Hemorrhage Following Small Polyp Resection in the Colon in Anticoagulated Patients: a Prospective Single-blinded Multicenter Study Comparing Warfarin vs. Low Molecular Weight Heparin Based Bridging Anticoagulation

Oral anti thrombotic medications are commonly prescribed for patients with venous thromboembolism, chronic atrial fibrillation, prosthetic heart valves, etc. As gastrointestinal endoscopy in often required in these patients, one should consider the urgency of the procedure, the risk of bleeding (related both to antithrombotic therapy itself and to the type of endoscopic procedure) and the risk for thromboembolic events related to interruption of antithrombotic therapy.Current ASGE guidelines state that aspirin may be continued for all diagnostic and most therapeutic endoscopic procedures . As to oral anticoagulants (ie. warfarin), a distinction is made as to the risk of thromboembolism (high vs. low patient risk of thrombosis) and the risk of bleeding ( high vs. low procedure risk of bleeding). ASGE and ACCP Guidelines suggest discontinuing anticoagulation in the periendoscopic period in patients with low risk of thromboembolic events (appendix I), while continuing anticoagulation in patients with high risk of thromboembolic events. Switching to LMWH , termed "bridging therapy", is suggested when anticoagulation need to be continued. However there is little evidence to support such an approach. In addition, there are a number of potential drawbacks to bridging therapy with heparin in the periprocedural period. This approach consumes considerable healthcare resources, involves a short period of normal coagulability (if not hypercoagulability) with an associated risk of thromboembolism. Finally, In a recent systematic review of 34 studies of anticoagulated patients (19 of which enrolled endoscopic procedures), bridging therapy was found to be associated with increased rates of overall and major bleeding, and no difference in thrombotic events, as compared to no bridging. Colonic polypectomy is considered to be a procedure with high risk for bleeding. The reported risk of polypectomy related bleeding ranges in various reports from as low as 0.3% to as high as 6.1 %, averaging in most studies 1-2.5% Bleeding can be immediate or delayed, with the latter being a bit more frequent, occurring in up to 2% of patients, as early as few hours and as late as 29 days after the procedure, though mostly in post procedure days. Polyp size greater than 1-2 cm was found to be associated with increased risk for immediate and delayed postpolypectomy bleeding. As an example, bleeding occurred in ~1% of polypectomies < 1 cm and in 6.5% of polypectomies > 2 cm.Other factors found to be related to bleeding risk are age, location (Cecal and right colon > rest of colon), cardiovascular and renal comorbidities, and use of anticoagulation. The continuation of anticoagulation further increases bleeding risk. In a 2004 retrospective study of 1657 patients undergoing polypectomy, post procedural bleeding rate was 2.2% (86% immediate, 14% delayed), and Warfarin was found to be associated with an Odds ratio of 13.37 for bleeding. In contrast to other studies, age, size and location of the polyp were not found to be associated with risk of bleeding. On the other hand, temporary suspension of anticoagulation therapy is associated, at least theoretically, with a risk of thromboembolic complications. The magnitude of that risk was reported to be low (~ 0.7%) in 2 retrospective studies and one meta-analysis but admittedly high risk patients were underrepresented. In fact, actual overall rates (with and without bridging) of perioperative thrombotic complications are higher and range from 0.9-1.8% , with a corresponding bleeding rate of 1.9%-2.7%.As to bridging therapy, evidence comes almost exclusively from retrospective studies. Recent meta-analysis showed that, compared to no anticoagulation, perioperative bridging therapy with heparin increased the overall risk of major bleeding without a significant decrease in the risk of thromboembolic events. Later on, a prospective, randomized study comparing bridging therapy with continued warfarin in patients with moderate-to-high risk of thromboembolism undergoing defibrillator or pacemaker surgery (a high bleeding risk procedure by definition) , found more major bleeding in the bridging group as compared to continued warfarin, with no difference in thrombotic outcome.Apart from the above mentioned paper, as far as the investigators know, no comparative prospective study compared bridging with continued warfarin.

Polyps up to 1 cm in diameter have been safely removed in patients on warfarin therapy. In one retrospective series, warfarin was discontinued 36 hours prior to colonoscopy to avoid supra therapeutic INR. 3 out of 123 patients who underwent 225 polypectomies on warfarin had bleeding, only one of which required treatment. All patients were prophylactically treated with clips.19 In a recent randomized trial, 70 patients with a total of 159 polyps up to 1 cm in diameter underwent polypectomy while taking warfarin. Patients were assigned to have their polyps removed either eith a cold snare technique or electrocautery. Immediate bleeding occurred in 10 of 70 patients (14%) and was more common in patients who had their polyps removed using electrocautery (23% vs 6%). No delayed bleeding occurred in the cold group whereas 5 (14%) patients required endoscopic hemostasis in the electrocautery group.

As immediate bleeding can be effectively managed endoscopically, the investigators should question if there is any potential benefit of periprocedural bridging in terms of preventing delayed bleeding (occurring during warfarin-LMWH overlap or following warfarin re-loading).

Considering the fact that ~ 25% of patients will be found to have colorectal polyps in screening colonoscopy, and that the majority of these polyps are < 20 mm, A cardinal question is whether the investigators should keep choosing among the two traditional policies: advise all our patients to stop warfarin ahead of screening colonoscopies,Or keep them anticoagulated and reschedule them to a therapeutic colonoscopy in the face of discovering colonic polyps (an approach that was found to be cost effective in one study comparing these two policies).

The investigators think a third option might be better : keeping patients anticoagulated with warfarin, and perform polypectomies for polyps up to 20 mm, while re-scheduling patients with larger polyps.