Treating thrombosis in cirrhosis patients with new oral agents: Ready or not?

Authors

  • Nicolas M. Intagliata M.D.,

    1. University of Virginia Health System, Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, VA
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  • Hillary Maitland M.D.,

    1. University of Virginia Health System, Division of Hematology and Oncology, University of Virginia, Charlottesville, VA
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  • Patrick G. Northup M.D.,

    1. University of Virginia Health System, Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, VA
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  • Stephen H. Caldwell M.D.

    1. University of Virginia Health System, Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, VA
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  • Potential conflict of interest: Dr. Maitland consults for Alexion.

To the Editor:

We read with interest the recent report by Martinez et al.[1] showing successful treatment of acute portal vein thrombosis (PVT) with rivaroxaban in a patient with compensated cirrhosis.

We would like to share our recent experience with a series of cirrhosis patients receiving oral factor Xa inhibitor anticoagulants (rivaroxaban and apixaban) for treatment of PVT (see Table 1). To date, we have treated five patients with cirrhosis with oral factor Xa inhibitor agents. Similar to this case report, all the patients are well compensated without high-risk varices prior to anticoagulation. Therapy has been well tolerated and all patients remain in follow-up. In the longest-treated patient, we confirmed repermeation of the portal vein after 6 months of therapy.

Table 1. Cirrhosis Patients Treated to Date
Patient CharacteristicsEsophageal Varices?Agent and DoseIndicationDurationaResolutionBleeding?
  1. a

    All patients currently remain on therapy.

  2. Abbreviations: NASH, nonalcoholic steatohepatitis; AIH, autoimmune hepatitis; CTP, Childs-Turcotte-Pugh Score; EVL, esophageal variceal ligation; mths, months; PVT, portal vein thrombosis; SMV, superior mesenteric vein; FV, factor V; APS, antiphospholipid syndrome.

61 yo male, NASH, CTP AEVL prior to therapyRivaroxaban 20 mg dailyPVT/SMV6 monthsCompleteNone
55 yo female, NASH, CTP ANoneWarfarin 3 mths → Rivaroxaban 20 mg daily 3 mths → Rivaroxaban 10 mg daily presentPVT/SMV; FV Leiden6 monthsCompleteNone
70 yo female, NASH, CTP ALow riskApixaban 2.5 mg twice dailyAcute PVT4 monthsUnknownNone
26 yo female, AIH, CTP ALow riskApixaban 2.5 mg twice dailyChronic PVT; APS1 monthUnknownNone
54 yo female, Cryptogenic, CTP ALow riskApixaban 2.5 mg twice dailyChronic PVT7 monthsStableNone

The coagulopathy of cirrhosis represents a precarious and rebalanced state of hemostasis. A recent study found that prevention of PVT with low molecular weight heparin significantly decreased development of PVT and reduced episodes of decompensation.[2] Compared with daily injections, we agree with the authors in that these “nontraditional” oral agents represent an attractive option for cirrhosis patients due to ease of administration. However, we would like to emphasize recent reports advancing a more cautionary tone concerning in vitro efficacy and safety of these medications.[3, 4] Cirrhosis patients are typically excluded from clinical trials assessing anticoagulants and clinicians are often left to extrapolate when developing treatment plans in this challenging population. While our series is small and no significant bleeding occurred, there is certainly risk when using these new agents, as the ability to monitor and rescue from bleeding is currently limited. Further, prospective studies are now needed in patients with cirrhosis to determine the safest, most effective dosing strategies and to better identify if patients with more advanced stages of cirrhosis are candidates for therapy.

  • Nicolas M. Intagliata, M.D.1

  • Hillary Maitland, M.D.2

  • Patrick G. Northup, M.D.1

  • Stephen H. Caldwell, M.D.1

  • 1University of Virginia Health System Division of Gastroenterology and Hepatology University of Virginia, Charlottesville, VA

  • 2University of Virginia Health System Division of Hematology and Oncology University of Virginia, Charlottesville, VA

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