Apixaban-induced haematoma causing small bowel intussusception

Abstract

Apixaban (Eliquis) is a direct acting oral anticoagulant (DOAC) indicated for treatment of deep vein thrombosis, non-valvular atrial fibrillation, pulmonary embolism and postoperative venous thromboprophylaxis following hip or knee replacement. Complications are minimal and include, but are not limited to, bleeding and intracranial haemorrhage, and haematoma formation. Our patient is a 73-year-old woman who presented with clinical and radiographic findings of small bowel obstruction. She was found to be taking apixaban for atrial fibrillation. CT scan showed small bowel intussusception. She underwent an exploratory laparotomy and resection of the small bowel intussusception with primary side-to-side anastomosis. Histopathological examination showed that the intussusception was caused by an intramural haematoma. This case presents a rare instance of adult intussusception caused by a DOAC. To our knowledge, no case of intussusception caused by apixaban has yet been found in literature.

Background

Apixaban is a reversible and selective site factor Xa inhibitor anticoagulant, which results in decreased thrombin generation and thrombus formation. It is commonly used to prevent clot formation in patients with atrial fibrillation and select patients undergoing hip or knee replacement. In a recent study looking at the effectiveness and safety of direct acting oral anticoagulants (DOACs) compared with warfarin, it was found that the combined risk of ischaemic stroke, systemic embolism and death as well as adverse events such as intracranial haemorrhage, gastrointestinal bleeding and other minor bleedings were lower for DOACs than for warfarin. Apixaban was found to have the most favourable effectiveness, safety and persistence profile.^{1 2} The most common complication of apixaban is bleeding, which can lead to a haematoma formation. With the increasing use of DOACs, we would like to bring awareness to the first reported apixaban-induced haematoma causing small bowel intussusception, a rare yet potential complication. Intussusception is uncommon in adults comprising only about 5% of the total cases of bowel obstruction with an annual incidence of about 2–3 cases per 1 000 000 of the population.³ It occurs when one segment of bowel telescopes into an adjacent segment resulting in partial to complete obstruction, and potential ischaemic injury to the intussuscepting segment.⁴ Of adult cases, 90% are associated with pathological processes⁵ such as neoplastic or enlarged lymph node which can create an anatomic lead point resulting to the telescoping of one segment of the intestine to another. In extremely rare cases, the intussusception resulted from haematoma formation caused by warfarin.⁶

This case examines a patient who presented with signs and symptoms of small bowel obstruction resulting in the diagnosis of intussusception due to a haematoma formation caused by apixaban.

Case presentation

The patient was a 73-year-old Caucasian woman with medical history significant for diabetes mellitus, hypertension, hypothyroidism, coronary artery disease, hyperlipidaemia, gastro-esophageal reflux disease (GERD) and atrial fibrillation with a CHA₂DS₂-VASc score of 4. Her medications include metformin, linagliptin, amiodarone, hydrochlorothiazide, lisinopril, levothyroxine, nitroglycerin prn, atorvastatin, pantoprazole and apixaban. She presented with a 1-week history of cramping abdominal pain. The pain was not related to medication or food intake, and was accompanied by anorexia, nausea, vomiting and obstipation. She denied any recent trauma, operation or any medical procedures. On physical examination, her abdomen was distended, with hypoactive bowel sounds, moderate left upper quadrant (LUQ) tenderness and direct and rebound tenderness on palpation. Vital signs showed elevated blood pressure at 159/69 mm Hg, heart rate of 58 beats/min and normothermia. The patient last took her apixaban for atrial fibrillation about 24 hours prior to admission. CT scan with intravenous and oral contrast showed small bowel intussusception with small bowel obstruction (figure 1).

Figure 1.

CT scan showing small bowel intussusception.

Investigations

Haemoglobin (120 g/L) and haematocrit (37%) were normal with white blood cells count elevated at 16.3×10⁹ /L. Sodium level at 142 mmol/L and potassium level at 3.8 mmol/L with elevated serum creatinine at 1.5 mg/dL. Coagulation profile was within the normal limits.

Differential diagnosis

Tumours, benign or malignant acts as lead point of intussusception in more than 65% of adult cases. A significant proportion of cases have been reported to occur after abdominal surgery for lesions other than neoplasm, such as suture line, adhesions and intestinal tubes.³ Since the patient has no recent abdominal surgery, trauma or procedures done, the aetiology of the intussusception cannot be established.

Treatment

Because of the presentation and uncertainty of the aetiology of the intussusception, surgical intervention was chosen as the appropriate course of action. Apixaban was discontinued, she was resuscitated, nasogastric tube was placed, which drained 1500 mL of gastrointestinal contents and the patient subsequently underwent emergent exploratory laparotomy. Intraoperative findings showed dilated small bowel proximal to the intussusception, which was located in the ileum about 80 cm from the ileocecal valve. The affected portion of the small intestine was resected followed by primary side-to-side anastomosis. The resected segment of the bowel was marked and sent for histopathological examination. Her postoperative course was without complication.

Outcome and follow-up

After discussion with the patient’s primary care physician, apixaban was restarted as soon as the patient tolerated her diet, which coincided with postoperative day 5. The patient was discharged on postoperative day 11 and had an unremarkable recovery. Histopathological report showed no malignancy with viable enteric mucosa with intramural haematoma or haemorrhage acting as a lead point for the intussusception (figure 2).

Figure 2.

Histopathological findings of haematoma acting as lead point for the intussusception.

Discussion

There have been rare published reports of intussusception as a complication of anticoagulation due to warfarin, but never with any of the DOAC drugs. Apixaban was first approved in 2012 and has since become a commonly prescribed medication, being a preferred alternative to warfarin. Bleeding is the major complication of anticoagulation therapy with the potential to cause adverse bleeding events such as intracranial and pericardial haemorrhage. Bleeding, presenting as a haematoma, is a rare complication seen in one out of every 2500 patients.⁷ A case published in 2009 reports an incident where a haematoma of the small bowel caused a jejunojejunal intussusception in a patient taking warfarin. The haematoma acted as the lead point, causing the intussusception.⁶ This case presents a 73-year-old woman on apixaban therapy, who came to the Emergency Department (ED) presenting with signs and symptoms of intestinal obstruction later confirmed to be due to intussusception secondary to intramural haematoma. This case is unique from the previous case report that a DOAC drug was involved and not warfarin.

Intussusception may lead to intestinal obstruction and thus may present with signs of obstruction or peritoneal signs. Diagnostic imaging will usually confirm the diagnosis and may reveal the underlying cause of the intussusception which is usually a neoplastic or an inflammatory process. Sometimes peristalsis may produce a transitory intussusception which can be discovered as an incidental finding on CT radiography of an asymptomatic patient. Careful correlation with patient’s clinical features is imperative to prevent negative laparoscopy or laparotomy, the standard management for intestinal examination. In cases of a CT scan reading of intussusception with benign abdominal examination, a follow-up oral contrast enhanced imaging either by CT or enteroclysis should be performed before definitive surgical management is considered.

Although currently rarely implicated as a cause of intussusception, intramural haematoma should be kept in mind given the growing popularity of DOACs and the widespread use of anticoagulation therapy in the general sick population. In a patient on anticoagulation with CT findings of intussusception, suspicion of haematoma-induced intussusception should be considered, which theoretically can be managed by correction of coagulopathy and non-surgical management, unless the patient presents with fulminant intestinal obstruction or signs of peritonitis in which case either a laparoscopy or laparotomy should be the management of choice.

Learning points.

• The direct acting oral anticoagulants (DOACs) are extremely effective, but it is essential to be aware of the rare side effects such as haematoma formation.

• Apixaban is a rare cause of intussusception in adults that necessitates prompt intervention to prevent bowel ischaemia and necrosis.

• In addition to a complete history and physical examination, medication list should be obtained and appropriate medication reconciliation performed in patients presenting with abdominal pain to ensure that haematoma or complications of DOACs are ruled out.