acenocoumarol and Drug-Overdose

Administration of vitamin K is the common mode of treatment in excessively anticoagulated patients. However, patient's response to vitamin K varies, depending on the vitamin K dose and the route of administration. Another potential source of variation is the pre-treatment INR which has not been accounted for in most previous studies. In the present study the effect of baseline INR on the response to a single dose of intravenous vitamin K (0.5 mg) was studied in 95 episodes of excessively anticoagulated patients (n = 76). In 67 episodes of moderately excessive baseline INR (6-10) mean INR declined from 8.0 +/- 1.2 to 2.6 +/- 0.9 at 24 hours, 59/67 (88%) responding within the first 12 hours and not requiring a second dose. In contrast, in 28 episodes with highly excessive baseline INR (> 10) response was slower; mean INR declining from 13.6 +/- 2.7 to 4.0 +/- 2.1 at 24 hours. In 14/28 of these episodes, patients failed to respond to vitamin K in the first 12 hours and required a second vitamin K dose. We conclude that INR at presentation affects the response to vitamin K and that this INR value should be considered in determining appropriate vitamin K doses.

Topics: Acenocoumarol; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Drug Overdose; Female; Follow-Up Studies; Hemorrhage; Humans; Infusions, Intravenous; International Normalized Ratio; Male; Middle Aged; Safety; Treatment Outcome; Vitamin K; Warfarin

Vitamin K antagonists (VKA) are widely used for the prevention and curative treatment of thromboembolic events. This study aims to describe the epidemiological, clinical and evolutionary aspects of overdose in Vitamin K antagonists administration and determine its hemorrhagic factors. We conducted a monocentric cross-sectional descriptive study at the Principal Hospital in Dakar. All patients with an INR greater than 5 were included. We studied patients' gender and age, VKA used, drug use period, indications, INR value, associated drugs, presence of hemorrhage, immediate management and evolution. We enrolled 154 patients. Acenocoumarol was the most prescribed VKA. Sex ratio favoured women. The average age was 63 years. Overdose was asymptomatic in 43% of patients. Hemorrhagic symptoms were mainly represented by gingival bleeding, epistaxis. Major bleeding episodes were found in 8.6% of patients and they were represented by melena in 6 patients (3.9%), deep muscle hematoma in 2 patients (1.3%) and intracerebral parenchymal hematoma in 2 patients. Two patients had cardiovascular collapse associated with deglobulisation. Nonsteroidal anti-inflammatory drugs (NSAIDs) assumption was noted in 21% of patients. VKA assumption was suspended transiently in all patients. Mortality was 2%, due to intracranial hemorrhage. The reduction in VKA overdose requires caregivers to manage overdose factors and provide proper patient education.

Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Anticoagulants; Cross-Sectional Studies; Drug Overdose; Female; Hematoma; Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Senegal; Vitamin K; Young Adult

Nowadays, anticoagulant therapy belongs to the most commonly used forms of pharmacotherapy in modern medicine. The most important representatives of anticoagulants are heparins (unfractionated heparin and low-molecular-weight heparin) and coumarin derivatives (vitamin K antagonists--VKA). Next to the many advantages of traditional oral anticoagulants may also have disadvantages. In Poland most often used two VKA: acenocoumarol and warfarin. The aim of the work is the analysis of the causes of the occurrence of bleeding disorders and symptoms of overdose VKA in patients to be hospitalized. In the years 2012 to 2014 were hospitalized 62 patients with overdose VKA (40 women and 22 men). The average age of patients was 75.3 years) and clotting disturbances and/or bleeding. At the time of the admission in all patients a significant increase in the value of the INR was stated, in 22 patients INR result was " no clot detected", on the remaining value of the INR were in the range of 7 to 13.1. On 51 patients observed different severe symptoms of bleeding (hematuria, bleeding from mucous membranes of the nose or gums ecchymoses on the extremities, bleeding from the gastrointestinal tract--as in 5 patients has led to significant anemia and transfusion of concentrated red blood cells. Up on 33 patients kidney function disorder were found--exacerbated chronic renal failure and urinary tract infection. 8 diagnosed inflammatory changes in the airways. On 13 patients, it was found a significant degree of neuropsychiatric disorders (dementia, cognitive impairment), which made impossible the understanding the sense of treatment and cooperation with the patient. In 6 patients the symptoms of overdose were probably dependent on the interaction with the congestants at the same time (change the preparation of anticoagulant, NSAIDs, antibiotics). In 2 cases, the overdose was a suicide attempt in nature. In addition to the above mentioned disorders, on two of those patients diagnosed with a malignant disease. Two patients died, the other has been improving and anticoagulant therapy with VKA was continued, in 4 VKA were changed to low-molecular-weight heparin, and on 4 commissioned new generation anticoagulant (rivaroxaban).

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Cognition Disorders; Dementia; Drug Interactions; Drug Overdose; Female; Humans; Male; Neoplasms; Poland; Suicide, Attempted; Vitamin K; Warfarin

Acenocumarol is widely used in long-term anticoagulant treatment. Overdose of this drug may result in suffusions in various parts of the body. In three cases, we observed suffusion in the rectus sheath, which is an unusual site of hematomas. At early stage, the lack of discoloration of the abdominal wall may lead to problems in differential diagnosis. Chronic anticoagulant treatment in a patient's history in combination with a palpable abdominal mass facilitate the correct diagnosis. In addition, high INR also makes hemorrhagic complications more likely. In simple cases, suggestive past medical history, abdominal palpation, INR and ultrasound examination can be sufficient to make a diagnosis. However, in more complicated cases, further assessment by CT is required to set up the diagnosis; while, in a further case discussed in this article, we could only establish an accurate diagnosis with laparoscopy. Decreased plasma prothrombin levels were always normalized with vitamin K.

Topics: Acenocoumarol; Aged; Anticoagulants; Antifibrinolytic Agents; Diagnosis, Differential; Drug Overdose; Female; Hematoma; Humans; International Normalized Ratio; Laparoscopy; Male; Middle Aged; Palpation; Rectus Abdominis; Tomography, X-Ray Computed; Vitamin K

Bleeding complications of oral anticoagulant therapy are not rare. The locations for bleeding are most often gastrointestinal, genitourinary and intracranial. Upper airway obstruction remains one of the reported complications. It is produced in most cases by a retropharyngeal haematoma. On the other hand, sublingual haematoma is exceptional and constitutes a problem to secure patient's airway. We report the case of a 16-year-old patient, admitted tenhours after accidental ingestion of 40mg of Sintrom((R)) with major breathing difficulty, haemoptysis and epistaxis. The endotracheal intubation was performed blindly using an Eschmann candle. This rare complication should be prevented by an adapted clinical and biological monitoring.

Topics: Accidents, Home; Acenocoumarol; Administration, Oral; Adolescent; Airway Obstruction; Anticoagulants; Drug Overdose; Erythrocyte Transfusion; Heart Valve Prosthesis; Hematoma; Humans; Intubation, Intratracheal; Male; Mouth Floor; Plasma

Haemobilia is a rare cause of acute upper gastrointestinal bleeding and is often associated with a history of hepatic or biliary tract injury, tumor growth, hepatic artery aneurysm, cholecystitis, or hepatic abscess. We report a case of a 79-year-old women with haemobilia due to acenocoumarol overdosage. She has been, taking 12 mg acenocoumarol by mistake for 5 days before admission because of atrial fibrillation. INR was 20 during an admission. Ultrasonographic evaluation demonstrated hepatomegaly, cholelithiasis, thick sludge in gallbladder represented blood clots and also dilated biliary tract. Cholecystectomy was carried out. The cut section of gall bladder showed stone, haemolysed blood and blood clots. Choledochotomy showed only blood clots within the duct. The treatment lasted long period and patient died because of multiorgan insufficiency in the course of sepsis.

Topics: Acenocoumarol; Aged; Anticoagulants; Atrial Fibrillation; Cholecystectomy; Cholecystitis, Acute; Cholelithiasis; Drug Overdose; Fatal Outcome; Female; Hemobilia; Humans; Medication Errors; Multiple Organ Failure; Pancreatitis; Polyps; Splenectomy; Treatment Failure

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

Topics: Acenocoumarol; Administration, Oral; Ambulatory Care; Anticoagulants; Antifibrinolytic Agents; Drug Overdose; Follow-Up Studies; Humans; International Normalized Ratio; Treatment Outcome; Vitamin K 1; Warfarin

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

Topics: Acenocoumarol; Adult; Anticoagulants; Blood Coagulation Disorders; Cardiovascular System; Drug Overdose; Female; Headache; Humans; Male; Middle Aged; Urticaria; Vitamin E

The authors report four cases of spontaneous retroperitoneal haematomas, which occurred in their department during a half year period. The patients were admitted from different internal medicine departments. They had anaemia, and bleeding with unknown origin and localisation, and were in a bad condition. Three patients could be suitable for operation after general preparation. One of these patients died and another one died without operation. Two of them went home after recovering. The patients were transferred to surgical department on average three days after the symptoms developed. Hypoprothrombinaemia was the reason for bleeding in three cases. One patient got overdosed Syncumar, and two patients suffered from alcoholic cirrhosis who had other serious diseases as well. The authors found that the fourth patient, who had the gluteal arterial rupture with inexplicable origin, also had hypoprothrombinaemia. It is very difficult to diagnose these disease. Bleeding always has to be taken into consideration, if the patients have liver disease, or any type of coagulopathy, or take some anticoagulant medicine. The blood test examinations, ultrasound, CT, MR, angiography, laparoscopy can be helpful in the diagnosis of these cases.

Topics: Acenocoumarol; Drug Overdose; Female; Hemorrhage; Humans; Hypoprothrombinemias; Liver Cirrhosis, Alcoholic; Magnetic Resonance Angiography; Male; Retroperitoneal Space; Tomography, X-Ray Computed; Treatment Outcome

Topics: Acenocoumarol; Adult; Drug Overdose; Humans; Male; Poisoning; Vitamin K