Title : Back to basics: The pharmacokinetics of direct oral anticoagulants in short-gut syndrome
Abstract:
Background: Direct-acting oral anticoagulants (DOACs) are absorbed in the upper gastrointestinal tract, but patients with gastrointestinal disease were not included in the Phase II and III drug investigations. This report details a patient with altered gastrointestinal anatomy and physiology who developed splenic infarcts while on oral anticoagulation.
Case: A 37-year-old male with Pelizaeus-Merzbacher Disease (an inherited hypomyelination leukodystrophy) and a JAK2 mutation with recurrent DVTs presented with abdominal pain. He had been taking half-doses of his rivaroxaban. A CT scan revealed a superior mesenteric vein thrombus that extended to his portal vein. He was started on catheter-directed thrombolytics. A TIPS procedure was attempted, but was complicated by hematochezia necessitating emergent exploratory laparotomy with resection of approximately 120 cm of necrotic small bowel. He underwent a second TIPS procedure and a second bowel resection leaving approximately 150 cm of small bowel intact.
Postoperatively, he developed hepatic encephalopathy that required high doses of lactulose. In the coming days, he was transitioned from heparin to 5 mg of apixaban twice-a-day. On hospital-day 31, he developed abdominal pain, decreased responsiveness, and had a large-volume emesis. A CT scan revealed multiple splenic infarcts and he was transitioned to heparin briefly before resuming apixaban. He continued to have high stool output.
Discussion: With concern for short-gut syndrome along with ongoing lactulose requirements, he was started on octreotide, transitioned to rifaximin from lactulose, and transitioned from apixaban to heparin indefinitely. Patients JAK2 mutations are at greater risk for thromboembolism and may require lifelong anticoagulation. In this patient with altered gastrointestinal anatomy and function the DOAC was likely not being absorbed. So, the decision was made to use heparin.
Conclusion: It is critical to be cognizant of the pharmacokinetics of DOACs and not just how they are cleared. In complex patients, it is critical to keep a broad perspective of their care to avoid tunnel vision in their management.
