D-dimer, a notable fibrinogen degradation byproduct, becomes elevated in the body’s cascade response to venous thrombosis. This condition prompts an enzymatic breakdown of blood clots and fibrinogen degradation, predominantly mediated by plasmin. Enhanced plasmin activity results in the cleavage of fibrinogen, giving rise to a spectrum of fibrin degradation products. As the breakdown persists, these larger molecules yield progressively smaller elements, including D-dimer, formed through the re-polymerization of fibrinogen monomers [8, 13]. The presence of D-dimer, detectable within two hours following thrombus formation [8], is a critical biomarker for timely clinical intervention. The utilization of the D-dimer assay is now common in diagnosing venous thromboembolism, attesting to its high sensitivity in reflecting acute thrombosis and fibrinolytic activation [9, 14, 15]. Our findings revealed that, following surgery, patients who suffered from flap loss demonstrated a rapid and significant elevation in plasma D-dimer levels on the first day. This insight underscores the promising utility of first-day post-surgical plasma D-dimer levels as an early biomarker for the detection of iliac crest flap thrombosis and the consequent flap loss.

However, the assay’s sensitivity is countered by its limited specificity due to possible D-dimer elevation from other conditions—such as malignancies, aging, hospitalization, inflammatory states, pregnancy, and surgical trauma [10, 11]. The data strongly supports the notion that surgical trauma can precipitate a rise in D-dimer concentrations. Our investigation centered on 143 individuals with uneventful iliac flap procedures, revealing a range of augmentations in plasma D-dimer levels post-surgery. Notably, by the 5th day post-surgery, these levels had plateaued. This stabilization suggests that the sustained physiological stress prompted by the surgery may engage both the coagulation and fibrinolysis mechanisms [16]. Consequently, we have established a positive correlation between postoperative D-dimer levels and the operation time. Additionally, various independent risk factors previously documented, including age, cancer, and gender exacerbate postoperative D-dimer elevation. With advancing age, there is a discernible escalation of pro-thrombotic factors that engender a hypercoagulable state [11, 17]. This phenomenon is augmented by the greater incidence of comorbid conditions in the elderly demographic, many of which are linked to increased plasma D-dimer concentrations [18]. Consequently, in older patients who experience surgical trauma, idiosyncrasies in microcirculation and clotting functions are likely to yield enhanced D-dimer levels throughout the healing period. The intricate relationship between oncology and coagulation is underscored by the ability of cancer cells to secrete a plethora of coagulation factors, which in turn amplify thrombin generation and precipitate a hypercoagulable milieu in patients with cancer. Such a state is conducive to the onset of venous thromboembolism, as reflected in escalated plasma D-dimer levels [19, 20]. Furthermore, studies suggest that women typically exhibit higher concentrations of both coagulation factors and D-dimer than men, hinting at a potentially heightened susceptibility to hypercoagulability. Consequently, female surgical patients may encounter an augmented risk for venous thrombosis, influenced by elevated coagulation factor levels [21]. Therefore, while the D-dimer assay is an invaluable tool in detecting thrombotic phenomena, its interpretation requires careful consideration of the patient’s full clinical picture and corroborative diagnostics to ensure precise diagnosis and appropriate therapeutic strategies.

In light of the myriads of independent risk factors that may elevate post-surgical plasma D-dimer levels, it is imperative to establish a multidimensional analytical model to unravel their respective impacts thoroughly. This incorporates a multivariate logistic regression analysis to scrutinize patient factors correlated with flap loss [16]. Through diligent clinical scrutiny, we selected five pivotal predictors to incorporate into the nomogram, thus enabling intricate risk differentiation. This nomogram, with precise graphical utility, allows for the assessment of individual thrombosis risk in a straightforward manner. Practitioners can establish the score for each variable by drawing a perpendicular line from the respective risk factor value to the score axis, then tallying these to ascertain the total risk score. The risk of flap loss due to venous thrombosis can be easily interpreted by aligning the cumulative score with the total score scale [16, 22]. Our findings reveal that the nomogram affords a commendable accuracy in prognosis, as reflected by the areas under the ROC curves in both training and validation stages. This model serves as a robust instrument for furnishing dependable risk estimates that can significantly inform clinical dialogues, therapeutic choices, and monitoring tactics. Crucially, our model leverages data that are effortlessly accessible within standard clinical procedures, markedly increasing its utility and relevance in real-world settings [22, 23]. This risk-scoring system reveals that individuals undergoing lengthier surgical procedures, those who are older in age, of the female sex, with certain pathological conditions such as SCC, and those registering higher absolute D-dimer figures tend to accumulate a greater risk score. This in turn indicates a higher propensity for a rise in postoperative plasma D-dimer levels, thereby suggesting a correspondingly increased likelihood of thrombotic events. Such a tool is instrumental in identifying patients at greater risk and implementing preventive strategies accordingly.

Several limitations should be acknowledged in this study. Primarily, it relied on retrospective analysis, which inherently introduces potential biases [24]. To minimize confounding bias, we separately analyzed potential influence factors related to changes in D-dimer levels between the non-complication and flap loss groups, such as age, gender, systemic diseases, and preoperative pathological classification. The results showed no statistically significant differences, ensuring that these confounding factors did not impact the exploration of the relationship between D-dimer level changes and flap outcomes. To reduce information bias as much as possible, this study included all patients who underwent vascularized iliac crest flap repair surgery at our hospital within indicated period, thereby avoiding information loss and ensuring an adequate sample size. Secondly, the study’s limitations include the modest sample size, limited to individuals from a single country and ethnicity, which may affect the predictive precision and generalizability of our model across diverse populations. Future research should include prospective, multicenter clinical trials to further validate and refine our proposed predictive approach. Despite these limitations, our study provides valuable insights and lays the foundation for future research on assessing flap loss risk in patients undergoing jaw defect reconstruction with iliac crest flaps, focusing on monitoring post-surgical plasma D-dimer concentrations.

In summary, our study stands at the forefront of introducing postoperative plasma D-dimer levels as a novel prognostic indicator for the possibility of iliac flap loss. Furthermore, we have successfully developed a novel prediction model that incorporates multiple factors to refine the prediction of patients prone to iliac crest flap loss. This avant-garde methodology is designed to bolster patient prognosis and finetune the handling of procedures involving iliac crest flaps, ultimately paving the way for enhanced surgical success rates and patient care. Our findings invite further research and validation to substantiate the clinical utility and broaden the application spectrum of our model.

Baseline level of D-dimer in patients who receive vascularized iliac crest flap transplantation

Upon reviewing the preoperative plasma D-dimer levels in 160 patients undergoing vascularized iliac crest flap procedures for the maxilla (Fig. 2A) and mandible (Fig. 2B), the analysis revealed no substantial correlation with variables such as patient age (Fig. 2C), gender (Fig. 2D), systemic diseases (including hypertension and diabetes) (Fig. 2E), or pathological classifications (Fig. 2F).

Fig. 2

Multidimensional analysis of preoperative D-dimer levels. Maxillary surgery (A) and mandibular surgery (B). The baseline levels are categorized by age (C), gender (D), presence or absence of systemic disease (E) and pathological types (F)

Postoperative alterations of D-dimer levels and their influencing factors in patients without complications

An analysis of the plasma D-dimer levels in a cohort of 143 patients, who manifested no post-surgical complications, uncovered a distinct pattern of fluctuation in these levels. It was noted that following the surgery, D-dimer concentrations ascended on the first and second days, peaking on the latter. A marginal decline was then noted on the third day, with levels rebounding on the fourth, stabilizing at a plateau congruent with first-day measurements. The levelling of D-dimer persisted thereafter. Quantitatively, post-surgical D-dimer levels surged to approximately 4.8 times the preoperative baseline on day one, 7.17 times on day two, and settled back to 3.18 times on day three. The highest elevation was recorded on the second day post-operation (Fig. 3A).

Patients diagnosed with squamous cell carcinoma exhibited a pronounced increment in plasma D-dimer levels, peaking two days post-surgery. Subsequent to a decline that aligned them with the non-complicated cohort on the third day, their levels witnessed further reduction by the fourth day. A resurgence to levels seen in the untroubled group characterized the fifth day. Initial escalation in D-dimer for SCC individuals reached about 7.81 times and 15.53 times above baseline on the first and second days, respectively (Fig. 3B). In contrast, those with ameloblastoma presented a moderate rise in D-dimer levels post-surgery, achieving equivalence with the non-complicated group on day one. A gradual downward trajectory ensued through days two and three, with a fourth-day upturn, before a fifth-day fall-off to levels matching those without complications. The D-dimer levels in ameloblastoma patients were about 3.45 to 4.66 baseline multiples from the first to the third day, surging to roughly 8.31 times the baseline on day four (Fig. 3B). Patients of different pathological types exhibit varying changes in postoperative plasma D-dimer levels.

Individual analysis of factors potentially linked to the escalated post-surgical plasma D-dimer levels revealed a significant correspondence with lesion pathology, with SCC showing notably greater increases compared to ameloblastoma, a difference proven statistically momentous (P < 0.05, Fig. 3 C, D). However, distinctions in D-dimer surges were not significantly related to either gender or systemic disease presence (Fig. 3E-H). A substantial association was established between the rise in D-dimer concentrations and both patient age (P ≤ 0.001, Fig. 3I, J) and the duration of the operation (P < 0.01, Fig. 3K, L).

Fig. 3

Post-op D-dimer level changes in uncomplicated patients. Post-op D-dimer levels (A) in SCC or ameloblastoma patients (B), variations on the first post-op day (C-H), and correlation with age (I, J) and operation time (K, L)

Postoperative alterations in D-dimer levels and their influencing factors in patients with complications

The study examined plasma D-dimer level changes within the first three days following surgery among different patient cohorts: those with an good recovery, those who suffered thrombosis culminating in flap loss (Fig. 4A, left side), and those who experienced a rejection of the titanium plate (Fig. 4A, right side). Preoperative baseline D-dimer readings were relatively consistent across the groups and indicated minor variations, with the good postoperative group (normal) showing levels at 0.47 mg/L, the thrombosis group (flap loss) at 0.27 mg/L, and the titanium plate rejection group at 0.40 mg/L (Fig. 4B). Additionally, there were no statistically relevant age differences among the patient cohorts (Fig. 4C). The data revealed that on the first postoperative day, patients afflicted with thrombosis that led to flap loss experienced a pronounced elevation in plasma D-dimer levels, markedly higher than those seen in patients who had a smooth postoperative course. These heightened levels subsided on the second and third days, eventually aligning with the levels observed in the complication-free group by the third day. Conversely, patients who rejected titanium plates demonstrated D-dimer levels and trajectories over the three-day post-surgery period that mirrored those observed in patients who had uneventful recoveries (Fig. 4D, F).

A meticulous analysis was conducted focusing on the first postoperative day’s plasma D-dimer levels among the three patient categories. The measurements from those patients who suffered titanium plate rejection (1.81 mg/L, 4.52 times above baseline) were found to be comparable to those of the patients with an uneventful postoperative trajectory (2.29 mg/L, 3.96 times above baseline). However, the thrombosis group, which faced complications resulting in flap loss, displayed significantly elevated D-dimer values (3.75 mg/L, 13.84 times above baseline). These differences reached a level of statistical significance (P < 0.05, Fig. 4E, G).

Fig. 4

D-dimer analysis in normal, flap loss and titanium plate rejection patients. (A) Imaging and clinical manifestations, (B) baseline D-dimer, (C) age distribution, (D, F) absolute and relative post-op D-dimer, (E, G) absolute and relative day-one post-op D-dimer

Predicting complications of vascularized iliac crest flap transplantation through a multifactor prediction model

While elevated plasma D-dimer levels show correlation with flap loss, it is essential to recognize that this association is influenced by various factors. Therefore, we conducted further multivariate logistic regression analysis to assess multiple independent risk factors, including surgical time, age, pathological type, absolute and relative D-dimer levels, and gender. The surgical time corresponds with a 0.90-fold rise in thrombosis risk (OR = 0.90, 95% CI: 0.22–1. 37, p = 0.016); age associates with a 0.01-fold increase in risk of thrombosis (OR = 0.01, 95% CI: -0.08–0.05, p = 0.667); the pathological type contributes a 0.30-fold increase (OR = 0.30, 95% CI: -0.15–0.75 p = 0.175); gender has a 2.79-fold increased risk of thrombosis (OR = 2.79, 95% CI: 0.84–5.33, p = 0.011); the absolute D-dimer value predicts a 0.15-fold increase in thrombosis risk (OR = 0.15, 95% CI: -0.18–0.45, p = 0. 289); and the relative D-dimer value shows a -0.02-fold increased risk of thrombosis (OR = -0.02, 95% CI: -0.13–0.07, p = 0.693, Fig. 5A). A comprehensive model encapsulating these independent risk factors was formulated, yielding a nomogram for clinical use (Fig. 5B). The performance of the nomogram was rigorously evaluated with two distinct sets of patient data—the training and the validation cohorts—reaching a diagnostic reliability represented by areas under the ROC curve (AUC = 0.630, 0.600, 95% confidence interval: 0.452–0.807, 0.243–0.957), respectively (Fig. 5C).

Fig. 5

Multifactor prediction model for post-op D-dimer levels. (A) Multivariate regression analysis of risk factors affecting post-op D-dimer levels, (B) integrated risk factors for prediction, (C) ROC curves for D-dimer prediction in training and validation sets