Postoperative deep venous thrombosis (DVT) is a critical complication following non-cardiac surgery, with an incidence ranging from 3.5 to 16% depending on surgical type and patient risk profiles (1–3). It remains a leading cause of prolonged hospitalization, pulmonary embolism, and mortality. Current risk stratification tools, such as the Caprini score, primarily rely on clinical variables and lack integration with objective biomarkers, limiting their precision.

Albumin directly regulates coagulation homeostasis by suppressing platelet activation and fibrin polymerization at physiological levels (4–6). It was reported that low levels of albumin induced experimentally verified hypercoagulability in animal studies (7). Thus, there might be a direct causal link between low level of albumin and the thrombotic risk.

Multiple biomarkers, especially D-dimer, are reported to be related to thrombotic risk, while D-dimer is merely a downstream fibrin degradation product reflecting clot turnover, and can easily be elevated by inflammation/tissue injury before surgery (8). Clinical studies revealed conflicting results regarding the role of preoperative D-dimer in the prediction of postoperative DVT (9–14), while preoperative hypoalbuminemia was an independent risk factor for postoperative DVT in orthopedic, colorectal, and neurosurgical patients (9–12). Albumin levels are stable and routinely measured before surgery, which makes albumin uniquely suited for preoperative risk stratification, as it reflects a patient’s baseline physiological state rather than acute perturbations. But the threshold of preoperative albumin to predict postoperative DVT is still unclear, which makes it difficult to prevent postoperative DVT precisely by regulating preoperative albumin level.

Thus, in this retrospective cohort study, we aimed to characterize the relationship (linear vs. non-linear) between preoperative albumin levels and postoperative DVT in patients undergoing elective non-cardiac surgery; identify critical albumin thresholds for stratifying postoperative DVT risk.

A total of 3513 patients met the inclusion criteria, among these, 753 patients did not receive Doppler ultrasound examination before or after surgery; 83 patients lacked complete Doppler ultrasound results in their medical records although undergoing ultrasound examination; 305 patients underwent emergency surgery; 6 patients had preexisting DVT; and 340 patients received local anesthesia (administered by surgeon). After these exclusions, 2026 patients were included in the final statistical analysis (Figure 1). All patients had a Caprini score ≤3 and received mechanical prophylaxis. Postoperative DVT occurred in 3.55% (n = 72) of the cohort. The basic characteristics in all participants, DVT cohort, and non-DVT cohort were summarized in Table 1.

Linear logistic regression demonstrated a significant dose-response relationship between preoperative albumin levels and postoperative DVT incidence (Figure 2a), and RCS analysis confirmed the linearity of this association (Figure 2b), and P = 0.098 for non-linearity test via Box-Tidwell procedure. Each 1 g/L decrement in preoperative albumin level increased the risk of postoperative DVT by 8.8% (adjusted OR (aOR): 1.088, 95%CI: 1.028–1.152) when analyzed as a continuous variable. The optimal preoperative albumin cut-off value was 41.9 g/L to predict the risk of postoperative DVT (aOR:2.169, 95%CI:1.144–4.115), and the AUC was 0.885 (Figure 3). Five independent risk factors were identified for postoperative DVT from multivariate logistic regression: preoperative albumin, age, gender, surgical duration, and Caprini score (VTE risk stratification) (VIF was between1.160 and 1.576) (Table 2). The AUC was 0.885–0.890 (incorporating preoperative albumin as a categorized or a continuous variable). The10-fold cross internal validation results showed that the AUC was 0.840–0.933, the Brier score was 0.012–0.056 (Supplementary Table 2).

Subgroup analysis revealed that elderly male patients, underwent general anesthesia combined with local anesthesia, or surgical duration >2 h were more likely to develop postoperative DVT when preoperative albumin level was below the cut-off value (Table 3).

Interaction analysis demonstrated no significant effect modification between preoperative albumin (below 41.9 g/L) and D-dimer (>0.5 mg/L) (P = 0.935).

In post hoc sensitivity analysis, patients with extreme preoperative albumin levels (<20 g/L or >50 g/L) were excluded. Each 1 g/L decrement of preoperative albumin level increased DVT risk by 8.9% (aOR:1.089, 95%CI: 1.029–1.152). Preoperative albumin below the cut-off value predicted postoperative DVT with an aOR of 2.083 (95%CI: 1.100–3.937).

In this study, preoperative albumin levels demonstrated a linear correlation with postoperative DVT risk in non-cardiac surgery patients, a preoperative albumin level < 41.9 g/L served as a critical threshold to predict postoperative DVT.

Physiologically, albumin within normal range inhibits platelet aggregation and enhances neutralization of coagulation factor Xa, thereby exerting anticoagulation effects (4, 15). An in vitro study showed that hypoalbuminemia promoted primary hemostasis, accelerates platelet aggregation, and strengthens clot formation (7), suggesting a potential mechanism for hypercoagulability. This aligns with clinical observations linking hypoalbuminemia to elevated DVT risk and mortality in cancer patients (16, 17). Several clinical studies identified preoperative hypoalbuminemia as an independent risk factor for postoperative DVT (9–12), but conflicting results exist (13). In which, elderly patients underwent hip arthroplasty, and the preoperative albumin levels were low in both groups (DVT and non-DVT groups), so the role of preoperative albumin in DVT may depend on patients, surgical type, and preoperative nutrition status.

Our findings confirmed that preoperative albumin was an independent predictor of postoperative DVT in non-cardiac surgery, with a high AUC value of 0.778 to predict postoperative DVT when below 41.9 g/L; and with high values of AUC when combined with the other 4 independent risk factors (0.885–0.890 as a categorized or a continuous variable), internal validation results also supporting its potential as a biomarker for DVT risk assessment.

Contrary to reports of a non-linear relationship between albumin and preoperative DVT in geriatric patients with hip fractures (18), our study exhibited a linear dose-response relationship. Each 1 g/L increase in preoperative albumin reduced postoperative DVT risk by 8.8%, the cut-off value was 41.9 g/L, underscoring the clinical relevance of correcting preoperative hypoalbuminemia as a targeted preventive strategy.

The role of D-dimer remains contentious; some studies have identified it as an independent predictor of postoperative DVT (9, 10, 13, 14), while others have not (11, 12). In our cohort, D-dimer was not found to be an independent risk factor, possibly due to differences in patient selection across various research studies. And subgroup analysis also revealed that elderly male patients, patients with surgical duration >2 h, or general anesthesia combined with regional anesthesia were more likely to develop postoperative DVT when preoperative albumin level was below the cut-off value. As aging could increase blood viscosity and endothelial dysfunction, elevate clotting factors, and reduce antithrombin (19). The interaction analysis in our study revealed no statistically significant effect modification between preoperative albumin levels (dichotomized at < 41.9 g/L) and elevated D-dimer levels (>0.5 mg/L) on postoperative DVT. Their contributions appear to be largely independent. Future studies with larger samples or different analytical approaches could further explore potential synergies.

There are some limitations of this study. First, this is a single-center retrospective study, the results might be affected by geographical location and medical level, and should be cautiously extrapolated to other institutions; second, some other factors such as postoperative nutrition and mobility might influence the postoperative albumin fluctuations, which were not recorded and retrieved, but might confound postoperative DVT risk. Despite these constraints, our findings highlighted preoperative albumin as a predictive biomarker and intervention target. However, the study population did not include individuals at critical thrombotic risk. Consequently, the model and conclusions are not applicable for guiding preventive decisions in extremely high-risk thrombosis patients, who should continue to follow existing intensified prevention guidelines based on the Caprini score. Despite this limitation in broad applicability, this research focuses on a large and clinically challenging group (intermediate-to-low risk patients). Within this cohort, identifying individuals with thrombotic risk exceeding Caprini score predictions (e.g., patients with Caprini score 2 but low albumin) holds significant clinical importance. For such patients, intensification of prophylactic measures may be warranted, though future studies are required to validate this approach.

In conclusion, preoperative albumin (the cutoff is 41.9 g/L) is may help stratify DVT risk in intermediate-risk non-cardiac surgical patients, though prospective validation is needed given study limitations.