Risk Stratification for Supratherapeutic Peak Anti-Xa Levels in Adult Patients on Therapeutic Enoxaparin.

BACKGROUND: The American Society of Hematology Guidelines for the management of venous thromboembolism recommend against the use of anti-Xa monitoring for assessing enoxaparin dosing based on a low level of evidence associating supratherapeutic levels with an increased risk of bleeding. However, institutions still utilize anti-Xa levels in select patient populations with altered volume of distribution and/or excretion to monitor and adjust therapy. OBJECTIVE: The primary objective of this study was to identify risk factors associated with supratherapeutic peak anti-Xa levels (≥1.10 IU/mL) for patients receiving therapeutic enoxaparin. METHODS: This was a retrospective single-center study performed at an academic tertiary care hospital. Patients who received enoxaparin at 1 mg/kg twice daily and peak anti-Xa monitoring were separated into supratherapeutic and therapeutic/subtherapeutic cohorts. RESULTS: A total of 436 patients were screened, and 215 were included, with a mean age of 62 years. There were 108 in the therapeutic/subtherapeutic cohort and 107 in the supratherapeutic cohort. Acute kidney injury (AKI), body mass index (BMI), weight, female sex, intensive care unit (ICU) service, Sequential Organ Failure Assessment (SOFA) score ≥4, and creatinine clearance at the time of peak anti-Xa level collection were associated with supratherapeutic anti-Xa levels in univariate models. Adjusted logistic regression models were created and identified BMI in the 30 to 34.9 kg/m2 (odds ratio [OR] 4.35; 95% confidence interval [CI] 1.70-11.13, P < 0.005) and ≥35 kg/m2 (OR 6.75; 95% CI 3.05-14.94, P < 0.005) and AKI (OR 2.62; 95% CI 1.04-6.62, P = 0.042) as significant risk factors for supratherapeutic anti-Xa levels. CONCLUSION AND RELEVANCE: Our study identified BMI ≥ 30 kg/m2, AKI, female sex, ICU service, SOFA score ≥4, and creatinine clearance as risk factors for supratherapeutic anti-Xa levels in patients receiving 1 mg/kg twice daily dosing of enoxaparin. Further research should be done to provide evidence for the association between anti-Xa levels and bleeding risk.

Safety of venetoclax rapid dose escalation in CLL patients previously treated with B-cell receptor signaling antagonists.

Venetoclax has efficacy in patients relapsing after B-cell receptor pathway inhibitors (BCRis); however, because of the risk of tumor lysis syndrome (TLS), a 5-week dose ramp-up is required to attain the target dose. Patients relapsing after BCRis frequently have proliferative disease, requiring a faster time to target dose than this scheme allows. This limitation can potentially be overcome with rapid dose escalation (RDE). We analyzed 33 chronic lymphocytic leukemia patients who underwent venetoclax RDE after prior BTKi treatment. Median time to target dose was 9 days. Seventeen patients (52%) developed laboratory TLS, and 5 (15%) developed clinical TLS, all as a result of renal injury. TLS was seen in more patients with a higher initial tumor burden. TLS occurred at all dose levels, with most episodes occurring at the 50- and 100-mg doses. Most interestingly, a decrease in absolute lymphocyte count (ALC) from pre-venetoclax dose to 24 hours post-venetoclax dose of 10 × 103/µL was associated with an increased risk of TLS (hazard ratio, 1.32; P = .02), after controlling for venetoclax dose level. Venetoclax RDE with close in-hospital monitoring at experienced centers and in select patients is feasible. The rapidity with which ALC drops helps predict TLS and could help guide dose-escalation decisions.