|Year : 2021 | Volume
| Issue : 9 | Page : 1343-1349
Blood Count Parameters can be Useful in Predicting Vascular Events in Microvascular Surgery: Results of a Preliminary Study
Ilkben Gunusen1, Ozlem Yakut Ozdemir1, Ersin Gur2, Yigit Ozer Tiftikcioglu2, Yusuf Can Ekin3, Kerem Ozturk4
1 Department of Anesthesiology and Reanimation, Ege University Medical School and Hospital, Izmir, Turkey
2 Department of Plastic and Reconstructive Surgery, Ege University Medical School and Hospital, Izmir, Turkey
3 Anesthesiology and Reanimation Clinic, Şanlıurfa Training and Research Hospital, Turkey
4 Department of Otolaryngology, Ege University Medical School and Hospital, Izmir, Turkey
|Date of Submission||31-Aug-2020|
|Date of Acceptance||19-Jan-2021|
|Date of Web Publication||16-Sep-2021|
Dr. Ilkben Gunusen
Department of Anesthesiology and Reanimation, Ege University Medical School and Hospital, Izmir
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Vascular events are a major cause of flap failure and identifying patients who are at risk is of paramount importance. In the past, many studies have been conducted to investigate the effect of blood count parameters for ischemic events such as peripheral vascular diseases. Aims: This study aimed to evaluate whether blood count parameters can have predictive value for vascular events in microvascular flap surgery. Methods: Elective cases with free flap microsurgery performed in a single center were reviewed from 2015 to 2019. Demographic data, comorbidities, flap types, perioperative complications, and preoperative blood count parameters from the hospital records were screened. Results: A total of 147 patients were included in the study, taken from the 163 patients undergoing free tissue transfer. The rate of thrombosis and partial necrosis was 8.8%, was 8.2%, respectively, and the total flap loss due to these complications was 5.4%. Only patient age, gender, and length of hospital stay were correlated with flap loss. According to the preoperative blood count results, there were significant differences between vascular events and leucocyte, and neutrophil counts. Conclusion: The findings of this preliminary study suggest that these parameters may be used in predicting vascular events in flap surgery.
Keywords: Blood count parameters, microvascular flap surgery, partial necrosis, thrombosis
|How to cite this article:|
Gunusen I, Ozdemir OY, Gur E, Tiftikcioglu YO, Ekin YC, Ozturk K. Blood Count Parameters can be Useful in Predicting Vascular Events in Microvascular Surgery: Results of a Preliminary Study. Niger J Clin Pract 2021;24:1343-9
|How to cite this URL:|
Gunusen I, Ozdemir OY, Gur E, Tiftikcioglu YO, Ekin YC, Ozturk K. Blood Count Parameters can be Useful in Predicting Vascular Events in Microvascular Surgery: Results of a Preliminary Study. Niger J Clin Pract [serial online] 2021 [cited 2022 Nov 29];24:1343-9. Available from: https://www.njcponline.com/text.asp?2021/24/9/1343/325915
| Introduction|| |
Microvascular free tissue transfer is an important and reliable technique in reconstructive surgery that provides the closure of various tissue defects and is often used to reconstruct head and neck, mastectomy, and traumatic extremity defects. Successful free flap reconstruction depends on good perfused tissue supplied by a donor artery and vein. Arterial and venous obstructions can result in irreversible tissue injury, necrosis, and flap loss. Failure in microvascular surgery often leads to additional surgeries and a prolonged hospital stay, with increased costs.,,
Venous and arterial thrombosis occur with similar mechanisms in which different risk factors in both veins and arteries trigger thrombus formation. Inflammation most likely represents the basic mechanism of arterial as well as venous thromboembolic disease, as inflammation appears to increase platelet activity. In recent years, inflammatory markers have been investigated in many ischemic or vascular diseases.,, Du et al. reported that flap venous crisis is accompanied by an increase in the number of inflammatory and thrombosis markers, in both the peripheral blood and the flaps. Leukocytes are one of the indicators of inflammation, and some studies suggest that leukocytosis directly enhances acute thrombosis and chronic atherosclerosis. The mechanism by which leukocytosis may predispose to ischemic vascular events has been explained as prothrombotic and vascular effects. Apart from leukocytes, neutrophils and lymphocytes, leukocyte subgroups and their ratios to each other, were also investigated for ischemic diseases.,
Since the routine blood count is the most basic and rapid detection method that can immediately provide insight into the patient's condition, we hypothesized that blood count parameters may be utilized for predicting vascular events such as thrombosis and partial necrosis in microvascular flap surgery; higher parameters may be related to a worse prognosis in terms of vascular events and flap loss. The aim of this study was to determine whether there is a relationship between vascular events and blood count parameters for predicting the prognosis in patients undergoing microvascular flap surgery.
| Subject and Methods|| |
After the approval of the Institutional Clinical Research Ethics Committee (IRB number: 19-5.1T/61), patients with elective cases of free flap surgery performed under anesthesia in a single institution were selected over a four-year period, from January 2015 to May 2019. Their surgical records were examined retrospectively. The following operative data were included: preoperative assessments and intraoperative and postoperative records. Data from anesthesia records, demographics (gender, age, height, weight, obesity as BMI >30), the patient's medical history (hypertension, diabetes mellitus, smoking, and drinking status etc.), intraoperative complications, fluid amounts and operation times were all recorded. Data from surgical records, including postoperative complications, flap loss, and hospital stay, were examined.
In the intraoperative period, a standard anesthesia protocol was applied to all patients. Considering the basal values of the patient, remifentanil (0.25 μg kg-1 min-1) was administered via an infusion during the operation to maintain a systolic blood pressure of 80-100 mmHg. Intraoperative complications, such as hypotension, bradycardia, hypoxia, hypothermia, and so forth, were recorded.
The authors performed all the operations as operating surgeons, and free-flap cases were performed by a single microsurgical team. The patients who underwent an emergent reoperation within 7 days after the initial reconstruction, were selected as the study group. Reoperation causes were categorized as thrombosis (arterial or venous), unknown cause partial necrosis and other reasons (hematoma, infections, kinking, etc.). Vascular events were detected in patients who underwent reoperation due to flap problems and were diagnosed with arterial-venous thrombosis. In addition, consistency of partial necrosis of the distal pedicle at the tip of the flap due to microcirculation insufficiency or micro thrombosis was accepted as vascular events. Many factors may lead to necrosis, including smoking, flap size, kinking, defect site, hematoma, and wound infection., Therefore, patients who underwent surgery due to partial necrosis of unknown cause were included in the study, but those who developed partial necrosis as a result of the abovementioned reasons were not. In addition, patients who underwent an operation due to other flap complications, such as seroma, infection, hematoma, wound dehiscence, and partial necrosis, that arose from the above causes were also excluded from the study. The success rate of microvascular surgery is highly dependent on the surgical technique. To exclude technical problems, including faulty flap design that exceeded the vascular territory, technical errors of micro anastomoses, and inappropriate vessel tension or geometry that would result in compression and kinking, only the operations performed by a single surgical team experienced in this subject were included in the study.
The results of the baseline complete blood count were collected from a routine hemogram of a blood sample obtained prior to the procedure during hospitalization. The hemoglobin level, white blood cell count (WBC), neutrophil count, lymphocyte count, and platelet count were obtained from an automated system and the ratio between the total neutrophil and lymphocyte count (NLR) and the ratio between the total platelet and lymphocyte count (PLR) were calculated. The patients who developed thrombosis and partial necrosis were compared with those who did not experience any of these complications.
Statistical analysis was performed with IBM SPSS software version 25.0 (IBM Statistical Package for the Social Sciences Corp., Armonk, NY, USA). Data are expressed as the mean ± standard deviation and percentage (%). Univariate analyses were performed by using Chi squared and Fisher's exact tests for categorical variables and Student's t-tests or Mann Whitney U test for continuous variables. Correlation, Chi-square, and Fisher's exact tests were used to analyze the relationship between complications of free flaps and concomitant diseases. For a comparison of numerical data, an independent t-test or a Mann–Whitney U-test (in nonnormally distributed variables) were used. A P value lower than 0.05 was accepted as statistically significant.
| Results|| |
A total of 163 patients who underwent a free flap operation between January 2015 and May 2019 were examined. However, when hospital records were reviewed, 16 cases were excluded because of incomplete records or follow-up. A total of 147 patients who met the inclusion criteria were identified. Fifty-eight (39.5%) male and 89 (60.5%) female patients were included. Among the 147 flaps, 67 (45.6%) were used for the breast, 63 (42.8%) for the head and neck, and 17 (11.6%) for extremity defects. All reconstructions in the head and neck surgeries were performed secondarily to oncological resections. Of the 147 flaps, 108 flaps survived completely without any complications. Thirty-nine flaps (26.5%) were returned to the operating room, and 25 (17%) were taken back due to vascular events. The remaining 14 of the 39 flaps were returned for other reasons, such as hematoma or infection. The flap success rate was 93.2% (n = 10) for all complications (thrombosis, partial necrosis, hematoma, infection, seroma, etc.) and 94.6% (n = 8) for vascular events. Thirteen patients developed arterial or venous thrombosis (8.8%) and in four of them, flap loss was observed. Partial necrosis was observed in 12 patients (8.2%), and similarly, four patients presented flap loss. Last, two flap loss cases were detected in 14 patients who were diagnosed with other complications.
Since we aimed to investigate whether blood count parameters may serve as predictors of vascular events in patients with flap surgery, only predisposing factors for thrombosis and partial necrosis due to capillary insufficiency were evaluated. Flap loss due to vascular events was observed only in patients who were operated on due to head-neck and traumatic defects (P=0.02). However, the distribution of vascular events exhibited no difference between flap type (thrombosis (p = 0.61) and partial necrosis (p = 0.71)). In addition, there was no statistically significant relationship between flap type, vascular complications (p = 0.53) and flap loss (p = 0.072) [Table 1]. A total of eight flaps were lost (5.4%): four due to thrombosis (2.7%) and four due to partial necrosis (2.7%). Age, gender, and duration of hospital stay were found to correlate in patients with flap loss [Table 2].
|Table 1: Distribution of free flap operations, vascular complications and flap failure|
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|Table 2: Demographic-surgical characteristics of patients, vascular complications, flap loss|
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All patients with a deep inferior epigastric perforator (DIEP) underwent a mastectomy due to a malignancy; approximately 88% of DIEP cases had undergone chemotherapy and/or radiotherapy at least 2 years prior. The remaining 12% were patients who did not receive chemotherapy and/or radiotherapy thanks to an early diagnosis. Sixty-three patients who received a free flap for head and neck surgery were reported to have a history of malignancy. Among the reconstructions performed, 97% were carried out after patients underwent chemotherapy and/or radiotherapy. In terms of vascular events and flap loss, malignancy, radiotherapy, chemotherapy, and concomitant diseases were not significantly different. Intravascular heparin was administered intraoperatively in approximately 19.04% of flap surgeries, and no relationship between intraoperative heparin administration, vascular complications and flap loss was reported. Postoperative anticoagulant therapy was administered in approximately 92.5% of cases with flap surgery (low molecular weight heparin and acetylsalicylic acid treatments). Similarly, no significant correlation was observed between postoperative heparin administration, vascular complications, and flap loss (p = 0.32 and P = 0.52, respectively).
Intraoperative complications in this study were as follows: 7 patients had hypotension (4 patients in the DIEP group, 3 patients in the other group), two patients had bradycardia (one patient in each group), and three patients had hypoxemia (one patient in the DIEP group, two patients in the other group). One patient had platelet dysfunction in the intraoperative period. Only one patient in the partial necrosis group developed hypotension. There was no statistically significant relationship between intraoperative complications, thrombosis, and partial necrosis (p = 0.84, 0.92, respectively). No flap failure was observed in any of these patients [Table 3].
With regard to preoperative blood count results, a significant correlation between vascular events, WBC count, and neutrophil count was detected. Although preoperative NLR values were higher than those of patients with other complications, no significant difference was observed [Table 4], [Figure 1].
|Figure 1: Correlation between the leukocyte count and vascular events (a), between neutrophil count and vascular events (b)|
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|Table 4: The relationship preoperative blood count parameters and vascular events|
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In the postoperative period, excluding flap complications, one patient had acute renal failure, and one patient with a history of chronic obstructive pulmonary disease developed respiratory distress. These patients were followed up in an intensive care unit and discharged having made a full recovery. Only one patient died due to sepsis.
| Discussion|| |
Despite the high success rates of large centers, flap loss is still a problem. The most significant causes of flap loss are vascular events, especially thrombosis. In our study, the incidence of vascular events was found to be 17% (thrombosis: 8.8%; partial necrosis: 8.2%), of which 32% resulted in flap loss. Among all flap cases, the rate of total flap loss due to these complications was 5.4%. Gong et al. showed that the flap necrosis rate in hand soft-tissue reconstruction was 11.04%, which included partial necrosis at 7.36%. Similar to our investigation, the study of Bui et al. revealed a thrombosis rate of 3.2% in all flap types, and of these, 37% resulted in flap loss. Again, in a large-series study of flaps applied to various parts of the body but not a specific site, the rate of vascular complications was found to be 3.34%, and there were 1.41% total flap failures. In our study, the distribution of vascular complications exhibited no difference between flap types or operation sites. However, all flap loss cases due to vascular events were observed in patients who underwent surgery for head and neck malignancies and traumatic defects (p = 0.02).
Flap success is affected by many factors, including flap type, surgical techniques, anticoagulant use, concomitant diseases, smoking, radio chemotherapy, and technical factors.,, However, published results are conflicting since the study protocols and designs, surgeons' experiences, evaluation of complications in flap surgery, and different inclusion criteria vary significantly; therefore, together these finding may be insufficient for determining risk factors.,,, For example, Herle et al. reported that radiotherapy reduces the clinical success rate of flap surgery while increasing the risk of free flap failure and complications. In addition, another study suggested that comorbidities such as smoking, diabetes, radiotherapy, and obesity are associated with complications. In contrast, in a systematic review, de Blacamet et al. showed that only venous insufficiency and increasing age are risk factors for complications; however, radiotherapy was found to be ineffective. Therefore, risk factors for complications and total flap loss are still unclear in microvascular flap surgery. In our study, no significant difference was detected between comorbidities, vascular events, and flap loss. Only age, gender, and length of hospital stay were found to correlate with flap loss.
The pathogenesis of thrombosis is based on stasis, hypercoagulability, and endothelial dysfunction. It has been suggested that inflammation can trigger the coagulation cascade and inhibit the anticoagulant pathway. However, in flap surgery, thrombosis may occur due to local and technical factors (e.g., intima damage, vessel kinking, compression, technical errors). Total or partial necrosis is also associated with risk factors, including age older than 60 years, diabetes, smoking, arteriopathy, venous insufficiency, location of the defect, flap size, and external compression, such as hematoma, wound infection, and prolonged anesthesia time.,,,, Lee et al. found that the partial flap necrosis incidence was 7% in 44 patients with calcified arteriosclerosis involving the flap vascular pedicle. In our study, no statistically significant correlation was found between partial necrosis and operation time, age, or comorbidities. When no cause could be detected in patients who underwent surgery due to partial necrosis (infection, bending, flap size, hematoma, etc.), they were included in the study since there may have been microcirculation insufficiency or micro thrombosis due to arteriopathy.
To exclude technical problems in both the thrombosis and partial necrosis groups, only operations performed by one surgical team were included. Perioperative antithrombotic therapy is widely given to prevent thrombosis in free tissue transfer; however, anticoagulant administration remains a highly controversial topic. Moreover, there is no optimal postoperative anticoagulation regimen following free flap surgery, as defined in the literature. Antithrombotic agents may be considered in cases of small vessels, significant size mismatches, vein grafts, or vessels with poor quality. Since flap failures may arise from microvascular thrombosis, several agents, such as heparin and acetylsalicylic acid, have been used for prevention., In our department, heparin is not used routinely in the perioperative period. In 147 flap cases, intraoperative heparin was administered in 28 patients, whereas low molecular weight heparin and/or aspirin was administered in 136 patients. In patients with vascular events, no significant difference was detected between anticoagulant use and flap loss.
With the initiation of inflammation that triggers the coagulation cascade by inducing tissue factors, thrombus formation is the result of activated endothelial cells, platelets, and leukocytes. Endothelial dysfunction also has a prominent role in most cases of vasculitis and thrombosis., Increasing evidence also supports a role for inflammation in the atherosclerotic process. The initiation, growth, and complications of atherosclerotic plaques are each judged to be an inflammatory response to vascular injury. Several studies indicating the effect of inflammation on many ischemic events, including stroke, coronary events, and peripheral arterial diseases, have been published.,, Madjid et al. revealed that leukocytosis, a simple inflammatory marker, can be used as an independent predictor for future cardiovascular events for patients with stable angina, unstable angina or a history of myocardial infarction, as well as healthy individuals free of coronary heart diseases at baseline. Therefore, we hypothesized that blood count parameters may serve as predictors of vascular events such as thrombosis and partial necrosis in patients with free flap surgery. Grau et al. reported that a leukocyte count is also associated with the risk of stroke and vascular death in patients with previous ischemic diseases. Arnaoutoglou et al. concluded that leukocyte counts in the preoperative period may have clinical significance for identifying high-risk vascular patients. Additionally, neutrophils, a leukocyte subgroup, secrete inflammatory mediators that can cause vascular wall degeneration. Conversely, lymphocytes regulate the inflammatory response and thus have an antiatherosclerotic role. Based on the hypothesis published in several studies, high neutrophil and low lymphocyte counts can lead to poor clinical outcomes in patients with acute coronary events and peripheral arterial disease., NLR was also found to be a predictor of morbidity and mortality after ischemic events. Tan et al. reported that pre-operative NLR (>3.3 in heart surgery, >5 in vascular surgery) was associated with mortality. In a retrospective study with 2121 patients, authors concluded that an NLR >3.95 also appears to correlate with critical limb ischemia despite adjusting for vascular risk factors. In addition, the latest studies have shown PLR to be a potential inflammatory marker in cardiovascular diseases., Li et al. performed a meta-analysis and included 8932 patients to systematically evaluate the prognostic role of PLR in acute coronary syndrome and demonstrated that PLR may be a promising biomarker in predicting a worse prognosis. Despite the higher NLR in the vascular complication group, in our study, we found no correlation between NLR, PRL, vascular events and flap loss because only neutrophil and leucocyte counts were high, while no statistically significant difference in lymphocyte counts was present. Therefore, NLR values in our study were below the cut-off values reported in other studies., In addition, although PRL was above the cut-off values only in the flap loss group, we did not observe any difference between the groups with regard to PRL. Vascular complications and associated flap loss after postoperative day seven are rare because of the decreased reliance of the flap on the pedicle vessels, depending on the type of the flap and the site of reconstruction. Bui et al. examined thrombosis cases in the first 7 days postoperatively since the diagnosis of microvascular thrombosis after 7 days is difficult due to other events, often infection. Therefore, in our study, we evaluated vascular events in patients who underwent reoperation in the first seven days after the initial operation.
| Conclusion|| |
The blood count is inexpensive, reliable, easy to interpret, and ordered routinely in inpatient and outpatient settings. An association between blood count parameters and outcome measures such as vascular events has not been investigated previously in patients undergoing free flap surgery. This preliminary study reveals the correlation between increased preoperative WBC count, neutrophil count and an increased risk for vascular events following microvascular flap surgery. Detection of high-risk patients at an early stage by blood count parameters, may be beneficial in terms of taking measures to improve clinical results. We believe that further studies will reveal the importance of these biomarkers in free flap surgery, especially in the prediction of thrombotic complications. Based on our findings, the WBC and neutrophil counts appear to be promising biomarkers for predicting vascular events in microvascular flap surgery.
We would like to thank Hatice Uluer from Ege University Department of Biostatistics, for her data processing and statistical work.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]