European Journal of Cardiovascular Medicine

Head and neck cancers constitute a significant global health burden, representing approximately 4-5% of all malignancies worldwide, with a higher prevalence in developing countries such as India [1]. Surgical resection remains the cornerstone of curative treatment for locally advanced head and neck cancers. Reconstruction following extensive resection often requires microsurgical free flap procedures to restore both form and function, improving patient quality of life and oncological outcomes [2,3]. Despite advances in microsurgical techniques and perioperative care, free flap surgeries are associated with considerable morbidity, one of the most significant being venous thromboembolism (VTE).

Venous thromboembolism, encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE), is a potentially life-threatening complication in oncological surgery patients [4]. The risk of VTE in cancer patients is multifactorial and significantly higher compared to the general population due to tumor-related hypercoagulability, immobility, endothelial injury, and systemic inflammation [5]. Surgical stress and prolonged anesthesia further increase thrombogenic risk, making postoperative surveillance for VTE crucial, especially in high-risk procedures such as free flap reconstruction in head and neck oncology [6].

Free flap reconstruction involves harvesting vascularized tissue from donor sites and microvascular anastomosis at the recipient site. The intricacy of these procedures, prolonged operative times, and postoperative immobilization create a favorable milieu for thrombus formation [7]. Moreover, patients undergoing head and neck cancer surgeries often have additional risk factors for VTE, including advanced age, malnutrition, smoking, and concurrent chemoradiation, compounding the thrombotic risk [8]. Despite these recognized risks, data on the incidence and risk factors of VTE in free flap reconstruction specifically in head and neck cancer patients are sparse, particularly in the Indian subcontinent.

In India, the burden of head and neck cancers is disproportionately high, accounting for nearly 30% of all cancer cases, largely attributed to tobacco use and related etiological factors [9]. However, there is a paucity of institution-based studies evaluating the incidence of VTE in patients undergoing complex reconstructive surgeries such as free flap procedures. The lack of robust data limits the development of standardized protocols for thromboprophylaxis in this subset of patients, potentially leading to under-recognition and suboptimal management of VTE. Furthermore, the applicability of Western guidelines on VTE prevention in the Indian context remains uncertain due to differences in patient demographics, healthcare infrastructure, and genetic predispositions [10].

Recognizing the critical need for localized evidence, this tertiary institution-based study aims to assess the incidence of venous thromboembolism in patients undergoing free flap reconstruction following head and neck cancer surgery in Eastern India. The study will also explore potential patient-related and perioperative risk factors associated with VTE, providing valuable insights to optimize perioperative care. Understanding the incidence and determinants of VTE in this context is imperative to develop effective prophylactic strategies and reduce morbidity and mortality associated with thromboembolic events.

Study design: Prospective, observational study.

Duration of the study: 1 year (January 2024 – January 2025)

Study Place: Department of Head & Neck Surgery, IPGMER and SSKM Hospital, Kolkata, West Bengal, India.

Sample Size: 50 patients undergoing free flap reconstruction after head and neck cancer surgery.

Inclusion Criteria:

• Age ≥ 18 years.
• Histologically confirmed head and neck malignancy.
• Undergoing free flap reconstruction post-tumor resection.
• Provided written informed consent

Exclusion Criteria:

• History of venous thromboembolism (VTE) or thrombophilia.
• On long-term anticoagulation therapy prior to surgery.
• Incomplete follow-up or postoperative care at a different facility.

Study variable: Age, Sex, BMI, Comorbidities, Smoking status, Alcohol use, Previous history of VTE, Use of anticoagulants or antiplatelet agents, ECOG performance status, Site of the primary tumor, TNM staging, Histological type and grade, Prior chemotherapy or radiotherapy, Type of free flap used, Duration of surgery, Intraoperative blood loss, Intraoperative transfusion, Use of microvascular anastomosis, Number of venous and arterial anastomoses, Use of DVT prophylaxis, Postoperative mobility, Duration of ICU stay, Postoperative complications, Hospital stay duration, Postoperative anticoagulation therapy, Time to diagnosis of VTE.

Caprini Score: The Caprini Score is a widely used risk assessment model designed to stratify patients based on their risk of developing venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE). Developed by Dr. Joseph A. Caprini, this scoring system assigns weighted points to various patient-specific risk factors such as age, body mass index, history of thrombosis, malignancy, recent surgery, immobility, and other clinical conditions. The cumulative score helps guide prophylactic measures, particularly in surgical and hospitalized patients, to reduce the incidence of VTE. It is endorsed by several clinical guidelines for its effectiveness in tailoring thromboprophylaxis according to individual risk profiles.

Khorana Score: The Khorana Score is a validated clinical risk assessment tool used to predict the risk of venous thromboembolism (VTE) in patients with cancer who are undergoing chemotherapy. Developed by Dr. Alok A. Khorana, this scoring system assigns points based on specific clinical and laboratory parameters, including the type of cancer (e.g., stomach or pancreatic cancer), platelet count, hemoglobin level or use of erythropoiesis-stimulating agents, leukocyte count, and body mass index (BMI ≥35 kg/m²). Patients are categorized into low, intermediate, or high risk of VTE based on their total score. The Khorana Score is widely used in oncology practice to guide decisions regarding prophylactic anticoagulation in ambulatory cancer patients.

Padua Prediction Score (PPS): This score is validated for medical inpatients and considers factors like age, previous VTE, immobility, and certain medical conditions. It's used to identify patients at high risk who may benefit from prophylactic anticoagulation.

Vienna CATS Score: This score includes factors like D-dimer levels, which can be particularly relevant in assessing VTE risk in cancer patients.

PROTECHT Score: This score includes factors like chemotherapy type and can be useful for assessing VTE risk in patients undergoing cancer treatment.

Caprini Score with Modifications: The Caprini score, while widely used, might be modified or combined with other factors to better predict VTE in specific populations like those undergoing head and neck reconstruction.

Individualized Risk Assessment: In addition to established scores, a thorough assessment of individual patient factors, including medical history, surgical complexity, and specific risk factors for VTE, is crucial in determining the overall risk.

Statistical Analysis: Data were entered and analyzed using IBM SPSS Statistics version XX (IBM Corp., Armonk, NY). Descriptive statistics were used to summarize patient demographics and clinical characteristics. Continuous variables were expressed as mean ± standard deviation or median (interquartile range) depending on normality, while categorical variables were presented as frequencies and percentages. Comparisons between patients with and without VTE were performed using the independent t-test or Mann-Whitney U test for continuous variables, and Chi-square or Fisher’s exact test for categorical variables. Variables found significant on univariate analysis (p < 0.1) were included in a multivariate logistic regression model to identify independent risk factors for VTE. A p-value of <0.05 was considered statistically significant.

Table 1: Demographic and Clinical Variables

Table 2: Tumor and Surgery-Related Variables

Table 3: Surgical and Postoperative Factors

Table 4: Postoperative Factors

Table 5: Time to Diagnosis of VTE

The comparative analysis between VTE-positive (Group 1) and VTE-negative (Group 2) patients revealed no statistically significant differences across the evaluated variables. The mean age of patients in Group 1 was slightly higher (58.2 ± 7.5 years) compared to Group 2 (54.8 ± 6.3 years), though this difference was not significant (p = 0.241). A male predominance was observed in both groups (16 males in Group 1 vs. 20 in Group 2), with no significant association between sex and VTE incidence (p = 0.331). Similarly, mean BMI was higher in the VTE-positive group (26.7 ± 3.4) than in the VTE-negative group (24.5 ± 3.2), but without statistical significance (p = 0.158). The presence of comorbidities (12 vs. 13 patients) and history of smoking (18 vs. 15 patients) were also more common in the VTE-positive group, yet the differences were not statistically significant (p = 0.412 and p = 0.265, respectively). Alcohol use and previous history of VTE were slightly more prevalent in the VTE-positive group, but these differences also lacked statistical significance (p = 0.467 and p = 0.348, respectively).

The comparison of oncologic and treatment-related variables between the VTE-positive (Group 1) and VTE-negative (Group 2) cohorts revealed no statistically significant differences. Regarding the site of the primary tumor, oral cavity cancers were most common in both groups, with a distribution of 10 oral, 6 pharyngeal, and 4 laryngeal cases in Group 1, and 12 oral, 12 pharyngeal, and 6 laryngeal in Group 2 (p = 0.341). TNM staging showed a higher number of advanced stage cases (stage III/IV) in both groups, but the distribution was not statistically significant (p = 0.291). Squamous cell carcinoma was the predominant histological type in both groups (18/2 in Group 1 and 22/8 in Group 2), with no significant association with VTE occurrence (p = 0.394). Histological grading showed a slight predominance of low-grade tumors in Group 1 (12 low, 8 high) compared to a nearly equal distribution in Group 2 (16 low, 14 high), again without statistical significance (p = 0.215). Similarly, prior exposure to chemotherapy (p = 0.510) and radiotherapy (p = 0.625) did not differ significantly between the groups.

The analysis of surgical variables revealed no statistically significant differences between the VTE-positive (Group 1) and VTE-negative (Group 2) patients. The most commonly used free flap was the anterolateral thigh flap in both groups, with a distribution of 8 radial forearm, 10 anterolateral thigh, and 2 other flaps in Group 1, compared to 10, 16, and 4 respectively in Group 2 (p = 0.515). The mean duration of surgery was longer in the VTE-positive group (280 ± 45 minutes) than in the VTE-negative group (245 ± 38 minutes), though this difference was not statistically significant (p = 0.213). Similarly, intraoperative blood loss was slightly higher in Group 1 (450 ± 120 mL vs. 400 ± 135 mL; p = 0.421). The requirement for intraoperative transfusion was observed in 8 patients in Group 1 and 10 in Group 2, with no significant association (p = 0.410). Microvascular anastomosis was performed in all VTE-positive cases and in 25 of the VTE-negative cases, with no statistical significance (p = 0.301). The mean number of venous and arterial anastomoses was comparable between the two groups (venous: 2.5 ± 0.7 vs. 2.3 ± 0.5, p = 0.315; arterial: 2.2 ± 0.6 vs. 2.1 ± 0.4, p = 0.675). The postoperative variables analysis demonstrated several statistically significant associations with VTE occurrence. The use of DVT prophylaxis was significantly lower in the VTE-positive group, with 18 patients receiving it compared to all 30 in the VTE-negative group (p = 0.002), indicating a strong correlation between inadequate prophylaxis and VTE development. Postoperative mobility was also significantly reduced in Group 1 (14 mobile vs. 6 non-mobile) compared to Group 2 (28 mobile vs. 2 non-mobile), with a p-value of 0.035, suggesting early mobilization may reduce VTE risk. The mean ICU stay duration was notably longer in the VTE-positive group (4.2 ± 1.5 days) than in the VTE-negative group (2.9 ± 1.2 days), and this difference was statistically significant (p = 0.029), indicating that prolonged immobilization in intensive care may contribute to thrombotic risk. While the mean hospital stay was longer in the VTE-positive group (15.6 ± 5.1 days vs. 12.8 ± 4.2 days), the difference did not reach statistical significance (p = 0.147). Postoperative complications were more frequent in the VTE-positive group (10 out of 20) compared to 6 in the VTE-negative group, and this trend approached statistical significance (p = 0.053). However, the use of postoperative anticoagulation therapy showed no significant difference between the two groups (p = 0.276).

In the VTE-positive group (Group 1), the mean time to diagnosis of venous thromboembolism was 6.1 ± 3.2 days postoperatively. This metric was not applicable to the VTE-negative group, and therefore no comparative p-value could be calculated. 

The current study assessed the incidence and associated risk factors of venous thromboembolism (VTE) in patients undergoing free flap reconstruction for head and neck cancers. While most demographic, oncologic, and surgical variables did not demonstrate a statistically significant association with VTE development, several postoperative factors—including the use of DVT prophylaxis, early postoperative mobility, and ICU stay duration—were significantly associated with increased VTE risk. Notably, patients who did not receive mechanical or pharmacologic thromboprophylaxis had a markedly higher VTE incidence (p = 0.002), which is consistent with findings from previous studies highlighting the protective role of prophylaxis in surgical oncology patients (11,12). Similar to our results, Abdel-Rahman et al. reported that the incidence of VTE in head and neck cancer surgery ranged from 1.4% to 7%, with major risk factors including reduced mobility and lack of prophylaxis use (13). The average time to VTE diagnosis in our cohort (6.1 ± 3.2 days postoperatively) aligns with the window reported by Zheng et al., who found that most VTE events occurred within 7–10 days post-surgery (14). This emphasizes the importance of vigilant monitoring during the immediate postoperative period. In contrast to prior studies identifying older age, higher BMI, or prolonged operative duration as independent risk factors (15,16), our study did not find these parameters to be statistically significant, possibly due to a limited sample size or uniform perioperative protocols across both groups. Nevertheless, a trend toward longer surgeries and higher intraoperative blood loss in the VTE-positive group does suggest a cumulative physiologic burden that may contribute to thrombosis, as similarly noted in the study by Lee et al. (17). Interestingly, the presence of comorbidities, prior chemotherapy or radiotherapy, and tumor-related characteristics (site, stage, histology) were not significantly associated with VTE in our cohort. These findings mirror the observations made by Gollapudy et al., who argued that patient-specific postoperative factors may outweigh disease-specific factors in determining thrombotic risk in head and neck cancer surgery (18). The significant correlation between reduced postoperative mobility and VTE (p = 0.035) is particularly noteworthy and aligns with studies advocating for enhanced recovery after surgery (ERAS) protocols in oncologic surgery to facilitate early ambulation (19). Furthermore, the longer ICU stay among VTE-positive patients in our study (4.2 vs. 2.9 days, p = 0.029) reflects the well-documented impact of immobilization and critical care-associated risk factors on thrombogenesis (20).

This institution-based study highlights a noteworthy incidence of venous thromboembolism (VTE) in patients undergoing free flap reconstruction for head and neck cancer. While most demographic, oncologic, and intraoperative factors did not show a significant association with VTE occurrence, the lack of DVT prophylaxis, delayed postoperative mobilization, and prolonged ICU stay were significantly correlated with increased VTE risk. These findings underscore the importance of early mobilization, adequate thromboprophylaxis, and minimizing ICU duration as part of comprehensive perioperative care. Routine risk assessment and implementation of individualized VTE prevention protocols are essential to reduce thromboembolic morbidity in this high-risk surgical population. Further large-scale, multicenter studies are warranted to refine risk stratification and optimize prophylactic strategies.

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