Abstract
Objective:
Several studies have reported an increase in platelet (PLT) count with chronic inflammation in the presence of obesity. Mean platelet volume (MPV) is an important marker for PLT activity. Our study aims to demonstrate if laparoscopic sleeve gastrectomy (LSG) has any effect on PLT, MPV and white blood cells (WBCs).
Methods:
A total of 202 patients undergoing LSG for morbid obesity between January 2019 and March 2020 who completed at least 1 year of follow-up were included in the study. Patients’ characteristics and laboratory parameters were recorded preoperatively and were compared in the 6th and 12th months.
Results:
Two hundred and two patients (50% – female) with a mean age of 37.5 ± 12.2 years and mean pre-operative body mass index (BMI) of 43 (34.1–62.5) kg/m2 underwent LSG. BMI regressed to 28.2 ± 4.5 kg/m2 at 1 year after LSG (P < 0.001). The mean PLT count, MPV and WBC during the pre-operative period were 293.2 ± 70.3 103 cells/μL, 10.22 ± 0.9 fL and 7.8 ± 1.9 103 cells/μL, respectively. A significant decrease was seen in mean PLT count, with 257.3 ± 54.2 103 cell/μL (P < 0.001) at 1 year post-LSG. The mean MPV was increased at 6 months 10.5 ± 1.2 fL (P < 0.001) and remained unchanged at 1 year 10.3 ± 1.3 fL (P = 0.9). The mean WBC levels were significantly decreased with 6.5 ± 1.7 103 cells/μL (P < 0.001) at 1 year. At the end of the follow-up, weight loss showed no correlation with PLT and MPV (P = 0.42, P = 0.32).
Conclusion:
Our study has shown a significant decrease in circulating PLT and WBC levels while MPV remained unchanged after LSG.
Keywords: Bariatric surgery, obesity, platelets, sleeve gastrectomy, thrombosis
INTRODUCTION
Obesity is a chronic condition with associated comorbidities, which consequently shorten one’s life. Obesity was found to be a major risk factor for the development of hypertension, stroke and coronary artery disease.[1-3] This risk appears to increase even further in the presence of metabolic syndrome components.[4,5] The increased risk is also associated with platelet (PLT) hyperactivity, which increases the adhesion of PLTs to the vascular endothelium and leads to hypercoagulability.[6] The main function of PLTs is to establish haemostasis. Circulating PLTs are different in size and haemostatic potential. Larger PLTs tend to be more reactive with a higher haemostatic potential. They contain a greater number of granules and prothrombotic factors compared to smaller PLTs.[7] Mean platelet volume (MPV) is the most widely used parameter in the assessment of PLT size. MPV is an important marker of PLT activity. Studies have shown that high MPV is a risk factor for coronary artery disease and myocardial infarction.[8-10] Furthermore, high MPV coupled with high PLT activity may also increase the risk of stroke.[7]
Bariatric surgery is the most effective treatment against morbid obesity and laparoscopic sleeve gastrectomy (LSG) has become the most common method in recent years.[11,12] Cardiovascular morbidity and mortality decrease significantly with weight loss following bariatric surgery.[13] There are only a limited number of studies that investigate the changes in blood components, especially those in PLTs after bariatric surgery.[14-16] The present study aims to demonstrate if LSG has any effect on PLT counts, MPV and white blood cells (WBCs).
METHODS
The study was approved by the Institutional Ethics Committee (ATADEK 2020-22/21). All patients were informed about the study in detail, and written consent was obtained. A total of 202 patients undergoing primary LSG for morbid obesity between January 2019 and March 2020 who completed at least 1 year of follow-up were included in the study.
Pre-operative workup
All the patients were screened by detailed laboratory tests with respect to haematologic and metabolic parameters and vitamin deficiency (ferritin, B12 and folic acid). Gastroscopy and abdominal ultrasound were performed for each patient. Each patient was evaluated by a multidisciplinary team (dietitian, psychiatrist, cardiologist, pulmonologist, endocrinologist and anaesthetist). Patients with anaemia or any other haematological conditions, such as with a history of thromboembolism, a history of splenectomy, aspirin or anticoagulant usage at the time of the pre-operative evaluation, were excluded from the study. Furthermore, those with suspected infection during the pre-operative or follow-up blood sampling periods were also excluded from the study.
Surgery
All LSG operations were done by the same team and the same technique. Using an optical trocar for first entry (Endopath Xcel) with a fivtrocar technique, and starting at 3-4 cm to the pylorus, sleeve gastrectomy was performed over a 36 French bougie. Than the entire length of the staple line was reinforced using 3.0 V-Loc™ suture by continuous suturing (V-Loc 180; Medtronic, Minneapolis, MN, USA).
Follow-up
All patients were followed up at the 3rd, 6th and 12th months after LSG and annually thereafter during which laboratory tests and clinical assessment were done. All blood samples were analysed in the same laboratory. Sysmex XN-550 (Japan) device was used for the analysis of blood samples. Normal reference values for PLT count were accepted as 150–400 103 cells/μL in men and women. Accordingly, the MPV normal reference range was 6.4–11.4 fL and the WBC reference range was 4000–10,000 cells/μL in both sexes.
Weight loss data are presented as percentage of excess weight loss and total weight loss. For this calculation, the upper limit of body mass index (BMI), i.e., 25 kg/m2, was taken as the reference value. Patients were evaluated for their BMI, comorbidities and haematological parameters before LSG as well as weight loss and haematological parameters at 6 months and 1 year of follow-up.
Statistical analysis
Statistical analysis was performed using SPSS software version 21 (IBM Corp., Armonk, NY, USA). Standard deviation and mean values were used for the variables with normal distribution and median values were used for the variables that were not normally distributed. Student’s t-test was used for paired samples. Chi-square or Fisher’s exact tests were used for categorical variables, while for continuous variables, independent-samples t-test or Mann–Whitney U-test was performed. Pearson bivariate correlation test was used to evaluate the relation between pre-operative BMI, weight loss, MPV and PLT count. P < 0.05 was considered statistically significant.
RESULTS
Between January 2019 and September 2020, 202 patients (50% – female) with a mean age of 37.5 ± 12.2 years and mean pre-operative BMI of 43 (34.1–62.5) kg/m2 underwent LSG. At baseline, 80%, 11%, 29%, 52% and 22% of the patients had insulin resistance, type 2 diabetes mellitus, hypertension, hyperlipidaemia and obstructive sleep apnoea, respectively. BMI regressed to 30.9 ± 5.2 kg/m2 at 6 months after LSG (P < 0.001) and regressed to 28.2 ± 4.5 kg/m2 at 1 year (P < 0.001).
The mean PLT count, MPV and WBC during the pre-operative period were 293.2 ± 70.3 103 cells/µL, 10.22 ± 0.9 fL and 7.8 ± 1.9 103 cells/μL, respectively. The median C-reactive protein (CRP) level was 6.3 mg/L (minimum: 1 mg/L, maximum: 27.7 mg/L, reference range: 0–5 mg/L). There was no correlation between pre-operative BMI and PLT and MPV levels (P = 0.42, P = 0.23).
A significant decrease was seen in the mean PLT count, with 257.8 ± 61.5 103cell/μL (P < 0.001) at 6 months and 257.3 ± 54.2 103cell/μL (P < 0.001) at 1 year post-LSG. The mean MPV was increased at 6 months 10.5 ± 1.2 fL (P < 0.001) and remained unchanged at 1 year 10.3 ± 1.3 fL (P = 0.9). The mean WBC levels were significantly decreased, with 6.7 ± 1.5 103cell/μL (P < 0.001) at 6 months and 6.5 ± 1.7 103 cell/μL (P < 0.001) at 1 year. At the end of the follow-up, weight loss showed no correlation with PLT and MPV (P = 0.42, P = 0.32). The baseline demographics and post-operative outcomes are shown in Table 1.
Table 1.
Baseline characteristics and post-operative outcomes
| (total: 202) | Baseline | 6th month | P | 12th month | P* |
|---|---|---|---|---|---|
| Mean BMI (kg/m2) | 43 (34.1–62.5) | 30.9±5.2 | <0.001 | 28.2±4.5 | <0.001* |
| Mean TWL (%) | N/A | 27±8 | N/A | 32.8±7.5 | N/A |
| Mean EWL (%) | N/A | 71±23.2 | N/A | 87.8±25.3 | N/A |
| Mean PLT (103 cell/µL) | 293.2±70.3 | 257.8±61.5 | <0.001 | 257.3±54.2 | <0.001* |
| Mean MPV (fL) | 10.22±0.9 | 10.5±1.2 | <0.001 | 10.3±1.3 | 0.9* |
| Mean WBC (103 cell/µL) | 7.8±1.9 | 6.7±1.5 | <0.001 | 6.5±1.7 | <0.001* |
*Statistical analysis between baseline characteristics and 12th-month outcomes. Values are means±SDs or number of subjects. BMI: Body mass index, TWL: Total weight loss, EWL: Excess weight loss, PLT: Platelet, MPV: Mean PLT volume, SD: Standard deviation, WBC: White blood cell, N/A: Not available
DISCUSSION
The present study revealed a significant decrease in PLT and WBC counts, but MPV level has not changed at 1 year of follow-up after LSG (P < 0.001). No cardiovascular morbidity occurred in any of the patients during the follow-up.
Obese individuals tend to have an increased number of adipocytes in the bone marrow, with associated effects on the stem cells in the marrow, which are highly sensitive to their environment.[17] In addition, obesity also causes an altered metabolism of adipocytokines such as leptin and ghrelin.[18] Leptin is the most important hormone of the adipose tissue and leptin has been found to have a prothrombotic effect.[18] Interestingly, the long form of the leptin receptor was detected in human PLTs, and high concentrations of leptin were reported to act synergistically with adenosine diphosphate to promote PLT aggregation in vitro.[19] A study demonstrated a marked decrease in leptin levels after LSG.[20]
The decrease in PLT count after LSG may be associated with reduced leptin levels, weight loss and the parallel decrease in inflammation.[14] In LSG, it is important to remove the gastric fundus, which is an important source of ghrelin. A relevant study has shown that ghrelin leads to increased inflammation in adipose tissue.[21] In the present study, the median CRP was as high as 6.3 mg/L preoperatively (minimum: 1 mg/L, maximum: 27.7 mg/L). The suppression of ghrelin after LSG may provide an important contribution to the decrease in inflammation and PLT count.[22,23] Our study has also shown that WBC, one of the most important components of the immune system and inflammation, significantly decreased during the follow-up after LSG (P < 0.001).
MPV is an important marker of PLT activity. Several studies have reported high MPV as an important risk factor for coronary artery disease and stroke.[7-10] There are a limited number of studies on the effect of bariatric surgery on MPV. Raoux et al. revealed that MPV levels increased at 3 months after surgery, followed by a decrease at the end of the 1st year.[24] Kutluturk and Ozsoy and Aykota et al. reported increased MPV levels at 6 months of follow-up.[25,26] In the present study, while there was a mild increase in MPV at 6 months (P < 0.001), we observed that MPV levels remained unchanged at the end of the 1st year (P = 0.9).
The limited number of patients and the absence of a control group are amongst the limitations of our study. Moreover, we did not assess the CRP levels of the patients during the follow-up and this constitutes another limitation.
CONCLUSION
The present study has shown a significant decrease in circulating PLT and WBC levels while MPV remained unchanged 1 year after LSG. No association was found between the decrease in PLT counts and weight loss. Further comprehensive studies are needed to better understand the effect of haematologic parameters in the pathophysiology of prothrombotic cardiovascular disease in obese and post-bariatric population.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
REFERENCES
- 1.Stein PD, Goldman J. Obesity and thromboembolic disease. Clin Chest Med. 2009;30:489–93. doi: 10.1016/j.ccm.2009.05.006. viii. [DOI] [PubMed] [Google Scholar]
- 2.Hubert HB, Feinleib M, McNamara PM, Castelli WP. Obesity as an independent risk factor for cardiovascular disease: A 26-year follow-up of participants in the Framingham heart study. Circulation. 1983;67:968–77. doi: 10.1161/01.cir.67.5.968. [DOI] [PubMed] [Google Scholar]
- 3.Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, Pi-Sunyer FX, et al. Obesity and cardiovascular disease: Pathophysiology, evaluation, and effect of weight loss. Arterioscler Thromb Vasc Biol. 2006;26:968–76. doi: 10.1161/01.ATV.0000216787.85457.f3. [DOI] [PubMed] [Google Scholar]
- 4.Yusuf S, Hawken S, Ounpuu S, Bautista L, Franzosi MG, Commerford P, et al. Obesity and the risk of myocardial infarction in 27,000 participants from 52 countries: A case-control study. Lancet. 2005;366:1640–9. doi: 10.1016/S0140-6736(05)67663-5. [DOI] [PubMed] [Google Scholar]
- 5.Alberti KG, Zimmet P, Shaw J IDF Epidemiology Task Force Consensus Group. The metabolic syndrome –A new worldwide definition. Lancet. 2005;366:1059–62. doi: 10.1016/S0140-6736(05)67402-8. [DOI] [PubMed] [Google Scholar]
- 6.Morange PE, Alessi MC. Thrombosis in central obesity and metabolic syndrome: Mechanisms and epidemiology. Thromb Haemost. 2013;110:669–80. doi: 10.1160/TH13-01-0075. [DOI] [PubMed] [Google Scholar]
- 7.Bath PM, Butterworth RJ. Platelet size: Measurement, physiology and vascular disease. Blood Coagul Fibrinolysis. 1996;7:157–61. [PubMed] [Google Scholar]
- 8.Vizioli L, Muscari S, Muscari A. The relationship of mean platelet volume with the risk and prognosis of cardiovascular diseases. Int J Clin Pract. 2009;63:1509–15. doi: 10.1111/j.1742-1241.2009.02070.x. [DOI] [PubMed] [Google Scholar]
- 9.Coban E, Ozdogan M, Yazicioglu G, Akcit F. The mean platelet volume in patients with obesity. Int J Clin Pract. 2005;59:981–2. doi: 10.1111/j.1742-1241.2005.00500.x. [DOI] [PubMed] [Google Scholar]
- 10.Kutlucan A, Bulur S, Kır S, Bulur S, Önder E, Aslantaş Y, et al. The relationship between mean platelet volume with metabolic syndrome in obese individuals. Blood Coagul Fibrinolysis. 2012;23:388–90. doi: 10.1097/MBC.0b013e328352e8fa. [DOI] [PubMed] [Google Scholar]
- 11.Sjöström L, Lindroos AK, Peltonen M, Torgerson J, Bouchard C, Carlsson B, et al. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med. 2004;351:2683–93. doi: 10.1056/NEJMoa035622. [DOI] [PubMed] [Google Scholar]
- 12.English WJ, DeMaria EJ, Brethauer SA, Mattar SG, Rosenthal RJ, Morton JM. American society for metabolic and bariatric surgery estimation of metabolic and bariatric procedures performed in the United States in 2016. Surg Obes Relat Dis. 2018;14:259–63. doi: 10.1016/j.soard.2017.12.013. [DOI] [PubMed] [Google Scholar]
- 13.Aminian A, Zajichek A, Arterburn DE, Wolski KE, Brethauer SA, Schauer PR, et al. Association of metabolic surgery with major adverse cardiovascular outcomes in patients with type 2 diabetes and obesity. JAMA. 2019;322:1271–82. doi: 10.1001/jama.2019.14231. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Johansson HE, Haenni A, Zethelius B. Platelet counts and liver enzymes after bariatric surgery. J Obes 2013. 2013:567984. doi: 10.1155/2013/567984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Brooks GC, Blaha MJ, Blumenthal RS. Relation of C-reactive protein to abdominal adiposity. Am J Cardiol. 2010;106:56–61. doi: 10.1016/j.amjcard.2010.02.017. [DOI] [PubMed] [Google Scholar]
- 16.Periasamy M, Lieb DC, Butcher MJ, Kuhn N, Galkina E, Fontana M, et al. Bariatric surgery decreases monocyte-platelet aggregates in blood: A pilot study. Obes Surg. 2014;24:1410–4. doi: 10.1007/s11695-014-1278-y. [DOI] [PubMed] [Google Scholar]
- 17.Adler BJ, Kaushansky K, Rubin CT. Obesity-driven disruption of haematopoiesis and the bone marrow niche. Nat Rev Endocrinol. 2014;10:737–48. doi: 10.1038/nrendo.2014.169. [DOI] [PubMed] [Google Scholar]
- 18.Woelnerhanssen B, Peterli R, Steinert RE, Peters T, Borbély Y, Beglinger C. Effects of post-bariatric surgery weight loss on adipokines and metabolic parameters: Comparison of laparoscopic Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy –A prospective randomized trial. Surg Obes Relat Dis. 2011;7:561–8. doi: 10.1016/j.soard.2011.01.044. [DOI] [PubMed] [Google Scholar]
- 19.Nakata M, Yada T, Soejima N, Maruyama I. Leptin promotes aggregation of human platelets via the long form of its receptor. Diabetes. 1999;48:426–9. doi: 10.2337/diabetes.48.2.426. [DOI] [PubMed] [Google Scholar]
- 20.Kalinowski P, Paluszkiewicz R, Wróblewski T, Remiszewski P, Grodzicki M, Bartoszewicz Z, et al. Ghrelin, leptin, and glycemic control after sleeve gastrectomy versus Roux-en-Y gastric bypass-results of a randomized clinical trial. Surg Obes Relat Dis. 2017;13:181–8. doi: 10.1016/j.soard.2016.08.025. [DOI] [PubMed] [Google Scholar]
- 21.Lin L, Lee JH, Buras ED, Yu K, Wang R, Smith CW, et al. Ghrelin receptor regulates adipose tissue inflammation in aging. Aging (Albany NY) 2016;8:178–91. doi: 10.18632/aging.100888. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Zhang Y, Ji G, Li G, Hu Y, Liu L, Jin Q, et al. Ghrelin reductions following bariatric surgery were associated with decreased resting state activity in the hippocampus. Int J Obes (Lond) 2019;43:842–51. doi: 10.1038/s41366-018-0126-x. [DOI] [PubMed] [Google Scholar]
- 23.Bohdjalian A, Langer FB, Shakeri-Leidenmühler S, Gfrerer L, Ludvik B, Zacherl J, et al. Sleeve gastrectomy as sole and definitive bariatric procedure: 5-year results for weight loss and ghrelin. Obes Surg. 2010;20:535–40. doi: 10.1007/s11695-009-0066-6. [DOI] [PubMed] [Google Scholar]
- 24.Raoux L, Moszkowicz D, Vychnevskaia K, Poghosyan T, Beauchet A, Clauser S, et al. Effect of bariatric surgery-induced weight loss on platelet count and mean platelet volume: A 12-month follow-up study. Obes Surg. 2017;27:387–93. doi: 10.1007/s11695-016-2292-z. [DOI] [PubMed] [Google Scholar]
- 25.Kutluturk F, Ozsoy Z. Effect of sleeve gastrectomy on platelet counts and mean platelet volumes. Obes Surg. 2018;28:3159–64. doi: 10.1007/s11695-018-3287-8. [DOI] [PubMed] [Google Scholar]
- 26.Aykota MR, Yılmaz S, Atabey M, Ozgen U, Simsek S. Efeect of sleeve gastrectomy on the neutrophil-to-lymphocyte ratio, the platelet-to- lymphocyte ratio, platelet counts and mean platelet volumes. Indian J Surg. 2021;83:261–7. [Google Scholar]
