Severe ulcerative colitis complicated by an arterial thrombus in the brachiocephalic trunk

To the Editor: Patients with inflammatory bowel disease (IBD) are at increased risk of both venous and arterial thromboembolism, resulting in considerable morbidity and mortality.1,–3 In March 2003 a 58-year-old woman with severe ulcerative colitis (UC) presented at our institution with a subacute critical ischemia of the right hand of 3 weeks duration. She was known to have UC for 30 years and received long-term treatment with 2.5 g mesalazine/day. Before this event she underwent an acute attack of UC with a clinical activity index (CAI) of up to 12 despite steroid treatment for 3 months, starting with 75 mg oral prednisolone/day and subsequent tapering.4 At presentation the patient had severe ischemic rest pain of the right hand, which was mottled and cool. Small necroses were present on the fingertips besides subungual splinter hemorrhages (Fig. 1A). The radial and ulnar pulses were absent and there were neither differences of systolic blood pressure at the level of the brachial arteries nor subclavian bruits. Duplex-sonography showed distal occlusions of the antebrachial arteries, whereas the carotid, subclavian, axillary, brachial, and cubital arteries appeared normal. However, CT-angiography of the aortic arch and the supraaortic vessels revealed a 2.5-cm long floating thrombus in the brachiocephalic trunk and otherwise normal vessels (Fig. 1B). A: Photograph showing ischemic discoloration and signs of mircroembolization (arrows) into several fingers of the right hand at the day of presentation. B: Multidetector CT-angiogram (sagittal multiplanar reformation) showing a floating thrombus (arrow) at the origin of the brachiocephalic trunk. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.] Routine blood tests gave normal results except for a high erythrocyte sedimentation rate (60/70), C-reactive protein (3.10 mg/dL), hyperfibrinogenemia (457 mg/dL), thrombocytosis (432 × 109/L), anemia (hemoglobin 10.4 g/L), and a significantly elevated level of lipoprotein(a) (90.5 mg/dL). Extensive screening for thrombophilia showed elevated activities of coagulation factors VIII and IX (276% and 165%, respectively) and a moderately raised homocysteine level (14.3 μmol/L), whereas the concentrations of folic acid and vitamin B12 were normal. Genetic analysis revealed heterozygosity for the mutation A/V223 of the methylenetetrahydrofolate reductase gene, which is found in 43% of the Austrian population. Therapeutic anticoagulation with unfractionated heparin was initiated immediately after presentation; furthermore i.v. prostanoids (iloprost, 3 μg/hr for at least 3 hr/day) and pentoxiphylline (300 mg/day) were administered. In addition, the patient received acetylic salicylic acid (50 mg/day). Due to the prolonged duration of ischemic symptoms and the very distal location of the arterial occlusions, we decided to apply thrombolytic therapy locally into the right forearm by the transvenous lysis-block technique on days 3 and 8 after presentation.5 The applied thrombolytic cocktail contained 250,000 IU urokinase, 1,500 IU unfractionated heparin, and 2.5 mL 1% lidocaine dissolved in 30 mL of 0.9% saline solution. This treatment was well tolerated after systemic opiate analgesia and resulted in clinically significant improvement, as the tenderness subsided and the ulcers healed uneventfully. Three months after the onset of symptoms the hand had gained full function and after 6 months the radial pulse was palpable again. Following lysis-block treatment, systemic anticoagulation was maintained by low molecular heparin in therapeutic dose for a further 3 weeks and then switched to oral anticoagulation aimed at an International Normalization Ratio (INR) of 2.5–3.0. Under this regime the floating thrombus in the brachiocephalic trunk resolved completely without any further embolic and especially neurologic symptoms as shown in a repeat CT angiogram 1 month after presentation. Under initial treatment of UC with i.v. prednisolone (100 mg/day), cyclosporine A (4 mg/kg/day), and metronidazole (1,500 mg/day) the clinical activity improved markedly (CAI 3). However, colonoscopy still disclosed highly active left-sided UC. Later on the medication was switched to oral therapy, prednisolone was tapered, and azathioprine was added. Cyclosporine was stopped after 3 months and the patient remained in remission. We think that this case is interesting for several reasons. To our knowledge, despite numerous descriptions of cryptogenic stroke in patients with IBD, no report documents a mural thrombus in the brachiocephalic trunk. As observed previously, therapeutic anticoagulation may be an effective alternative to surgical thrombectomy in the prevention of further embolic events and the promotion of complete resolution of arterial mural thrombi.3 The close temporal relationship between the aggravation of UC and peripheral ischemia seems to indicate that active IBD is the main trigger of arterial thromboembolism in this case. Hyperhomocysteinemia, which was present in our patient, is a well-known phenomenon in IBD, but does not appear to be a major contributor to thromboembolic complications in these patients.6 In the absence of a biopsy, we cannot fully rule out Takayasu arteritis in our patient, although the lack of a typical thickening of supraaortic vessel walls makes this comorbidity unlikely. Heparin prophylaxis is a safe and effective strategy in the prevention of venous thromboembolism in patients with acute medical illnesses. In the MEDENOX trial, 40 mg enoxaparin/day reduced the rate of venous thromboembolism from 14.9% to 5.5% in an unselected group of such patients.7 Therefore, based on extrapolation from this and other studies, heparin prophylaxis is clearly recommended also in patients with severely active IBD despite the lack of specific randomized controlled trials.8 We can only speculate whether heparin, which seems to be effective in the treatment of arterial thromboembolic complications of IBD, is also efficient in their prevention.