Biomarkers Associated with Thrombosis in Patients with Peripherally Inserted Central Catheter: A Systematic Review and Meta-Analysis

Abstract

Background: The measurement and identification of plasma biomarkers can support the estimation of risk and diagnosis of deep vein thrombosis (DVT) associated with the use of a peripherally inserted central catheter (PICC).

Objectives: This systematic review and meta-analysis aimed to identify the association between the levels of potential biomarkers that reflect the activation of the blood system, long-term vascular complications, inflammatory system, and the occurrence of PICC-related DVT.

Methods: Seven electronic databases (Embase, Web of Science, Medline, Scopus, Cinahl, Cochrane Central Register of Controlled Trials, and ERIC) were searched to identify literature published until December 2022. Studies were required to report: (I) adult and pediatric patients, outpatient or admitted to clinical, surgical, or ICU with PICC; (II) patients with PICC-related DVT and patients without PICC-related DVT as a comparator; and (III) at least one biomarker available. The Newcastle-Ottawa Scale was used to evaluate the quality of the studies. Study precision was evaluated by using a funnel plot for platelets level. We provided a narrative synthesis and meta-analysis of the findings on the biomarkers' outcomes of the studies. We pooled the results using random effects meta-analysis. The meta-analysis was conducted using Review Manager software v5.4. This systematic review is registered in PROSPERO (CRD42018108871).

Results: Of the 3564 studies identified (after duplication removal), 28 were included. PICC-related DVT was associated with higher D-dimers (0.37 μg/mL, 95% CI 0.02, 0.72; p = 0.04, I² = 92%; p for heterogeneity < 0.00001) and with higher platelets (8.76 × 10⁹/L, 95% CI 1.62, 15.91; p = 0.02, I² = 41%; p for heterogeneity = 0.06).

Conclusions: High levels of D-dimer and platelet were associated with DVT in patients with PICC. However, biomarkers such as APTT, fibrinogen, FDP, glucose, hemoglobin, glycated hemoglobin, INR, prothrombin time, prothrombin fragment 1.2, the thrombin-antithrombin complex, and WBC were not related to the development of DVT associated with PICC.

Keywords: catheterization; peripheral; systematic review; thrombosis.

Figure 1

PRISMA 2020 flow diagram for new systematic reviews, which included searches of databases and registers only.

Figure 2

Forest plot. (A) D-dimer [3,8,13,17,18,21,34,36]; (B) platelets [1,3,8,13,14,15,16,18,19,21,22,34,35,36]; (C) activated partial thromboplastin time [8,13,18,21]; (D) fibrinogen [3,8,13,20,21,36].

Figure 3

Forest plot. (A) Fibrinogen degradation product [3,8,13,20]; (B) international normalized ratio [1,8,13,16]; (C) prothrombin time [8,13,21,35]; (D) white blood cell [1,3,13,15,18,19,21,22,34,35].