Viscoelastic testing: Critical appraisal of new methodologies and current literature

United States Food and Drug Administration (FDA)-approved viscoelastic testing (VET) methodologies have significantly changed in the last 10 years, with the availability of cartridge-based VET. Some of these cartridge-based methodologies use harmonic resonance-based clot detection. While VET has always allowed for the evaluation of real-time clot formation, cartridge-based VET provides increased ease of use as well as greater portability and robustness of results in out-of-laboratory environments. Here we review the use of VET in a variety of clinical contexts, including cardiac surgery, trauma, liver transplant, obstetrics, and hypercoagulable states such as COVID-19. As of now, high quality randomized trial evidence for new generation VET (TEG 6s, HemoSonics Quantra, ROTEM sigma) is limited. Nevertheless, the use of VET-guided transfusion algorithms appears to result in reduced blood usage without worsening of patient outcomes. Future work comparing the new generation VET instruments and continuing to validate clinically important cut-offs will help move the field of point-of-care coagulation monitoring forward and increase the quality of transfusion management in bleeding patients

The Challenge Of Russell’s Viper Venom Time Interpretation For Lupus Anticoagulant Diagnosis: A Two-Year Retrospective Institutional Review

Abstract The UCSF hematology laboratory uses the Precision Biologic LA Check and LA Sure reagents for the Russell’s viper venom time (RVVT), as part of the laboratory diagnosis of a lupus anticoagulant (LA). Currently, manufacturer’s FDA-approved guidelines for interpretation differ from the recommended diagnostic criteria of the International Society for Thrombosis and Hemostasis (Pengo V et al. JTH. 2009, 7:1737). The manufacturer’s guideline for positivity is patient results 1) >2 SD above the mean of normal donors for the screening test and 2), >2 SD above the mean of the ratio of the LA Check time to phospholipid-supplemented LA Sure time in normal donors. The ISTH guideline for positivity is patient results 1) >99th percentile of normal donors for the screening test, 2) >99th percentile of the ratio of mix of patient and pooled normal plasma (PNP) to the mix of normal donors and PNP with the screening reagent, and 3) >50thpercentile of the mean of the ratio of the LA Check time to phospholipid-supplemented LA Sure time in normal donors. Therefore, some cases meet one or the other definition of LA, but not both. We interpret the RVVT as positive when both manufacturer’s and ISTH guidelines are met, negative when neither criteria are met, and equivocal when one set of criteria is met but not the other. Some authors have advocated using a similar “third” category of “indeterminate lupus anticoagulant” in order to highlight the potentially elevated risk for these patients to have pro-thrombotic events (Park SH et al. Korean J Hematol. 2012, 47:83). Here we report our two-year experience (7/6/2011-7/6/2013) with patients with prolonged screening RVVT (using LA Check). Those samples with prolonged screening RVVT greater than 2 standard deviations above the average of normal donors undergo additional testing: a 1:1 mix with PNP (using LA Check) and high phospholipid confirmatory testing (using LA Sure). We retrospectively reviewed all samples with a prolonged screening RVVT in a two year period to determine the frequency of deviations between the manufacturer’s and ISTH guidelines, as well as the frequency of prolonged screening RVVT. We also correlate the RVVT results with the other lupus anticoagulant assay used at UCSF, the Staclot® LA 20 (utilizing hexagonal phase phosphatidylethanolamine) 329 samples had a prolonged screening RVVT, representing 321 patients (24 patients had two RVVT performed, 2 patients had three RVVT). 1477 total RVVT were performed in the study period (i.e. 22.3% had a prolonged screen). Of the 329 samples with a prolonged screening RVVT, 116 were positive (35.3%), 139 were negative (42.2%), and 74 were equivocal (22.5%). Of the 74 cases with an equivocal RVVT, 36 (48.6%) had a positive result according to manufacturer’s guidelines and 38 (51.4%) had a positive result according to ISTH guidelines Of the 329 samples with a prolonged screening RVVT, 122 had a concurrent negative Staclot® LA 20 assay (37%), 16 had a concurrent equivocal Staclot® LA 20 assay (4.9%), 172 had a concurrent positive Staclot® LA 20 assay (52.3%), and 19 did not have a concurrent Staclot® LA 20 assay (5.8%). Of the 74 cases with an equivocal RVVT, 71 had a concurrent Staclot® LA 20 assay. Of those 71, 25 (35.2%) had a negative Staclot® LA 20, and 4 (5.6%) had an equivocal Staclot® LA 20, and 42 (59.2%) had a positive Staclot® LA 20. Of the 42 cases with an equivocal RVVT and a concurrent positive Staclot® LA 20 assay, 13 (31%) met RVVT criteria for manufacturer’s guidelines and 29 (69%) met RVVT criteria for ISTH guidelines. Of the 329 samples with a prolonged screening RVVT, 47 were associated with identified concurrent anticoagulant treatment. 17 (36.2%) of these 47 had a negative RVVT, 13 (27.7%) had an equivocal RVVT, and 17 had a positive RVVT (36.2%). Overall, this study has shown that there are frequent cases (22.5%) where the RVVT assay meets one or the other guidelines for a positive LA. The equivocal diagnoses were approximately evenly split between those cases positive by manufacturer’s guidelines or positive by ISTH guidelines. Compared to the overall sample, those cases with an equivocal RVVT did not more frequently have a positive Staclot® LA 20 assay. Those cases with an equivocal RVVT who were positive by ISTH guidelines did seem to enrich for a positive Staclot® LA 20 assay, potentially reflecting a better sensitivity of the ISTH guidelines for those patients with an LA as compared to the manufacturer's guidelines. Disclosures: No relevant conflicts of interest to declare

Editorial: The immunological role of platelet activation in the pathophysiology of COVID-19

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Dilute Russell viper venom time interpretation and clinical correlation: A two‐year retrospective institutional review

IntroductionThe dilute Russell viper venom time (dRVVT) detects lupus anticoagulant (LA). International Society for Thrombosis and Haemostasis (ISTH) guidelines specify positivity criteria, which differ from the assay manufacturer's criteria.MethodsTwo years of dRVVT testing at our institution were reviewed. For patients with prolonged dRVVT screening times, we evaluated dRVVT results by ISTH and manufacturer's criteria and correlated with the results of other antiphospholipid syndrome (APS) testing (LA-sensitive activated partial thromboplastin time and antiphospholipid antibodies) and with history of thromboembolism and other APS manifestations.ResultsApproximately one-fifth of dRVVTs exhibited a prolonged screening time. Among first prolonged dRVVTs, 35% were positive by both ISTH and manufacturer criteria, 44% met neither criteria, and 20% were equivocal (positive by only ISTH or manufacturer). Positivity by ISTH guidelines alone correlated better with other positive APS tests than manufacturer criteria positivity. Positive dRVVTs by both criteria correlated even more strongly with other positive APS assays. We investigated the likelihood of eventual APS diagnosis depending on the testing indication. No patient tested for LA solely for prolonged screening aPTT was subsequently diagnosed with APS. In patients with thrombosis, prolonged dRVVT clotting time not meeting both ISTH and manufacturer criteria was rarely associated with eventual APS diagnosis.ConclusionWe examined the correlation of dRVVT results with other APS testing and clinical outcomes. Interpretation method impacted how dRVVT results related to other APS testing, and, in limited data, to clinical findings. Patients with prolonged dRVVTs meeting only one set of positivity criteria rarely received an APS diagnosis

Dilute Russell viper venom time interpretation and clinical correlation: A two-year retrospective institutional review.

IntroductionThe dilute Russell viper venom time (dRVVT) detects lupus anticoagulant (LA). International Society for Thrombosis and Haemostasis (ISTH) guidelines specify positivity criteria, which differ from the assay manufacturer's criteria.MethodsTwo years of dRVVT testing at our institution were reviewed. For patients with prolonged dRVVT screening times, we evaluated dRVVT results by ISTH and manufacturer's criteria and correlated with the results of other antiphospholipid syndrome (APS) testing (LA-sensitive activated partial thromboplastin time and antiphospholipid antibodies) and with history of thromboembolism and other APS manifestations.ResultsApproximately one-fifth of dRVVTs exhibited a prolonged screening time. Among first prolonged dRVVTs, 35% were positive by both ISTH and manufacturer criteria, 44% met neither criteria, and 20% were equivocal (positive by only ISTH or manufacturer). Positivity by ISTH guidelines alone correlated better with other positive APS tests than manufacturer criteria positivity. Positive dRVVTs by both criteria correlated even more strongly with other positive APS assays. We investigated the likelihood of eventual APS diagnosis depending on the testing indication. No patient tested for LA solely for prolonged screening aPTT was subsequently diagnosed with APS. In patients with thrombosis, prolonged dRVVT clotting time not meeting both ISTH and manufacturer criteria was rarely associated with eventual APS diagnosis.ConclusionWe examined the correlation of dRVVT results with other APS testing and clinical outcomes. Interpretation method impacted how dRVVT results related to other APS testing, and, in limited data, to clinical findings. Patients with prolonged dRVVTs meeting only one set of positivity criteria rarely received an APS diagnosis

Decreasing blood wastage during ex vivo lung perfusion recovery through utilization of thermal control technology

Background: The Organ Care System (OCS) is a revolutionary ex vivo organ perfusion technology that can potentially expand the organ retrieval range. The OCS Lung device uses packed red blood cells (pRBC) with a proprietary solution. We report the ability to reduce blood waste during this procedure by using a thermal packaging solution in conjunction with the OCS platform. Methods: We retrospectively reviewed all OCS Lung recoveries performed by our recovery team, using pRBCfrom May 2019 to January 2021. Initially, units were stored using passive refrigeration with the Performance cooler at a temperature range of 1-6°C for 4 h. Subsequently, thermal control technology with the ProMed cooler was utilized to maintain the same temperature range for 72 h. Results: Twenty-three recoveries were initiated with 63 pRBC. The Performance cooler was used for 8, while the ProMed cooler for 13. 37.5% of pRBC transported with the Performance cooler was used within the validated time range, while 25.0% were used beyond the validated time range based on clinical judgment. In addition, 37.5% of pRBC transported with the Performance cooler were returned to the institution after canceled recoveries with an estimated loss of $1800; the ProMed cooler had no wastage. Conclusions: This study showed that using an advanced thermal packaging solution facilitates proper storage of pRBC and represents an advancement for extended donor lung preservation. The elimination of blood wastage in this initial study portends ongoing benefits for the limited blood supply and reduced cost.</p