Acenocoumarol Is Not a Safe Alternative for Anticoagulation in Phenprocoumon-Induced Hepatic Failure

Neef, Markus; Kerekes, Z; Fischer, Hans‐Peter; Sauerbruch, Tilman; Spengler, Ulrich

doi:10.1159/000070397

Cited by 8 publications

(14 citation statements)

References 12 publications

(7 reference statements)

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“…One patient showed a strong reaction to both substances, whereas the other was negative, indicating that different side chains of the molecules may be involved in the induction of immunological reactions. This may explain why reports about the safety of acenocoumarol in patients with phenprocoumoninduced liver diseases are contradictory [21][22][23].…”

Section: Discussionmentioning

confidence: 99%

Evidence for immunological (allergic) mechanisms in a subgroup of patients with phenprocoumon-induced liver disease

Klein

2009

Eur J Clin Pharmacol

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To cite this version:Reinhild Klein. Evidence for immunological (allergic) mechanisms in a subgroup of patients with phenprocoumon-induced liver disease. Abstract Purpose Phenprocoumon-induced liver injury is a rare complication of oral anticoagulation. The mechanisms leading to this side effect are not entirely clear. Here we present data that at least in a subgroup of patients in whom phenprocoumon-induced liver disease was suspected, immunological processes may play an important role. Patients and methods Thirty patients with suspected phenprocoumon-induced liver disease from different hospitals in Germany were analyzed. Peripheral blood mononuclear cells (PBMC) of these patients were tested in the lymphocyte transformation test (LTT) for reactivity with phenprocoumon in vitro. As controls, PBMC were isolated from ten individuals treated with phenprocoumon but without any side effects, and from ten healthy individuals who have never received the drug. Results Fifteen of the 30 patients had sensitized lymphocytes toward phenprocoumon as shown by LTT. Four patients had taken the drug for more than 5 years; in one patient, liver disease appeared after 1 day of phenprocoumon intake. There was no correlation between a positive LTT and clinical/ laboratory parameters. None of the 20 controls had sensitized lymphocytes toward phenprocoumon. Conclusions Applying the LTT, we were able to unravel the cause of suspected phenprocoumon-induced liver injury as a drug allergic reaction in 15 out of 30 analyzed patients.

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Section: Discussionmentioning

confidence: 99%

Evidence for immunological (allergic) mechanisms in a subgroup of patients with phenprocoumon-induced liver disease

Klein

2009

Eur J Clin Pharmacol

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“…Seitdem sind weitere Fälle von leberspezifischen Komplikationen, welche von einer milden Hepatopathie bis hin zum akuten Leberversagen reichen können, veröffentlicht worden. Die Mehrzahl der Publikationen bezieht sich auf eine Therapie mit Phenprocoumaron [23,26,31,32,33,34,35,36,37,38,39,40,41,42,43], jedoch finden sich in der Literatur auch Fälle von mit Dicumarol [44], Warfarin [45,46] oder Acenocoumarol [47,48] assoziierter Hepatopathie.…”

Section: Leberspezifische Komplikationenunclassified

“…Die zweithäu-figste Ursache in der Gruppe der Medikamententoxizität war das Phenprocoumaron (n = 9; 6,7%; [50] [23,26,31,32,33,34,35,36,37,38,39,40,41,42,43], bei 2 Patienten unter Therapie mit Warfarin [45,46], bei 2 weiteren Patienten unter Therapie mit Acenocoumarol [47,48] und bei einem Patienten unter Therapie mit Dicumarol [44] beschrieben.…”

Section: Reduktase Vitamin-k-reduktaseunclassified

“…3). In 5 Fällen bestanden initial positive Titer der antinukleä-ren Antikörper (ANA; [23,26,34,38]). In einem Fall wurde über einen positiven ANA-Titer nach Reexposition berichtet [37].…”

Section: Klinische Parameterunclassified

“…Bei 9 der 31 Patienten trat ein Leberversagen auf [23,26,33,36,38,44]. In 4 Fäl-len wurde eine Lebertransplantation notwendig [26,33,38].…”

Section: Outcomeunclassified

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Rolle der Vitamin-K-Antagonisten aus Sicht des Hepatologen

Kneiseler

Canbay

Gerken

2012

Herz

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Vitamin K antagonists are often used as oral anticoagulants for primary and secondary prevention of thromboembolic events. Vitamin K antagonists induce an anticoagulant effect by interfering with the vitamin K metabolism in the liver. Well-known complications are bleeding events and skin necrosis. Recent data indicate increasing numbers of cases with hepatic complications due to vitamin K antagonists ranging from mild hepatopathy to acute liver failure with high mortality. Hepatotoxicity is usually developed after a few months of latency, which is associated with unspecific symptoms, jaundice, elevated transaminase levels as well as cholestatic enzymes. Hepatotoxicity due to vitamin K antagonists is seldom; however, it should be considered in cases of elevated liver enzymes. In this case coumarin therapy should be discontinued. Caution is needed when changing to another coumarin derivative because cross-reactivity has been described.

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Current awareness: Pharmacoepidemiology and drug safety

2003

Pharmacoepidemiology and Drug

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In order to keep subscribers up‐to‐date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of pharmacoepidemiology and drug safety. Each bibliography is divided into 19 sections: 1 Books, Reviews & Symposia; 2 General; 3 Anti‐infective Agents; 4 Cardiovascular System Agents; 5 CNS Depressive Agents; 6 Non‐steroidal Anti‐inflammatory Agents; 7 CNS Agents; 8 Anti‐neoplastic Agents; 9 Haematological Agents; 10 Neuroregulator‐Blocking Agents; 11 Dermatological Agents; 12 Immunosuppressive Agents; 13 Autonomic Agents; 14 Respiratory System Agents; 15 Neuromuscular Agents; 16 Reproductive System Agents; 17 Gastrointestinal System Agents; 18 Anti‐inflammatory Agents ‐ Steroidal; 19 Others. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted.

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Acenocoumarol Is Not a Safe Alternative for Anticoagulation in Phenprocoumon-Induced Hepatic Failure

Cited by 8 publications

References 12 publications

Evidence for immunological (allergic) mechanisms in a subgroup of patients with phenprocoumon-induced liver disease

Evidence for immunological (allergic) mechanisms in a subgroup of patients with phenprocoumon-induced liver disease

Rolle der Vitamin-K-Antagonisten aus Sicht des Hepatologen

Current awareness: Pharmacoepidemiology and drug safety

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