phenprocoumon and Hemorrhagic-Disorders

Coumarin anticoagulants are prone to drug-drug interactions. For example, antibiotic drugs may enhance the anticoagulant effect of coumarins. However, whether such interactions are associated with an increased risk of bleeding, and if so, how frequently this occurs remains unknown.. To assess the risk of major bleeding associated with the concomitant use of antibiotic drugs and coumarin anticoagulant therapy.. We analyzed a retrospective cohort study including all users of acenocoumarol or phenprocoumon in the PHARMO Record Linkage System (age range: 40-80 years). All patients were followed up until end of last coumarin treatment, hospitalization for bleeding, death, or end of study period. For each patient, the number of days on either coumarins alone, or on coumarins in combination with antibiotic drugs was determined. From these data, the relative risks of major bleeding were calculated.. A total of 52,102 users of acenocoumarol and 7885 users of phenprocoumon met the inclusion criteria of our study cohort and contributed 139,159 person-years of follow-up. During follow-up, 838 patients (1.4%) were hospitalized for a bleeding while taking coumarins. Of the 62 different antibiotics taken by study members, 19 were associated with a bleeding episode. Of these, 10 were associated with a statistically significant increased bleeding risk. The relative risk of bleeding was three to five for doxycycline, amoxicillin, amoxicillin/clavulanic acid, ciprofloxacin, cotrimoxazole, azithromycin and pheneticillin, nine for tetracycline and 43 for cefradine and neomycin.. Based on relative risks and incidence of use, amoxicillin (alone or with clavulanic acid) and doxycycline are the main antibiotic drugs associated with major bleeding when used in combination with coumarin.

Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Amoxicillin; Anti-Bacterial Agents; Anticoagulants; Doxycycline; Drug Synergism; Female; Follow-Up Studies; Hemorrhage; Hemorrhagic Disorders; Hospitalization; Humans; Male; Middle Aged; Netherlands; Phenprocoumon; Retrospective Studies; Risk

A 76-year-old man under long term oral anticoagulant treatment showed unclottable prothrombin time (PT) without overt bleeding. After oral administration of vitamin K1, PT remained severely prolonged and the patient was hospitalized. INR was 8.0 and responded to parenteral vitamin K. Cholestasis resulting in poor intestinal vitamin K resorption was assumed to have caused "overanticoagulation". Quick test is a global clotting test for the extrinsic and common pathways of the coagulation system. Increased PT, i.e. decreased Quick percentage, may be due to different conditions and should--if unexplained--be further analyzed by assaying factors II, V, VII, X and fibrinogen. Preanalytical problems, plasma dilution with clotting factor-free volume replacement, decreased vitamin K-dependent clotting factors (oral anticoagulation, intoxication with certain rodenticides, vitamin K deficiency), impaired liver synthetic capacity, disseminated intravascular coagulation, or massive heparin contamination may cause prolonged PT. Newborns physiologically have longer PT and should receive vitamin K prophylaxis.

Topics: Administration, Oral; Aged; Anticoagulants; Blood Coagulation Tests; Cholestasis, Intrahepatic; Diagnosis, Differential; Heart Valve Prosthesis Implantation; Hemorrhagic Disorders; Humans; International Normalized Ratio; Male; Phenprocoumon; Postoperative Complications; Vitamin K

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

It is frequently difficult to disclose covert ingestion of cumarins being the underlying cause of a bleeding disorder.. We report on 16 cases (15 patients) of phenprocoumon (Marcumar) abuse. All patients (9 females, 6 males) were admitted to the hospital because of bleeding and/or prolonged thromboplastin times. Analysis of phenprocoumon in the blood was performed by HPLC.. The clinical presentation of the bleeding was highly variable. Thromboplastin times ranged from < 5 to 58%. With the exception of two patients with hepatic dysfunctions factor V activity was normal. All but one patient denied the ingestion of Marcumar. One patient died from hemorrhage. Two types of patients emerge from our series: Type I is the young nurse (8 cases), type II the usually male patient formerly treated with phenprocoumon (5 cases). Type I patients had long medical histories and showed autoaggressive behavior including the artificial manipulation of disorders other than hemorrhage. Thromboplastin times however were within or close to the therapeutic range (10 to 25%). Type II patients did not simulate other diseases in addition to hemorrhage. Thromboplastin times were longer than in type I patients. In all instances discrimination between non suicidal and suicidal behaviour was difficult. Psychiatric consultance is indicated.

Topics: Administration, Oral; Blood Coagulation Tests; Chromatography, High Pressure Liquid; Female; Hemorrhagic Disorders; Humans; Male; Middle Aged; Munchausen Syndrome; Patient Care Team; Phenprocoumon; Retrospective Studies

A 62-year-old man developed resistance to coumarin congeners during treatment with phenprocoumon (Marcoumar) and acenocoumarol (Sintrom), requiring at least triple the usual therapeutic dose and plasma concentration of phenprocoumon for satisfactory anticoagulation. After 8 months on this high dosage, the patient suddenly developed haemorrhagic diathesis. The medication was therefore discontinued. The resistance could not be ascribed to impaired absorption or enhanced metabolism.

Topics: 4-Hydroxycoumarins; Acenocoumarol; Drug Resistance; Hemorrhagic Disorders; Humans; Male; Middle Aged; Phenprocoumon

The first known case of attempted murder by means of a coumarine-containing drug, administered by a nurse to her husband, is reported. Small doses of phenprocoumon were regularly added to his food or drinks. He was admitted to hospital with a severe haemorrhagic diathesis which, at first, was thought to be a familial haemorrhagic disease, his mother having died of recurrent hypoprothrombinaemia a few years earlier, the cause of her bleeding trouble never having been established. The wife was sentenced to eight years imprisonment.

Topics: Adult; Aged; Coumarins; Female; Germany, West; Hemorrhagic Disorders; Homicide; Humans; Hypoprothrombinemias; Jurisprudence; Male; Nurses; Phenprocoumon

Topics: Blood Coagulation Disorders; Coumarins; Hemorrhagic Disorders; Phenprocoumon