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Abstract Background The use of autonomous mobile robots (AMRs) to move materials/supplies is long-standing in manufacturing/warehouse settings and is expanding into hospitals and clinical laboratories. The recently launched Proxie robot (Collaborative Robotics i.e. Cobot) is an AMR that can autonomously move existing carts between defined locations. However, AMRs pose new challenges compared to traditional lab automation. The aims of this study were to: i) perform functional validation to verify Proxie*s manufacturer performance specifications within the laboratory, ii) assess the risk of using Proxie to deliver laboratory specimens, and iii) pilot the use of the Proxie robot to autonomously deliver loaded carts from the Pathology case intake area to the sorting station at Mayo Clinic Laboratories. Methods Functional validation of Proxie consisted of verifying manufacturer’s performance specifications for the following robot parameters (5 test runs): maximum speed, emergency-stop, and ability to maintain localization, travel autonomously, stop and/or avoid moving/fixed objects, and park/unpark. Risk assessment for the robotic use case was performed by a multi-disciplinary team utilizing an AMR risk assessment tool developed by the institutional robotics group. Hazards were categorized as mechanical, electrical, noise, ergonomic, environmental, material/substance or combination risks. Injury severity, exposure(frequency), and avoidance scores were assigned to each hazard to determine negligible-, low-, medium-, high- or very high-risk levels. Proxie’s workstream was evaluated weekly over four weeks by measuring number of cart deliveries, total time/miles traveled, % autonomous deliveries(goal >80%), % on-time deliveries, average±standard deviation(SD) time (min:sec±min:sec) for delivery/return trips, and dwell times at intake/sorting stations. Results Manufacturer’s performance specifications were verified in 100% of test runs. Proxie traveled at human walking speed, stopped within 1 second of emergency stop being enabled, maintained localization, and traveled autonomously for =5 consecutive workflow cycles. Proxie navigated through spaces =4’ wide along fixed pathways and stopped safely when encountering obstacles. Proxie navigated around people and carts in the main 6’ hallway if they were blocking <2’ hallway width. For objects blocking >2’, Proxie stopped and resumed motion after the object moved. After task completion, Proxie side-shifted into the AMR parking space stopping no closer than 7.8” from any object. Twenty-four potential hazards were identified through the risk assessment tool with all risk levels scored as negligible or low. Proxie completed 304 cart deliveries/returns operating 17:35 hours and traveling 11.5 miles during the pilot. The % autonomous deliveries for week 1-4 was 82%,88%,91% and 88%, respectively with =99% on-time deliveries. Delivery from pathology case intake to sorting station averaged 5:43±0:25 min and return trips averaged 3:32±0:34. Proxie dwell times were 13:10±0:33 and 37:34±0:23 min at the pathology intake and sorting stations, respectively. Conclusions The Proxie AMR was capable of successfully and autonomously moving carts with laboratory specimens between the pathology intake and sorting stations of the laboratory during the pilot study. Adding Proxie to this workstream translated to eliminating 5,800 steps and 4 hours 24 min of human cart-pushing per week. Incorporating Proxie into laboratory operations as a cart-moving AMR would increase efficiency and allow laboratory staff to focus on technical, non-repetitive work.

Abstract Background Hemolysis, a common pre-analytical interferent in clinical laboratory testing, can significantly affect accuracy and reliability of laboratory results. One test particularly susceptible to interference is direct bilirubin (D-bil). For example, during December 2024, 40% (500/1239) of specimens rejected due to hemolysis were orders for D-bil. The recently released Roche (Roche Diagnostics) direct bilirubin reagent (BILD2) has a lower threshold for hemolysis (H-index [HI]=25)) than the previous generation (HI=30). The aims of our study were to (1) establish concentration-specific hemolysis thresholds for D-bil and (2) investigate the instrument’s reduced volume function (dilution) as a possible mitigation strategy for samples with hemolysis indices exceeding the established thresholds. Methods Residual serum specimens from physician-ordered D-bil testing were used and analyzed on Roche cobas c701 and c501 analyzers. The instrument’s decreased volume function, intended for results outside the measuring range, was used as a 1:2 dilution and validated using 9 non-hemolyzed negative control specimens with D-bil results from 9.8-13.4 mg/dL. Recovery within 10% neat value was considered acceptable. EDTA whole blood was used to prepare hemolysate pools by washing red cells and lysing by freezing (-80 °C). Twenty-six serum pools with varying D-bil concentrations (0.2-3.4 mg/dL) were prepared. Each pool was split into 10 aliquots and spiked with increasing amounts of hemolysate, not exceeding 10% serum to interferent ratio. The decreased volume function (dilution) was utilized on a subset of the hemolysate-spiked aliquots (N=55) with D-bil results from 0.2-2.5 mg/dL. HI values were estimated to be 50% of neat HI due to the instrument’s inability to measure indices on specimens tested with the decreased volume function. Acceptance criteria for experiments utilizing hemolyzed specimens were ±0.1 mg/dL or 20% of neat sample. Results All non-hemolyzed specimens tested with the decreased volume function passed within acceptance criteria with average recovery of 109% (range: 106-110%) from undiluted specimens. Serum pools with D-bil <0.3 mg/dL (N=7) spiked with hemolysate (HI range: 7-191) had an average difference of -0.1 mg/dL (range: -0.2-0.0 mg/dL) from non-hemolyzed pools, D-bil pools 0.4-0.9 mg/dL (N=10; HI range: 6-173) had an average difference of -0.2 mg/dL (range: -0.5-0.0 mg/dL), and D-bil pools >1.0 mg/dL (N=9; HI range: 5-182) had an average difference of -20.7% (range –45.5-0.0%). Serum pools with D-bil <0.3 mg/dL (N=23; HI range: 43-191) tested using the decreased volume function had an average difference –0.1 mg/dL (range: -0.2-0.0 mg/dL; HI range: 22-96) from the non-hemolyzed specimens, D-bil pools 0.4-0.9 mg/dL (N=20; HI range: 39-173) had an average difference -0.1 mg/dL (-0.3-0.0 mg/dL; HI range: 19-86), and D-bil pools >1.0 mg/dL (N=12; HI range: 37-182 ) had an average difference of -0.2 mg/dL (-0.5-0.2 mg/dL; HI range: 19-91). Conclusion We established a new hemolysis interference threshold of 75 for samples with D-bil <0.3 mg/dL. Using the decreased volume function, we expanded the hemolysis interference threshold to HI=100 for specimens =0.3 mg/dL. All specimens with HI>100 will result in a recollection. With these changes, we estimate that we can reduce our D-bil recollections by up to 6% over six months.

Abstract Background Lymphocyte function and immune competence can be measured by proliferative response to stimuli and is useful in several clinical contexts including primary (or genetic) and secondary immunodeficiencies (e.g., immunosuppression following transplantation). Proliferation assays have traditionally been prepared manually due to the difficulty in maintaining the sterile environment required to prevent bacterial and fungal impact on cell growth. On most automated liquid handlers, the sample and reagents are placed inside a cabinet whose inner surfaces include rails, pullies, pumps, and circuitry that face the sample and are not amenable to sterilization. The Andrew+ (Waters, MA) is a small surface cleanable liquid handler with all machinery enclosed. We demonstrate here the use of an Andrew+ placed in a biological safety cabinet (BSC) to perform sterile assay setup. Methods Peripheral blood monocytes (PBMCs) from five individuals were manually generated via buffy coat isolation, then brought to standardized concentration. An Andrew+ was placed in a 4’ BSC and all surfaces disinfected with Oxivir Tb (Diversey, SC). The Andrew+ prepared three serial dilutions of two stimulant reagents (phytohemagglutinin (PHA) and pokeweed (PWM)), then dispensed stimulant and control reagents horizontally and PBMCs vertically to a 48 well plate. This process was duplicated manually from the same specimens to create a reference plate. The plates were incubated at 37°C and 5% CO2 for three days, then pulsed with EdU (Thermo Fisher, MA) and incubated for one additional day. Cells were harvested and counted via flow cytometry. Overall time and hands-on time were measured. Results A total of five samples were tested inside a using both manual and automation setup under eight conditions including with isotype control, media without stimulant, three concentrations of PHA, and three concentrations of PWM. The percent proliferation for various cell types as induced by each stimulant was calculated from the difference of the highest stimulant signal from the background (media-only) signal. Comparing the automated and manual method results showed a slope of 1.0217 and R2 of 0.9966. For a simulated run of 6 samples, technologist time for automated steps was under 8 minutes with a total time of 56 minutes. When these steps were performed manually, the time was 30 minutes. Automation increased total time by 26 minutes but saved 22 minutes of technologist hands-on time. Conclusion The Andrew+ was able to perform sterile setup of a cell culture assay. While slower overall than manual processing, technologist time was reduced. Ergonomic, inter-tech variability, and sample transcription error issues were subjectively observed to be less likely. The Andrew+ can work with up to four “dominos” (reagent or tip blocks) in width and up to three dominos in depth. Non-custom, standard depth BSCs from a variety of manufacturers (Labconco, Nuaire, ThermoFisher) have room for one domino in depth so, except for timings performed in this evaluation, all steps were broken down to be performed with a max of four dominos. Efficient sterile use of the system would require an extended depth BSC.

Abstract Background Hemoglobin A1c is used to assess glycemic control to both diagnose and monitor diabetes mellitus. Several different methodologies are available including high performance liquid chromatography (HPLC), capillary electrophoresis (CE), and immunoassay (IA). These methods are standardized and traceable to the Diabetes Control and Complications Trial (DCCT). The aim of this study was to evaluate the difference in HbA1c results between methods and percent of reportable results in variant samples. Methods The HPLC (Bio-Rad Laboratories, Inc; D-100), the CE(Sebia Inc; Capillarys 3), and IA(Roche Diagnostics Inc; Tina-quant Generation 3) were compared using two sets of residual patient samples left after physician ordered testing was complete: 1) samples with an absence of abnormal hemoglobin peaks (i.e. non-variant) detected by HPLC; 2) samples with abnormal hemoglobin peaks (i.e. variant) characterized by hemoglobin electrophoresis performed clinically or lacking an A1c peak by HPLC/CE. The samples were tested within manufacturers stability claims. 317 non-variant samples were compared between the HPLC and CE methods. The absolute difference was calculated for each method using this equation (HbA1c%avg – HbA1c%X) where HbA1c%avg is the average of the methods that produced reportable results and X is the result from each method evaluated. Differences less than or equal to +/-0.3% were considered acceptable. 28 of the 317 non-variant and 47 variant samples were tested by all 3 methodologies. The 47 variant samples grouped into 3 cohorts: common heterozygous variants (HbC, HbD, HbE, HbS and HbF, n=10), uncommon heterozygous variants (n=29) and homozygous variants lacking HbA (n=8). The absolute differences in variant sample results were calculated for samples that did not surpass manufacturer’s claims for producing an accurate result. The frequency of producing a numeric result in variant samples was calculated for each method. Results The HPLC/CE non-variant sample comparison (N=317) had results spanning the measuring range (3.8% - 14.0%) with average(range) of absolute difference=0.1(-0.4to0.6%) with 293/317(92.4%) samples within +/-0.3%. The HPLC/CE/IA non-variant sample comparison (N=28) had a result range=4.0%-9.4%, the average(range) of difference=0.1(-0.2to0.5%) with 25/28 (89.2%) of samples within +/-0.3%. Common heterozygous variant samples gave numeric results with no disqualifying flags in 9 of 10(HPLC), 8 of 10(CE), and 9 of 10(IA) samples tested. The average(range) difference from average=0.0(-0.3,0.5%) for HPLC, 0.0(-0.2,0.3%) for CE, and -0.1(-0.6,0.2%) for IA. Uncommon variant samples gave results in 4 of 29 (HPLC), 20 of 29 (CE), and 26 of 29 (IA) of samples tested. The average(range) difference from average=-0.1(-0.3,0.1%) for HPLC, 0.0(-1.0,1.1%) for CE, and 0.0(-1.1,1.0%) for IA. The homozygous variant (no HbA) samples gave results in 0 of 8 (HPLC), 0 of 8 (CE), and 4 of 8 (IA) of those tested. Conclusion All three methods meet their claims for accurately measuring hemoglobin A1c from non-variant and common hemoglobin variants. The advantage of HPLC and CE is the ability to identify hemoglobin variants that may impact HbA1c quantitation. The IA method provides the most numeric results. IA gave results even when HbA was absent. The lab should understand the capabilities and limitations of their HbA1c method on the population served.

Background: The use of validated risk stratification tools for the workup of suspected pulmonary embolism (PE) is a recommendation of the American Society of Hematology and the American College of Emergency Physicians. Methods: We designed and implemented electronic clinical pretest probability (PTP) tools for use in emergency departments (ED). Overall, 38 EDs (tertiary and regional EDs) in the United States were involved across three health systems. PTP use was analyzed between September 12, 2022 and January 11, 2023 in 270,247 ED visits. PTP use was examined in terms of the percentage of visits for which patients underwent computed tomography pulmonary angiography (CTPA). Each site chose the 3-tier Wells’ score for implementation and Site 2 designed a combined Wells’, pulmonary embolism rule-out criteria (PERC), and YEARS score. Results: At Site 3, forced use resulted in documented PTP scores in 49–53% of ordered CTPAs. At Sites 1 and 2, where PTP scores were optional, documented PTP scores occurred in 2–3% and 1–3% of CTPA orders, respectively. At Site 1, the use of PTP increased slightly over the study period, with signs that PE yield on imaging was also increasing (3.4–5.9%). At Site 2, PE yield on imaging was 9–10%, and it remained similar, with similar use of PTP tools over the study period. PE yield (6–8%) on imaging also remained similar throughout the study at Site 3. Conclusions: Guideline-endorsed PTP scores for PE at three independent health systems in the United States did not increase PE yield on imaging. Novel implementation strategies involving interdisciplinary teams are urgently needed.

Abstract Background We evaluated the Tecan Fluent Mix and Pierce Workstation as an automated platform to aliquot directly from whole blood collection tubes. The Fluent Mix and Pierce Workstation uses the Tube Rotator™, an on-deck rotisserie, to keep whole blood in suspension, and 8 Piercing Tips™ to cross the pierceable caps of collection tubes to aliquot samples. Methods We performed accuracy and precision testing by aliquoting residual whole blood specimens into an on-deck gravimetric scale. To test carryover, we aliquoted alternating blanks and high calibrators for several analytes and performed mass spectrometry on the blanks. We performed 168 runs over a 21-day period to test the robustness of the platform. We aliquoted and analyzed 2 batches of samples on both our clinical platform and the Mix and Pierce Workstation to check concordance. Results We observed that the Fluent Mix and Pierce Workstation can aliquot 200 µL with 0.5% inaccuracy and 0.9%CV and can aliquot 300 µL with 0.1% inaccuracy and 0.7%CV. We were unable to detect any analyte carryover using mass spectrometry. We observed no hardware failures during the instrument stress test. Clinical comparison runs indicated that the performance of aliquots made on the Fluent Mix and Pierce Workstation was equivalent to that of aliquots made by our current clinical method. Conclusions Overall, our evaluation showed that the Tecan Fluent Mix and Pierce Workstation is a viable platform for aliquoting whole blood for downstream work flows and can eliminate labor-intensive sample decapping and recapping in high-throughput settings.

Guidelines for diagnosing pulmonary embolism (PE) start with a risk assessment using a pretest probability (PTP) tool, followed by D-dimer testing or computed tomography pulmonary angiography (CTPA) depending on risk. The project aimed to develop an electronic clinical quality measure (eCQM) to encourage broader use of a validated PTP scoring tool in emergency departments (EDs) to more accurately diagnose PE and to reduce unnecessary CTPAs. To identify a value set to accurately identify CTPA and abnormal D-dimer tests using standard classification systems and clinical vocabularies (ie, Current Procedural Terminology [CPT], Logical Observation Identifiers Names and Codes [LOINC], systematized nomenclature of medicine clinical terms [SNOMED CT]) across 3 academic United States health care systems. A comprehensive value set to identify CTPAs was selected, which contained 31 codes. Additionally, each health care system had unique, site-specific codes to more granularly identify CTPAs. Three health care systems representing 38 EDs from across the country submitted data from all ED encounters between September 12, 2022, and January 11, 2023. Imaging types were reviewed from each of the CPT codes and LOINC. The project evaluated whether a D-dimer was obtained using CPT and LOINC and whether the D-dimer result was elevated using SNOMED CT. The number of ED encounters, PTP use, and diagnosis of PE using different codes were determined. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value for selected codes were calculated. Over a 4-month study period, 270,214 encounters were included from 38 EDs. 11,794 ED encounters with CTPAs during the study period, using the site-specific codes were identified. The comprehensive value set had a PPV of 63.4%. Restricting the CTPA value set to CPT code 71275 or LOINC 88322-3 improved the PPV to 82% with 100% sensitivity and 99% specificity. The restricted value set captured the highest proportion of relevant site-specific codes. D-dimer values were identified using LOINC codes 48065-7 and 91556-1 at Site 1 and 48067-3 at Site 2. SNOMED CT codes were not used at any site to identify elevated D-dimer results. Different D-dimer tests with different normal ranges were used at each site, and only one site provided an abnormal flag for D-dimer results. Heterogeneity in the use of nationally standardized codes for labs and imaging tests limits the ability to measure and compare quality across health care organizations for CTPA and D-dimer results. Restricting the identification of CTPA to CPT Code 71275 or LOINC 88322-3 resulted in high sensitivity and specificity, but false positives remain. Additionally, coding for an abnormal D-dimer test result is not standardized across institutions. Therefore, the currently available value sets cannot be used to develop eCQMs whose aim is to evaluate whether CTPA is ordered appropriately based on the PTP risk level and laboratory testing.

AbstractBackgroundPatterns of regional atrophy and hypometabolism have been observed in dementia with Lewy bodies (DLB). However, determinants of regional vulnerability to structural and functional neurodegeneration remain largely unexplored. First, we investigated the association between regional gene expression and grey matter volumes in probable DLB patients. Since hypometabolism presumably precedes overt brain atrophy, we additionally investigate the association between regional gene expression and hypometabolism in DLB.MethodTo investigate the association between gene expression and regional volumes, 165 DLB patients along with 165 age‐ and sex‐matched healthy controls from three European centres and the Mayo Clinic (USA) were included. Regional volumes were quantified from MRI using SPM12 in 112 cortical, subcortical, and cerebellar brain regions, and compared between groups, using w‐scores. Regional expression data of seven genes involved in the formation and degradation of pathological protein aggregates (APOE, APP, BIN1, GBA, MAPT, SNCA, TMEM175) was extracted from six healthy donors from the Allen Human Brain Atlas and correlated with regional volumetric w‐scores. To assess the predictive value of regional gene expression on regional volumes we used Gaussian stepwise backwards linear regression including all seven genes as predictors. To investigate the association between gene expression and hypometabolism, we are currently applying the same analysis pipeline to FDG‐PET data of 139 DLB patients from 8 European centres.ResultMost brain regions showed lower volumes in DLB patients compared to healthy controls, with differences being most pronounced in occipital and parietal lobes. Regional expression of APOE correlated positively with regional volumes in DLB. Conversely, regional expression of MAPT correlated negatively with regional volumes. Both APOE and MAPT gene expression were significant predictors of regional volumes in the regression analysis. None of the other gene expression values was significantly associated with regional volumes in DLB.ConclusionOur findings show that regional expression of genes associated with the abnormal accumulation of amyloid and tau, common co‐pathologies in DLB, partially account for the brain atrophy pattern observed in DLB patients. Analyses are ongoing for the hypometabolism pattern. Our finding emphasises the relevance of co‐pathologies in predicting atrophy progression and identifying potential targets for future disease‐modifying treatments.

Severe COVID-19 is a multisystem condition with thromboinflammation as a significant driver of morbidity and mortality. Cellular components involved in inflammatory and coagulation responses include platelets, endothelium, monocytes, and neutrophils. Thrombotic manifestations, such as arterial thrombosis, venous thromboembolism, and tissue microthrombosis, occur in at least 20% of ICU COVID-19 patients, possibly more based on postmortem studies. This study investigates the presence of prothrombotic antibodies similar to those found in heparin-induced thrombocytopenia (HIT), a condition caused by platelet-activating antibodies targeting platelet factor 4 (PF4) when complexed with heparin (PF4/H). In a study of samples from 130 hospitalized patients collected on average 3.6 days after COVID-19 diagnosis, 80% were found to have IgG antibodies recognizing PF4/H. This percentage is significantly lower than in 22 HIT patients (100%) but higher than in 51 non-COVID-19 patients with acute respiratory symptoms (ARS) (25%) and 12 healthy subjects (0%). Additionally, 41% of the 130 patients had antibodies inducing PF4-dependent P-selectin expression in CpG-treated normal platelets, a rate significantly lower than in 12 HIT patients (100%) but higher than in 51 non-COVID-19 ARS patients (20%) and 12 healthy subjects (0%). Significantly, platelet-activating antibodies in COVID-19 patients were associated with a specific elevation of platelet α-granule proteins in the plasma and correlated with inflammation and tissue damage markers, suggesting these antibodies' functionality in patients. Significantly, unlike HIT, both PF4/H-reactive and platelet-activating antibodies were found in COVID-19 patients regardless of recent heparin exposure, indicating different antigenic stimuli for these antibodies in COVID-19. Notably, certain antibodies against the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 possessed sequence motifs, RKH and Y5, in the heavy-chain complementarity-determining region 3 (HCDR3) resembling those in pathogenic HIT antibodies identified in our previous studies, suggesting that these antibodies can activate platelets. Introducing exogenous RBD to COVID-19 plasma or IgG purified from COVID-19 plasma significantly reduced their ability to activate platelets. Furthermore, immunodepleting RBD-reactive antibodies from COVID-19 plasma or IgG purified from COVID-19 plasma using RBD-coated beads significantly reduced their ability to activate platelets. These findings demonstrate that some RBD-specific plasma IgG antibodies can activate platelets. To demonstrate the presence of RBD-specific, platelet-activating antibodies at the clonal level, we produced recombinant antibodies from 42 RBD-binding IgG+ B cells, tested their ability to activate platelets, and identified four that could do so. Interestingly, three antibodies possess HCDR3 sequences resembling RKH or Y5 motifs. Additionally, we identified RKH or Y5 motifs in RBD-specific antibodies reported by other groups, produced 15 such antibodies recombinantly, tested their ability to activate platelets, and identified four more that could do so. IgG+ B cells with these HCDR3 motifs were markedly expanded in severe COVID-19 patients, suggesting an expansion of B cells producing platelet-activating antibodies. The demonstration of functional and structural similarities between certain RBD-specific antibodies in COVID-19 patients and pathogenic HIT antibodies suggests a novel mechanism by which RBD-specific antibodies might contribute to thrombosis in COVID-19.

Background: Myeloproliferative neoplasms (MPNs) are chronic leukemias with increased thrombotic risk. Venous thrombosis in MPN often occurs in atypical sites, such as splanchnic vein thrombosis (SVT), defined by thrombosis in the portal, hepatic, mesenteric, or splenic veins. Data to guide anticoagulation management of SVT in MPN patients is lacking. Objectives: The purpose of this study is to evaluate outcomes as well as the safety and efficacy of different anticoagulation strategies in MPN patients with SVT. Methods: A retrospective cohort study of MPN patients with SVT from 10 international centers was conducted. All centers performed systematic identification of adults with a World Health Organization 2016 diagnosis of an MPN (polycythemia vera [PV], essential thrombocythemia [ET], myelofibrosis [MF], prefibrotic MF, MPN-unclassifiable [MPN-U]) and confirmed SVT. Inclusion criteria were met if first SVT occurred after or within one year before MPN was diagnosed. The primary outcome was 1-year cumulative incidence of recurrent venous (VT) or arterial thrombosis (AT). Secondary outcomes included 1-year cumulative incidence of (1) major and clinically relevant non-major bleeding (CRNMB) by International Society on Thrombosis and Hemostasis criteria, (2) SVT recanalization; and (3) 1-year overall survival. Death as a competing risk was used for cumulative incidence analyses of recurrence and bleeding. Results: 486 MPN patients (median age at first SVT 51 years; 62.3% female) were identified. MPN diagnosis preceded SVT in 35.2% of patients (median time 4.8 years) and occurred simultaneously or within 1 year of first SVT in 64.8% of patients. 43.8% of patients had PV, 23.7% ET, 14.2% MF, 3.1% prefibrotic MF and 13.2% MPN-U. The most common driver mutation was in JAK2 (90.7%) followed by CALR (4.4%) and MPL (1.6%). SVT localization was isolated to portal (25.7%), hepatic (15.4%), mesenteric (1.9%), and splenic veins (4.3%), and in 51.2% of cases SVT occurred in multiple vessels. Prior VT or AT occurred in 8.8% and 4.1% of subjects, respectively. Cytoreduction (most commonly hydroxyurea [36.9%], interferon [9.6%] or JAK inhibitor [6.8%]) was started after SVT in 58.7% of newly diagnosed MPN patients and 40.6% of those with known MPN. 57.6% of patients were anticoagulated, 3.5% of patients were treated with an antiplatelet agent, and 11.7% were treated with both. The most common initial anticoagulants were vitamin K antagonists (VKA) (29.2%), direct oral anticoagulants (DOAC; 20.4%), and low-molecular-weight heparin (LMWH; 10.5%). DOACs were more commonly used in the USA and Asia than Europe (21.2%, 52%, and 13.5%; p<0.001). The median duration of anticoagulation was 23.9 months, with 62.8% still on anticoagulation after 3 years or at last follow-up. 1-year cumulative incidence of recurrent VT and AT was 14% (95% CI 11-18) (5.8% for recurrent SVT [95% CI 3.9-8.3]; 6.3% for other VT [95% CI 4.3-8.8]; 2.4% for AT [95% CI 1.3-4.2]), with an overall time to event 89 (IQR 34-193) days. Thrombosis incidence was similar in patients initially treated with VKA (13%), DOAC (15%) or LMWH (16%) (p=0.93); in comparison, individuals not treated with anticoagulation had 1-year thrombosis incidence of 13% (p=0.22). 1-year major and CRNMB cumulative incidence in all patients was 5.8% (95% CI 3.9-8.2) and 8.5% (95% CI 6.1-11), with median time to event 68 (IQR 13-150) days. Incidence of major bleeding was similar in VKA, DOAC, and LMWH-treated patients (5.9%, 6.6%, and 4.0%; p=0.89). 1-year cumulative incidence of SVT (partial) recanalization was 13% (95% CI 9.8-16) in all patients, with a median time to recanalization of 127 (IQR 40-323) days; recanalization rates were similar in anticoagulated and non-anticoagulated patients (p=0.76). There was a trend toward higher recanalization rates in patients treated with DOAC (26.9%) than with VKA (21.5%) or LMWH (13.6%; p=0.28). 1-year overall survival was 94.2% (95% CI 91.8-96.1) and similar between treatment groups (VKA 96.7%, DOAC 95.6%, LMWH 89.7%; p=0.11) and for no anticoagulation (82.3%; p=0.32). Conclusions: This is the largest contemporary cohort of MPN patients with SVT. MPN patients with SVT remain at risk for short-term thrombosis and bleeding complications regardless of treatment. We found no significant differences in outcomes between anticoagulation strategies, including in patients treated with DOACs compared to VKA or LMWH.