We read with great interest the article by Delgado et al
recently published in Clinical Gastroenterology and Hepatology
that evaluated the outcome of anticoagulation with low-molecular-weight heparin (LMWH) or vitamin K antagonists (VKA) in a large series of patients with liver cirrhosis. In their retrospective analysis, the authors show that partial or complete recanalization of splanchnic vessels (portal, splenic, and mesenteric vein) is possible in up to 60% of patients with acute or subacute thrombosis, although rethrombosis may occur in 38.5% of these patients after anticoagulation withdrawal. Indeed, these results further add to the hypothesis that the road to this “predictable milestone” in patients with cirrhosis is not one-way only.
As the accompanying editorial article by Campbell et al
points out, one of the most fearsome side effects of anticoagulation in these patients is bleeding, and although patients with chronic liver disease may show a rebalanced coagulation homeostasis and even a thrombotic tendency,
9% of the patients studied by Delgado et al
had a bleeding event that was deemed related to anticoagulant therapy. Notably, these events occurred in patients on VKA alone, and the only risk factor for bleeding in these patients, as previously shown also in other settings, was severe thrombocytopenia.
Although anticoagulation was started with LMWH in 47 study patients (85%), approximately half of them (45%) were later switched to VKA, and the remainder were kept on LMWH for the entire follow-up period of 6.8 months. Unfortunately, the authors did not report the proportion of patients who achieved partial or complete recanalization of the splanchnic vessels on LMWH, VKA, or sequential treatment LMWH/VKA, and whether they observed different success rates among these treatment schedules. The question regarding success rate of anticoagulation with different treatment regimens goes beyond simple scientific curiosity because the retrospective nature of the study and the absence of a predefined rule for switching/stopping treatment preclude a definitive answer, but rather it points to safety of anticoagulation in patients with chronic liver disease. It is likely that the decision to start with, or switch to, VKA may be due to difficulties in prolonged subcutaneous administration of LMWH and facilitation of patient compliance. However, because LMWH does not alter von Willebrand factor levels, which in these patients are elevated and help contribute to the induction of primary hemostasis despite the presence of thrombocytopenia,,
this treatment option currently seems to offer the best balance between efficacy and safety. Nevertheless, the study by Delgado et al and the results of a large prospective study of portal vein thrombosis treatment with LMWH seem to show that to be beneficial, anticoagulation should be continued after recanalization for a period of time that has not yet been established, and possibly lifelong in patients with thrombophilic conditions, because of the occurrence of rethrombosis after treatment withdrawal in a proportion of patients ranging between 8% and 38%, and this may negatively affect patient compliance and ultimately therapeutic efficacy.
In this regard, it remains to be established whether the use of new, orally available anticoagulant drugs that do not require routine monitoring by coagulation tests may be equally safe and beneficial.
Published online: August 20, 2012
Conflicts of interest The authors disclose no conflicts.
© 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.