phenprocoumon and Blood-Coagulation-Disorders

For patients who suffered a TIA or a stroke the risk of a second event is high. The recurrence rate, however, can be significantly reduced by a number of prophylactic strategies. Methods for secondary stroke prevention include a healthy lifestyle, intensive body exercise, a low cholesterol diet, and the cessation of smoking. High levels of blood pressure, cholesterol and blood glucose should be rigorously controlled. In particular, blood pressure levels should remain below 135/85 mmHg including a physiological day/night profile. All patients at high risk for cardiac embolism should receive oral anticoagulants. As the risk for embolic events increases with age (especially in patients with atrial fibrillation), a rigid "age-cutoff" for anticoagulation is not justified.

Topics: Administration, Oral; Adult; Anticholesteremic Agents; Anticoagulants; Antihypertensive Agents; Blood Coagulation Disorders; Brain Ischemia; Carotid Artery, Internal; Carotid Stenosis; Cerebral Infarction; Clinical Trials as Topic; Contraceptives, Oral; Embolism; Endarterectomy, Carotid; Exercise; Female; Humans; Hypertension; Hypolipidemic Agents; Ischemic Attack, Transient; Life Style; Male; Phenprocoumon; Platelet Aggregation Inhibitors; Recurrence; Simvastatin; Smoking Cessation; Stroke

The coincidence of coagulatopathy and chronic subdural haematoma (CSH) requires correction of coagulation to facilitate surgery. We investigated the correlation between coagulopathy and outcome in CSH patients.. We analysed past medical history, surgical treatment and coagulation parameters of 114 patients.. Coagulation disorders were found in 42%. Preoperative treatment with prothrombin complex concentrate was necessary in 14%. A significant difference (P < 0.05) of the preoperative level of platelets was found between recurrent CSH and non-recurrent group. Totally, we had to perform re-operations in 17.5%. Eighty-one patients presented with Glasgow coma scale (GCS) > or = 13. After surgery GCS was > or = 13 in n = 92. There was an improvement of GCS in 46 cases, 61 patients maintained GCS score levels. Outcome was significantly worse in the alcoholic group (P < 0.001), and in the recurrent group (P < 0.05). In patients with substitution of coagulation factors, outcome was worse in the group with post-operative substitution only (P < 0.05).. In CSH, the coagulation parameters and a subtle correction of coagulation are of special interest, regarding the worse outcome in patients with recurrent CSH and in those requiring post-operative substitution.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Alcoholism; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Chronic Disease; Craniotomy; Factor XIII Deficiency; Female; Glasgow Coma Scale; Hematoma, Subdural; Humans; Male; Middle Aged; Phenprocoumon; Platelet Count; Postoperative Hemorrhage; Preoperative Care; Recurrence; Reoperation; Survival Rate; Tomography, X-Ray Computed; Treatment Outcome

The risk of hemorrhage when coumarin anticoagulants are used sharply increases when the international normalized ratio (INR) is > or = 6.0. Such overanticoagulation may be caused by drug interactions. We performed a case-control study among previously stable outpatients of an anticoagulation clinic using phenprocoumon or acenocoumarol to identify changes in the use of potentially interacting drugs related to overanticoagulation.. Three hundred case patients with INR values > or = 6.0 were compared with 302 randomly selected matched control subjects with INR values within the target zone. Information on changes in the use of 87 potentially interacting drugs in the 4 weeks before the index day was collected by interviewing patients and by reviewing the anticoagulant medical record.. Forty-five potentially interacting drugs were not used in the 4-week study period, and only 15 drugs were used by at least 10 patients. For a number of drugs, too few patients had a relevant change in use to judge their association with overanticoagulation. A course of a combination product of sulfamethoxazole and trimethoprim strongly increased the risk of overanticoagulation (adjusted odds ratio, 24.2; 95% confidence interval [CI], 2.8 to 209.1; population attributable risk percentage [PAR%], 5.7%), especially in patients receiving acenocoumarol. Penicillins were associated with a risk of overanticoagulation of 2.4 (95% CI, 1.00 to 5.5); the corresponding PAR% was 3.4%. The effect was confined to amoxicillin (INN, amoxicilline) plus clavulanic acid.. Drug interactions as a cause of overanticoagulation predominantly concerned antibacterial drugs. If possible, the use of sulfamethoxazole-trimethoprim and amoxicillin plus clavulanic acid should be avoided in patients receiving coumarins. If there is no therapeutic alternative available, increased monitoring of INR values is warranted to prevent overanticoagulation and potential bleeding complications.

Topics: Acenocoumarol; Aged; Anti-Infective Agents; Anticoagulants; Blood Coagulation Disorders; Case-Control Studies; Cohort Studies; Drug Interactions; Female; Hemorrhage; Humans; Male; Middle Aged; Phenprocoumon; Risk Factors

In a double blind study on 20 anticoagulated patients, the influence of the anti-inflammatory drug 1-isopropyl-4-phenyl-7-methyl-2 (1H) quinazolone on the degree of hypocoagulability was examined. In comparison to a placebo group, there was no statistical difference in the Quick precentage, in coagulation factors II, VII, and X, and in platelet aggregation induced by collagen and by epinephrine respectively. In addition, no increased bleeding tendency could be observed during the study.

Topics: 4-Hydroxycoumarins; Adult; Aged; Anti-Inflammatory Agents; Blood Coagulation; Blood Coagulation Disorders; Clinical Trials as Topic; Double-Blind Method; Drug Interactions; Factor VII; Factor X; Female; Humans; Male; Middle Aged; Phenprocoumon; Placebos; Platelet Aggregation; Prothrombin; Quinazolines

Topics: Acenocoumarol; Algorithms; Anticoagulants; Blood Coagulation Disorders; Cross-Sectional Studies; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Cytochrome P450 Family 4; Drug Administration Schedule; Genotype; Humans; Pharmacogenetics; Phenprocoumon; Polymorphism, Single Nucleotide; Vascular Diseases

Phenprocoumon is a derivative of coumarin, used as a preventative anticoagulant and in the treatment of thromboembolisms. On account of its pharmacodynamic and pharmacokinetic properties, strict surveillance of the patient is necessary. We report on two cases of undocumented administration of this active pharmaceutical ingredient. A 57-year-old woman was discovered by her husband in an inanimate state. The post-mortem examination revealed many extensive haematomas. On account of a suspicion of third-party negligence, an autopsy was performed the same day, during which was established that the cause of death was a clotting abnormality, the cause of which remained unclear. Toxicological analyses revealed a concentration of phenprocoumon of 7.8 mg/l. A 76-year-old man admitted himself to hospital immediately upon returning from a stay abroad. In hospital, extensive haematomas and a massive clotting abnormality (prothrombin ratio<10%) were discovered. A blood sample taken the following day yielded evidence of a phenprocoumon concentration of 3.1 mg/l. According to his general practitioner, no corresponding medications had been prescribed. Suspicion of foul play in the introduction of this active agent resulted in a police investigation. Both cases demonstrate the necessity of toxicological analyses in cases of clotting abnormalities.

Topics: Aged; Anticoagulants; Blood Coagulation Disorders; Female; Forensic Pathology; Forensic Toxicology; Hematoma; Humans; Male; Middle Aged; Phenprocoumon; Prothrombin Time

A 15 year old Oldenburger gelding was treated during 3 weeks for laminitis with the anticoagulant phenprocoumone (27 mg orally, once daily) and concurrent administration of phenylbutazone (2-4 g orally, twice daily). After this treatment the animal was presented to the Equine Clinic University of Zurich with a history of acute colic and advanced symptoms of shock. On the basis of the clinical signs and laboratory values, a diagnosis of combined drug induced coagulopathy was made. The horse was treated with the antidote Vitamine-K1 (0.5 mg/kg, subcutaneously). Eventually, the general condition of the animal worsened and it was therefore euthanized. Necropsy revealed profound, multifocal hemorrhagic diathesis of the serosal surface of the viscera, as well as bleeding into the visceral cavities. This case shows that concurrent administration of phenprocoumone and phenylbutazone may lead to drug interactions that increase the anticoagulation effect of the coumarine-derivative. Simultaneous use of coumarine-derivatives and phenylbutazone is therefore contraindicated due to the higher risk of bleeding. A reasonable treatment of horses with anticoagulants requires regular monitoring with constant evaluation of coagulation status and special attention to potential drug interactions.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Blood Coagulation Disorders; Drug Synergism; Fatal Outcome; Horse Diseases; Horses; Male; Phenprocoumon; Phenylbutazone

Topics: Aged; Anticoagulants; Antitrichomonal Agents; Blood Coagulation Disorders; Carcinoma, Squamous Cell; Drug Interactions; Hemoptysis; Humans; Laryngeal Neoplasms; Male; Nimorazole; Phenprocoumon

We report one patient who presented with a spontaneous bleeding complication under phenprocoumon therapy. Oral anticoagulation was initiated due to deep-vein thrombosis which was attributed to an antiphospholipid antibody syndrome. Coagulation analysis revealed a strong and selective reduction of factor IX (F IX) activity to 1%, whereas the other vitamin K-dependent factors (II, VII, X), the prothrombin time and International Normalized Ratio (INR) were within the therapeutic range. After withdrawal of phenprocoumon, all vitamin K-dependent factors including F IX normalized. Because the patient suffered from a recurrence of thrombotic events, he was re-exposed to phenprocoumon and the disproportionate decline of F IX was observed again. These findings indicate an increased sensitivity of F IX to vitamin K antagonists, representing an uncommon mechanism associated with bleeding complications under oral anticoagulant treatment.

Topics: Adult; Antibodies, Antiphospholipid; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Factor IX; Humans; Male; Phenprocoumon; Prothrombin Time; Thrombosis; Time Factors

A 23-year-old woman with deep (leg) vein thrombosis was hospitalised because the Quick value had not decreased despite administration of phenprocoumon. Two years previously she had sustained an anterior wall myocardial infarction and a scar on her right kidney had been an incidental sonographic finding. There was bluish, fine reticular discoloration over the toes of both legs. Physical examination was otherwise unremarkable except for obesity.. The concentration of creatine kinase was raised to 250 U/l and that of lactate dehydrogenase to 300 U/l. The platelet count was decreased to 75/nl. The level of IgG anti-cardiolipin antibodies was raised (204 U/l) and the test for lupus anticoagulant positive. A biopsy of the skin from a toe revealing livedoid vasculitis, primary antiphospholipid syndrome (PAPS) was diagnosed.. Noncompliance, excessive vitamin K ingestion, drug interaction and malabsorption were excluded as cause of the lacking action of phenprocoumon. Despite anti-coagulation with high-dosage low-molecular heparin and inhibition of platelet aggregation with ticlopidine and finally also immunosuppressive treatment with cyclophosphamide, skin necroses developed on the toes and she had recurrent pulmonary embolisms of which she died.. Standard treatment of PAPS is effective anti-coagulation with coumarin derivatives. Secondary resistance to coumarin is a rare occurrence: its cause remains unknown.

Topics: Adult; Anticoagulants; Blood Coagulation Disorders; Drug Resistance; Fatal Outcome; Female; Humans; Phenprocoumon; Pulmonary Embolism; Syndrome

A new sensitive test--platelet-induced thrombin generation time (PITT)--is described, in which the formation of thrombin in partially anticoagulated platelet-rich plasma (PRP) leads to aggregation immediately followed by coagulation of PRP. 0.6 ml PRP are rotated in a disk-shaped cuvette within the light beam of a photometer. In PITT, platelets stick to the cuvette wall and, mediated by a large PRP/surface/air interface at the cuvette wall, are activated and participate in thrombin formation which leads to aggregation and clotting. The times from onset of rotation until aggregation (Ta) and until coagulation (Tc) of the PRP samples are recorded. PITT was very sensitive and detected low concentrations of unfractionated heparin (0.01 IU/ml) in vitro. PITT parameters were significantly prolonged ex vivo 2 h after oral administration of acetylsalicylic acid (0.5 g) and after single subcutaneous injections of heparin (5,000 IU). Patients receiving phenprocoumon prophylaxis had markedly prolonged Ta and Tc values (longer than 20 min, n = 23). Patients with recent thrombotic episodes had markedly shorter values than healthy volunteers. PITT may become a very sensitive global test to detect mild hemorrhagic disorders, to monitor the effects of antithrombotic drugs and to detect patients with a risk of vascular occlusions.

Topics: Adult; Aspirin; Blood Coagulation Disorders; Blood Coagulation Tests; Heparin; Heparin, Low-Molecular-Weight; Humans; Iloprost; Middle Aged; Phenprocoumon; Platelet Aggregation; Platelet Function Tests; Reproducibility of Results; Sensitivity and Specificity; Thrombin; Time Factors

Topics: Adolescent; Adult; Animals; Antithrombins; Blood Coagulation; Blood Coagulation Disorders; Female; Guinea Pigs; Heparin; Humans; Male; Middle Aged; Phenprocoumon; Rats; Reference Values; Sheep; Streptokinase; Swine

In healthy persons, patients with thrombocytopenia and patients with arterial disturbances of blood flow with and without administration of Falithrom the pressure recording was carried out after the combined aggregation and adhesion of thrombocytes. The reaction time particularly observed after administration of ADP revealed marked differences in the groups examined, likewise the maximal pressure amplitude in front of the pumped through filter. When Falithrom was administered the thrombocyte functions were clearly impaired. The reduction of the capacity of platelets to obstruct filter pores can impressively be proved even in those thrombocytes stored in ACD-AG-plasma.

Topics: Adenosine Diphosphate; Blood Coagulation Disorders; Humans; Phenprocoumon; Platelet Aggregation; Thrombocytopenia; Thrombocytosis

Topics: 4-Hydroxycoumarins; Basophils; Blood Coagulation Disorders; Humans; Lead; Long-Term Care; Phenprocoumon; Reticulocytes

Topics: 4-Hydroxycoumarins; Abdomen, Acute; Blood Coagulation Disorders; Diagnosis, Differential; Gastrointestinal Hemorrhage; Humans; Ileum; Intestinal Obstruction; Jejunum; Phenprocoumon

Topics: Anticoagulants; Blood Coagulation Disorders; Coumarins; Embolism; Phenprocoumon; Thrombosis

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