AIM: Acute gastrointestinal bleeding is a severe complication in patients receiving long-term oral anticoagulant therapy. The purpose of this study was to describe the causes and clinical outcome of these patients.

METHODS: From January 1999 to October 2003, 111 patients with acute upper gastrointestinal bleeding (AUGIB) were hospitalized while on oral anticoagulants. The causes and clinical outcome of these patients were compared with those of 604 patients hospitalized during 2000-2001 with AUGIB who were not taking warfarin.

RESULTS: The most common cause of bleeding was peptic ulcer in 51 patients (45%) receiving anticoagulants compared to 359/604 (59.4%) patients not receiving warfarin (P<0.05). No identifiable source of bleeding could be found in 33 patients (29.7%) compared to 31/604 (5.1%) patients not receiving anticoagulants (P = 0.0001). The majority of patients with concurrent use of non-steroidal anti-inflammatory drugs (NSAIDs) (26/35, 74.3%) had a peptic ulcer as a cause of bleeding while 32/76 (40.8%) patients not taking a great dose of NSAIDs had a negative upper and lower gastrointestinal endoscopy. Endoscopic hemostasis was applied and no complication was reported. Six patients (5.4%) were operated due to continuing or recurrent hemorrhage, compared to 23/604 (3.8%) patients not receiving anticoagulants. Four patients died, the overall mortality was 3.6% in patients with AUGIB due to anticoagulants, which was not different from that in patients not receiving anticoagulant therapy.

CONCLUSION: Patients with AUGIB while on long-term anticoagulant therapy had a clinical outcome, which is not different from that of patients not taking anticoagulants. Early endoscopy is important for the management of these patients and endoscopic hemostasis can be safely applied.

Acute upper gastrointestinal bleeding (AUGIB) is a severe complication in patients receiving long-term oral anticoagulant therapy. The number of people presenting with AUGIB while on warfarin therapy is increasing because of the expanding indications for long-term anticoagulant therapy[1]. Patients with prosthetic heart valves, chronic or paroxysmal atrial fibrillation, recurrent deep venous thrombosis, hypercoagulable diseases, and vascular diseases are currently maintained on long-term anticoagulants. Despite advances in monitoring the gastrointestinal bleeding in these patients, frequent and major bleeding occurs in up to 20% patients[1-5]. The risk of bleeding is influenced by the intensity of anticoagulant therapy, age (over 65 years), history of gastrointestinal bleeding, presence of serious comorbid conditions (acute myocardial infraction, renal insufficiency, severe anemia) and concurrent use of aspirin[1,6-8]. These patients are usually old in age and the majority has coexisting diseases, which are known to increase the morbidity and mortality of AUGIB[9,10].

We reviewed all cases of AUGIB, occurring in patients on oral anticoagulant therapy. The purpose of this study was to describe the causes and clinical outcome of these patients as well as the efficacy of diagnostic and therapeutic endoscopy. Moreover, endoscopic findings, emergency surgical hemostasis and mortality were compared with those of patients with AUGIB not taking anticoagulants.

The gastrointestinal tract is the most common site of significant bleeding in patients receiving long-term oral anticoagulant therapy[11]. Bleeding can be caused by many different lesions. The most common cause is peptic ulcer (duodenal or gastric) although less frequent in patients not taking anti-coagulant drugs (45% vs 59.4%, P<0.0001). Of those patients with concurrent use of NSAIDs, the majority had peptic ulcer bleeding (74.3%). NSAIDs have ulcerogenic activity and also inhibit platelet cyclooxygenase resulting in suppression of thromboxane A2-dependent platelet aggregation. Although many drugs are known to interact with warfarin, there have been no conclusive data to indicate an increased risk of bleeding except for NSAIDs especially aspirin during warfarin therapy[1,7].

Early endoscopy in patients on warfarin therapy is mandatory, as it can reveal lesions requiring endoscopic hemostasis. In up to two-thirds of patients, endoscopy could lead to the diagnosis of previously unrecognized lesions such us peptic ulcer, polyps, arteriovenous malformation or tumors. On the other hand, a great number of patients had no lesion on upper and complementary lower gastrointestinal endoscopy (29.7%). However, this increased to 40.8% in patients not taking NSAIDs higher than that in the unselected patients with AUGIB (5.1%). In our sub-group of patients with negative endoscopy or lesions at trivial risk of rebleeding (e.g., gastroduodenitis), only one had re-bleeding and none required emergency surgical hemostasis. In these patients, due to the favorable outcome, we could avoid the introduction of heparin therapy, and continue oral anti-coagulant therapy after correcting INR in therapeutic range with fresh frozen plasma. This could reduce the hospitalization time. The achievement of a therapeutic INR needed approximately 4 d, resulting in several hospital days waiting a targeted coagulation status[12-15].

No patient in our group had any procedure-related complications or uncontrollable bleeding due to diagnostic and/or therapeutic endoscopy, although in the majority of patients anti-coagulation was not completely reversed. Emergency surgical hemostasis was required in 5.4% of patients, which was not different from that in patients not taking anti-coagulants (3.8%). Endoscopic hemostasis injection with adrenaline solution could be safely performed in anti-coagulated patients after their resuscitation. The efficacy of hemostasis was good, even if anti-coagulation was incompletely reversed. Although bleeding was greater in anti-coagulated patients from the injection sites, no patient suffered from uncontrollable bleeding after endoscopic injection therapy. Successful endoscopic diagnosis and therapy at rates comparable with those achieved in non-anti-coagulated patients were also reported by Choudari et al[16] in a group of bleeding anti-coagulated patients, by applying injection therapy or a heater probe. Among the patients suffering from peptic ulcer bleeding who received endoscopic hemostasis after partial correction of the INR to 1.5 to 2.5, the incidence of uncontrollable bleeding and emergency surgery were similar to those of patients not taking warfarin.

The overall mortality rate was low and was not different from that of patients not receiving anti-coagulant therapy. It is known that the majority of deaths in patients with acute gastrointestinal bleeding were due to untreatable diseases, especially, end stage malignancies, cirrhosis and irreversible cardiac diseases. Although the majority of anti-coagulated patients had concurrent diseases, the presence of end stage malignancies, cirrhosis or other irreversible diseases would discourage doctors to prescribe oral anti-coagulant drugs. Moreover, symptomatic thromboembolism after transient withdrawal of long-term anti-coagulant therapy was uncommon and death was rare. The risk of a major thromboembolic event in the absence of antithrombotic therapy in patients with mechanical heart valves was 4/100 patient-years[17]. The risk of thromboembolic events during the interruption of warfarin treatment was even lower in patients at low risk of embolic events (deep venous thrombosis, atrial fibrillation not associated with valvular disease, bioprosthetic valves and mechanical valves in the aortic position) and was estimated to be 1-2 per 1000 patients[18].

In conclusion, patients with AUGIB while on long-term anti-coagulant therapy had a clinical outcome, which was not different from that of patients not taking anti-coagulants. Early endoscopy is important because endoscopic findings have a prognostic value regarding the final outcome and may direct the management of these patients. Endoscopic hemostasis is the treatment of choice and can be safely applied.