Emergency (****); * (*): *-* This open-access article distributed under the terms of the Creative Commons Attribution Non Commercial 3.0 License (CC BY-NC 3.0). Copyright © 2016 Shahid Beheshti University of Medical Sciences. All rights reserved. Downloaded from: www.jemerg.com 41 Emergency (2016); 4 (1): 41-44 CASR REPORT From Pulmonary Embolism to Inflammatory Bowel Disease; Give Tunnel Vision up Masih Tajdini1*, Seyed Mohammad Reza Hosseini2 1- Department of cardiology, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran. 2- Department of Radiology, Massachusetts General Hospital, Massachusetts, USA. *Corresponding Author: Masih Tajdini; Department of cardiology, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran. Tel: 00989125645406 E-mail: drmasih84@yahoo.com Received: June 2015; Accepted: June 2015 Abstract Inflammatory bowel disease (IBD) is a multisystem disorder with gastrointestinal tract involvement. These pa- tients have the higher risk for thromboembolic events compared to normal population. This report describes a unique case of pulmonary embolism as a first manifestation of inflammatory bowel disease. Key words: Inflammatory bowel disease; pulmonary embolism; venous thrombosis Cite this article as: Tajdini M, Hosseini SMR. From pulmonary embolism to inflammatory bowel disease; give tunnel vision up. Emergency. 2016;4(1):41-44. Introduction: nflammatory bowel disease (IBD) is a multisystem dis- order with gastrointestinal tract involvement. This dis- ease is usually characterized by specific features like chronic or nocturnal diarrhea, abdominal pain, weight loss, fever and rectal bleeding. This disease can correlate with systemic and extra-intestinal complications (1). Elevated thrombin–antithrombin complexes, prothrombin frag- ments, and D-dimer levels and their increases with disease activity are other evidence pointing toward the relation be- tween inflammation and coagulation. These factors lead to higher risk of thromboembolic events in IBD patients com- pared to normal population (2-4). The incidence of sys- temic thromboembolic events in IBD ranges from 1%– 7.7% and 39%–41% in clinical and postmortem studies, re- spectively. Similar to other patients, deep vein thrombosis (DVT) and/or pulmonary thromboembolism (PTE) are the most common thrombotic events. Cerebral, portal, mesen- teric, and retinal veins thrombosis have fewer occurrences (5). These events are associated with increased risk of mor- tality and require improved awareness and prevention (6). This report describes a unique case of pulmonary embo- lism as a first manifestation of inflammatory bowel disease. Case report: A 46-year-old female was referred to t department with pain and edema of her right leg. She was a known case of hypertension and hyperlipidemia and had a history of left leg DVT about two years ago. In previous admission she was discharged on warfarin but after few months of treatment, warfarin had been stopped due to active pep- tic ulcer disease. Collagen vascular markers such as anti- nuclear antibody (ANA), anti-double stranded DNA (anti-dsDNA), anticardiolipin and lupus anticoagulant antibodies were negative in first admission which were requested due to recurrent abortions (three times) in her past medical history. Doppler ultrasound was per- formed to evaluate her leg pain and edema. Findings re- vealed popliteal and superficial femoral vein thrombosis. I Figure 1: Chest computed tomography angiography of patient, arrow pointed the location of embolus in the right main pulmo- nary artery. This open-access article distributed under the terms of the Creative Commons Attribution Non Commercial 3.0 License (CC BY-NC 3.0). Copyright © 2016 Shahid Beheshti University of Medical Sciences. All rights reserved. Downloaded from: www.jemerg.com Tajdini et al 42 She was admitted again and anticoagulant therapy was started. During her admission, dyspnea was developed; so pulmonary computed tomography angiography (CTA) was performed and pulmonary emboli was demonstrated (Figure 1). In addition to dyspnea she was complaining of abdominal pain and non-bloody diar- rhea. Thrombosis of intra-abdominal vessels was ruled out with magnetic resonance venography (MRV). Since her abdominal pain was resistant to analgesics and she had a past surgical history of appendectomy, abdominal CT scan was performed which showed sub-mucosal bleeding and thickness of jejunum indicating probable IBD diagnosis. The patient underwent colonoscopy due to abdominal pain, past medical history, intermittent non-bloody diarrhea, and abdominal CT findings. Unex- pectedly, patchy ulceration was seen coincident of IBD (Figure 2). The patient was treated by intravenous un- fractionated heparin and discharged on warfarin. Follow up in out-patient clinic for international normalized ra- tio (INR) level monitoring (target between 2 and 3) was arranged. Discussion: Venous thromboembolism incidence differs from 1.3% to 6.2 % and has a mortality rate of 8% to 25% in IBD population. Most of thromboembolic events occur in IBD patients who are younger than 50 and is more common in females compared to males (7). Like IBD pathogene- sis, the mechanism of hypercoagulability state is not fully understood. Despite the role of inflammation in activa- tion of coagulation cascade, it seems that this higher in- cidence rate of thrombosis in IBD is not linked to inflam- matory process and evidence in literature has been con- sidered IBD as an independent risk factor for thrombo- embolism (table 1) (8, 9). Some studies have implicated platelet activation by endothelial dysfunction and hyper- homocysteinemia activation of the coagulation cascade (10). Inherited causes of thrombophilia such as factor V Leiden mutation, prothrombin gene mutation, inherited hyperhomocysteinemia, MTHFR gene polymorphism, deficiency of protein C and S, antithrombin III mutation does not associate with thrombotic events in patients with IBD. For patients who are diagnosed with venous thromboembolism (VTE), work-up is often necessary to indicate the underlying cause. The first diagnostic steps are rectal examination, fecal occult blood testing and co- lonoscopy to rule out malignancy which is a strong risk factor for VTE. In absence of inherited causes, acquired one may play a crucial role, but all of them including pro- longed immobilization, surgery, fluid depletion, steroid therapy, central venous catheters, smoking and oral con- traceptive were absent in our patient (4, 11-13). Bleed- ing tendency makes the treatment of these patients so difficult. Heparin has been implicated in the therapeutic management of ulcerative colitis with thromboembo- lism. Two studies showed controversial role for heparin. One of them revealed benefits of use but another failed to repeat this finding and was associated with increased risk of bleeding. Evidence is not enough to utilize low molecular weight heparin. Thrombolytic agents can be life saver in IBD patient with massive PTE. Cardiogenic shock and/or right ventricular dysfunction are the main indication of administration. Vitamin k antagonists should be used with caution due to risk of causing large hemorrhage. Considering above; management of these patients needs multi specialist consultation (14). Based on new consensus, testing for hereditary or acquired hy- percoagulability states is not necessary in IBD patients with VTE. In the absence of another provoking factor in clinical remission state of IBD, anticoagulant therapy at least for 3 months has been recommended with periodic reevaluation. There is no recommended follow up time for these patients but based on new consensus echocar- diography and CTA can be repeated for reevaluation of anti-coagulation therapy. It seems that persistent use of anticoagulant is not obligatory in patients with good right ventricular function or no evidence of PTE in men- tioned investigations (15). However, there is no differ- ence between the management of an acute thrombotic event in patients with IBD and other patients. Patients with diagnosis of PTE need electrocardiography and echocardiography evaluation. In patients with massive saddle emboli, evidence of right heart strain or hyper- tension is an independent predictor of mortality. Hence, thrombolysis should be considered. Currently, there is no preferred medication and low-molecular-weight hep- arin (LMWH) or un-fractionated heparin (UFH) have equal effects (16). Conclusion: Inflammation and coagulation have been implicated in the pathogenesis of numerous diseases like IBD. Imbal- ance between prothrombotic and protective mecha- nisms leads to thrombosis and pathologic blood coagula- tion. Therefore, finding and treatment of probable un- derline causes of thrombosis should be considered in all VTE patients referred to the emergency department. Figure 2: Colonoscopy views of patient’s sigmoid (left) and rectum (right), arrow pointed to location of patchy ulceration compatible with inflammatory bowel disease. This open-access article distributed under the terms of the Creative Commons Attribution Non Commercial 3.0 License (CC BY-NC 3.0). Copyright © 2016 Shahid Beheshti University of Medical Sciences. All rights reserved. Downloaded from: www.jemerg.com 43 Emergency (2016); 4 (1): 41-44 Acknowledgment We would like to express our special thanks to the cardi- ology Department staff of Tehran Heart Center, Tehran, Iran. Conflict of interest: None Funding support: None Authors’ contributions: All authors passed four criteria for authorship contribu- tion based on recommendations of the International Committee of Medical Journal Editors. References: 1. Tajdini M, Mirbagheri SA, Nikooie R, et al. Tissue hypoxia in pathogenesis of ulcerative colitis: should we change all our beliefs? Scand J Gastroenterol. 2013;48(12):1487-8. 2. 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Systemic thromboembolism in inflammatory bowel disease: Table 1: Review of the literature (IBD and Thrombotic events) Authors Publication date Major presentation Wlodarczyk et al. (17) 2014 In this paper authors report three cases of VTE in IBD pa- tients. Temel et al. (6) 2013 Two case of pulmonary thromboembolism active inflamma- tory bowel disease patients. Merrill and Millham (18) 2012 Patients with IBD are at increased risk for developing post- operative DVT or PE. O'Connor et al. (19) 2009 Case of a patient with ulcerative colitis who has had recur- rent thromboembolism. Choi et al. (7) 2008 Case of a man who was hospitalized with massive PE and deep vein thromboembolism and subsequently was diag- nosed with underlying ulcerative colitis. Kafkas et al. (14) 2008 Massive PE in a patient with ulcerative colitis. Jin et al. (20) 2005 Exacerbation of ulcerative colitis and developed extensive arterial and venous thrombosis. Katsanos et al. (21) 2005 Patients with CVT and IBD were significantly younger than CVT patients without IBD (review and analysis of 65 case reports of IBD patients with CVT). Solem et al. (22) 2004 Venous thromboembolism is a serious complication of IBD. Bernstein et al. (23) 2001 IBD patients have a threefold increased risk of developing DVT or PE. IBD: inflammatory bowel disease; VTE: venous thromboembolism; DVT: deep vein thrombosis; PE: pulmonary embolism; CVT: cerebral vein thrombosis. This open-access article distributed under the terms of the Creative Commons Attribution Non Commercial 3.0 License (CC BY-NC 3.0). Copyright © 2016 Shahid Beheshti University of Medical Sciences. All rights reserved. Downloaded from: www.jemerg.com Tajdini et al 44 mechanisms and clinical applications. Ann N Y Acad Sci. 2005;1051(1):166-73. 13. Kasmaei HD, Baratloo A, Soleymani M. A 33-year-old woman with severe postpartum headache. Emergency. 2013;1(1):27-9. 14. Kafkas NV, Deboneras CC, Babalis DK. Massive pulmonary embolism and ulcerative colitis. Hellenic J Cardiol. 2008;49(5):365-70. 15. Nguyen GC, Bernstein CN, Bitton A, et al. Consensus statements on the risk, prevention, and treatment of venous thromboembolism in inflammatory bowel disease: Canadian Association of Gastroenterology. Gastroenterology. 2014;146(3):835-48. e6. 16. Büller HR, Agnelli G, Hull RD, Hyers TM, Prins MH, Raskob GE. Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(3_suppl):401S-28S. 17. Wlodarczyk M, Sobolewska A, Fichna J, Wisniewska- Jarosinska M. Prevention and Therapeutic Strategies of Thromboembolic Events in Patients with Inflammatory Bowel Diseases: A Report of Three Cases. Curr Drug Targets. 2015;16(3):194-8. 18. Merrill A, Millham F. Increased risk of postoperative deep vein thrombosis and pulmonary embolism in patients with inflammatory bowel disease: a study of National Surgical Quality Improvement Program patients. Arch Surg. 2012;147(2):120-4. 19. O'Connor MB, O'Donovan N, Phelan MJ, Regan MJ. Inflammatory bowel disease, such as Ulcerative colitis, is a risk factor for recurrent thromboembolic events: a case report. Cases J. 2009;2(1):173. 20. Jain S, Bhatt P, Muralikrishna GK, Malhotra P, Kumari S, Varma S. Extensive arterial and venous thrombosis in a patient with ulcerative colitis--a case report. Med Gen Med. 2005;7(2):10. 21. Katsanos AH, Katsanos KH, Kosmidou M, Giannopoulos S, Kyritsis AP, Tsianos EV. Cerebral sinus venous thrombosis in inflammatory bowel diseases. QJM. 2013;106(5):401-13. 22. Solem CA, Loftus EV, Tremaine WJ, Sandborn WJ. Venous thromboembolism in inflammatory bowel disease. Am J Gastroenterol. 2004;99(1):97-101. 23. Bernstein CN, Blanchard JF, Houston DS, Wajda A. 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