phenprocoumon and Drug-Overdose

Topics: Coumarins; Drug Overdose; Female; Humans; Iliac Vein; International Normalized Ratio; Pharmacogenetics; Phenprocoumon; Prothrombin; Thromboembolism; Vena Cava, Inferior; Young Adult

An 84-year-old woman was admitted to the emergency room with hemoptysis consisting of relevant amounts of fresh blood. She was treated with phenprocoumon for 11 years following mechanical aortic valve replacement without any complication. Laboratory results revealed phenprocoumon over dosage with international normalized ratio over 6. Chest radiograph showed diffuse alveolar infiltrates conformable to diffuse alveolar hemorrhage. Besides the pulmonary complication no other bleeding occurred. She needed noninvasive ventilatory support for 24 h to cope with the symptoms of an acute respiratory failure. After substitution of vitamin K dependent blood clot factors resulting in a normalized coagulation hemoptysis which persisted for another 3 days followed by a slow recovery. Other causes of diffuse alveolar hemorrhage were excluded in our patient. This case report presents a rare case with diffuse alveolar hemorrhage as the leading and sole symptom due to phenprocoumon overdose.

Topics: Aged, 80 and over; Drug Overdose; Female; Hemorrhage; Humans; International Normalized Ratio; Phenprocoumon; Pulmonary Alveoli; Respiratory Distress Syndrome

Topics: Aged, 80 and over; Airway Obstruction; Anticoagulants; Atrial Fibrillation; Cough; Deglutition Disorders; Drug Overdose; Hematoma; Humans; Male; Neck; Phenprocoumon; Prothrombin Time; Skin Diseases; Venous Insufficiency

Cytochrome P450 (CYP) plays a key role in the metabolism of coumarin anticoagulants and nonsteroidal anti-inflammatory drugs (NSAIDs). Because CYP2C9 is a genetically polymorphic enzyme, genetic variability could play an important role in the potential interaction between NSAIDs and coumarins. We investigated whether NSAIDs were associated with overanticoagulation during therapy with coumarins and evaluated the effect of the CYP2C9 polymorphisms on this potential interaction.. We conducted a population-based cohort study among patients of an anticoagulation clinic who were treated with acenocoumarol or phenprocoumon between April 1, 1991, and May 31, 2003, and whose CYP2C9 status was known. Patients were followed up until an international normalized ratio (INR) of 6.0 or greater was reached or until the end of treatment, death, or the end of the study. Proportional hazards regression analysis was used to estimate the risk of an INR of 6.0 or greater in relation to concomitant use of a coumarin anticoagulant and NSAIDs after adjustment for several potentially confounding factors. To study effect modification by CYP2C9 genotype, stratified analyses were performed for wild-type patients and patients with a variant genotype.. Of the 973 patients in the cohort, 415 had an INR of 6.0 or greater. Several NSAIDs increased the risk of overanticoagulation. The risk of overanticoagulation was 2.98 (95% confidence interval, 1.09-7.02) in coumarin-treated patients taking NSAIDs with a CYP2C9*2 allele and 10.8 (95% confidence interval, 2.57-34.6) in those with a CYP2C9*3 allele.. Several NSAIDs were associated with overanticoagulation. For NSAIDs that are known CYP2C9 substrates, this risk was modified by allelic variants of CYP2C9. More frequent INR monitoring of patients taking NSAIDs is warranted.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Alleles; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Cohort Studies; Cytochrome P-450 CYP2C9; Drug Interactions; Drug Overdose; Female; Humans; Male; Middle Aged; Phenprocoumon; Polymorphism, Genetic

Several case reports associated combined use of coumarins and antibacterial drugs with overanticoagulation. Despite the fact that these drugs are frequently prescribed concurrently, there is little quantitative information on the risks of such complications.. To study which antibacterial drugs are associated with overanticoagulation during therapy with coumarins.. Population-based cohort study in a sample of the Rotterdam Study.. All patients who were treated with acenocoumarol or phenprocoumon in the study period from April 1, 1991 through December 31, 1998 and for whom INR data were available.. Patients were followed until an INR >/= 6.0, the end of their treatment, death or end of the study period. Proportional hazards regression analysis was used to estimate the risk of an INR >/= 6.0 in relation to concomitant use of an oral anticoagulant and antibacterial drugs after adjustment for several potentially confounding factors such as age, gender, hepatic dysfunction, malignancies, and heart failure.. Of the 1,124 patients in the cohort, 351 developed an INR >/= 6.0. The incidence rate was 6.9 per 10,000 treatment days. Sulfamethoxazole combined with trimethoprim most strongly increased the risk of overanticoagulation with an adjusted relative risk of 20.1 (95% CI: 10.7-37.9). Stratification showed that the induction period of overanticoagulation varied between different antibacterial drugs.. In this study among outpatients of an anticoagulation clinic using acenocoumarol or phenprocoumon, several antibacterial drugs strongly increased the risk of overanticoagulation. Awareness of these drug interactions and more frequent monitoring of INR values during the initial stages of antibacterial drug therapy are warranted to minimize the risk of bleeding complications.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anti-Infective Agents; Anticoagulants; Cohort Studies; Drug Interactions; Drug Overdose; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Netherlands; Phenprocoumon; Proportional Hazards Models; Sulfamethoxazole; Trimethoprim

A 46-year old nurse complaining of multiple hematomas including bleeding into the tongue was referred for hemostasis evaluation. A very low Quick percentage value, i.e. a severely prolonged prothrombin time with severely depressed vitamin K-dependent coagulation factors (FII:C, FVII:C, FX:C) and normal FV:C and fibrinogen level was found. In the absence of cholestasis, malabsorption and broad-spectrum antibiotic therapy, ingestion of vitamin K antagonists was suspected. Three years previously, she had been on oral anticoagulant treatment with phenprocoumon (Marcoumar) for postoperative pulmonary embolism. She denied having voluntarily ingested anticoagulant drugs. A high plasma level of coumarins was found. To exclude accidental ingestion, the patient's son living in the same household was tested as well. Surprisingly, a low level of coumarin was found also in his plasma. We suspect that the patient voluntarily intoxicated herself and gave a low dose of coumarin anticoagulant to her son as well.

Topics: Anticoagulants; Blood Coagulation Tests; Drug Overdose; Female; Hematoma; Hemorrhagic Disorders; Humans; Middle Aged; Phenprocoumon; Tongue Diseases; Warfarin

A case report demonstrates a possibility of successful treatment in a patient with high-dosage phenprocoumon intoxication.. The use of plasmapheresis is an appropriate method to treat phenprocoumon-intoxicated patients by exchange of endogenous with supplied fresh frozen plasma.

Topics: Anticoagulants; Drug Overdose; Exchange Transfusion, Whole Blood; Humans; Male; Middle Aged; Phenprocoumon; Plasma; Plasmapheresis; Suicide, Attempted

Topics: Aged; Anticoagulants; Drug Overdose; Hematoma; Hematuria; Humans; Male; Medication Errors; Phenprocoumon; Retroperitoneal Space; Time Factors

A 32-year-old patient died of a cerebellar haemorrhage and the blood coagulation analysis before death suggested defective synthesis of vitamin K-dependent clotting factors due to vitamin K deficiency. The post-mortem toxicological examination of different tissues revealed phenprocoumon poisoning as the cause of death. The differential diagnosis of vitamin K deficiency and the toxicology of hydroxycoumarins are discussed.

Topics: Adult; Blood Coagulation Tests; Brain; Brain Death; Cerebellar Diseases; Cerebral Hemorrhage; Dose-Response Relationship, Drug; Drug Overdose; Humans; Male; Phenprocoumon; Vitamin K Deficiency

Topics: Abdominal Pain; Aged; Drug Overdose; Female; Gastritis; Gastrointestinal Hemorrhage; Hematoma; Humans; Phenprocoumon; Self Medication; Skin Diseases; Vitamin K Deficiency