haptoglobin. Total artificial heart and durable ventricular assist devices were more likely to be associated with aPTT > anti-Xa than temporary MCS devices. CONCLUSIONS:aPTT and anti-Xa were frequently discordant in MCS patients receiving heparin anticoagulation. Clinical conditions common in MCS patients such as concurrent warfarin use, malnutrition, haemolysis, and thrombocytopenia, as well as durable type of MCS devices were associated with a high aPTT relative to anti-Xa.

TransfusionVolume 63, Issue S5 p. 274A-275A SUPPLEMENT ARTICLE P-TS-30 | Evaluating Hemolysis Due to Incompatible Plasma in a Rapid Infuser Y. Jung, Y. Jung University of WashingtonSearch for more papers by this authorO. Luo, O. Luo University of WashingtonSearch for more papers by this authorN. Sen, N. Sen University of WashingtonSearch for more papers by this authorF. Li, F. Li University of WashingtonSearch for more papers by this authorR. Hasan, R. Hasan University of WashingtonSearch for more papers by this authorA. Hess, A. Hess University of WisconsinSearch for more papers by this authorJ. Hess, J. Hess University of WashingtonSearch for more papers by this authorD. Sabath, D. Sabath University of WashingtonSearch for more papers by this authorH. Tsang, H. Tsang University of WashingtonSearch for more papers by this authorM. Pagano, M. Pagano University of WashingtonSearch for more papers by this author Y. Jung, Y. Jung University of WashingtonSearch for more papers by this authorO. Luo, O. Luo University of WashingtonSearch for more papers by this authorN. Sen, N. Sen University of WashingtonSearch for more papers by this authorF. Li, F. Li University of WashingtonSearch for more papers by this authorR. Hasan, R. Hasan University of WashingtonSearch for more papers by this authorA. Hess, A. Hess University of WisconsinSearch for more papers by this authorJ. Hess, J. Hess University of WashingtonSearch for more papers by this authorD. Sabath, D. Sabath University of WashingtonSearch for more papers by this authorH. Tsang, H. Tsang University of WashingtonSearch for more papers by this authorM. Pagano, M. Pagano University of WashingtonSearch for more papers by this author First published: 12 October 2023 https://doi.org/10.1111/trf.367_17554Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume63, IssueS5October 2023Pages 274A-275A RelatedInformation

Hemoglobin disorders are among the most common genetic diseases worldwide. Molecular diagnosis is helpful in cases where the diagnosis is uncertain and for genetic counseling. Protein-based diagnostic techniques are frequently adequate for initial diagnosis. Molecular genetic testing is pursued in some cases, particularly when a definitive diagnosis is not possible and especially for the purpose of assessing genetic risk for couples wanting to have children. The expertise available in the clinical hematology laboratory is essential for the diagnosis of patients with hemoglobin abnormalities. Initial diagnoses are made using protein-based techniques such as electrophoresis and chromatography. Based on these findings, genetic risk to an individual's offspring can be assessed. In the setting of β-thalassemia and other β-globin disorders, coincident α-thalassemia may be difficult to diagnose, which can have potentially serious consequences. In addition, unusual forms of β-thalassemia caused by deletions in the β-globin locus cannot be definitively characterized using standard techniques. Molecular diagnostic testing has an important role in the diagnosis of hemoglobin disorders and is important in the setting of genetic counseling. Molecular testing also has a role in prenatal diagnosis to identify fetuses affected by severe hemoglobinopathies and thalassemias.

OBJECTIVES:The US Food and Drug Administration (FDA)-approved CELLSEARCH assay (Menarini Silicon Biosystems) for circulating tumor cells (CTCs) relies on expression of an epithelial cell adhesion molecule to enrich for CTCs. We sought to validate a CTC assay (RareCyte) for clinical use that instead collects a buffy coat preparation enriched for CTCs.METHODS:Normal peripheral blood specimens spiked with cultured breast and prostate cancer cells and 47 clinical samples were used to validate assay performance. Specimens were enriched for buffy coat cells and applied onto 8 glass slides. The slides were immunofluorescently stained and imaged by automated microscopy and computer-aided image analysis.RESULTS:The assay was 100% specific for detecting spiked tumor cells. For samples spiked with 25, 50, and 125 cells, the percentage coefficients of variation were 42%, 21%, and 3.7%, respectively. Linearity studies demonstrated a slope of 0.99, an intercept of 1.6, and R2 of 0.96. Recoveries at the 25-, 50-, and 125-cell levels were 92%, 111%, and 100%, respectively. Clinical samples run on both CELLSEARCH and RareCyte correlated with an R2 of 0.8 after log-transformation and demonstrated 87.5% concordance using the CELLSEARCH criteria for predicting adverse outcomes.CONCLUSIONS:The RareCyte CTC assay has comparable performance to the FDA-cleared method and is ready for further clinical validation studies.

Background Low quality evidence exists to support an association between retinal vascular occlusion and thrombophilia. However, testing may be complicated by the impact of anticoagulants, hormone use and other factors on the results. Even when test results are interpretable, the implications for clinical decision-making are not established. We performed a retrospective chart review to assess patterns of test selection, result interpretation, and clinical outcomes in a cohort of patients who received thrombophilia testing after presenting to a tertiary care center for retinal vascular occlusion. Methods Eligible patients were >18 years with retinal vein occlusion (RVO) or retinal artery occlusion (RAO) and referred for thrombophilia testing by an ophthalmologist between 3/16/2011 and 3/22/2021 at the University of Washington. Electronic medical records were extracted for relevant clinical characteristics, test results, use of antithrombotic therapy, and recurrent arterial or venous events. Continuous variables are summarized by means and standard deviations or medians and range, as applicable. Categorical variables are described by proportions. Differences between groups were assessed using Student's t-tests and Fisher's exact tests for continuous and categorical variables, respectively. Analyses were conducted in R. Results A cohort of 57 patients were identified, with median age of 44 years at diagnosis (Table 1). 38 (66.7%) presented with RVO and 23 (40.4%) presented with RAO, including 4 patients with concurrent RVO and RAO at diagnosis. Baseline characteristics were not significantly different between patients presenting RAO versus RVO, apart from a trend toward higher prevalence of stroke history in the RAO group (4/23 vs 1/38, p = 0.06). Thrombophilia test selection varied: protein C activity was most commonly tested (80.7%) while activated protein C resistance (40.4%) was least commonly ordered (Figure 1). Among the 50 patients who received some combination of antiphospholipid antibody (aPL) testing, only 44% had all Sydney criteria aPL assays performed. The underlying prevalence of thrombophilia was 3.5% (2/57). One patient was found to be homozygous for the factor V Leiden mutation (FVL) after presenting with a central RVO and 1 was diagnosed with antiphospholipid syndrome (APS) in the context of a branch RAO plus persistent positivity of anti-beta-2 glycoprotein I (IgM) and anticardiolipin (IgM) antibodies. Another 5 patients had abnormal test results that were not diagnostic of an underlying thrombophilia (1 heterozygous FVL, 1 heterozygous prothrombin gene mutation, and 3 positive aPL). In total, 15 patients were initiated on low-dose aspirin following diagnosis, including the patient diagnosed with APS. Four patients were treated with anticoagulation, including the heterozygous FVL and heterozygous prothrombin gene mutation patients, who were placed on indefinite anticoagulation. The patient found to be homozygous for FVL briefly received prophylactic dosing of rivaroxaban before switching to low-dose aspirin due to side effects. After a median follow-up of 3.1 years, 3 patients had recurrent events (1 RVO, 2 strokes). One developed recurrent stroke while taking rivaroxaban for atrial fibrillation, while the other 2 were not receiving antithrombotic therapy at the time of thrombosis recurrence. Conclusion A low prevalence of thrombophilia was observed in a young cohort of patients presenting with retinal vascular occlusion. Incomplete testing was common, including for antiphospholipid syndrome, which is associated with 2-fold increased risk of retinal vascular occlusion. Thrombophilia testing did not clearly aid in clinical decision making; the tests ordered and the actions taken based on the test result were inconsistent. Both patients identified to have underlying thrombophilia lacked other history of venous or arterial thromboembolism and ultimately opted against long-term anticoagulation. An additional 14 patients opted for antithrombotic therapy with low-dose aspirin after an entirely negative thrombophilia workup. Misinterpretation of test results likely led to inappropriate recommendations for indefinite anticoagulation in at least 2 patients. The utility of thrombophilia testing in retinal vascular occlusion is poorly studied. In this cohort, we found no evidence that such testing should influence clinical decision-making. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Analysis of circulating tumor cells (CTCs) by multiparameter immunofluorescence (IF) microscopy allows non-invasive characterization of cancer cell biomarker expression in real time. This information can be helpful in prognosis, treatment selection, and stratification of cancer patients. AccuCyte® is a density-based unbiased isolation method that transfers nucleated cells from whole blood to slides for the characterization of CTCs and other rare cells. RarePlex® panel kits are IF staining reagents used on automated slide staining instruments to label cells to differentiate CTCs from white blood cells (WBC). CyteFinder® is a seven-channel automated fluorescent imaging system that rapidly scans microscope slides and applies machine learning algorithms to identify CTCs. Together, these technologies provide an end-to-end solution for CTC characterization. For analysis, blood is drawn into AccuCyte blood collection tubes (BCTs) containing a preservative which maintains cell properties prior to processing onto slides. Once slides are prepared, they can be stored at -20°C without significant biomarker degradation. This flexible workflow allows investigators to bank samples for batch analysis and to begin sample collection prior to validating the IF assay to be used. This study was designed to evaluate: (1) stability time between collection in the AccuCyte BCT and sample processing; (2) performance of an improved version of the AccuCyte kit with higher nucleated cell isolation capacity; and (3) storage time that AccuCyte prepared slides can be banked frozen prior to staining. The study was performed using model CTCs and cancer patient samples. Metrics to determine performance were CTC recovery and mean fluorescence intensity (MFI) of biomarker expression. Our results demonstrate that the AccuCyte BCT preserves blood components for at least 5 days after collection without significant effect on CTC recovery or biomarker expression. The latest version of the AccuCyte kit demonstrated a higher cell isolation capacity and could collect up to 60% more nucleated blood cells than the previous version, increasing CTC recovery. The increased capacity was demonstrated in patients treated with hematopoietic growth factors, whose WBC count was significantly higher than the normal range. Finally, accelerated-aging study results demonstrated that AccuCyte-prepared slides can be stored at -20°C for at least 4 years without significant effect on most biomarkers tested. In conclusion, enhancements to the AccuCyte-CyteFinder platform reported here increase flexibility and performance for analysis of CTCs in global clinical trials by allowing longer periods of time before collected blood samples need to be processed and by extending the length of time processed slides can be banked before they are stained. Citation Format: Arturo B. Ramirez, Lillian Costandy, Brady S. Gardner, Ryan H. Huston, A Anders Larson Tevis, Casey E. Helmicki, Alisa C. Clein, Daniel E. Sabath, Joshua J. Nordberg, Tad C. George. Validation of enhanced performance of the AccuCyte®-CyteFinder® platform for circulating tumor cell characterization [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1952.

Frequent prothrombin time (PT) and international normalized ratio (INR) testing is critical for millions of people on lifelong anticoagulation with warfarin. Currently, testing is performed in hospital laboratories or with expensive point-of-care devices limiting the ability to test frequently and affordably. We report a proof-of-concept PT/INR testing system that uses the vibration motor and camera on smartphones to track micro-mechanical movements of a copper particle. The smartphone system computed the PT/INR with inter-class correlation coefficients of 0.963 and 0.966, compared to a clinical-grade coagulation analyzer for 140 plasma samples and demonstrated similar results for 80 whole blood samples using a single drop of blood (10 μl). When tested with 79 blood samples with coagulopathic conditions, the smartphone system demonstrated a correlation of 0.974 for both PT/INR. Given the ubiquity of smartphones in the global setting, this proof-of-concept technology may provide affordable and effective PT and INR testing in low-resource environments.