Featured patient case from the AGA Community

The AGA Community is a member-only online forum where you can connect with GIs from around the world. In recent years, it has become a steadfast sounding board for physicians to gain insight into their difficult patient scenarios. AGA members have reached out to their colleagues to determine best practices for therapies, diagnoses and disease-management options for patients spanning the GI spectrum.

Bleeding risk of ulceration occurring after endoscopic variceal ligation in a patient with severe thrombocytopenia on anticoagulation

One of our most popular recent cases involves a 64-year-old man with a history of Child-Turcotte-Pugh (CTP) class A cirrhosis secondary to nonalcoholic steatohepatitis who presented for evaluation. The patient was placed on warfarin five years ago after placement of a metallic aortic valve. An upper endoscopy was performed demonstrating large esophageal varices. The patient had no prior history of variceal bleeding and laboratory values demonstrated a platelet count (PC) of 30 x 109/L. An AGA Community Expert Moderator provides his review of the case. View the full case here.

In this scenario, should endoscopic variceal ligation (EVL) be performed? Or, given an increased risk of bleeding, is a nonselective beta blocker (NSBB) the best option for primary prophylaxis of variceal hemorrhage?

Current AASLD guidelines recommend use of an NSBB in CTP class A cirrhosis with large esophageal varices without red wale signs. While NSBB therapy has been found to be as effective as EVL for primary prophylaxis of variceal hemorrhage, EVL carries an increased risk of serious adverse events, including bleeding from postligation ulcers. Thus, treatment selection should be based on patient factors and comorbidities. In the above clinical scenario, there is a presumed increased risk of postligation ulcer bleeding given the presence of severe thrombocytopenia and use of anticoagulation. Despite the ease and cost effectiveness of NSBB therapy, 30 percent of patients will possess contraindications or develop medication intolerance. Therefore, EVL may ultimately be required in select cases. The prevalence of bleeding as a result of post-EVL ulceration ranges from 5.7 to 7.7 percent and can lead to death in up to 50 percent of cases. Risk factors for bleeding secondary to post-EVL ulceration include a prior history of active variceal bleeding, high Model for End-Stage Liver Disease (MELD) score, peptic esophagitis, presence of large gastric varices and a low prothrombin index. While use of anticoagulation is associated with a relatively low propensity for bleeding episodes in patients with cirrhosis, factors such as severe thrombocytopenia (platelet count < 50 x 109/L) can lead to increased risk.

A variety of methods have been used for management of acute bleeding secondary to post-EVL ulceration, including performance of repeat EVL, endoscopic variceal obturation, placement of a Sengstaken-Blakemore tube, esophageal stent placement, insertion of a transjugular intrahepatic portosystemic shunt (TIPSS), and medical management with octreotide and a proton pump inhibitor (PPI). In patients who are not found to have active bleeding on endoscopic evaluation, medical management has been shown to be an effective means of treatment. Cases of active ulcer bleeding are best managed with emergent endoscopic intervention and subsequent TIPSS placement in the event that bleeding cannot be controlled.

What proactive steps can be taken to prevent post-EVL ulcer bleeding in patients at high risk? PPI therapy has not been shown to effectively decrease bleeding risk despite evidence showing a reduction in post-EVL ulcer size. While sucralfate and octreotide have been shown to improve healing and decrease bleeding risk in postsclerotherapy ulcers, studies demonstrating their effects on EVL ulceration are lacking. Thrombopoietin receptor agonists have been studied as potential therapies in patients with liver disease who are at increased risk for postprocedural bleeding. Eltrombopag was shown in a phase 3 trial to decrease the need for platelet transfusion in patients with cirrhosis and severe thrombocytopenia undergoing elective, invasive procedures. Concerns related to the development of portal vein thrombosis and a lack of evidence demonstrating a decreased bleeding risk have limited its widespread use within this patient population. Two phase 3 trials that demonstrated a reduction in the need for platelet transfusion or rescue procedure in patients treated with avatrombopag without a significant increase in thromboembolic events led to FDA approval of this drug in May 2018. Despite these findings, it must be recognized that there is currently no data regarding use of avathrombopag in patients with cirrhosis, severe thrombocytopenia, and concomitant use of anticoagulation or antiplatelet therapy.

In conclusion, patients with cirrhosis and severe thrombocytopenia (platelet count < 50 x 109/L) who are also on anticoagulation are at increased risk for bleeding from post-EVL ulceration. Thus, use of an NSBB for primary prophylaxis of bleeding from esophageal varices is favored over EVL in this patient population. Individuals who are intolerant or have a contraindication to an NSBB may ultimately require EVL. It is important to provide education regarding the inherent potential for bleeding and use of post-procedural therapy with a PPI and sucralfate is encouraged.

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