Phenprocoumon-assoziierte nekrotisierende 
Hepatitis

Schneider, Annika; Arnold, Jorge; Bohrer, M. H.; Riemann, J F

doi:10.1055/s-2001-12889

Cited by 8 publications

(15 citation statements)

References 7 publications

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“…Thus, in 15 of 30 patients (50%) with hepatitis or cholestatic liver disease in whom phenprocoumon was highly suspected to be the causative agent due to appropriate time interval and history [13], sensitized lymphocytes against this substance were observed in vitro by LTT, revealing stimulation indices up to 17. These data confirm previous case reports showing either a positive LTT or activated lymphocytes by flow cytometry [5][6][7].…”

Section: Discussionsupporting

confidence: 82%

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17], that is, they had sensitized lymphocytes against this substance. The reaction was strictly dose dependent, showing positive results in most instances at 10 µg phenprocoumon/ml (Fig.…”

Section: Demonstration Of Sensitized Lymphocytes In Patients With Phementioning

confidence: 99%

“…The mechanisms leading to phenprocoumoninduced liver injury are not entirely clear. There are three case reports suggesting immunological processes due to a positive liver transformation test (LTT) or the activation of CD4-positive memory T cells [5][6][7]. Also, eosinophilic infiltrates in liver biopsies of patients with phenprocoumoninduced liver disease would support the concept of an immunologically mediated process, although eosinophilia in the blood or clinical signs of allergy (exanthema, fever) has not been observed [1,8,9].…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionsupporting

confidence: 82%

Section: Demonstration Of Sensitized Lymphocytes In Patients With Phementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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“…On the other hand, low titers of antinuclear antibodies in our first patient, were also observed by other investigators and have been considered to indicate a possible immunoregulatory abnormality [21]. In support of an immunoallergic mechanism, drug-specific lymphocyte activation could be demonstrated by different investigators [13, 22]. Finally, hepatotoxicity following acenocoumarol exposure in our second patient can also be better explained by an immunoallergic mechanism, because it is likely that the putatively underlying abnormalities of drug metabolism would have been corrected by the liver transplantation.…”

Section: Discussionsupporting

confidence: 52%

“…Further reports confirmed the hepatotoxic potential of phenprocoumon by recurrence of symptoms with drug re-exposure. In most reports a rather typical course of events was observed [1, 2, 3, 7, 8, 9, 10, 11, 12, 13, 14, 15]: Phenprocoumon-induced hepatotoxicity occurred 10 weeks to 8 months after initiation of the drug. After discontinuation of phenprocoumon therapy, recovery of hepatic function occurred gradually over 1–5 months.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2003

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Acenocoumarol has been proposed repeatedly as a safe alternative drug regimen for oral anticoagulation in patients who have suffered phenprocoumon-induced fulminant hepatic failure. The current report describes 2 patients with phenprocoumon-induced hepatic failure, necessitating liver transplantation in 1 case, who showed recurrence of liver damage when oral anticoagulation with acenocoumarol was attempted. Thus, acenocoumarol may not be a safe therapeutic alternative for patients who survived severe phenprocoumon-induced hepatotoxicity.

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Current Awareness

2001

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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Phenprocoumon-assoziierte nekrotisierende Hepatitis

Cited by 8 publications

References 7 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

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

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