Portal vein thrombosis occurrence in a cirrhotic patient during treatment with rivaroxaban

De Gottardi et al.1 have reported a safe use of direct oral anticoagulants\r\n(DOACs) in patients with splanchnic vein thrombosis with or\r\nwithout cirrhosis. A few cases of portal vein thrombosis (PVT) resolution\r\nin cirrhotic patients after treatment with DOACs have been reported\r\nto date, whereas their efficacy in the prevention of PVT has not\r\nbeen investigated yet.\r\nWe have recently observed a case of PVT occurred in a 81-year-\r\nold\r\nwoman with cryptogenic cirrhosis, Child-Pugh\r\nscore B8, under treatment\r\nwith the DOAC rivaroxaban 20 mg daily for chronic atrial\r\nfibrillation.\r\nPortal vein thrombosis was diagnosed during the periodic liver\r\nultrasound study and involved the splenomesenteric confluence, the\r\nportal vein trunk, and right and left portal vein branches. The last ultrasound\r\nexamination performed 3 months before showed a patent\r\nportal vein but a reduced mean flow velocity (9 cm/s). Genetic or acquired\r\nthrombophilic factors were excluded. Peak rivaroxaban plasma\r\nconcentration at 2 h after the assumption was within therapeutic limits\r\n(Cmax: 241 ng/mL), ruling out drug malabsorption. Rivaroxaban\r\ntreatment was stopped and the patient was switched to low molecular\r\nweight heparin (LMWH), but developed portal vein cavernoma.\r\nIn our experience, rivaroxaban was not able to prevent the occurrence\r\nof PVT. Although in the study by De Gottardi et al. DOAC\r\nserum levels were not provided, a recent in vitro study has reported a\r\ndecreased anticoagulant potency of rivaroxaban in plasma of cirrhotic\r\npatients compared to samples from control subjects, whereas a similar\r\nanticoagulant potency of dabigatran, heparin and LMWH in patients\r\nand controls was shown.2 Previous studies showed that in patients\r\nwith moderate liver dysfunction rivaroxaban plasma level 12 hours\r\nafter intake of a single dose of 10 mg was higher than in healthy subjects.\r\nIn our case, rivaroxaban plasma level two hours after the assumption\r\nwas comparable to that reported for healthy subjects and\r\nfor cirrhotic patients with mild hepatic impairment.3 However, the\r\nreduced portal vein flow velocity might have further favoured the occurrence\r\nof PVT in our patient.4\r\nIn conclusion, although preliminary evidences such as the study of\r\nDe Gottardi et al. support a safe use of DOACs in cirrhotic patients,\r\npharmacokinetics and pharmacodynamics may be altered and should\r\nbe further and extensively investigated. We agree with the VALDIG\r\nInvestigators that large studies are essential to definitively assess the\r\nrole of rivaroxaban and other DOACs in the treatment and prevention\r\nof PVT in these patients.