Journal of Pediatric Surgery 49 (2014) 614–617
Contents lists available at ScienceDirect
Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
Intra-abdominal venous thrombosis after colectomy in pediatric patients with chronic ulcerative colitis: Incidence, treatment, and outcomes Ryan M. Antiel a, Yassar Hashim a, Christopher R. Moir a, Vilmarie Rodriguez b, Tarig Elraiyah c, Abdalla E. Zarroug a,⁎ a b c
Division of Pediatric Surgery, Mayo Clinic, Rochester, MN 55905, USA Division of Pediatric Hematology-Oncology, Mayo Clinic, Rochester, MN, USA Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN, USA
a r t i c l e
i n f o
Article history: Received 15 July 2013 Received in revised form 8 October 2013 Accepted 9 October 2013 Key words: Venous thromboembolism Ulcerative colitis Colectomy Thrombus Anticoagulation
a b s t r a c t Purpose: Children with chronic ulcerative colitis (CUC) are at increased risk for venous thromboembolism, especially after colectomy procedures. We aim to review our patients with CUC who underwent a colectomy and suffered intra-abdominal thrombosis; moreover we wanted to define thrombotic incidence and outcomes Methods: In this is IRB approved retrospective study, we reviewed our patients who underwent colectomy for CUC from January 1999 to December 2011 for development of intra-abdominal thrombosis. Results: Of 366 patients with CUC who underwent colectomy, 15 (4%) were diagnosed with a venous thromboembolism. All patients presented with acute abdominal pain. The locations of thrombus formation varied: 13 (87%) developed thrombi in the portal vein, 4 (27%) in the splenic vein, 2 (13%) in the superior mesenteric vein, 1 (7%) in the hepatic vein, and 1 (7%) in the hepatic artery. The mean number of postoperative days at diagnosis of thrombus was 38.7 days (range 3–180 days). Fourteen patients (93%) underwent anticoagulation for treatment. The mean number of days of anticoagulant therapy until documented resolution of thrombus on imaging was 96.3 days (range 14–364 days). All thrombi resolved with therapy. There was no mortality during follow-up. Conclusions: Four percent of our pediatric patients with chronic ulcerative colitis who underwent colectomy developed symptomatic intra-abdominal venous thromboembolism. 3 to 6 months of anticoagulant therapy is adequate treatment in almost all patients. Practitioners should have a high index of suspicion for intra-abdominal venous thrombus when these patients complain of abdominal pain postoperatively. Based on our experience, prophylactic anticoagulation should be strongly considered perioperatively in this population. © 2014 Elsevier Inc. All rights reserved.
Venous thromboembolisms (VTEs) are very rare in the general pediatric population with a reported incidence between 0.7 and 1.4 per 100,000 [1]. However, the clinical significance of such an event can be devastating with a mortality rate of approximately 2% [2]. Furthermore, over the past 15 years the frequency of VTE diagnosis has increased 3 to 10 fold in hospitalized children [3]. The vast majority of VTEs in children are found to be in conjunction with a coexisting medical condition [4]. Common coexisting conditions include: central venous catheters, sepsis, malignancy, and a history of recent surgery [2]. Data from a Canadian registry of children showed that cancer was the most commonly associated condition with the development of VTEs [5]. Other studies in children from the US showed that although VTEs were most commonly associated with cardiovascular disease, inflammatory bowel disease (IBD) puts patients at an increased risk of thromboembolism development [6–8]. ⁎ Corresponding author. Mayo Clinic, 200 First Street SW, Rochester, MN 55905. E-mail address: [email protected] (A.E. Zarroug). 0022-3468/$ – see front matter © 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpedsurg.2013.10.004
Thromboembolic events in IBD patients were first described in 1936 [9]. The majority of these of complications are related to deep vein thrombosis (DVT) or pulmonary emboli. Adult studies demonstrate that patients with IBD are at a 3 fold increased risk for systemic thromboembolic events when compared to the general population [10,11]. The incidence of thromboembolic events in children with IBD is between 1.3% and 2.3% [12,13]. The greatest risk in this population seems to be for lower extremity deep vein thrombosis and cerebrovascular thromboembolic events [13]. Although IBD is a hypercoagulable state, no consensus exists regarding the mechanism that predisposes IBD patients to thromboembolic events [8]. Thromboembolic events in children with IBD most commonly occur during active disease (82%), and specifically in children with chronic ulcerative colitis (CUC) (OR 3.7, 95% CI 1.8–7.6) [14]. While abdominal venous thrombi have been described in adult IBD populations after total colectomy with ileoanal anastomosis [15–19], this remains a rare postoperative complication in the pediatric population. Among a cohort of 70 IBD pediatric patients who had
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experienced some sort of thrombosis or thromboembolism, 11 (16%) had developed an abdominal venous thrombosis [13]. A recent case report documents portal vein thrombus development following proctocolectomy with pouch ileoanal anastomosis in 2 CUC patients [20]. Yet, the incidence of postoperative abdominal venous thrombosis in pediatric patients with CUC remains unknown. In our IBD practice, we anecdotally noted a number of patients with CUC who have subsequently developed intra-abdominal thrombosis post-colectomy. These patients often present to clinic or the emergency department with abdominal pain following surgery. Furthermore, when we looked to the literature to help guide adequate therapy, we found very little data. Thus, we sought to review our CUC pediatric population who presented with an intra-abdominal thrombus after colectomy in order to better understand the incidence of this complication and the efficacy and duration of anticoagulation given to our patients. 1. Methods We reviewed all patients, age 21 and younger, who underwent colectomy for CUC from January 1999 to December 2011. We included patients who developed intra-abdominal thrombosis following colectomy, including portal, mesenteric, splenic, or hepatic thrombus formation. Patients with Crohn’s disease were not included in this study. Colectomy included all laparoscopic, open, subtotal, total abdominal, proctocolectomy, with or without reconstruction. Patients with other thromboembolic disease, such as lower extremity and upper extremity DVT, or internal jugular vein thrombosis, were not included in this analysis; however we did analyze if patients who had intra-abdominal thrombosis also had other complications such as DVT. Data were tabulated and summarized with frequencies and percentages. All analyses were performed using JMP version 9.0 (SAS Institute Inc). This study was approved by the Mayo Clinic institutional review board and is HIPPA compliant. 2. Results We reviewed a total of 366 patients who underwent colectomy for CUC. Fifteen of these patients (incidence of 4%) were diagnosed with a portal, mesenteric, splenic, or hepatic venous thrombus. The mean age of this cohort (n = 15) was 17.9 years (range 14–21 years). Nine patients were female (60%). Eight patients (53%) underwent total colectomy, four underwent proctocolectomy (27%), and three underwent subtotal colectomies (20%). Three patients (20%) underwent open surgery, compared to 12 patients (80%) who underwent laparoscopic surgery. All of the patients (n = 15) presented with acute onset of abdominal pain. The locations of thrombus formation varied among patients. Thirteen (87%) developed thrombi in the portal vein, 4 (27%) in the splenic vein, 2 (13%) in the superior mesenteric vein, 1 (7%) in the hepatic vein, and 1 (7%) in the hepatic artery. None of these 15 patients experienced lower or upper extremity DVT or internal jugular vein thrombosis. All of these mesenteric thrombi were noted on computer tomography scan except for one patient who was diagnosed with ultrasound (Fig. 1). The mean number of postoperative days at the time of diagnosis of thrombus was 38.7 days (range 3–180 days). One patient developed a thrombus three days before his scheduled colectomy diagnosed by pre-operative ultrasound, but underwent emergent colectomy. None of the patients in our cohort had any known underlying hypercoagulable state, besides the diagnosis of CUC and undergoing a surgical procedure. We did not find a significant relationship between risk of thrombus formation and age, gender, or other patient factors. Fourteen of 15 patients (93%) underwent anticoagulation for treatment. Ten patients were initially anticoagulated with lowmolecular weight heparin and subsequently sent home on warfarin.
Fig. 1. Computer tomography image of hepatic venous thrombosis in a patient following total colectomy.
Others were treated with low-molecular-weight heparin only (dalteparin sodium) (n = 3). One patient was treated with aspirin only. The remaining patient’s splenic vein thrombi dissolved, based on follow up imaging, without anticoagulation. The shortest duration of therapy (when given) was 7 weeks with a mean duration of 16 weeks, median duration 12.7 weeks; and 2 patients were put on therapy indefinitely. The mean number of days until documented resolution on imaging was 96.3 days (range 14–364 days). All thrombi in these patients did resolve based upon subsequent imaging. One patient developed acute pancreatitis associated with her splenic vein thrombus. There was no mortality during follow-up (Table 1). 3. Discussion Intra-abdominal thrombosis is an uncommon, but potentially serious complication in pediatric patients who undergo any type of colectomy for CUC. These patients represent a high risk self-selected population since only patients with surgical indications undergo colectomy. Many of those patients are on high doses of medication such as steroids, have lost significant amounts of blood, and/or have Table 1 Characteristics of CUC patients who presented with an intra-abdominal thrombus following colectomy. Characteristic Demographics Female Male Mean age (range) Mean postoperative days at diagnosis (range) Operation Total colectomy Proctocolectomy Subtotal colectomy Location of thrombus Portal vein Splenic vein Superior mesenteric vein Hepatic vein Hepatic artery Anticoagulation LMWHa and Coumadin LMWHa only Aspirin only None a
LMWH: low molecular weight heparin.
No. (%) 9 (60) 6 (40) 17.9 (14–21) 38.7 (3–180) 8 (53) 4 (27) 3 (20) 13 (87) 4 (27) 2 (13) 1 (7) 1 (7) 10 (66) 3 (20) 1 (7) 1 (7)
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severe medically refractory disease. Therefore, they are often sick patients thus placing them at higher risk for any venous thrombus after intra-abdominal surgery. Furthermore, when we looked for guidance in the literature to help us decide who is high risk, what medication is best to treat with and how long to treat for, we found surprisingly little data, if any. To compound the issue, we often received different opinions from various specialties for the types of therapy and the duration. Therefore, we decided to look at our experience with intra-abdominal thrombosis in patients with CUC. This study represents the largest cohort of these types of complications in pediatric patients with CUC. We identified 15 patients with CUC who developed a post-operative thrombus. This accounted for a prevalence of 4% considering the total number of CUC patients who underwent a colectomy during this time period (366 patients). All of these 15 patients underwent examination for thrombus after they presented with post-operative abdominal pain. Previous retrospective studies, however, have demonstrated that most IBD patients who develop portal or mesenteric vein thrombosis are asymptomatic [21,22]. Our cohort is probably an underestimate of the real number of patients with intra-abdominal thrombus since we do not routinely screen all patients for thrombus. In our cohort, the most common vessels for thrombi formation were the portal vein and splenic vein. All of our patients had complete resolution of their thrombi based on imaging. Our patients did have CT scanning as their main mode of imaging. Given the risks of radiation to children, consideration should be given to use Duplex ultrasound as a means of surveillance and/or diagnosis instead of CT scanning. However, ultrasound sometimes may not be diagnostically adequate such as when bowel gas prevents adequate imaging; therefore in patients with abdominal pain a CT scan is often reasonable. We also noted that most of the intra-abdominal venous thrombosis occurred in the laparoscopic versus the open procedures. It is possible that increased intra-abdominal pressure via insufflation may have been a contributing factor. We have not routinely prophylactically anticoagulated (such as intraoperative subcutaneous heparin injections) our pediatric CUC patients undergoing colectomy given what we considered potential bleeding risks associated with prophylactic anticoagulation. However, no data exist that specify the risk of minor or major bleeding after major surgery with prophylactic anticoagulation in the pediatric population. A recent systematic review of thirty-three randomized controlled trials in adults demonstrated a minor bleeding risk (injection site bruising, wound hematoma, drain site bleeding, or hematuria) of 1.6%–6.9% and a major bleeding risk (GI tract bleeding, retroperitoneal bleeding) of b0.1%–0.2% in adults who received pharmacologic DVT thrombosis prophylaxis [23]. Prophylaxis is indicated for patients with a known thrombosis or a history of thrombophilia [24]. Remzi et al. report an increased risk of portal venous thrombi in adult patients after restorative proctocolectomy who had not received preoperative or postoperative subcutaneous heparin therapy (P = .0001) [25]. A recent review of venous thromboembolism in pediatric trauma patients documented that the reported incidence of venous thromboembolism in the overall pediatric trauma population ranges from 0.02% to 0.33% [26]. At best, we can only extrapolate data from DVT thrombosis to intra-abdominal venous thrombosis and also extrapolate the data from adults to children; clearly these are unsatisfactory data to make final recommendations. Also, we neither screened every post-operative patient nor recommend imaging in all patients who undergo colectomy for CUC. All of the patients in this cohort presented with abdominal pain, therefore, we strongly recommend that physicians have a high index of suspicion for intraabdominal thrombus whenever these patients complain of abdominal pain post-operatively either in-hospital or as outpatients. Therefore, we recommend a low threshold for use of imaging such for patients who are symptomatic. Regarding treatment of the thrombus, it is interesting
to note that although one patient had no treatment and another had aspirin only, their thrombi resolved. We do however recommend full anticoagulation, beyond simply salicylic acid, until resolution of the thrombus is confirmed with imaging since the associated complications of complete portal thrombus formation can be devastating. All intra-abdominal venous thrombus should be treated with anticoagulation unless a major contraindication exists. While there are no randomized controlled trials on pediatric anticoagulation, our data suggest that 3–6 months of anticoagulant therapy is sufficient for the vast majority of patients, if not all. We do not recommend indefinite anticoagulation therapy unless there are other indications for it. Our data and recommendations appear to be consistent with common practice for intraabdominal VTEs in general [3]. Our study has several important limitations. Associations from this retrospective review cannot establish causal relationships. This study does not propose a specific mechanism for CUC patient’s hypercoagulable state; rather we sought to report the incidence and treatment in our practice, something that was previously unknown. Our data are limited in that the incidence of venous thrombus was identified retrospectively from medical records rather than prospectively via a standardized protocol. It is probable that there were others who developed asymptomatic venous thrombi that went undetected. Therefore, our incidence rate of 4% is most likely an underestimation of the actual incidence of CUC patients who develop a postoperative thrombus. Finally, prospective studies or at least protocol basedstudies will need to be designed to understand the bleeding risk of prophylactic anticoagulation in the pediatric population as well as the most effective treatment and duration of thrombi in this special population. The best data we have from adult studies estimate the risks of major complications from prophylactic anticoagulation to be around 0.2%. Given our finding of a 4% chance of intra-abdominal venous thrombosis, it is reasonable to consider prophylactic anticoagulation when undergoing colectomy. Future prospective studies should dissect which patients are at very high risk and really should receive prophylactic anticoagulation and which patients are low risk and should not receive anticoagulation. Notwithstanding these limitations, this is to our knowledge the first and largest report of the incidence, treatment, and duration of therapy of intra-abdominal thrombus post-colectomy among children with CUC. In conclusion, 4% of our pediatric patients with chronic ulcerative colitis who underwent colectomy developed symptomatic intraabdominal venous thromboembolism. 3 to 6 months of anticoagulant therapy is adequate treatment in almost all patients; resolution of the thrombus should be documented with imaging as well. Practitioners should have a high index of suspicion for intra-abdominal venous thrombus when these patients complain of abdominal pain postoperatively. Although more research is needed to answer if prophylactic anticoagulation should be administered, based on our experience, peri-operative prophylactic anticoagulation should be considered in this population on an individualized case-by-case basis.
References [1] Chalmers EA. Epidemiology of venous thromboembolism in neonates and children. Thromb Res 2006;118:3–12. [2] Ha C, Magowan S, Accortt NA, et al. Risk of arterial thrombotic events in inflammatory bowel disease. Am J Gastroenterol 2009;104:1445–51. [3] Chan A, Monagle P. Updates in thrombosis in pediatrics: where are we after 20 years? Hem 2012;2012:439–43. [4] Kuhle S, Massicotte P, Chan A, et al. Systemic thromboembolism in children. Data from the 1-800-NO-CLOTS Consultation Service. Thromb Haemost 2004;92:722–8. [5] Andrew M, David M, Adams M, et al. Venous thromboembolic complications (VTE) in children: first analysis of the Canadian Registry of VTE. Blood 1994;83(5):1251–7. [6] Setty B, O'Brien S, Kerlin B. Pediatric venous thromboembolism in the United States: a tertiary care complication of chronic diseases. Pediatr Hematol Oncol 2012;59(2):258–64. [7] Raffini L, Huang Y, Witmer C, et al. Dramatic increase in venous thromboembolism in children's hospitals in the United States from 2001 to 2007. Pediatrics 2009;124(4):1001–8.
R.M. Antiel et al. / Journal of Pediatric Surgery 49 (2014) 614–617 [8] Twig G, Zandman-Goddard G, Szyper-Kravitz M, et al. Systemic thromboembolism in inflammatory bowel disease: mechanisms and clinical applications. Ann N Y Acad Sci 2005;1051:166–73. [9] Bargen JA, NB. Extensive arterial and venous thrombosis complicating ulcerative colitis. Arch Intern Med 1936;58:17–31. [10] Miehsler W, Reinisch W, Valic E, et al. Is inflammatory bowel disease an independent and disease specific risk factor for thromboembolism? Gut 2004;53: 542–8. [11] Bernstein CN, Blanchard JF. Prophylaxis is indicated for patients with a known clot or a history of coagulopathies, Houston DS, et al: The incidence of deep venous thrombosis and pulmonary embolism among patients with inflammatory bowel disease: a population-based cohort study. Thromb Haemost 2001;85: 430–4. [12] Patterson M, Castiglioni L, Sampson L. Chronic ulcerative colitis beginning in children and teenagers. A review of 43 patients. Am J Dig Dis 1971;16:289–97. [13] del Rosario JF, Orenstein SR, Bhargava S, et al. Thrombotic complications in pediatric inflammatory bowel disease. Clin Pediatr (Phila) 1994;33:159–61. [14] Lazzerini M, Bramuzzo M, Maschio M, et al. Thromboembolism in pediatric inflammatory bowel disease: systematic review. Inflamm Bowel Dis 2011;17: 2174–83. [15] Farkas LM, Nelson RL, Abcarian H. A case of portal venous system thrombosis in ulcerative colitis. J Am Coll Surg 2000;190:94. [16] Fichera A, Cicchiello LA, Mendelson DS, et al. Superior mesenteric vein thrombosis after colectomy for inflammatory bowel disease: a not uncommon cause of postoperative acute abdominal pain. Dis Colon Rectum 2003;46:643–8.
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[17] Hatoum OA, Spinelli KS, Abu-Hajir M, et al. Mesenteric venous thrombosis in inflammatory bowel disease. J Clin Gastroenterol 2005;39:27–31. [18] Ball CG, MacLean AR, Buie WD, et al. Portal vein thrombi after ileal pouch-anal anastomosis: its incidence and association with pouchitis. Surg Today 2007;37:552–7. [19] Baker ME, Remzi F, Einstein D, et al. CT depiction of portal vein thrombi after creation of ileal pouch-anal anastomosis. Radiology 2003;227:73–9. [20] Ibele AR, Kennedy GD, Lund DP, et al. Portal vein thrombus after pediatric proctocolectomy with ileoanal anastomosis. J Pediatr Surg 2010;45(5):1026–9. [21] Grainge M, West J, Card T. Venous thromboembolism during active disease and remission in inflammatory bowel disease: a cohort study. Lancet 2010;375(9715): 657–63. [22] Jackson C, Fryer J, Danese S, et al. Mesenteric vascular thromboembolism in inflammatory bowel disease: a single center experience. J Gastrointest Surg 2011;15(1):97–100. [23] Leonardi MJ, McGory ML, Ko CY. The rate of bleeding complications after pharmacologic deep venous thrombosis prophylaxis: a systematic review of 33 randomized controlled trials. Arch Surg 2006;141(8):790–7. [24] Monagle P, Chan AK, Goldenberg NA, et al. Antithrombotic therapy in neonates and children: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012;141(2 Suppl):e737S–801S. [25] Remzi FH, Fazio VW, Oncel M, et al. Portal vein thrombi after restorative proctocolectomy. Surgery 2002;132(4):655–61. [26] Thompson AJ, McSwain SD, Webb SA, et al. Venous thromboembolism prophylaxis in the pediatric trauma population. J Pediatr Surg 2013 Jun;48(6):1413–21.
Contents lists available at ScienceDirect
Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
Intra-abdominal venous thrombosis after colectomy in pediatric patients with chronic ulcerative colitis: Incidence, treatment, and outcomes Ryan M. Antiel a, Yassar Hashim a, Christopher R. Moir a, Vilmarie Rodriguez b, Tarig Elraiyah c, Abdalla E. Zarroug a,⁎ a b c
Division of Pediatric Surgery, Mayo Clinic, Rochester, MN 55905, USA Division of Pediatric Hematology-Oncology, Mayo Clinic, Rochester, MN, USA Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN, USA
a r t i c l e
i n f o
Article history: Received 15 July 2013 Received in revised form 8 October 2013 Accepted 9 October 2013 Key words: Venous thromboembolism Ulcerative colitis Colectomy Thrombus Anticoagulation
a b s t r a c t Purpose: Children with chronic ulcerative colitis (CUC) are at increased risk for venous thromboembolism, especially after colectomy procedures. We aim to review our patients with CUC who underwent a colectomy and suffered intra-abdominal thrombosis; moreover we wanted to define thrombotic incidence and outcomes Methods: In this is IRB approved retrospective study, we reviewed our patients who underwent colectomy for CUC from January 1999 to December 2011 for development of intra-abdominal thrombosis. Results: Of 366 patients with CUC who underwent colectomy, 15 (4%) were diagnosed with a venous thromboembolism. All patients presented with acute abdominal pain. The locations of thrombus formation varied: 13 (87%) developed thrombi in the portal vein, 4 (27%) in the splenic vein, 2 (13%) in the superior mesenteric vein, 1 (7%) in the hepatic vein, and 1 (7%) in the hepatic artery. The mean number of postoperative days at diagnosis of thrombus was 38.7 days (range 3–180 days). Fourteen patients (93%) underwent anticoagulation for treatment. The mean number of days of anticoagulant therapy until documented resolution of thrombus on imaging was 96.3 days (range 14–364 days). All thrombi resolved with therapy. There was no mortality during follow-up. Conclusions: Four percent of our pediatric patients with chronic ulcerative colitis who underwent colectomy developed symptomatic intra-abdominal venous thromboembolism. 3 to 6 months of anticoagulant therapy is adequate treatment in almost all patients. Practitioners should have a high index of suspicion for intra-abdominal venous thrombus when these patients complain of abdominal pain postoperatively. Based on our experience, prophylactic anticoagulation should be strongly considered perioperatively in this population. © 2014 Elsevier Inc. All rights reserved.
Venous thromboembolisms (VTEs) are very rare in the general pediatric population with a reported incidence between 0.7 and 1.4 per 100,000 [1]. However, the clinical significance of such an event can be devastating with a mortality rate of approximately 2% [2]. Furthermore, over the past 15 years the frequency of VTE diagnosis has increased 3 to 10 fold in hospitalized children [3]. The vast majority of VTEs in children are found to be in conjunction with a coexisting medical condition [4]. Common coexisting conditions include: central venous catheters, sepsis, malignancy, and a history of recent surgery [2]. Data from a Canadian registry of children showed that cancer was the most commonly associated condition with the development of VTEs [5]. Other studies in children from the US showed that although VTEs were most commonly associated with cardiovascular disease, inflammatory bowel disease (IBD) puts patients at an increased risk of thromboembolism development [6–8]. ⁎ Corresponding author. Mayo Clinic, 200 First Street SW, Rochester, MN 55905. E-mail address: [email protected] (A.E. Zarroug). 0022-3468/$ – see front matter © 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpedsurg.2013.10.004
Thromboembolic events in IBD patients were first described in 1936 [9]. The majority of these of complications are related to deep vein thrombosis (DVT) or pulmonary emboli. Adult studies demonstrate that patients with IBD are at a 3 fold increased risk for systemic thromboembolic events when compared to the general population [10,11]. The incidence of thromboembolic events in children with IBD is between 1.3% and 2.3% [12,13]. The greatest risk in this population seems to be for lower extremity deep vein thrombosis and cerebrovascular thromboembolic events [13]. Although IBD is a hypercoagulable state, no consensus exists regarding the mechanism that predisposes IBD patients to thromboembolic events [8]. Thromboembolic events in children with IBD most commonly occur during active disease (82%), and specifically in children with chronic ulcerative colitis (CUC) (OR 3.7, 95% CI 1.8–7.6) [14]. While abdominal venous thrombi have been described in adult IBD populations after total colectomy with ileoanal anastomosis [15–19], this remains a rare postoperative complication in the pediatric population. Among a cohort of 70 IBD pediatric patients who had
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experienced some sort of thrombosis or thromboembolism, 11 (16%) had developed an abdominal venous thrombosis [13]. A recent case report documents portal vein thrombus development following proctocolectomy with pouch ileoanal anastomosis in 2 CUC patients [20]. Yet, the incidence of postoperative abdominal venous thrombosis in pediatric patients with CUC remains unknown. In our IBD practice, we anecdotally noted a number of patients with CUC who have subsequently developed intra-abdominal thrombosis post-colectomy. These patients often present to clinic or the emergency department with abdominal pain following surgery. Furthermore, when we looked to the literature to help guide adequate therapy, we found very little data. Thus, we sought to review our CUC pediatric population who presented with an intra-abdominal thrombus after colectomy in order to better understand the incidence of this complication and the efficacy and duration of anticoagulation given to our patients. 1. Methods We reviewed all patients, age 21 and younger, who underwent colectomy for CUC from January 1999 to December 2011. We included patients who developed intra-abdominal thrombosis following colectomy, including portal, mesenteric, splenic, or hepatic thrombus formation. Patients with Crohn’s disease were not included in this study. Colectomy included all laparoscopic, open, subtotal, total abdominal, proctocolectomy, with or without reconstruction. Patients with other thromboembolic disease, such as lower extremity and upper extremity DVT, or internal jugular vein thrombosis, were not included in this analysis; however we did analyze if patients who had intra-abdominal thrombosis also had other complications such as DVT. Data were tabulated and summarized with frequencies and percentages. All analyses were performed using JMP version 9.0 (SAS Institute Inc). This study was approved by the Mayo Clinic institutional review board and is HIPPA compliant. 2. Results We reviewed a total of 366 patients who underwent colectomy for CUC. Fifteen of these patients (incidence of 4%) were diagnosed with a portal, mesenteric, splenic, or hepatic venous thrombus. The mean age of this cohort (n = 15) was 17.9 years (range 14–21 years). Nine patients were female (60%). Eight patients (53%) underwent total colectomy, four underwent proctocolectomy (27%), and three underwent subtotal colectomies (20%). Three patients (20%) underwent open surgery, compared to 12 patients (80%) who underwent laparoscopic surgery. All of the patients (n = 15) presented with acute onset of abdominal pain. The locations of thrombus formation varied among patients. Thirteen (87%) developed thrombi in the portal vein, 4 (27%) in the splenic vein, 2 (13%) in the superior mesenteric vein, 1 (7%) in the hepatic vein, and 1 (7%) in the hepatic artery. None of these 15 patients experienced lower or upper extremity DVT or internal jugular vein thrombosis. All of these mesenteric thrombi were noted on computer tomography scan except for one patient who was diagnosed with ultrasound (Fig. 1). The mean number of postoperative days at the time of diagnosis of thrombus was 38.7 days (range 3–180 days). One patient developed a thrombus three days before his scheduled colectomy diagnosed by pre-operative ultrasound, but underwent emergent colectomy. None of the patients in our cohort had any known underlying hypercoagulable state, besides the diagnosis of CUC and undergoing a surgical procedure. We did not find a significant relationship between risk of thrombus formation and age, gender, or other patient factors. Fourteen of 15 patients (93%) underwent anticoagulation for treatment. Ten patients were initially anticoagulated with lowmolecular weight heparin and subsequently sent home on warfarin.
Fig. 1. Computer tomography image of hepatic venous thrombosis in a patient following total colectomy.
Others were treated with low-molecular-weight heparin only (dalteparin sodium) (n = 3). One patient was treated with aspirin only. The remaining patient’s splenic vein thrombi dissolved, based on follow up imaging, without anticoagulation. The shortest duration of therapy (when given) was 7 weeks with a mean duration of 16 weeks, median duration 12.7 weeks; and 2 patients were put on therapy indefinitely. The mean number of days until documented resolution on imaging was 96.3 days (range 14–364 days). All thrombi in these patients did resolve based upon subsequent imaging. One patient developed acute pancreatitis associated with her splenic vein thrombus. There was no mortality during follow-up (Table 1). 3. Discussion Intra-abdominal thrombosis is an uncommon, but potentially serious complication in pediatric patients who undergo any type of colectomy for CUC. These patients represent a high risk self-selected population since only patients with surgical indications undergo colectomy. Many of those patients are on high doses of medication such as steroids, have lost significant amounts of blood, and/or have Table 1 Characteristics of CUC patients who presented with an intra-abdominal thrombus following colectomy. Characteristic Demographics Female Male Mean age (range) Mean postoperative days at diagnosis (range) Operation Total colectomy Proctocolectomy Subtotal colectomy Location of thrombus Portal vein Splenic vein Superior mesenteric vein Hepatic vein Hepatic artery Anticoagulation LMWHa and Coumadin LMWHa only Aspirin only None a
LMWH: low molecular weight heparin.
No. (%) 9 (60) 6 (40) 17.9 (14–21) 38.7 (3–180) 8 (53) 4 (27) 3 (20) 13 (87) 4 (27) 2 (13) 1 (7) 1 (7) 10 (66) 3 (20) 1 (7) 1 (7)
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severe medically refractory disease. Therefore, they are often sick patients thus placing them at higher risk for any venous thrombus after intra-abdominal surgery. Furthermore, when we looked for guidance in the literature to help us decide who is high risk, what medication is best to treat with and how long to treat for, we found surprisingly little data, if any. To compound the issue, we often received different opinions from various specialties for the types of therapy and the duration. Therefore, we decided to look at our experience with intra-abdominal thrombosis in patients with CUC. This study represents the largest cohort of these types of complications in pediatric patients with CUC. We identified 15 patients with CUC who developed a post-operative thrombus. This accounted for a prevalence of 4% considering the total number of CUC patients who underwent a colectomy during this time period (366 patients). All of these 15 patients underwent examination for thrombus after they presented with post-operative abdominal pain. Previous retrospective studies, however, have demonstrated that most IBD patients who develop portal or mesenteric vein thrombosis are asymptomatic [21,22]. Our cohort is probably an underestimate of the real number of patients with intra-abdominal thrombus since we do not routinely screen all patients for thrombus. In our cohort, the most common vessels for thrombi formation were the portal vein and splenic vein. All of our patients had complete resolution of their thrombi based on imaging. Our patients did have CT scanning as their main mode of imaging. Given the risks of radiation to children, consideration should be given to use Duplex ultrasound as a means of surveillance and/or diagnosis instead of CT scanning. However, ultrasound sometimes may not be diagnostically adequate such as when bowel gas prevents adequate imaging; therefore in patients with abdominal pain a CT scan is often reasonable. We also noted that most of the intra-abdominal venous thrombosis occurred in the laparoscopic versus the open procedures. It is possible that increased intra-abdominal pressure via insufflation may have been a contributing factor. We have not routinely prophylactically anticoagulated (such as intraoperative subcutaneous heparin injections) our pediatric CUC patients undergoing colectomy given what we considered potential bleeding risks associated with prophylactic anticoagulation. However, no data exist that specify the risk of minor or major bleeding after major surgery with prophylactic anticoagulation in the pediatric population. A recent systematic review of thirty-three randomized controlled trials in adults demonstrated a minor bleeding risk (injection site bruising, wound hematoma, drain site bleeding, or hematuria) of 1.6%–6.9% and a major bleeding risk (GI tract bleeding, retroperitoneal bleeding) of b0.1%–0.2% in adults who received pharmacologic DVT thrombosis prophylaxis [23]. Prophylaxis is indicated for patients with a known thrombosis or a history of thrombophilia [24]. Remzi et al. report an increased risk of portal venous thrombi in adult patients after restorative proctocolectomy who had not received preoperative or postoperative subcutaneous heparin therapy (P = .0001) [25]. A recent review of venous thromboembolism in pediatric trauma patients documented that the reported incidence of venous thromboembolism in the overall pediatric trauma population ranges from 0.02% to 0.33% [26]. At best, we can only extrapolate data from DVT thrombosis to intra-abdominal venous thrombosis and also extrapolate the data from adults to children; clearly these are unsatisfactory data to make final recommendations. Also, we neither screened every post-operative patient nor recommend imaging in all patients who undergo colectomy for CUC. All of the patients in this cohort presented with abdominal pain, therefore, we strongly recommend that physicians have a high index of suspicion for intraabdominal thrombus whenever these patients complain of abdominal pain post-operatively either in-hospital or as outpatients. Therefore, we recommend a low threshold for use of imaging such for patients who are symptomatic. Regarding treatment of the thrombus, it is interesting
to note that although one patient had no treatment and another had aspirin only, their thrombi resolved. We do however recommend full anticoagulation, beyond simply salicylic acid, until resolution of the thrombus is confirmed with imaging since the associated complications of complete portal thrombus formation can be devastating. All intra-abdominal venous thrombus should be treated with anticoagulation unless a major contraindication exists. While there are no randomized controlled trials on pediatric anticoagulation, our data suggest that 3–6 months of anticoagulant therapy is sufficient for the vast majority of patients, if not all. We do not recommend indefinite anticoagulation therapy unless there are other indications for it. Our data and recommendations appear to be consistent with common practice for intraabdominal VTEs in general [3]. Our study has several important limitations. Associations from this retrospective review cannot establish causal relationships. This study does not propose a specific mechanism for CUC patient’s hypercoagulable state; rather we sought to report the incidence and treatment in our practice, something that was previously unknown. Our data are limited in that the incidence of venous thrombus was identified retrospectively from medical records rather than prospectively via a standardized protocol. It is probable that there were others who developed asymptomatic venous thrombi that went undetected. Therefore, our incidence rate of 4% is most likely an underestimation of the actual incidence of CUC patients who develop a postoperative thrombus. Finally, prospective studies or at least protocol basedstudies will need to be designed to understand the bleeding risk of prophylactic anticoagulation in the pediatric population as well as the most effective treatment and duration of thrombi in this special population. The best data we have from adult studies estimate the risks of major complications from prophylactic anticoagulation to be around 0.2%. Given our finding of a 4% chance of intra-abdominal venous thrombosis, it is reasonable to consider prophylactic anticoagulation when undergoing colectomy. Future prospective studies should dissect which patients are at very high risk and really should receive prophylactic anticoagulation and which patients are low risk and should not receive anticoagulation. Notwithstanding these limitations, this is to our knowledge the first and largest report of the incidence, treatment, and duration of therapy of intra-abdominal thrombus post-colectomy among children with CUC. In conclusion, 4% of our pediatric patients with chronic ulcerative colitis who underwent colectomy developed symptomatic intraabdominal venous thromboembolism. 3 to 6 months of anticoagulant therapy is adequate treatment in almost all patients; resolution of the thrombus should be documented with imaging as well. Practitioners should have a high index of suspicion for intra-abdominal venous thrombus when these patients complain of abdominal pain postoperatively. Although more research is needed to answer if prophylactic anticoagulation should be administered, based on our experience, peri-operative prophylactic anticoagulation should be considered in this population on an individualized case-by-case basis.
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