Dynamic assessment of venous thromboembolism risk in patients with cancer by longitudinal D‐Dimer analysis: A prospective study

Abstract

Background Venous thromboembolism (VTE) is a frequent complication of cancer. Elevated D‐dimer is associated with an increased risk of cancer‐associated VTE. Whether changes in D‐dimer over time harbor additional prognostic information that may be exploited clinically for dynamic prediction of VTE is unclear. Objectives To explore the potential role of longitudinal D‐dimer trajectories for personalized prediction of cancer‐associated VTE. Patients/Methods A total of 167 patients with active malignancy were prospectively enrolled (gastrointestinal: n = 59 [35%], lung: n = 56 [34%], brain: n = 50 [30%], others: n = 2 [1%]; metastatic disease: n = 74 [44%]). D‐dimer (median = 0.8 µg/mL [25th‐75th percentile: 0.4‐2.0]) was measured at baseline and during 602 monthly follow‐up visits. Joint models of longitudinal and time‐to‐event data were implemented to quantify the association between D‐dimer trajectories and prospective risk of VTE. Results VTE occurred in 20 patients (250‐day VTE risk = 12.1%, 95% confidence interval [CI], 7.8‐18.5). D‐dimer increased by 34%/month (0.47 µg/mL/month, 95% CI, 0.22‐0.72, P < .0001) in patients who developed VTE, but remained constant in patients who did not develop VTE (change/month = −0.06 µg/mL, 95% CI, −0.15 to 0.02, P = .121). In joint modeling, a doubling of the D‐dimer trajectory was associated with a 2.8‐fold increase in the risk of VTE (hazard ratio = 2.78, 95% CI, 1.69‐4.58, P < .0001). This finding was independent of established VTE risk factors. Highly personalized, dynamic predictions of VTE conditional on individual patients’ D‐dimer trajectories could be obtained. Conclusions D‐dimer increases before the onset of cancer‐associated VTE, but remains constant over time in patients without VTE. This study represents proof‐of‐concept that longitudinal trajectories of D‐Dimer may advance the personalized assessment of VTE risk in the oncologic setting.

C-Reactive Protein (CRP) Levels in Immune Checkpoint Inhibitor Response and Progression in Advanced Non-Small Cell Lung Cancer: A Bi-Center Study

“…In the present study, we applied the recently developed joint model analysis approach, which represents a powerful biostatistical tool for assessing the association between a longitudinal biomarker trajectory and a time-to-event outcome such as disease progression. Based on the incorporation of longitudinal biomarker trajectories within each patient joint models allow to provide individualized outcome predictions at each timepoint a new measurement of the respective marker is entered into the model [ 31 , 41 , 42 , 43 ]. For this purpose, we analyzed 1150 CRP measurements obtained from 90 patients during anti-PD(L)-1 treatment.…”

Course of D-Dimer and C-Reactive Protein Levels in Survivors and Nonsurvivors with COVID-19 Pneumonia: A Retrospective Analysis of 577 Patients

“… 12 13 14 Therefore, the in-hospital course of D-dimer and other coagulation parameters may reflect disease activity in COVID-19 patients. Indeed, the velocity of D-dimer increase may predict VTE in patients with cancer, 15 whereas elevated D-dimer levels during anticoagulation for VTE or after discontinuation may predict recurrence. 16 Our finding further supports the notion that the dynamics of coagulation and inflammatory biomarkers may be considered for integration in clinical risk-assessment models for the management of patients with COVID-19 8 and for use as surrogate outcomes in the early stages of the clinical development of pharmaceuticals for patients with COVID-19, especially in patients with no initial biomarker elevation.…”

Dynamics of D‐dimer in non‐small cell lung cancer patients receiving radical surgery and its association with postoperative venous thromboembolism

“…16 However, it seems irresponsible to omit the fluctuations of D-dimer levels after surgery. Actually, increased attention is being paid to long-term D-dimer level changes and the relationship with VTE, 36 and in our experience, a more meticulous tracking of D-dimer levels can depict a more detailed hematological profile, and can be achieved by following the level changes closely in adjacent days instead of at subsequent relatively longer intervals. Given the purpose of cutting healthcare costs and future clinical practicability, we measured D-dimer concentration before surgery and the first, third, and fifth day after surgery.…”