Laboratory Assessment of the Anticoagulant Activity of Direct Oral Anticoagulants: A Systematic Review.

BACKGROUND: Direct oral anticoagulants (DOACs) are the treatment of choice for most patients with atrial fibrillation and/or noncancer-associated venous thromboembolic disease. Although routine monitoring of these agents is not required, assessment of anticoagulant effect may be desirable in special situations. The objective of this review was to summarize systematically evidence regarding laboratory assessment of the anticoagulant effects of dabigatran, rivaroxaban, apixaban, and edoxaban. METHODS: PubMed, Embase, and Web of Science were searched for studies reporting relationships between drug levels and coagulation assay results. RESULTS: We identified 109 eligible studies: 35 for dabigatran, 50 for rivaroxaban, 11 for apixaban, and 13 for edoxaban. The performance of standard anticoagulation tests varied across DOACs and reagents; most assays, showed insufficient correlation to provide a reliable assessment of DOAC effects. Dilute thrombin time (TT) assays demonstrated linear correlation (r2 = 0.67-0.99) across a range of expected concentrations of dabigatran, as did ecarin-based assays. Calibrated anti-Xa assays demonstrated linear correlation (r2 = 0.78-1.00) across a wide range of concentrations for rivaroxaban, apixaban, and edoxaban. CONCLUSIONS: An ideal test, offering both accuracy and precision for measurement of any DOAC is not widely available. We recommend a dilute TT or ecarin-based assay for assessment of the anticoagulant effect of dabigatran and anti-Xa assays with drug-specific calibrators for direct Xa inhibitors. In the absence of these tests, TT or APTT is recommended over PT/INR for assessment of dabigatran, and PT/INR is recommended over APTT for detection of factor Xa inhibitors. Time since last dose, the presence or absence of drug interactions, and renal and hepatic function should impact clinical estimates of anticoagulant effect in a patient for whom laboratory test results are not available.

Measurement and reversal of the direct oral anticoagulants.

Direct oral anticoagulants (DOACs) offer noninferior efficacy and improved safety compared to vitamin K antagonists (VKAs) for the prevention and treatment of venous thromboembolism and for the prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. Unlike VKAs, DOACs do not require routine laboratory monitoring of anticoagulant effect and dose adjustment. In certain situations, however, laboratory assessment of anticoagulant effect may be desirable. Here we review the utility of currently available assays for assessment of DOAC effect and recommend an optimal assessment strategy for each drug, including calibrated dilute thrombin time or ecarin-based assays for dabigatran and calibrated anti-Xa activity assays for the factor Xa inhibitors. We also discuss reversal strategies, both specific and nonspecific, for each drug, including the preferential use of idarucizumab for the reversal of dabigatran and two agents, andexanet and ciraparantag, currently under development for the reversal of rivaroxaban, apixaban, and edoxaban.

The impact of ruxolitinib on thrombosis in patients with polycythemia vera and myelofibrosis: a meta-analysis.

The Food and Drug Administration approval of ruxolitinib for treatment of myelofibrosis and polycythemia vera has changed the management of patients with myeloproliferative neoplasms. Yet the impact of this therapy on risk of thrombosis, a major cause of morbidity and mortality among these patients, remains unknown. The aim of this study was to evaluate the impact of ruxolitinib on the risk of thrombosis among patients with polycythemia vera or myelofibrosis. Following identification of randomized controlled trials comparing ruxolitinib to standard care or placebo, rates of thrombosis, including venous and arterial thrombosis, were analyzed using fixed effects models. Rates of thrombosis were significantly lower among patients treated with ruxolitinib [risk ratio 0.45, 95% confidence interval (CI) 0.23-0.88]. Subgroup analysis of venous and arterial thrombosis demonstrated similar risk ratios, which did not reach statistical significance (risk ratio 0.46, 95% CI 0.14-1.48 and RR 0.42, 95% CI 0.18-1.01, respectively). In conclusion, our analysis suggests that JAK2 inhibition with ruxolitinib decreases the risk of arterial and/or venous thrombosis in patients with polycythemia vera or myelofibrosis. These findings will require confirmation in a prospective study.

Use of a computer-based provider order entry (CPOE) intervention to optimize laboratory testing in patients with suspected heparin-induced thrombocytopenia.

INTRODUCTION: Heparin-induced thrombocytopenia (HIT) is a rare but frequently considered diagnosis in hospitalized patients. Despite the availability of clinical prediction tools, HIT is often over-diagnosed and patients can be subjected to unnecessary and expensive testing. METHODS: A decision-support tool requiring providers to calculate the 4Ts (HIT risk) score prior to ordering laboratory-based tests for anti-PF4/heparin antibody enzyme-linked immunosorbent assay (ELISA) testing was implemented at our institution in January 2014. Charts of adult patients who underwent ELISA or serotonin release assay (SRA) testing during the 8-month time periods prior to and following this intervention were reviewed and 4Ts scores at the time of ELISA or SRA testing were calculated. RESULTS: A total of 443 ELISA and SRA tests were sent for 411 patients during the time periods studied. We observed a significant decrease from 43 tests/month before to 22 tests/month (p < 0.001) after the intervention. A total of 337 charts were reviewed. We observed a trend toward decrease in the proportion of tested patients with low 4Ts scores (66% vs 56%, p = 0.069), as well as an increase in the average 4Ts score of tested patients (3.0 vs 3.4, p = 0.010) following our intervention. DISCUSSION: Over-testing and treatment for HIT are frequent and potentially harmful occurrences in hospitalized patients. Our study demonstrates that a clinical decision support tool embedded within the electronic ordering process can decrease unnecessary testing for HIT.

Changes in spirituality and quality of life in patients undergoing radiation therapy.

PURPOSE: Investigations into the role of spirituality in cancer confirm the association of good spiritual well-being with many positive outcomes. This study aimed to evaluate potential changes in spirituality over the course of radiation therapy (RT). PATIENTS AND MATERIALS: The Functional Assessment of Chronic Illness Therapy-Spiritual questionnaire measuring spiritual well-being and quality of life (QOL) was administered to adult patients undergoing RT. Scores were compared using student t tests and chi-square analysis. RESULTS: Despite statistically significant declines in QOL measures such as physical well-being (P < .001) and overall well-being (P < .001), no significant changes were noted in spirituality for all comers. A significant increase in the Sp-12 spirituality measure (P = .001) was noted in patients with breast cancer, independent of age, gender, and purpose of treatment. Sp-12 scores were positively correlated with overall QOL scores (P < .001).

Using complications associated with postmastectomy radiation and immediate breast reconstruction to improve surgical decision making.

OBJECTIVES: To identify factors independently associated with surgical complications in oncologic and reconstructive surgery and to examine sentinel lymph node (SLN) biopsy data, along with variables that are typically known prior to definitive resection, for their ability to impact the prediction of need for postmastectomy irradiation (PMRT). DESIGN: Retrospective review. SETTING: University hospital. PATIENTS: Mastectomy patients with stage I to III breast cancer treated in 2000 to 2008. MAIN OUTCOME MEASURES: Complication rates of oncologic and reconstructive surgery requiring reoperation and clinicopathologic variables that independently predict complications and/or PMRT administration by multivariate analysis. RESULTS: Among 100 of 302 mastectomy patients who underwent PMRT, complications occurred in 44% who underwent immediate breast reconstruction (IBR) and 7% who did not (P < .001). Postmastectomy irradiation independently predicted the occurrence of a complication (odds ratio, 3.3; P < .001). Implants were removed in 31% of patients who underwent PMRT and 6% of patients who did not (P = .005). Three percent of patients with T2 or smaller tumors and zero positive SLN required PMRT. Among those with T2 tumors, 49% with a positive axilla lymph node underwent PMRT. Independent predictors of PMRT need were T2 vs T1 tumors, positive axillary lymph node status, and the number of positive SLNs, with odds ratios of 5.8 (P < .001), 14.5 (P < .001), and 2.1 (P = .001), respectively. CONCLUSIONS: Postmastectomy irradiation was associated with a high rate of surgical complications and implant loss among patients who underwent IBR. Determining the number of positive SLNs prior to definitive resection and reconstructive operations may reduce complications and implant loss by guiding surgical decision making. Patients with a negative SLN are unlikely to require PMRT. Those with positive SLN(s) are high-risk IBR candidates with a quantifiable PMRT risk.