From Pages to Practice
Published February 1, 2023
Some anticoagulation decisions in patients with thrombosis are straightforward, thanks to a preponderance of data. First provoked deep-vein thrombosis (DVT)? There’s a guideline for that (no less than 3 months of anticoagulation). Recurrent DVT, pulmonary embolism, or decisions between a direct oral anticoagulant (DOAC) or warfarin? There’s data for each of these settings. What we lack is data on anticoagulation in patients with portal vein thrombosis (PVT), specifically in noncirrhotic patients.
Nonmalignant extrahepatic PVT is rare but most common in patients with underlying risk factors for thrombosis, such as myeloproliferative disease, factor V mutations, and antiphospholipid syndrome. Why is PVT a problem? Clot burden in the portal vein can lead to portal hypertension and even recurrent thrombosis, which can cause intestinal infarct. Ischemic intestinal infarcts can be a major cause of mortality, particularly in a frail population.
The authors of a recent open-label, controlled trial published in NEJM Evidence examined the safety and efficacy of the DOAC rivaroxaban in 111 patients (58% male) with noncirrhotic PVT. Patients were randomized to receive rivaroxaban (15 mg daily) or no prophylactic anticoagulation for 28 months. Rivaroxaban was given once daily rather than twice daily because of the higher risk for bleeding due to portal hypertension, the need for invasive procedures, and a high incidence of concurrent thrombocytopenia. Patients who received prior anticoagulation were not excluded but patients who had two or more episodes of acute thrombus were excluded.
The primary endpoint was the occurrence of venous thromboembolic events or death within 2 years. Secondary endpoints included minor and severe bleeding. At 1 year, none of the 55 patients in the rivaroxaban group had experienced a new thrombosis episode (versus 10 in the control group), and all patients in the control group were invited to receive rivaroxaban and remain under observation for at least 24 months. At 2.5 years, only two patients who received rivaroxaban experienced major bleeding.
The authors concluded that once daily rivaroxaban at a dose of 15 mg reduced the risk of thromboembolism without excess risk of major bleeding. However, the small number of major bleeding events limit the generalizability of the results.
In sum, the researchers used a randomized approach to evaluate a prophylactic option for patients with a rare disease. Although a larger trial to confirm these findings and validate the safety profile would be beneficial, these results take us a step closer to understanding the best approach for patients without cirrhosis who are at high risk for PVT.
The following NEJM Journal Watch summary provides more details of the study.
Andrew S. Parsons, MD, MPH, reviewing Plessier A et al. NEJM Evid 2022 Nov 22
The two major complications of chronic portal-vein thrombosis (PVT) are gastrointestinal bleeding related to portal hypertension and recurrent thrombosis. However, the benefits and risks of anticoagulation therapy in patients with histories of PVT are not clear. In this French multicenter trial, 111 adults with noncirrhotic chronic PVT were randomized to rivaroxaban (15 mg daily) or no anticoagulation.
After 1 year, no thrombotic events had occurred in the rivaroxaban group, but 10 events had occurred in the control group (4 splanchnic vein thromboses, 3 deep venous thromboses, 3 pulmonary embolisms); the difference was highly significant. At this point, an independent data safety monitoring board recommended switching all study patients to the anticoagulation group. After 2.5 years, major bleeding had occurred in two patients who were in the rivaroxaban group and in one patient in the original control group.
Comment: This study provides strong evidence that patients with noncirrhotic chronic PVT benefit from long-term rivaroxaban therapy — risk for thrombosis is lowered without excess risk for major bleeding. In addition, the incidence of thrombosis among patients who received no anticoagulation was high, which suggests that PVT is a major risk factor for recurrent thrombosis even in the absence of other prothrombotic conditions.