Abstract
Background/Aim: Low molecular weight heparin (LMWH) is widely employed to prevent postoperative venous thromboembolism (VTE). This study aimed at analyzing LMWH use and evaluating its efficacy and safety in immediate implant-based post-mastectomy breast reconstruction. Patients and Methods: A monocentric retrospective analysis was conducted on patients who underwent immediate implant-based breast reconstruction (IBR) from January 2021 to December 2023. Preoperative characteristics, Caprini score, type of mastectomy procedure, administration of LMWH, postoperative outcomes, and any adverse events linked to LMWH usage, with particular attention to hematoma or VTE, were collected and analyzed. Results: A total of 211 breast procedures were performed on 179 patients - with a mean age of 50.9 years (SD 12.3) and a mean Caprini score of 6.8 (SD 1.4). In total, 133 patients received LMWH by subcutaneous injection (enoxaparin 40 mg/day) post-operatively and 46 only had mechanical thromboprophylaxis. The overall complication rate was higher but statistically significant in the LMWH group with 27.8% compared to 17.4% in the no-LMWH group (p=0.159). Hematoma occurred in 17 patients (12.8%) in the LMWH group compared to two (4.4%) patients in the no-LMWH group (p=0.164). Moreover, 15 (11.2%) patients who received LMWH required reoperation compared to one (2.2%) in patients who did not receive LMWH (p=0.074). There were no VTE events in either group. Conclusion: There were no significant differences in complications and especially hematoma rate in patients who received LMWH after mastectomy and immediate IBR, compared to patients who did not. Moreover, no difference in VTE rate was observed across groups.
Breast cancer is the most common cancer type and one of the leading causes of cancer-related deaths among women worldwide (1). Immediate breast reconstruction (BR) following mastectomy has become the preferred management strategy over delayed reconstruction (2-4), as it allows for a seamless transition and mitigates the psychological impact of breast loss (4). Depending on patient preference and individual circumstances, various techniques can be employed for BR, including implant-based reconstruction, autologous tissue reconstruction or oncoplastic breast reduction (5).
Mastectomy-related complications may arise in the context of a mastectomy, either in conjunction with immediate BR or later with delayed BR. These complications range from wound infections, wound dehiscence, skin-flap necrosis to hematomas or seromas at the mastectomy site, which may require ultrasound-guided aspiration or surgical drainage (6-8).
In the postoperative period, special attention is also directed towards venous thromboembolic events (VTE). It has been observed that tumor resection combined with immediate BR can induce a hypercoagulable state in the majority of patients during the postoperative period, especially in those receiving chemotherapy (9-12).
To prevent the occurrence of VTE in surgical patients, preventive measures can be implemented, including early ambulation, mechanical prophylaxis, and pharmacological thromboprophylaxis (13, 14). Some authors like Emoto et al. advocate for the evaluation of the necessity of anticoagulation therapy in patients who undergo breast cancer surgery (15).
While effective, pharmacological prophylaxis, also called chemoprophylaxis is not harmless, and may lead to complications, such as heparin-induced thrombocytopenia, osteoporosis, hypoaldosteronism, hypersensitivity reaction, and more frequently excessive bleeding and hematoma (16). Such complications may cause higher reoperation rates (17, 18). While patients undergoing breast surgery are at risk for thromboembolism, the rate of venous thromboembolism is lower than that in other types of surgeries (17, 19).
Considering this, numerous medical institutions endorse alternative approaches for thromboprophylaxis, encompassing the implementation of mechanical devices (such as pneumatic compression stockings) and the encouragement of early ambulation during the postoperative phase (20, 21). An assessment of the advantages and drawbacks of each method of thromboprophylaxis is imperative to achieve the most effective reduction in thromboembolic events, while limiting the risk for thromboprophylaxis-related complications. Although specific clinical scores, such as the Caprini score, are employed to inform decisions regarding the method and duration of prophylaxis, the ultimate discretion often rests with the surgeon (22-24). For instance, in patients at high risk of bleeding, surgeons sometimes choose to forego pharmacological thromboprophylaxis for mechanical thromboprophylaxis - most frequently intermittent pneumatic compression (IPC) stockings or graduated compression stockings (GCS) (18). Conversely, in patients that are at high-risk of a thromboembolic event following surgery, either low-molecular weight heparin (LMWH) or a combination of LMWH and GCS or IPC may be used (25, 26).
Limited research exists on the utilization of pharmacological thromboprophylaxis, particularly with LMWH, in the context of mastectomy with immediate implant-based breast reconstruction (IBR) leading to a lack of established guidelines (20, 27, 28). This is in contrast with the available data on thromboprophylaxis in autologous breast reconstruction surgery (29, 30).
The aim of this study was to evaluate the rate of VTE and pharmacological thromboprophylaxis-related complications, such as hematoma, bleeding, and reoperation in patients undergoing mastectomy with immediate implant-based BR.
Patients and Methods
A retrospective chart review including patients undergoing mastectomy followed by immediate IBR in the context of breast cancer from January 2021 to December 2023 was conducted. Exclusion criteria included the use of other surgical techniques for BR, active metastatic disease, incomplete thromboprophylaxis treatment data and an incomplete medical record. Demographic data, ASA (American Society of Anesthesiology) scores, VTE risk assessed via the Caprini Score, intra-operative details, type of surgical technique, operative duration, thromboprophylaxis treatment data and postoperative outcomes were extracted from medical records.
Informed consent was obtained from all patients. Ethics approval for the study was granted by the “Commission Cantonale d’Ethique de la Recherche sur l’être humain (CCER)” (project ID 2023-02243).
Surgical procedure and postoperative thromboprophylaxis. The procedure always followed a two-stage approach. The preoperative markings were performed by our team. Then, the mastectomy along with the sentinel lymph node resection were conducted by the gynecological team first and our team then conducted the IBR. We always use a silicone prothesis wrapped in Vicryl mesh. After meticulous hemostasis and betadine rinsing, surgical drainage was placed in the mastectomy pocket. The procedures performed were either unilateral (82.1%) or bilateral (17.9%), using skin sparing mastectomy (SSM) (51.2%) or nipple sparing mastectomy (NSM) (48.8%). In the postoperative period, mechanical thromboprophylaxis using IPC stocking was employed for all patients immediately after the operation, and all patients were encouraged to begin mobilizing on the first postoperative day. Additionally, pharmacological thromboprophylaxis with enoxaparin 40 mg (Sanofi-Aventis®, Vernier, Switzerland) LMWH was administered according to each patient’s VTE risk calculated using the Caprini score, as well as the quantity and appearance of drainage fluid in the redon drain. When LMWH was administered, patients received the 40 mg subcutaneous injections every 24 h during their hospital stay until discharge.
Statistical analysis. Continuous variables were assessed using independent two-sided t-tests for means or Mann-Whitney U-tests for medians, depending on the distribution’s normality, confirmed using the Shapiro-Wilk test. Categorical variables were compared using either a two-sided Chi-square or Fisher’s exact test, as applicable. Statistical significance was set at a p<0.05. Statistical analysis was performed using R version 4.2.1 (R Foundation for Statistical Computing, Vienna, Austria).
Results
Demographic data. Data from 179 patients (211 breasts) who underwent mastectomy and an immediate IBR was included. The study cohort was separated into two groups, one including 133 patients (74.3%) who received both chemical thromboprophylaxis with LMWH and IPC during the postoperative period and the other group including 46 patients (25.7%) who did not receive LMWH during this period.
Patient characteristics. Both the LMWH group and the non-LMWH group had comparable baseline characteristics, with a mean age of 51.7 years [standard deviation (SD)=12.3] and 48.7 years (SD=11.9), respectively (p=0.166). The mean BMI was similar between groups, with a mean of 24.4 kg/m2 (SD=10.9) in the LMWH group and 22.9 kg/m2 (SD=9.7) in the non-LMWH group (p=0.495). In our cohort, there were 35 active smokers (26.3%) and 11 active smokers (13%) in the LMWH and non-LMWH group, respectively (p=0.748). There were no statistically significant differences in ASA scores and mean Caprini scores across groups (Table I).
Baseline characteristics.
Surgical characteristics. During the study period, a total of 179 mastectomies with immediate implant-based reconstruction were performed on 211 breasts. There was a significantly higher rate of bilateral procedures in the non-LMWH group (p=0.014).
The mean resection weight per breast was 415 g (SD=254.2) and 358.2 g (SD=227.7) in the LMWH group and non-LMWH group, respectively, trending towards a higher resection weight per breast, but not statistically significant, in the LMWH group (p=0.128). The mean operative time was 191.8 min (SD=53.1) in the LMWH group and 198.5 min (SD=65.4) in the non-LMWH group (p=0.490) (Table II).
Surgical characteristics.
Postoperative use of LMWH. In total, 133 patients received LMWH associated with mechanical thromboprophylaxis from 6 h postoperatively until discharge. A total of 46 patients did not receive chemical thromboprophylaxis, and therefore only benefited from mechanical thromboprophylaxis until mobilization. Subcutaneous administration of 40 mg LMWH was performed once a day during all the hospitalization corresponding to a mean of 6.9 days (SD=4, min-max 3-36 days) in LMWH group and 6.2 days (SD=3.2, min-max 1-17 days).
Postoperative complications and hospital length of stay. In the LMWH group, 37 patients (27.8%) had a postoperative complication during the hospitalization compared to eight patients (17.4%) in non-LMWH group (p=0.16). Hematoma was the most frequent complication, occurring in 17 patients (12.8%) in the LMWH group and two patients (4.4%) in non-LMWH group (p=0.164), followed by 12 (9%) skin complications (scar necrosis or wound dehiscence) in the LMWH group versus two (4.4%) in non-LMWH group (p=0.524). Postoperative anemia was defined by the need of transfusions of one unit of red blood cells due to a decrease in hemoglobin levels on the first day after surgery (ranging from 70 to 83 g/l), caused by spoliation anemia. It occurred in four patients (3%) in the LMWH group compared with four patients (8.7%) in the non-LMWH group (p=0.207). Only one patient who presented a postoperative anemia had also presented a hematoma. No occurrences of VTE were observed in either group.
Reoperation was required in 15 patients (11.2%) in the LMWH group and one patient (2.2%) in non-LMWH group (p=0.074). The most frequent indication for reoperation in the LMWH group was scar revision in eight cases, and evacuation of hematoma in four cases, followed by implant removal due to infection in three cases. The only reoperation or revision in the non-LMWH group was for a scar revision (2.2%) and there was no significant difference between the two groups.
The hospital length of stay was 6.9 days (SD=4) in the LMWH group compared to 6.2 days (SD=3.2) in the non-LMWH group (p=0.129) (Table III).
Postoperative outcomes.
Discussion
In recent years, there has been an increased focus on optimizing the care provided to patients with breast cancer, not only in terms of oncological outcomes but also in terms of perioperative care and reducing postoperative complications (21).
Several studies have investigated the role of chemical thromboprophylaxis and mastectomy with immediate reconstruction. Maesaka et al. favor chemical thromboprophylaxis in the oncology population, due to the increased risk of VTE (13). Other authors prefer to reserve this option for high-risk patients because of the risk of bleeding and hematoma formation in the postoperative period (31).
In addition, most centers have issued guidelines for VTE prophylaxis, but there is considerable variability in the indications, method, and duration of prophylaxis (8, 19, 22, 25, 27, 32, 33). Clear recommendations on thromboprophylaxis are therefore essential to reduce the risk of postoperative complications associated with the use of LMWH (29). In our study, we analyzed prophylactic use of LMWH following mastectomy and IBR with a focus on the occurrence of postoperative hematoma and reoperation rates. Our results show a higher proportion of complications in the group of patients receiving LMWH chemoprophylaxis, albeit non-statistically significant (27.8% vs. 17.4%). This complication rate is in line with those reported in the literature (6), although complication rates vary widely from one study to another. Blok et al. report a 18.7% complications rate, with a 1.3% hematoma rate (34), whereas Knoedler et al. observed a complication rate of 11% and a reoperation rate of 7.3% following implant-based immediate breast reconstruction in their case series (35). It should be noted, however, that the use and methods of thromboprophylaxis is not specified in these two studies.
The most frequent complication in the LMWH group of the current study was the occurrence of a hematoma and skin complications in 12.8% and 9% of cases. We did not find statistically significant differences in hematoma rate between the two groups. Our results show a higher hematoma rate in both groups compared with several studies in the literature. Nealon et al. observed hematoma in 5.1% of patients after immediate IBR, although the authors did not specify whether anticoagulation was administered (36). In a case-control study by Yan et al. comparing 37 IBRs in patients chronically anticoagulated (>6 months) with Warfarin, ACOD or LMWH with 74 IBRs in the control group, the hematoma rate was 2.7% and 1.4%, respectively. The authors note that there was no difference in hematoma occurrence between the anticoagulated and control groups, although their cohort was more heterogeneous than ours, with immediate, delay BR, expander or prosthesis (only 12 direct-to-implant, equivalent to 10.8% of the cohort) (37).
Anemia rate was statistically similar between the two groups (p=0.210). However, we observed a higher but significant anemia rate in the non-LMWH group with 8.7% compared to 3% in LMWH group. This likely influenced the decision to refrain from administering LMWH during the postoperative period. Indeed, in a large study involving 477,000 breast cancer surgery patients, Konishi et al. found that postoperative anemia was an additional risk factor for bleeding (38).
There were no occurrences of VTE in either group in our study. In the literature, patients who have undergone autologous BR benefit from chemical thromboprophylaxis during hospitalization, due to an increased thromboembolic risk (25). Regarding thromboembolic risk during IBR, there is no clear recommendation. Thromboprophylaxis use is rarely mentioned in the literature (39). However, the risk of VTE is lower than that with autologous BR (40). Nwaogu et al. report an incidence of 0.52% at 30 days after mastectomy with reconstruction in large studies involving over 60,000 patients, which may explain why we have not observed any VTE (39). This could also explain why some authors advocated that IPC can be sufficient as thromboprophylaxis when breast conservative surgery is performed (18). However, according to the American Society of Plastic Surgeons, patients undergoing immediate mastectomy and BR are considered high-risk for VTE. In these cases, 7 to 10 days of pharmacological thromboprophylaxis, with or without mechanical thromboprophylaxis, is recommended. The committee also approved the use of the Caprini Risk Assessment Model (21).
An interesting finding from this study is the trend towards higher, but not statistically significant reoperation rate in the LMWH group with 11.2% compared to 2.2% in the non-LMWH group (p=0.074). This has already been observed in other studies such the case control study from Yan et al. who noticed 10.8% of reoperation rate in the anticoagulated group and 6.9% in the control group, although this difference was also not statistically significant (37). In other words, further research is needed to confirm these results, which at present do not allow any conclusions to be drawn. One of the most frequent indications for revision was the need for surgical evacuation of hematoma, which in our study occurred at a rate of 4.5% in the LMWH group. Brantley et al., conducted a large retrospective study involving nearly 22,000 patients, comparing those discharged on the same day of surgery with those hospitalized after undergoing immediate BR. The authors noted that the most frequent reason for reoperation in both groups was incision and drainage of hematoma, serum, or fluid collection, accounting for 7.8% of reoperations in the same-day discharge group and 15% of reoperations in hospitalized patients (41).
Our study has several limitations inherent to its retrospective non-randomized nature, but also due to its small size. The relatively low numbers of patients in both groups provides limited statistical power. Our results are not statistically significant but interesting because they deal with a little explored subject in the literature that could contribute to future research work such metanalysis or larger randomized studies to evaluate the use of LMWH and confirm our results.
Conclusion
The present study compared the combination of mechanical thromboprophylaxis and LMWH to mechanical thromboprophylaxis alone following mastectomy and immediate IBR. It shows no significant differences in complication rate, and especially hematoma rate in patients receiving chemical thromboprophylaxis and those who did not. Moreover, there were no VTE events in both groups. This suggests that the choice of LMWH use should be mostly based on the VTE risk following mastectomy and IBR, given that there were no significant increases in bleeding or hematoma rates in patients with LMWH.
Footnotes
Authors’ Contributions
All Authors have contributed to Conceptualization; Data curation; Formal analysis; Investigation; Methodology; Resources; Supervision; Validation; Visualization; Writing; Review and Editing.
Funding
None.
Conflicts of Interest
The Authors have no conflicts of interest to declare in relation to this study.
- Received September 19, 2024.
- Revision received October 1, 2024.
- Accepted October 2, 2024.
- Copyright © 2025 The Author(s). Published by the International Institute of Anticancer Research.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).
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