Os preditores da mortalidade em esplenectomias não traumáticas

Arq Gastroenterol ag Arquivos de Gastroenterologia Arq. Gastroenterol. 0004-2803 1678-4219 Instituto Brasileiro de Estudos e Pesquisas de Gastroenterologia e Outras Especialidades - IBEPEGE. RESUMO CONTEXTO: Há alguns estudos que examinam fatores prognósticos em esplenectomias não traumáticas em comparação com os traumáticos. OBJETIVO: Este estudo teve como objetivo avaliar os preditores de mortalidade em pacientes submetidos à esplenectomia para doenças do baço não traumático. MÉTODOS: Os prontuários dos pacientes, submetidos à esplenectomia total não traumática para doenças do baço em um centro terciário entre janeiro de 2009 e dezembro de 2019, foram revisados retrospectivamente. Os critérios de exclusão incluíram pacientes menores de 18 anos, esplenectomias parciais, esplenectomias aplicadas para facilitar a cirurgia para a malignidade em órgãos contíguos e esplenectomias realizadas durante o transplante hepático. As lesões esplênicas iatrogênicas foram consideradas trauma e esses casos também foram excluídos. RESULTADOS: O presente estudo incluiu 98 pacientes. Nove (9,2%) pacientes morreram. Na análise univariada, idade, presença de neoplasia hematológica, hematócrito, hemoglobina, contagem de glóbulos brancos, razão entre neutrófilos-linfócitos, indicações de esplenectomia, aplicação de cirurgia de emergência, técnica cirúrgica e transfusão de componentes sanguíneos foram significativamente associadas à mortalidade. Na análise multivariada, a presença de malignidade hematológica [P=0,072; OR=7,17; (IC: 0,386-61,56)], aplicação de cirurgia de emergência [P=0,035; OR=8,33; (IC: 1,165-59,595)] e leucocitose [P=0,057; OR=1,136; (IC: 0,996-1,296)] verificou-se que estão positivamente associados à mortalidade. CONCLUSÃO: Neoplasia hematológica, cirurgia de emergência e leucocitose foram os preditores independentes da mortalidade em pacientes, operados por doenças não traumáticas do baço. Uma avaliação pré-operatória minuciosa, intervenção terapêutica precoce e técnicas cirúrgicas avançadas são importantes e podem servir para minimizar complicações e mortalidade em caso de inevitável esplenectomia. Pesquisas imunológicas podem fornecer novas oportunidades terapêuticas que podem impactar positivamente nos pacientes, minimizando a morbidade e a mortalidade. INTRODUCTION Although the Roman historian, Pliny, had reported splenectomies in the first century a.D., the first detailed description of a splenectomy was that performed by Adrian Zaccarelli in 15491. While this surgery, which was carried out for non-traumatic spleen disease on a 24-year-old Greek woman with a giant spleen, splenectomies were mainly performed because of traumatic injury1. Mortality rates for splenectomies, which were performed before the 20th century, were high and many surgeons attributed adverse outcomes not to the removal of the spleen, but rather to the surgical procedure itself1. Within 20 years, the mortality rate had fallen from 30% to 15% and splenectomy was recommended for all traumas (including iatrogenic trauma), any form of splenomegaly, hematological diseases, leukemias, lymphomas, abdominal neoplasms and even for the facilitation of surgery on contiguous organs2,3. Nowadays, recommendations for the complete removal of the spleen have become more restrictive due to its pivotal role in the immune system as the largest lymphoid organ in the human body, and for its role in hematopoiesis. Non-operative management of splenic trauma, minimally invasive surgery, and the increasing preference for partial splenectomy, in cases in which total splenectomy is not mandatory, are among significant trends in splenic surgery. There are quite a few studies examining prognostic factors in non-traumatic splenectomies compared to traumatic ones4-8. This study aimed to evaluate the predictors of mortality in patients who underwent splenectomy for non-traumatic spleen diseases. METHODS Medical records of the patients, who had undergone total splenectomy for non-traumatic spleen diseases at a tertiary center between January 2009 and December 2019, were retrospectively reviewed. Exclusion criteria included patients younger than 18 years of age, partial splenectomies, splenectomies applied to facilitate surgery for malignancy on contiguous organs, and splenectomies performed during liver transplantation. Iatrogenic splenic injuries were regarded as trauma and these cases were also excluded. The data included demographics, clinical findings, laboratory findings, radiological findings, and therapeutic interventions. The following characteristics were recorded: Demographics: age and gender; Clinical findings: comorbid factors (any systemic or hematological diseases, and hematological neoplasia), indications for splenectomy, postoperative hospital stay, perioperative complications, and mortality. Mortality was defined as any death that was considered to be a direct consequence of splenectomy; Laboratory findings: preoperative complete blood count (hematocrit, hemoglobin, white blood cell, and platelet) and inflammatory markers [neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR)], which were calculated based on complete blood count results; Radiological findings: the largest diameter of the spleen based on ultrasonography and/or computerised tomography findings; and Therapeutic interventions: application of emergency surgery, surgical technique (open or laparoscopic), and transfusion of blood components. The study was conducted according to the principles as have set forth by the Helsinki Declaration of 1975. An approval from the Human Ethics Committee of Institution was obtained. Statistical analysis Data were analyzed using SPSS 17.0 for Windows. Continuous variables were presented as means with standard deviations (SDs), categorical variables were presented as numbers with percentages. A logistic model was set up to describe the relationship between mortality and variables associated with mortality. The Shapiro-Wilk test was used to analyze normality of the groups. The Student’s t-test was used for continuous variables with normal distribution. The Mann-Whitney U-test was applied for non-normally distributed variables. The chi-squared test or Fisher’s exact test was used for categorical variables. Significant variables were included in multivariate binary logistic regression analysis. A bivariate correlation test was used to determine whether there was a relationship between independent variables to be analyzed before multivariate binary logistic regression analysis. In multivariate binary logistic regression analysis, a backward stepwise method (Likelihood ratio) was used. The level of significance used at the entry of the variables was 0.05, the level of significance used for removal was 0.1. The level of significance used in testing the model in general was 0.05. RESULTS The current study included 98 patients (62.2% women), who underwent splenectomy for non-traumatic spleen diseases. The mean age was 44.14±16.19 (range: 18-75) years. Of 98 patients, 83 (84.7%) had one or more systemic diseases including autoimmune hematological diseases (n=48), hematological neoplasias (n=16), hypertension (n=14), diabetes mellitus (n=9), coronary artery diseases (n=2), congestive heart disease (n=1), congenital heart disease (n=1, including atrial septal defect), pulmonary diseases (n=3, including one with chronic obstructive pulmonary disease, one with a pulmonary cyst that had been operated on, and one with pneumonia), hepatobiliary and/or portal venous system disorders (n=10), end-stage renal diseases (n=3), rheumatological diseases [n=2, including one with rheumatoid arthritis, and one with familial mediterranean fever (FMF)], neurologic disease (n=1, including multiple sclerosis), and hypothyroidism (n=1). The mean length of the hospitalization was 7.02±6.97 (range: 1-41) days. The rates of mortality and morbidity were 9.2% and 33.7%, respectively (Table 1). TABLE 1 The univariate analysis associated with mortality. Characteristics Total Mortality (-) Mortality (+) P (n=98) (n=89) (n=9) mean ± SD or n (%) mean ± SD or n (%) mean ± SD or n (%) Age (years) 44.1±16.19 42.96±15.9 55.8±144 0.018 Gender Male 37 (37.8) 31 (34.8) 6 (66.7) 0.078 Female 61 (62.2) 58 (65.2) 3 (33.3) Systemic disease (any) Yes 83 (84.7) 74 (83.1) 9 (100) 0.347 No 15 (15.3) 15 (16.9) (-) Hematological disease Yes 65 (66.3) 60 (67.4) 5 (55.6) 0.480 No 33 (33.7) 29 (32.6) 4 (44.4) Hematological neoplasia Yes 16 (16.3) 11 (12.4) 5 (55.6) 0.005 No 82 (83.7) 78 (87.6) 4 (44.4) Indications for splenectomy Autoimmune hematological diseases 48 (49) 47 (52.8) 1 (11.1) 0.043 Hematological neoplasia 12 (12.2) 10 (11.2) 2 (22.2) Infectious diseases 12 (12.2) 11 (12.4) 1 (11.1) Non-traumatic splenic rupture 8 (8.2) 5 (5.6) 3 (33.3) Portal hypertension 9 (9.2) 8 (9) 1 (11.1) Splenic neoplasia 9 (9.2) 8 (9) 1 (11.1) Largest diameter of the spleen (cm) 14.39±5.97 14.11±5.79 17.16±7.33 0.421 Laboratory findings Hematocrit value 35.9±7.4 36.5±7.36 30.34±5.57 0.017 Hemoglobin value 11.7±2.56 12±2.53 9.43±1.61 0.004 Platelet value 170.4±121.01 163.3±109.59 240.2±198.48 0.319 White blood cell count 13.4±22.2 9.75±5.56 49.52±63.59 0.000 Neutrophil-to-lymphocyte ratio 4.6±5.8 3.91±3.94 11.7±13.30 0.033 Platelet-to-lymphocyte ratio 114.1±137.1 106.13±115.25 192.85±272.7 0.810 Application of emergency surgery Yes 14 (14.3) 9 (10.1) 5 (55.6) 0.003 No 84 (85.7) 80 (89.9) 4 (44.4) Surgical technique Open 52 (53.1) 44 (49.4) 8 (88.9) 0.034 Laparoscopic 46 (46.9) 45 (50.6) 1 (11.1) Transfusion of blood components Yes 43 (43.9) 35 (39.3) 8 (88.9) 0.009 No 55 (56.1) 54 (60.7) 1 (11.1) The majority of the patients (49%) were operated on for autoimmune hematological diseases, including immune thrombocytopenic purpura (ITP) (n=45), autoimmune hemolytic anemia (AIHA) (n=2) and hereditary spherocytosis (HS) (n=1). Hematological neoplasias were found in 16 patients. However, hematological neoplasias were the primary indication for splenectomy in 12 of them. Half of the splenectomies, which were performed for infectious diseases were due to splenic hydatid cysts (n=6). Of these, one patient had been treated with the PAIR (puncture, aspiration, injection, respiration) technique before. One patient with a splenic hydatid cyst presented with an allergic reaction due to the cyst rupturing. Six patients were operated on for splenic abscess, four of them were secondary to splenic infarct (one patient with Felty Syndrome) and two were secondary to diffuse large B-cell lymphoma (DLBCL). One patient with splenic abscess had a previous history of percutaneous drainage. Nine patients were operated on for splenic neoplasia, and histopathologic results included benign epithelial cysts (n=6), multiple cavernous hemangioma (n=1), angiosarcoma (n=1) and splenic infarct (n=1). Nine patients underwent splenectomy with esophagogastric devascularization (The Shugiura procedure) for esophageal varices secondary to portal hyertension (PHT). Seven of them were the result of cirrhotic portal hypertension (CPHT), and two were the result of non-cirrhotic portal hypertension (NCPHT). Among eight patients, who were operated on for non-traumatic splenic rupture, three were on hemodialysis for ESRD, one had Von Willebrand Disease (VWD), one had chronic myeloproliferative disease (CMD), one had FMF, one had a septic splenic emboli secondary to infective endocarditis. One patient had a splenic rupture without any identifiable cause. Emergency surgery was conducted in 14.3% of the cases (all with the open technique). It was conducted mainly for non-traumatic splenic rupture (eight cases) and infectious diseases (five cases including four splenic abscesses, and one splenic hydatid cyst). One patient with esophageal variceal bleeding also underwent emergency surgery. All of the surgeries, which were planned for autoimmune hematological diseases, were elective. All of the patients with hematological neoplasia, except three, who were operated on for non-traumatic splenic rupture (n=2) and splenic abscess (n=1), were operated on in an elective setting. The laparoscopic technique was preferred in 52 cases. However, six cases required open surgery due to splenomegaly (n=3), bleeding (n=2) and severe adhesion (n=1) (conversion rate: 11.5%). Thus, in 46 (46.9%) cases, splenectomies were completed with the laparoscopic technique. One or more of the following complications developed in 34 (34.6%) patients: pulmonary complications (n=20), subphrenic abscess (n=12), portal venous system thrombosis (PVST) (n=9), liver failure (n=2), postoperative bleeding (n=6), gastric injury (n=1), gastric leakage (n=1), pancreatic fistula (n=1), pancreatitis (n=2), fascial dehiscence (n=4), acute inflammatory demyelinating polyneuropathy (AIDP) (n=1), myocardial infarction (n=1) and ischemic stroke (n=1). Pulmonary complications were the most common complications (20.4%) including atelectasia (n=12), pneumonia (n=11), pleural effusion (n=10) and pneumothorax secondary to diaphragm injury (n=3). PVST developed in 9.18% of cases. Three had PHT (two patients with CPHT and one patient with NCPHT). Two patients had AIHD (one had HS, the other had ITP with multiple sclerosis). One patient had splenic abscess with HT and DM, two patients had splenic neoplasia. One patient with FMF had non-traumatic splenic rupture. Two patients with PVST died due to liver faiure. Nine (9.2%) patients died. The rates of mortality in cases, operated on for AIHD, infectious diseases, splenic neoplasia, PHT, hematological neoplasia and non-traumatic splenic rupture, were 2.08%, 8.3%, 11.1%, 11.1%, 16.6%, and 37.5%, respectively. The mortality of the patients with hematologic neoplasia, independent of indications for surgery, was much higher (31.25%). The mortality rate in emergency surgery was 35.7%. The characteristics of the deceased patients are presented in Table 2. TABLE 2 Characteristics of the deceased patients. Characteristics I II III IV V VI VII VIII IX Age (years) 63 51 68 65 65 49 67 51 23 Gender Female Female Male Male Female Male Male Male Male Systemic disease ESRD ESRD CMD Cirrhosis DLBCL DLBCL DLBCL HT ASD Pneumonia DM DM HT CHF Splenectomy indications NTSR NTSR NTSR CPHT Abscess HN HN Splenic AIHD neoplasia (ITP) (angiosarcoma) Spleen size (cm) 9 9 30 18 21.5 15 20 23 9 Laboratory values Hematocrit 25 29.2 22.4 24.9 30.6 38.8 37.5 33.6 30.4 Hemoglobin 8.8 8.5 6.5 8.3 10 12 10.9 9.9 10 Platelet value 274000 107000 129000 128000 599000 281000 57000 519000 68.000 WBC 19.5 19.3 186 20.3 32.2 11.7 131 13.3 12.4 NLR 19.11 1.94 8.5 12.7 43.7 9.8 1.79 1.75 6.375 PLR 304.4 18.1 8.1 98.4 855.7 281 9.12 118.2 42.5 Emergency surgery (+) (+) (+) (+) (+) (-) (-) (-) (-) Surgical technique Open Open Open Open Open Open Open Open LS Transfusion (+) (+) (+) (+) (+) (+) (+) (+) (-) Complications Gastric Hemorrhagic Hemorrhagia Hemorrhagia Diaphragm Atelectasia PVST CVA injury shock Abscess Gastric injury Pneumonia Liver failure Atelectasia Atelectasia Atelectasia leakage Atelectasia PTX AIDP Atelectasia Pneumonia Pleural Abscess Pneumonia Atelectasia Pneumonia effusion Atelectasia Pneumonia Pneumonia Pleural effusion Liver failure WBC: white blood cell, NLR: neutrophil to lymphocyte ratio, PRL: platelet to lymphocyte ratio, ESRD: end stage renal disease, CMD: chronic myeloproliferative disease, DLBCL: diffuse large B-cell lymphoma, DM: diabetes mellitus, HT: hypertension, CHF: congestive heart failure, PVST: portal venous system thrombosis, PTX: pneumothorax, NTSR: non-traumatic splenic rupture, CPHT: cirrhotic portal hypertension, HN: hematological neoplasia AIDP: acute inflammatory demyelinating polyneuropathies LS: laparoscopic surgery. In univariate analysis, age, the presence of hematological neoplasia, hematocrit, hemoglobin, white blood cell counts, NLR, indications for splenectomy, application of emergency surgery, surgical technique, and transfusion of blood components were all significantly associated with mortality (TABLE 1). In multivariate analysis, the presence of hematological malignancy [P=0.072; OR= 7.17; (CI: 0.386-61.56)], the application of emergency surgery [P=0.035; OR= 8.33; (CI: 1,165-59.595)] and leukocytosis [P=0.057; OR=1.136; (CI: 0.996-1.296)] were found to be positively associated with mortality. The characteristics of the patients with hematological neoplasias and patients treated by emergency surgery are presented in Table 3 and Table 4, respectively. TABLE 3 The characteristics of the patients with hematological neoplasia. Characteristics Hematological Hematological P neoplasia (-) neoplasia (+) (n=82) (n=16) mean ± SD or n mean ± SD or (%) n (%) Age (years) 41.23±15.4 59.06±11.01 0.000 Gender Male 27 (32.9) 10 (62.5) 0.026 Female 55 (67.1) 6 (37.5) Indications for splenectomy Autoimmune hematological diseases 48 (58.5) (-) 0.000 Hematological neoplasia (-) 12 (75) Infectious diseases 10 (12.2) 2 (12.5) Non-traumatic splenic rupture 7 (8.5) 1 (6.3) Portal hypertension 9 (11) (-) Splenic neoplasia 8 (9.8) 1 (6.3) Largest diameter of the spleen (cm) 13.1±4.7 20.9±7.47 0.000 Laboratory findings Hematocrit value 37.02±7.06 30.38±6.88 0.001 Hemoglobin value 12.15±2.45 9.78±2.24 0.001 Platelet value 167.07±108.1 187.5±176.6 0.848 White blood cell count 10.3±5.14 28.9±52.4 0.784 Neutrophil-to-lymphocyte ratio 4.3±4.34 6.32±10.6 0.492 Platelet-to-lymphocyte ratio 100.13±97 15.68±253.27 0.384 Application of emergency surgery Yes 11 (13.4) 3 (18.8) 0.695 No 71 (86.6) 13 (81.3) Surgical technique Open 36 (43.9) 16 (100) 0.000 Laparoscopic 46 (56.1) (-) Transfusion of blood components Yes 30 (36.6) 13 (81.3) 0.001 No 52 (63.4) 3 (18.8) Mortality Yes 4 (4.9) 5 (31.3) 0.005 No 78 (95.1) 11 (68.8) SD: standard deviation. TABLE 4 The characteristics of the surgical planning and scheduling. Characteristics Elective surgery Emergency surgery P (n: 84) (n: 14) Mean ± SD or n Mean ± SD or (%) n (%) Age (years) 42.04±15.84 56.71±12.49 0.002 Gender Male 29 (34.5) 8 (57.1) 0.106 Female 55 (65.5) 6 (42.9) Systemic disease (any) Yes 72 (85.7) 11 (78.6) 0.364 No 12 (14.3) 3 (21.4) Hematological disease Yes 61 (72.6) 4 (28.6) 0.002 No 23 (27.4) 10(71.4) Hematological neoplasia Yes 13 (15.5) 3 (21.4) 0.409 No 71 (84.5) 11 (78.6) Indications for splenectomy Autoimmune hematological diseases 48 (57.1) (-) 0.003 Hematological neoplasia 12 (14.3) (-) Infectious diseases 7 (8.3) 5 (35.7) Non-traumatic splenic rupture (-) 8 (57.1) Portal hypertension 8 (9.5) 1 (7.1) Splenic neoplasia 9 (10.7) (-) Largest diameter of the spleen (cm) 14.46±6.02 13.96±5.89 0.818 Laboratory findings Hematocrit value 36.58±7.03 32.09±8.71 0.035 Hemoglobin value 11.98±2.4 10.48±3.19 0.043 Platelet value 288.9±148.88 150.66±104.30 0.001 White blood cell count 10.9±14.34 28.42±45.77 0.000 Neutrophil-to-lymphocyte ratio 3.35±2.79 12.31±11.35 0.001 Platelet-to-lymphocyte ratio 87.76±75.84 272.1±268.93 0.019 Surgical technique Open 38 (45.2) 14 (100) 0.000 Laparoscopic 46 (54.8) (-) Transfusion of blood components Yes 30 (35.7) 13 (92.9) 0.000 No 54 (64.3) 1 (7.1) Mortality Yes 4 (4.8) 5 (35.7) 0.003 No 80 (95.2) 9 (64.3) SD: standard deviation. DISCUSSION The majority of elective splenic surgery is performed for diagnosis, palliation, or the definitive management of hematological disorders as in the current study. In the current study, the mortality rate was 9.2%, which was consistent with the rates (6-9%) reported in the literature4-8. Hematologic neoplasia, emergency surgery, and leukocytosis were the independent predictors of mortality. Patients with hematological neoplasia become less well after splenectomy than those with autoimmune hemolytic disorders9. According to the current study, patients with hematologic neoplasia had a 7.17-fold greater mortality. The increased mortality may be attributed to the subgroup of patients included in the study and the underlying disease itself. Hematological neoplasias were found in 19.5% of the cases, predominantly in older patients. Elderly patients with hematological disorders may be at an increased risk of surgical morbidity, as concluded in previous studies4,5,8,10,11. Hematocrit and hemoglobin values were significantly lower in cases with hematological neoplasias than in cases without. Anemia itself may contribute to clinical deterioration and result in an increased need for transfusion compared to patients without hematologic neoplasias. Emergency cases had an 8.33-fold greater mortality rate compared to that of those who underwent elective surgery. It was not surprising that hematocrit, hemoglobin and platelet values were all lower in patients treated by emergency surgery than those in patients treated by elective surgery, while the white blood cell count, NLR and PLR were higher. Bleeding due to splenic rupture and underlying infection may cause anemia and leucocytosis in patients, who undergo emergency surgery. The low platelet count may be a reflection of several factors such as splenic sequestration, blood loss, uremia, heparin use, and sepsis in those patients. In the current study, leukocytosis was among the independent predictors of mortality. It may be a reflection of an altered immunity in those patients. The immune system plays a critical role in many processes involving chronic diseases and neoplasia. For many diseases, this altered immune activity is characterized as inflammatory dysregulation12. Furthermore, neoplasia itself triggers chronic inflammation13. Along with hematological neoplasias, chronic diseases, non-hematological malignancy, and splenic abscess itself may have been responsible for leukocytosis in the deceased patients. In patients with chronic disease and neoplasia, the microorganisms easily thwart the immune system’s defenses. Considering the pivotal role of the spleen in the immune system, it is not surprising that infections lead to mortality in such patients. Despite recognition of the critical role of inflammatory dysregulation in chronic diseases and neoplasms, there are many areas of the immune mechanism that remain unelucidated. Increasing knowledge of the unique role of the spleen has attracted attention with respect to the development of therapeutic alternatives to total splenectomy. Several studies reported pulmonary complications as the most common complications after splenectomy, occurring in nearly 30% of cases7-9. Furthermore, a study concluded that pneumonia was the only independent factor for mortality in patients, who had undergone splenectomy for non-traumatic spleen disease8. According to the current study, pulmonary complications were the most common complications, and developed in all of the deceased patients. Postoperative bleeding occurs mostly when splenectomy is performed for hypersplenism, particularly in patients with thrombocytopenia9. In the current study, postoperative bleeding developed in 6.1% of the cases. Of the deceased patients, two had hypersplenism with thrombocytopenia, which resulted in postoperative bleeding. Gastric injury and leakage are rare and preventable complications of splenic surgery9. In the current study, it occurred in two of the deceased patients leading to intraabdominal abscess in one, who had undergone the Shugiura procedure. In that patient, complicated emergency surgery led to decompensated cirrhosis. Acute inflammatory demyelinating polyneuropathy is one form of acquired demyelinating polyneuropathy, which are inflammatory-demyelinating diseases of the peripheral nervous system, and have an immunologic pathogenesis14. A preceding event is most commonly a respiratory tract infection or gastroenteritis14. They are also associated with other infections (EBV, CMV, toxoplasmosis), malignant diseases including Hodgkin’s disease and non-Hodgkin’s lymphoma, and surgery14. Along with peripheral nerves, the muscles that control breathing and the bulbus may be affected, resulting in respiratory failure and pneumonia. Autonomic dysfunction may cause sudden death, likely related to cardiac dysrhythmia14. A 67-year-old male, who had undergone splenectomy for hematological neoplasia, died due to AIDP and pneumonia. Portal venous system thrombosis is a lethal disease characterized by the development of thrombosis within the portal vein, mesenteric vein, and splenic vein15. It has a wide spectrum of clinical manifestations that range from a partial obstruction of the vessel to a complete obstruction of portal venous blood flow, leading to hepatic decompensation, variceal bleeding and intestinal infarction16. Its incidence after splenectomy varies from 0% to 50%, depending upon the heterogeneity of the cases included15. It has been reported most commonly in patients who had undergone splenectomy for CMDs9,17. Splenomegaly, hypercoagulability and surgical trauma to the splenic vein may be the predisposing factors for clot formation at the hilum of the spleen9. In the current study, PVST developed in 9 cases following splenectomy, and two patients died due to liver failure. PVST is a well-known complication that occurs during the natural course of liver cirrhosis16,18-20. In our patients, only three had previous PHT. One of the deceased patients, who had developed liver failure had a CPHT, the other had not. A 51-year-old male, who underwent splenectomy for splenic neoplasia (angiosarcoma), died due to sepsis and hepatic decompensation secondary to PVST. As far as we know, this was the first case reported, in which PSVT after splenectomy, led to liver decompansation without predisposing liver disease. Although patients with ITP have a low platelet count with a tendency to bleeding, they occasionally develop venous and/or arterial thromboembolic events by a mechanism, which has not been fully elucidated. In a retrospective study, the incidence of venous, arterial and combined thromboembolic events was reported as 2.9%, 4.1%, and 6.1%, respectively21. In the current study, thromboembolic events were developed in three patients with ITP [PVT (n=1), myocardial infarction (n=1), ischemic stroke (n=1)]. The literature usually focuses on case series (from one to seven cases; in 13 studies, there was a total of 19 cases) including ITP with ischemic stroke22. They reported good outcomes in all cases, except for one22. Of those cases, 57.9% had some of the conventional risk factors for stroke22, as in our patient with ASD. Unfortunately, a 23-year-old male with ITP experienced an ischemic stroke following splenectomy and died. The surgery itself may exacerbate the underlying risk conditions. Retrospective design and small case numbers were limitations of this study. CONCLUSION Hematologic neoplasia, emergency surgery and leukocytosis were the independent predictors of mortality in patients, who were operated on for non-traumatic spleen diseases. A thorough preoperative evaluation, early therapeutic intervention, and advanced surgical techniques are important and can serve to minimize complications and mortality in case of inevitable splenectomy. Immunological research can provide new therapeutic opportunities that may impact positively on patients by minimizing morbidity and mortality. REFERENCES 1 1. Petroianu A. Historical aspects of the spleen and splenic surgeries. In: Petroianu A (editor): The spleen. Bentham Science Publishers: Brazil; 2011, p. 3-19. Petroianu A Historical aspects of the spleen and splenic surgeries Petroianu A The spleen. Bentham Science Publishers Brazil 2011 3 19 2 2. Delpero JR, Houvenaeghel G, Gastaut JA, Orsoni P, Blache JL, Guerinel G, et al. Splenectomy for hypersplenism in chronic lymphocytic leukemia and malignant non-Hodgkin’s lymphoma. Br J Surg. 1990;77:443-49. Delpero JR Houvenaeghel G Gastaut JA Orsoni P Blache JL Guerinel G Splenectomy for hypersplenism in chronic lymphocytic leukemia and malignant non-Hodgkin’s lymphoma Br J Surg 1990 77 443 449 3 3. Coco D, Leanza S. Indications for Surgery in Non-Traumatic Spleen Disease. Open Access Maced J Med Sci. 2019;7:2958-60. Coco D Leanza S Indications for Surgery in Non-Traumatic Spleen Disease Open Access Maced J Med Sci 2019 7 2958 2960 4 4. Aksnes J, Abdelnoor M, Mathisen O. Risk factors associated with mortality and morbidity after elective splenectomy. Eur J Surg. 1995;161:253-8. Aksnes J Abdelnoor M Mathisen O Risk factors associated with mortality and morbidity after elective splenectomy Eur J Surg 1995 161 253 258 5 5. Al Harbi M. Predictors for morbidity and mortality following non-traumatic splenectomy at the University Hospital, Jeddah, Saudi Arabia. Int Surg. 2000;85:317-21. Al Harbi M Predictors for morbidity and mortality following non-traumatic splenectomy at the University Hospital, Jeddah, Saudi Arabia Int Surg 2000 85 317 321 6 6. Arnoletti JP, Karam J, Brodsky J. Early postoperative complications of splenectomy for hematologic disease. Am J Clin Oncol. 1999;22:114-8. Arnoletti JP Karam J Brodsky J Early postoperative complications of splenectomy for hematologic disease Am J Clin Oncol 1999 22 114 118 7 7. Horowitz J, Smith JL, Weber TK, Rodriguez-Bigas MA, Petrelli NJ. Postoperative complications after splenectomy for hematologic malignancies. Ann Surg. 1996;223:290-6. Horowitz J Smith JL Weber TK Rodriguez-Bigas MA Petrelli NJ Postoperative complications after splenectomy for hematologic malignancies Ann Surg 1996 223 290 296 8 8. Gianchandani Moorjani R, Marchena-Gomez J, Casimiro-Perez J, Roque-Castellano C, Ramirez-Felipe J. Morbidity-and mortality-related prognostic factors of nontraumatic splenectomies. Asian J Surg. 2014;37:73-9. Gianchandani Moorjani R Marchena-Gomez J Casimiro-Perez J Roque-Castellano C Ramirez-Felipe J Morbidity-and mortality-related prognostic factors of nontraumatic splenectomies Asian J Surg 2014 37 73 79 9 9. Scott-Conner CEH, Mancino AT, Lawrence J. Surgery of the Spleen. In: Bowdler AJ (editor): The complete spleen structure, functıon, and clınıcal dısorders. 2nd ed. Springer Science + Business Media: New York; 2002, p. 281-315. Scott-Conner CEH Mancino AT Lawrence J Surgery of the Spleen Bowdler AJ The complete spleen structure, functıon, and clınıcal dısorders 2nd ed Springer Science + Business Media New York 2002 281 315 10 10. Rosen M, Brody F, Walsh RM, Tarnoff M, Malm J, Ponsky J. Outcome of laparoscopic splenectomy based on hematologic indication. Surg Endosc. 2002;16:272-9. Rosen M Brody F Walsh RM Tarnoff M Malm J Ponsky J Outcome of laparoscopic splenectomy based on hematologic indication Surg Endosc 2002 16 272 279 11 11. Ziemski JM, Rudowski WJ, Jaskowiak W, Rusiniak L, Scharf R. Evaluation of early postsplenectomy complications. Surg Gynecol Obstet. 1987;165:507-14. Ziemski JM Rudowski WJ Jaskowiak W Rusiniak L Scharf R Evaluation of early postsplenectomy complications Surg Gynecol Obstet 1987 165 507 514 12 12. Zhong J, Shi G. Editorial: Regulation of Inflammation in Chronic Disease. Front Immunol. 2019;10:737. Zhong J Shi G Editorial: Regulation of Inflammation in Chronic Disease Front Immunol 2019 10 737 737 13 13. Roxburgh CS, McMillan DC. Role of systemic inflammatory response in predicting survival in patients with primary operable cancer. Future Oncol. 2010;6:149-63. Roxburgh CS McMillan DC Role of systemic inflammatory response in predicting survival in patients with primary operable cancer Future Oncol 2010 6 149 163 14 14. Albers JW, Kelly JJ Jr. Acquired inflammatory demyelinating polyneuropathies; clinical and electrodiagnostic features. Muscle Nerve. 1989;12:435-51. Albers JW Kelly JJ Jr Acquired inflammatory demyelinating polyneuropathies; clinical and electrodiagnostic features Muscle Nerve 1989 12 435 451 15 15. Qi X, Bai M, Guo X, Fan D. Pharmacologic Prophylaxis of Portal Venous System Thrombosis after Splenectomy: A Meta-Analysis. Gastroenterology Research and Practice. 2014. doi: 10.1155/2014/292689. Qi X Bai M Guo X Fan D Pharmacologic Prophylaxis of Portal Venous System Thrombosis after Splenectomy: A Meta-Analysis Gastroenterology Research and Practice 2014 10.1155/2014/292689 16 16. Faccia M, Ainora ME, Ponziani FR, Riccardi L, Garcovich M, Gasbarrini A, et al. Portal vein thrombosis in cirrhosis: Why a well-known complication is still matter of debate. World J Gastroenterol. 2019;25:4437-51. Faccia M Ainora ME Ponziani FR Riccardi L Garcovich M Gasbarrini A Portal vein thrombosis in cirrhosis: Why a well-known complication is still matter of debate World J Gastroenterol 2019 25 4437 4451 17 17. Winslow ER, Brunt LM, Drebin JA, Soper NJ, Klingensmith ME. Portal vein thrombosis after splenectomy. Am J Surg. 2002;184:631-5; discussion 635-636. Winslow ER Brunt LM Drebin JA Soper NJ Klingensmith ME Portal vein thrombosis after splenectomy Am J Surg 2002 184 631 635 discussion 635-636 18 18. Amitrano L, Guardascione MA, Brancaccio V, Margaglione M, Manguso F, Iannaccone L, et al. Risk factors and clinical presentation of portal vein thrombosis in patients with liver cirrhosis. J Hepatol. 2004;40:736-41. Amitrano L Guardascione MA Brancaccio V Margaglione M Manguso F Iannaccone L Risk factors and clinical presentation of portal vein thrombosis in patients with liver cirrhosis J Hepatol 2004 40 736 741 19 19. Bagheri Lankarani K, Homayon K, Motevalli D, Heidari ST, Alavian SM, Malek-Hosseini SA. Risk factors for portal vein thrombosis in patients with cirrhosis awaiting liver transplantation in Shiraz, Iran. Hepat Mon. 2015;15:e26407. Bagheri Lankarani K Homayon K Motevalli D Heidari ST Alavian SM Malek-Hosseini SA Risk factors for portal vein thrombosis in patients with cirrhosis awaiting liver transplantation in Shiraz, Iran Hepat Mon 2015 15 e26407 20 20. Qi X, Han G, Ye C, Zhang Y, Dai J, Peng Y, et al. Splenectomy causes 10-fold increased risk of portal venous system thrombosis in liver cirrhosis patients. Med Sci Monit. 2016;22:2528-50. Qi X Han G Ye C Zhang Y Dai J Peng Y Splenectomy causes 10-fold increased risk of portal venous system thrombosis in liver cirrhosis patients Med Sci Monit 2016 22 2528 2550 21 21. Sarpatwari A, Bennett D, Logie JW, Shukla A, Beach KJ, Newland AC, et al. Thromboembolic events among adult patients with primary immune thrombocytopenia in the United Kingdom General Practice Research Database. Haematologica. 2010;95:1167-75. Sarpatwari A Bennett D Logie JW Shukla A Beach KJ Newland AC Thromboembolic events among adult patients with primary immune thrombocytopenia in the United Kingdom General Practice Research Database Haematologica 2010 95 1167 1175 22 22. Zhao H, Lian Y, Zhang H, Xie N, Gao Y, Wang Z, et al. Ischemic stroke associated with immune thrombocytopenia. J Thromb Thrombolysis. 2015;40:156-60. Zhao H Lian Y Zhang H Xie N Gao Y Wang Z Ischemic stroke associated with immune thrombocytopenia J Thromb Thrombolysis 2015 40 156 160 Disclosure of funding: no funding received