Ashrani, Aneel

The NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease provide strategies for the prevention, diagnosis, and treatment of venous thromboembolism (VTE) in adult patients with cancer. VTE is a common and life-threatening condition in patients with cancer, and its management often requires multidisciplinary efforts. The NCCN panel is comprised of specialists spanning various fields, including cardiology, hematology, medical oncology, internal medicine, interventional radiology, and pharmacology. The content featured in this issue specifically addresses the evaluation and recommended treatment options outlined in the NCCN Guidelines for the diverse subtypes of cancer-associated VTE.

AbstractBackgroundClot based assays used for lupus anticoagulant (LAC) detection are typically interpreted in a qualitative fashion and may not reflect LAC potency. In this cross‐sectional study, we describe a method for quantifying the LAC titer using serial (dependent) two‐fold dilutions in normal pooled plasma.MethodsSerial dilutions of 51 residual plasma samples from 50 patients were tested using the Russell's viper venom screening time (DRVVT) and activated partial thromboplastin screening time (APTT) methodologies. The measured clotting times and the corresponding dilution factors were then used to derive a four‐parameter logistic model. The LAC titer for each patient was interpolated as the sample dilution that corresponds to the upper reference interval limit of the corresponding assay.ResultsCalculated APTT and DRVVT LAC titers displayed a strong linear correlation (R2 = 0.84) between each other, but not with the degree of prolongation of the APTT/DRVVT screening time in the neat undiluted samples. Using data driven partitioning, patients could be grouped into low (<10) or high (≥10) DRVVT LAC titer. There were no significant differences in anticardiolipin (aCL) or anti‐beta 2 glycoprotein 1 (aB2GPI) antibody levels or prevalence of thromboembolic events between low and high LAC titer groups. In contrast, antiphosphatidylserine/prothrombin (aPS/PT) IgM antibody levels, but not IgG, were significantly higher in the high LAC titer group.ConclusionsThe degree of prolongation of the APTT/DRVVT screening time is not correlated with the LAC titer. Only aPS/PT IgM antibodies levels were strongly correlated with the LAC titers. Additional studies are warranted to determine clinical implications of high LAC titers.

AbstractPatients with thrombophilia remain concerned about venous thromboembolism (VTE) risk with COVID‐19 vaccinations. The aim of this study was to examine VTE outcomes in patients with inherited or acquired thrombophilia who were vaccinated for COVID‐19. Vaccinated patients ≥18 years between November 1, 2020 and November 1, 2021 were analyzed using electronic medical records across the Mayo Clinic enterprise. The primary outcome was imaging confirmed acute VTE occurring 90 days before and after the date of the first vaccine dose. Thrombophilia patients were identified through laboratory testing results and ICD‐10 codes. A total of 792 010 patients with at least one COVID‐19 vaccination were identified. Six thousand sixty‐seven of these patients were found to have a thrombophilia, among whom there was a total of 39 VTE events after compared to 51 VTE events before vaccination (0.64% vs. 0.84%, p = .20). In patients with Factor V Leiden or prothrombin gene mutation, VTE occurred in 27 patients before and in 29 patients after vaccination (0.61 vs. 0.65%, p = .79). In patients with antiphospholipid syndrome, VTE occurred in six patients before and four patients after vaccination (0.59% vs. 0.39%, p = .40). No difference was observed in the overall VTE rate when comparing the postvaccination 90 days to the prevaccination 90 days, adjusted hazard ratio 0.81 (95% confidence interval: 0.53–1.23). In this subgroup of COVID‐19 vaccinated patients with thrombophilia, there was no increased risk for acute VTE postvaccination compared to the prevaccination timeframe. These results are consistent with prior studies and should offer additional reassurance to patients with inherited or acquired thrombophilia.

Abstract Objectives Despite more than 40 years of experience performing the Bethesda assay (BA), poor intra- and interlaboratory precision remains the biggest laboratory challenge to date. Methods The BA procedure was modeled using stochastic simulation techniques to determine the precision of the BA up to dilutions of 1:4,096, to estimate the minimum significant relative change at various inhibitor titers, and to understand the laboratory procedural variables that could significantly affect the performance of the BA at high dilutions. Results Selecting the lowest dilution tube with a residual activity closest to 25% for calculating the reported Bethesda titer (BT), using a factor activity assay with a coefficient of variation less than or equal to 7.5% in the range of 15% to 50% factor activity level, performing the factor activity measurement in replicates, and minimizing pipette volumetric error resulted in the lowest imprecision in the reported BT. The factor neutralization kinetics of the inhibitor appear to have little impact on the precision of the assay if the incubation time is greater than 90 minutes. Conclusions This in silico model will assist future laboratory efforts in standardizing the quantification of specific coagulation factor inhibitors and improving the precision of the reported results.

AbstractBackgroundCancer‐associated venous thromboembolism (VTE) carries a high rate of recurrence and death. Guidelines recommend continued anticoagulation therapy as long as active cancer persists. Apixaban 2.5 mg twice daily is the FDA‐approved dose for secondary prevention regardless of VTE causation. Whether this apixaban dose is appropriate for secondary VTE prevention in cancer patients is not clear. The rationale and design of this investigator initiated phase III, multicenter, randomized, double‐blind, trial assessing apixaban 2.5 mg vs 5 mg twice daily for 12 months for the secondary VTE prevention in cancer patients (n = 370) who have completed 6 months (but no more than 12 months) of anticoagulation is provided (NCT03080883).Methods/DesignThe primary study objective is to estimate differences in the combined rate of major plus clinically relevant non‐major bleeding for apixaban 2.5 mg vs 5 mg twice daily. Secondary efficacy outcome is to assess rates of venous or arterial thromboembolism. Participating centers are chosen from the Academic and Community Cancer Research United (ACCRU) consortium.ConclusionWe anticipate these trial results to provide evidence supporting low‐dose apixaban as a safe agent for secondary prevention of cancer‐associated VTE for patients who have already completed 6‐12 months of anticoagulation.