vitamin-k-semiquinone-radical and Drug-Overdose

Physicians often come across with cases of vitamin K antagonists-dependent coagulopathy for reasons such as accidental use of the vitamin K antagonists (VKA), excessive administration of prescribed anticoagulants of indirect action or not reported administration of vitamin K antagonists due to memory impairment and/or other mental disorders, even deliberate use thereof (attempt to murder or suicide). Rodenticide-poisoning (coumarins, warfarins) via food or occupational accidents are difficult to diagnose. This article discusses different types of acquired vitamin K-dependent coagulopathy. Differential diagnosis is primarily based on patient statements before additional causes of vitamin K deficiency are explored. Even when pathological vitamin K deficiency is not determined, appropriate and urgent medical treatment is necessary: administration of fresh frozen plasma or concentrated factors of the prothrombin complex, administration of vitamin K remedies along with symptomatic therapy. With early diagnosis and prescription of appropriate therapy, prognosis is favorable. Reasons for vitamin K antagonists-dependent coagulopathy cases.

Topics: Anticoagulants; Blood Coagulation Disorders; Drug Overdose; Humans; Vitamin K

Anticoagulant agents have been approved by international regulatory agencies to prevent and treat venous thromboembolism (VTE). However, chronic kidney disease (CKD) is: (1) highly frequent in VTE patients; (2) strongly linked to VTE; and (3) a risk factor for cardiovascular morbidity/mortality and fatal pulmonary embolism. Therefore, an increasing number of patients are presented with CKD and VTE and more and more physicians must face the questions of the management of these patients and that of the handling of anticoagulant agents in CKD patients because of the pharmacokinetic modifications of these drugs in this population. These modifications may lead to overdosage and dose-related side effects, such as bleeding. It is therefore necessary to screen VTE patients for CKD and to modify the doses of anticoagulants, if necessary.

Topics: Anticoagulants; Cardiovascular Diseases; Drug Overdose; Heparin; Heparin, Low-Molecular-Weight; Humans; Kidney; Pulmonary Embolism; Renal Insufficiency, Chronic; Risk Factors; Venous Thromboembolism; Vitamin K

In recent years, several direct-acting oral anticoagulants (DOAC) have become available for use in Europe and other regions in indications related to prophylaxis and treatment of venous and arterial thromboembolism. They include the oral direct thrombin inhibitor dabigatran etexilate (Pradaxa, Boehringer Ingelheim) and the oral direct FXa inhibitors rivaroxaban (Xarelto, Bayer HealthCare), apixaban (Eliquis, Bristol-Myers Squibb), and edoxaban (Lixiana/Savaysa, Daiichi-Sankyo). The new compounds have a predictable dose response and few drug-drug interactions (unlike vitamin k antagonists), and they do not require parenteral administration (unlike heparins). However, they accumulate in patients with renal impairment, lack widely available monitoring tests for measuring its anticoagulant activity, and no specific antidotes for neutralization in case of overdose and/or severe bleeding are currently available. In this review, we describe the pharmacology of the DOAC, the efficacy, and safety data from pivotal studies that support their currently approved indications and discuss the postmarketing experience available. We also summarize practical recommendations to ensure an appropriate use of the DOAC according to existing data. Finally, we discuss relevant ongoing studies and future perspectives.

Topics: Administration, Oral; Drug Overdose; Factor Xa Inhibitors; Hemorrhage; Humans; Vitamin K

To review the current state of the science regarding intravenous fat emulsions (IVFEs), with an emphasis on their safety profile.. Articles were identified via a search of the MEDLINE database, including publications from 1979 to December 2009, using a search string that included the terms parenteral nutrition, lipid emulsion, fat emulsion, IVFE, safety, adverse effect, neonate intralipid, and terms describing a range of specific adverse events (AEs) such as pancreatitis.. We selected articles that allowed us to compare the results of clinical trials involving delivery of medications via IVFEs with the historical use and effects of IVFEs in parenteral nutrition, with an emphasis on AEs. We focused on 2 drugs in current use that are administered intravenously in lipid emulsions: propofol and clevidipine.. Clearance of the fat particles in IVFEs is mediated by the enzyme lipoprotein lipase. AEs are more likely if the rate or duration of IVFE administration exceeds the enzyme's clearance capacity. AEs are also more likely after administration of a 10% IVFE formulation than a 20% formulation, because the higher concentration of free phospholipid in the 10% formulation interferes with lipoprotein lipase activity. AEs can be reduced by administering IVFEs at a dosage < or = 2.5 g/kg/day and at a rate < or = 0.11 g/kg/h. The anesthetic agent propofol, which is formulated in a 10% IVFE, has been used clinically for 25 years. Typical AEs associated with propofol use include infection, high plasma triglyceride concentrations, and pancreatitis. Recent clinical trials involving clevidipine, which is formulated in a 20% IVFE, have demonstrated a low rate of lipid-related AEs.. The results of this review demonstrate that IVFEs are well tolerated when administered in accordance with guideline recommendations.

Topics: Anticoagulants; Antidotes; Bacteria; Drug Delivery Systems; Drug Interactions; Drug Overdose; Fat Emulsions, Intravenous; Humans; Hypertriglyceridemia; Immune System; Infant, Newborn; Infant, Premature; Infant, Small for Gestational Age; Liver Function Tests; Pancreatitis; Parenteral Nutrition; Respiratory Function Tests; Vitamin K

The present report from several French medical societies in the field and the French National Authority for Health provides an expert consensus for the management of patients on vitamin K antagonists in at-risk situations (overdose, risk of bleeding, and active bleeding). Asymptomatic VKA overdose is defined as an International Normalized Ratio (INR) value above the upper limit of the therapeutic target. In this case, the guidelines describe the rapid reduction of the INR down to the therapeutic range, either by omitting a dose or using vitamin K. Regarding the haemorrhagic complications, the guidelines address the management of these patients according to the severity of bleeding, and especially focus on the use of prothrombin complex concentrate. Finally, the consensus addresses the management of patients in cases of elective or emergency surgery or other invasive procedures, and discusses whether treatment should be continued or not, and whether VKA substitution by heparin--"bridging anticoagulation"--is needed.

Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Factors; Blood Loss, Surgical; Coagulants; Drug Overdose; Elective Surgical Procedures; Hemorrhage; Heparin; Humans; International Normalized Ratio; Postoperative Hemorrhage; Risk Assessment; Risk Factors; Societies, Medical; Vitamin K

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

Topics: Algorithms; Anticoagulants; Blood Component Transfusion; Drug Overdose; Hemorrhage; Humans; International Normalized Ratio; Plasma; Practice Guidelines as Topic; Risk Factors; Vitamin K; Warfarin

We cared for a patient who ingested an unknown amount of acetaminophen with zopiclone and warfarin. The only liver function test that was abnormal was an increased international normalized ratio (INR), which remained elevated despite treatment with subcutaneous phytonadione and a prolonged infusion of N-acetylcysteine. An interaction between acetaminophen and warfarin may have decreased the hepatic metabolism of warfarin. The patient received numerous antibiotics that may have contributed to the increased INR. The prolonged elevation of INR also may have been due to infrequent administration of phytonadione.

Topics: Acetaminophen; Acetylcysteine; Aged; Analgesics, Non-Narcotic; Anti-Bacterial Agents; Anticoagulants; Antidotes; Antifibrinolytic Agents; Azabicyclo Compounds; Charcoal; Drug Interactions; Drug Overdose; Female; Gastric Lavage; Humans; Hypnotics and Sedatives; International Normalized Ratio; Piperazines; Vitamin K; Vitamin K 1; Warfarin

Treatment with coumarin oral anticoagulants, such as warfarin, is effective antithrombotic therapy, but patients treated with these drugs are at significant risk of bleeding. The risk of haemorrhage increases with increasing intensity of anticoagulation and overanticoagulation is common. Reversal can be achieved by stopping the coumarin drug or administration of vitamin K, fresh frozen plasma or coagulation factor concentrates. However, there are surprisingly few studies defining the optimum dose of these products and there are no randomized studies comparing the relative benefit and risk of coagulation factor concentrates versus fresh frozen plasma. Guidelines for the management of overdose are based on level III and IV evidence and are, therefore, only grade B recommendations at best. Further studies are required to determine the most effective use of products and the dose required for safe reversal of overanticoagulation.

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Drug Overdose; Hemorrhage; Humans; Plasma; Vitamin K; Warfarin

The increased prevalence of rodents resistant to warfarin led to the development of the hydroxycoumarin anticoagulant brodifacoum. A 25-year-old man attempted suicide by consuming four boxes of d-CON Mouse-Prufe II; each box contains 42 g of bait that is 0.005% brodifacoum. He presented to a hospital nine days later with syncope, hematochezia, gross hematuria, epistaxis, anemia, and a severe coagulopathy. Radiographic studies were consistent with pleural, pericardial, and mediastinal hemorrhages. Vitamin K and fresh frozen plasma were given, and he was later discharged on oral phytonadione (vitamin K1). The patient's coagulopathy recurred, necessitating multiple plasma transfusions and prolonged treatment with oral phytonadione. Fifteen weeks after hospital discharge, he presented again with a history of additional brodifacoum ingestion. Neurologic status was initially normal, but in the emergency department he suddenly became comatose soon after emesis was induced with syrup of ipecac. Computed tomography of the brain revealed a subarachnoid hemorrhage that led to brain death less than 24 hours later. This case demonstrates the severe and prolonged coagulopathy that can result from ingestion of brodifacoum, a compound that has a toxic potency about 200-fold that of warfarin and a half-life as much as 60 times longer.

Topics: 4-Hydroxycoumarins; Adult; Blood Coagulation Disorders; Blood Transfusion; Drug Overdose; Emergency Service, Hospital; Humans; Ipecac; Male; Partial Thromboplastin Time; Patient Readmission; Phenobarbital; Plasma; Poisoning; Prothrombin Time; Rodenticides; Subarachnoid Hemorrhage; Suicide; Tomography, X-Ray Computed; Vitamin K

The optimal management of asymptomatic overanticoagulated patients remains unknown. We measured international normalized ratio (INR), activated partial thromboplastin time (APTT) and prothrombin fragment 1 + 2 (F1 + 2) over 7 d in 24 asymptomatic or mildly haemorrhagic patients on warfarin with prolonged INR of > 7.0 who were randomized to receive 0.5 mg, 1 mg or 2 mg intravenous vitamin K. Of six severely overanticoagulated patients (INR > 9.5 with APTT ratio > 2), five failed to achieve an INR < or = 4.0 on day 1, irrespective of vitamin K dose given. In the remaining 18 cases, an optimal response (INR 2-4 at day 1) was observed in 67% of those receiving 0.5 mg vitamin K, but only in 33% of those receiving 1 or 2 mg, the majority of whom developed an INR < 2.0. Our results support an optimal dose of 0.5 mg i.v. vitamin K for most overanticoagulated patients, with possibly a repeat dose in the small group of severely overanticoagulated patients.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Drug Administration Schedule; Drug Overdose; Female; Humans; Infusions, Intravenous; International Normalized Ratio; Male; Middle Aged; Partial Thromboplastin Time; Prospective Studies; Vitamin K; Warfarin

Warfarin induces coagulopathy. Guidelines protocolize reversal of supratherapeutic international normalized ratio (INR) in patients dependent on anticoagulation, but practices vary for reversing warfarin-induced coagulopathy after overdose in non-warfarin-dependent patients.. A restrictive approach to coagulopathy reversal in non-warfarin-dependent patients with intentional warfarin overdose may result in worsening coagulopathy, bleeding, and lengthy hospital stay. Given the risk for significant, prolonged coagulopathy, these patients should be treated early with VK1, with subsequent serial INR monitoring and probable additional VK1 dosing. Delayed peak warfarin concentrations support consideration of gastrointestinal decontamination in late presenters.

Topics: Adolescent; Anticoagulants; Blood Coagulation Disorders; Drug Overdose; Female; Hemorrhage; Humans; International Normalized Ratio; Vitamin K; Warfarin

Topics: 4-Hydroxycoumarins; Aged, 80 and over; Allopurinol; Anticoagulants; Drug Interactions; Drug Overdose; Humans; Iatrogenic Disease; Indenes; Macular Degeneration; Male; Phenindione; Retinal Detachment; Retinal Hemorrhage; Vitamin K

Vitamin K antagonists (VKA) are drugs with a major risk of side effect. Guidelines have been published in 2008 by the Haute Autorité de santé (HAS) concerning the management of an excessively elevated INR ratio. Our research aimed to assess physicians' adherence to those guidelines.. We realized a retrospective, multicentric study. One hundred and ten cases of excessively elevated INR ratio were identified and analyzed.. Overall physicians adherence was 58%. However, patients with the most elevated INR, i.e., INR>6, were treated according to guidelines in only 33% of the cases. The use of vitamin K was the major source of mistakes. The rate of mortality was 20%.. Adherence to HAS guidelines seems finally limited. It is necessary to put in place procedures to secure the behavior of physicians.

Topics: 4-Hydroxycoumarins; Aged; Anticoagulants; Drug Overdose; Female; France; Guideline Adherence; Humans; Indenes; International Normalized Ratio; Male; Middle Aged; Physicians; Practice Guidelines as Topic; Retrospective Studies; Vitamin K

Topics: Aged, 80 and over; Anticoagulants; Dabigatran; Dementia; Drug Overdose; Fatal Outcome; Humans; Intracranial Hemorrhages; Male; Multiple Organ Failure; Skull Fractures; Vitamin K

Apixaban is a novel oral anticoagulation agent that exerts its effect through direct factor Xa inhibition. We present a case of multi-drug overdose including apixaban with associated apixaban concentrations.. A 53 year-old man presented to our metropolitan hospital following a deliberate self-poisoning with 200 mg apixaban, 35 mg ramipril, 105 mg bisoprolol, 280 mg atorvastatin, 6 mg colchicine, 37.4 mg magnesium, 4 × 500 mg paracetamol/9.5 mg codeine/5 mg phenylephrine and alcohol. He developed hypotension that was treated with noradrenaline. His initial and peak apixaban concentration was 1022.6 ng/ml and was associated with only minor bleeding from his femoral central line insertion site, which improved with local compression. Vitamin K 10 mg (at 9 h post-ingestion) and Prothrombinex-VF 2000 units (at 13 h post-ingestion) were also administered without any observed effect on coagulation studies. Apixaban elimination appeared to display first-order kinetics with an elimination half-life of 7.4 h. His plasma apixaban concentration was within the therapeutic dose range 10 h post-ingestion and he recovered uneventfully.. A case of apixaban overdose with associated apixaban concentrations is presented. There was rapid resolution of anticoagulation with no demonstrable benefit of currently available clotting factor replacement.

Topics: Administration, Oral; Antifibrinolytic Agents; Blood Coagulation Factors; Drug Overdose; Factor Xa; Factor Xa Inhibitors; Half-Life; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Vitamin K

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

Topics: 4-Hydroxycoumarins; Aged; Drug Hypersensitivity; Drug Overdose; Female; Humans; Indenes; Jaundice; Urticaria; Vitamin K

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

Warfarin, a vitamin K antagonist, is widely used for the prophylaxis and treatment of thromboembolic disease. While guidelines exist for management of a supratherapeutic international normalized ratio following therapeutic warfarin use, these guidelines are not designed for management of the acute warfarin overdose. There is a paucity of literature describing the latter. The primary objective of this manuscript is to characterize the coagulopathy and describe the bleeding events that occur after a warfarin overdose. A secondary goal is to describe the amount of vitamin K administered to patients presenting with warfarin overdoses. A retrospective chart review of patients admitted with an acute warfarin overdose at two tertiary care medical centers in the USA was conducted. Clinical characteristics were abstracted, and bleeding categories (major, minor, trivial) were defined a priori. Twenty-three patients were admitted during the time period; males accounted for 15/23 (62.5 %) subjects. The median (interquartile range (IQR)) age was 43 (32-48.5) years. Seventeen subjects received vitamin K, with a median (IQR) dose of 15 (10-50) mg. The maximal total amount of vitamin K administered to a single patient during the index hospitalization was 110 mg. Three bleeding events occurred; one classified as major, and two as minor. All patients made a full recovery. In this case series of acute warfarin overdose, nearly all patients developed a coagulopathy, and nearly three-quarters of patients received vitamin K. Bleeding events occurred in a minority of patients.

Topics: Accidents, Home; Adult; Anticoagulants; Antidotes; Child Behavior; Child, Preschool; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Overdose; Female; Hemorrhage; Humans; Male; Middle Aged; Referral and Consultation; Retrospective Studies; Tertiary Care Centers; Treatment Outcome; United States; Vitamin K; Warfarin

Vitamin K antagonist (VKA) treatment is associated with significant risks and requires strict monitoring by measuring the international normalized ratio (INR), either by conventional methods or by self-measurement under medical supervision. We present a case of blindness occurring secondary to a moderate head injury, in a pediatric setting with no VKA therapeutic education.. A 7-year-old child with a single ventricle had been operated on for a total cavopulmonary shunt at the age of 5 years. He took VKA therapy with an INR target between 2 and 3. After a head trauma, he had a frontal hematoma. His parents did not request a medical exam and did not check his INR. Six days after the injury, the INR was 2.23. The parents went to the emergency ward because the child had bilateral orbital hematoma. At admission, the INR was 5.6. The orbital hematoma was surgically evacuated in the emergency setting. Unilateral blindness occurred and remains a sequelae of the overdose.. VKA treatment requires close supervision to prevent overdose, whose complications such as internal bleeding can have terrible consequences such as the case of blindness reported herein. This case report is a strong argument in favor of an educational program for children with VKA treatment.

Topics: Anticoagulants; Blindness; Child; Craniocerebral Trauma; Drug Overdose; Heart Defects, Congenital; Hematoma; Humans; Male; Monitoring, Physiologic; Patient Education as Topic; Prognosis; Retrobulbar Hemorrhage; Thromboembolism; Treatment Failure; Treatment Outcome; Vitamin K

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

Vitamin K antagonists (VKA) are very currently used. Nevertheless, they are known to interact with numerous drugs and foods. Grapefruit juice is known to interact with some drugs metabolized by the enterocytary cytochrome P450 3A4 but its interaction with drugs as VKA that have a good biodisponibility is not clearly demonstrated. We report here the case of a woman treated with VKA in whom massive absorption of grapefruit juice entailed an excessive VKA dosage and a severe haemorrhage.

Topics: Absorption; Anticoagulants; Beverages; Citrus paradisi; Drug Overdose; Female; Food-Drug Interactions; Humans; Middle Aged; Phenindione; Severity of Illness Index; Vitamin K

Timely reversal of excessive anticoagulation is important in preventing bleeding complications. The use of vitamin K in correcting over-anticoagulation is widely accepted to be superior to discontinuation of therapy but its effectiveness and safety in large scale cohort studies has not been assessed.. According to our protocol, 2 mg of oral vitamin K in addition to omitting the day's dose of warfarin, were administered to all patients presenting INR levels >or=5.0 and below 10.0; the INR values were checked 20 h after vitamin K administration. The rate of decay of INR, bleeding and thromboembolic complications at presentation and the following 30 days, as well as resistance to warfarin were assessed.. Of the 1,611 events, 1,043 (878 patients) met the selection criteria. The median (interquartile range) INR was 6.64 (6.12-7.52) at presentation (day zero) and fell to a median (interquartile range) INR of 2.72 (2.18-3.52, P < 0.0001) after the vitamin K administration (day one) and 90.6% of the INRs were below 4.5. In 98 (9.4%) instances the INR values did not fall below the safe limit of 4.5 and in 173 (17%) instances the INR values were overcorrected to below 2.0. Median INR value on day zero in these two groups was higher (7.3 vs. 6.6, P < 0.0001) and lower (6.5 vs. 6.7, P = 0.049) than that of the remaining cases, respectively. Overcorrection occurred more frequently in women (P = 0.0002). Female gender was an independent factor associated with INR overcorrection (P = 0.001; OR = 1.7, 95% CI 1.3-2.3). The INRs on day one were inside, above and below the therapeutic range in 44%, 36% and 20% respectively. Warfarin resistance was observed in six cases (0.6%). Major bleeding was reported in one case (1.1 per 100 patient-years), minor bleeding in 14 cases (16.1 per 100 patient-years) and thromboembolic events in six high risk patients (6.9 per 100 patient-years) during the one month period following vitamin K administration.. This adopted protocol for the reversal of excessive anticoagulation in asymptomatic or minor symptom presenting patients is easily applied, effective in lowering the INR and preventing complications. Its use in high risk thromboembolic patients warrants caution.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Cohort Studies; Disease Management; Drug Evaluation; Drug Overdose; Drug Resistance; Drug-Related Side Effects and Adverse Reactions; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Retrospective Studies; Sex Factors; Thromboembolism; Vitamin K; Warfarin

Topics: Ambulatory Care; Anticoagulants; Atrial Fibrillation; Drug Overdose; Hemorrhage; Heparin; Humans; Inpatients; Prothrombin Time; Vitamin K

Topics: 4-Hydroxycoumarins; Anticoagulants; Drug Overdose; Factor IX; Heart Atria; Heart Diseases; Heart Ventricles; Humans; Indenes; Male; Middle Aged; Thrombosis; Vitamin K

There have been concerns regarding the interference in the absorption of fat-soluble vitamins in long-term treatment with mineral oil; however, there is no clear evidence in the literature to support this claim. We present a case report illustrating the effect of prolonged (5 months) large doses of mineral oil on the fat-soluble vitamin absorption in a 17-year-old girl.

Topics: Adolescent; Biomarkers; Chronic Disease; Constipation; Dose-Response Relationship, Drug; Drug Overdose; Emollients; Female; Humans; Malabsorption Syndromes; Mineral Oil; Polyethylene Glycols; Vitamin A; Vitamin D; Vitamin E; Vitamin K; Vitamins

The report published by the French Agency for the Medical Safety of Health Products in 2001 estimated the number of hospital admissions in France for hemorrhagic accidents caused by oral anticoagulants (OA) to be 17,000. For this reason, we have set up pharmaceutical counselling for hospitalized patients treated with OA. The object of this article is to describe this therapeutic education program and to present the level of knowledge that patients have of their OA treatment. Among 68 patients treated prior to their admission, 87% knew the name of the OA, 86% the role of this treatment, 80% the dosing schedule, 57% what to do if a dose had been forgotten, 34% the signs of overdose, 48% the signs of and risks associated with not following the treatment schedule, 94% the advantage of biological follow-up and 68% the principal combinations of drugs that should be avoided. Among 118 patients whose treatment was begun during hospitalization, the level of knowledge for each item were respectively: 41%, 61%, 38%, 37%, 19%, 23%, 34% and 24% at the time of counselling. Newly treated patients acquired their knowledge from contact with nurses. The least known items were the symptoms and risks associated with overdosing or underdosing. This knowledge is therefore fragmentary and does not guarantee the patients' safety, which justifies the proposition of this type of counselling to such hospitalized patients.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Counseling; Drug Overdose; Female; Hemorrhage; Hemostatics; Humans; Male; Middle Aged; Patient Compliance; Patient Education as Topic; Pharmacy; Vitamin K

The purpose of this case report is to describe oral vitamin K resistance in a patient with concomitant Crohn's disease (CD) relapse and supratherapeutic anticoagulation. Additionally, a literature review was conducted to explore the mechanism and supporting evidence for poor response to oral vitamin K during CD relapse.. A 36 year-old female presented with an elevated International Normalized Ratio (INR) of 7.8 during a relapse of CD including symptoms of severe, persistent diarrhea and reduced appetite. For excessive anticoagulation, initial management consisted of withholding warfarin for seven days, administering vitamin K in a total dose of 10 mg orally and 1 mg intravenously. One week later, the INR remained elevated at 8.09. Subcutaneous vitamin K, in a dose of 5 mg, was administered on day eight, and the INR was reduced to a subtherapeutic result of 1.2 on day eleven.. The case report illustrates a poor response to recommended and repeated doses of oral vitamin K and a single, small dose of intravenous vitamin K during CD relapse. However, the patient responded favorably to vitamin K by the subcutaneous route. Current literature and consensus guidelines recommend the oral route of vitamin K as first-line management of overanticoagulation due to warfarin. Present data supports that patients with inflammatory bowel disease including CD have a greater incidence of vitamin K deficiency and malabsorption, and this is likely due to multiple pathological mechanisms.. Based on this case report, treatment of overanticoagulation in patients with CD relapse should include aggressive management, close monitoring, and consideration of an alternative, parenteral route of vitamin K administration rather than by the oral route due to potential for poor absorption.

Topics: Adult; Anticoagulants; Crohn Disease; Drug Overdose; Drug Resistance; Female; Humans; International Normalized Ratio; Treatment Failure; Vitamin K; Warfarin

Cytochrome P450 2C9 (CYP2C9) allelic variant carriers have been shown to experience hyper-responsiveness to small doses of oral anticoagulants (OAs) (warfarin or acenocoumarol) and a higher bleeding rate.. To determine the relative frequencies of different risk factors for OA overdose including diet, concomitant diseases, drug interactions, recent increment of OA dose and CYP2C9 genetic polymorphism among hospitalised patients.. Frequencies of the different risk factors for OA overdose were determined in a prospective case-control study. Seventy-five consecutive patients with an International normalised ratio (INR) greater than 4 were matched with seventy-five control patients with an INR greater than 2 but less than 3.5 with respect to age, prescribed OA and daily dose. Genotyping of CYP2C9*2 and CYP2C9*3 allelic variants was detected by the TaqMan allelic discrimination assay.. Drug interactions and a recent increment of OA dose were the only significant independent risk factors identified in the first analysis with odds ratio 2.13 (95% CI: 1.06-4.28) and 3.38 (95%CI: 1.51-7.57), respectively. A recent increment of OA dose was the only significant independent risk factor identified among the patients treated with coumarin derivatives (acenocoumarol or warfarin), excluding those treated with fluindione; the odds ratio was 4.3 (95% CI: 1.5-12.3). CYP2C9 genetic polymorphism did not significantly predict the increased risk of OA overanticoagulation in this study. However three homozygous CYP2C9*3/CYP2C9*3 genotype patients were found among the cases, whereas no such patients could be identified among controls.. This is the first observational study investigating the role of CYP2C9 genetic polymorphism together with other environmental OA overdose risk factors. Our results support the view that although the CYP2C9*3/CYP2C9*3 genotype is associated soon after the introduction of OA with dramatic overanticoagulation, OA overdose is mostly related to environmental factors.

Topics: Administration, Oral; Aged; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Case-Control Studies; Cytochrome P-450 CYP2C9; Dose-Response Relationship, Drug; Drug Interactions; Drug Overdose; Female; Food-Drug Interactions; Genotype; Hemorrhage; Humans; Inpatients; International Normalized Ratio; Male; Mutation; Polymorphism, Genetic; Prospective Studies; Risk Factors; Vitamin K

Antivitamin K treatments (AVK) are related to increased morbidity and mortality, notably in elderly patients. The International Normalized Ratio (INR) should be well controlled and its stabilisation within the therapeutic range help to prevent the haemorrhagic complications.. A one-year prospective survey on all the cases of excess AVK was conducted in hospitalised patients aged over 70.. During the study period, 225 hospitalised patients treated with AVK (mean age 84 years) were identified: 62% received warfarin, 19% fluindione, 8% acenocoumarol and 11% received several successive AVK. During this period, 1.904 INR measurements were recorded: 97 (5.1%) were > or =5.0 and 12 (0.63%) were > or =9.0. In all, 59 patients (23.1%) exhibited one or several episodes of excess AVK (INR > or =5.0) and 57 exhibited a target INR of 2.5. Three patients died of accidental haemorrhage--two of them due to intra-cerebral bleeding--among the 59 patients with excess AVK. In three cases, the INR was greater than 7.0 at the time of the accident.. In half of the cases of excess, the episode occurred during the month following initiation of treatment with AVK. In nearly two thirds of cases, a change had been made in drug therapy in the 10 days preceding the excess, with the prescription of a drug enhancing the effect of the AVK: anti-infection agents (antibiotics and anti-fungals) and amiodarone were the drugs most frequently involved. Oral or intravenous vitamin K1 was administered in only 19% of cases.. In very old patients treated with oral anticoagulants, certain risk factors must be identified: the initiation period of treatment, the occurrence of an intercurrent disease and the subsequent change in the drug therapy. INR monitoring should be intensified in order to detect any excess and, if detected, ensure the optimal management of the patient.

Topics: 4-Hydroxycoumarins; Aged; Aged, 80 and over; Amiodarone; Anti-Arrhythmia Agents; Anti-Bacterial Agents; Anticoagulants; Antifungal Agents; Coma; Drug Administration Schedule; Drug Overdose; Drug Synergism; Female; Hematoma, Subdural; Hemorrhage; Hospitalization; Humans; Indenes; International Normalized Ratio; Male; Prospective Studies; Pulmonary Embolism; Thrombocytopenia; Vitamin K; Warfarin

Coumarin anticoagulants impair the biological activity of the vitamin K-dependent procoagulant and anticoagulant proteins. There are no reports that focus on the levels of these proteins in over-anticoagulated patients. Therefore, we determined the levels of factor II, factor VII, factor IX and factor X, protein C and protein S in 25 randomly selected over-anticoagulated patients (International Normalized Ratio >/= 6.0) and in 25 matched, therapeutically anticoagulated patients with an International Normalized Ratio within the therapeutic zone. Furthermore, to study a possible effect of the cause of over-anticoagulation, coagulant levels were compared between 16 over-anticoagulated patients with fever in the preceding 2 weeks and 24 over-anticoagulated patients with stable congestive heart failure. The pattern of procoagulant level reductions in the three groups of over-anticoagulated patients was largely the same as in therapeutically anticoagulated patients: factor X was the lowest and factor IX the highest. The difference was that, in over-anticoagulated patients, factor VII was relatively low among the procoagulant factors compared with therapeutically anticoagulated patients. Protein C was lower than protein S in over-anticoagulated patients with congestive heart failure, but was similar to protein S in the other study groups. In over-anticoagulated patients with fever, the vitamin K-dependent coagulation proteins except factor X were significantly lower than in over-anticoagulated patients with congestive heart failure, especially factor VII and protein S.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Factor Inhibitors; Blood Coagulation Factors; Case-Control Studies; Coumarins; Drug Overdose; Female; Fever; Heart Failure; Humans; International Normalized Ratio; Male; Middle Aged; Prospective Studies; Vitamin K

Topics: Anticoagulants; Cholestyramine Resin; Drug Overdose; Humans; Vitamin K; Warfarin

Topics: Anticholesteremic Agents; Anticoagulants; Cholestyramine Resin; Diarrhea; Drug Overdose; Humans; Injections, Intravenous; Vitamin K; Warfarin

Topics: Aged; Atrial Fibrillation; Drug Overdose; Humans; Injections, Intravenous; Male; Therapeutic Equivalency; Vitamin K; Warfarin

Ingestion of long-acting anticoagulant rodenticides such as brodifacoum can lead to prolonged and life-threatening coagulopathy. A paucity of conflicting information is available on brodifacoum's half-life and elimination pharmacokinetics. In addition, the optimal dose, duration, and route of administration of vitamin K(1) therapy are unknown. We report the case of a 52-year-old man who ingested eight 43-g boxes of a rodenticide (d-Con Mouse-Prufe II; 0.005% brodifacoum; Reckitt & Colman, Wayne, NJ). This case demonstrates that after stabilization with fresh frozen plasma, high-dose oral vitamin K(1) therapy ( congruent with 7 mg/kg per 24 hours divided every 6 hours) was effective in treating brodifacoum-induced coagulopathy. The concentration of vitamin K(1) required for normal coagulation in this case was less than the accepted value of 1 microg/mL, which is derived from a rabbit model. In this case, brodifacoum appears to follow zero-order elimination pharmacokinetics. In future cases of patients with ingestions of long-acting anticoagulants who present with coagulopathy, it may be useful to obtain serial brodifacoum concentrations to determine elimination curves to help predict the duration of oral vitamin K(1) therapy.

Topics: 4-Hydroxycoumarins; Administration, Oral; Drug Overdose; Follow-Up Studies; Half-Life; Hemorrhage; Humans; Male; Metabolic Clearance Rate; Middle Aged; Plasma; Rodenticides; Suicide, Attempted; Vitamin K

To document the short- and long-term effects of accidental administration of ergometrine in adult dosage to the newborn infant.. The case records of all infants admitted to the Royal Children's Hospital (RCH) since 1970 with a diagnosis of acute ergometrine overdose were reviewed, and details of the acute symptomatology, management, and the neurodevelopmental outcome at follow-up were noted. Similar information was obtained, where available, from previous case reports, and from two major drug information services. Additionally, data relating to administration of uterotonic agents and vitamin K were collected from tertiary perinatal centres around Australia.. Seven cases of neonatal ergometrine overdose were identified at RCH. The major features of the acute toxicity syndrome were: encephalopathy (100% RCH cases, 79% combined cases); seizures (100%, 70%); peripheral vascular disturbances (100%, 83%); and oliguria (43%, 34%). Other important symptoms were hypoxaemia, hypertension and feed intolerance. 86% of RCH cases (72% overall) required ventilatory support. Virtually all symptoms resolved within 4 days, and 86% of RCH infants (86% all cases) were neurologically intact at the time of discharge. Long-term neurodevelopmental outcome was normal in 100% of RCH infants (n=6). All the perinatal centres surveyed give vitamin K in the labour ward soon after delivery, and 7 of 18 (39%) reported using Syntometrine (ergometrine 0.5 mg, Syntocinon 5 IU) routinely during the third stage of labour. Thus the circumstances in which ergometrine overdose can occur still exist in many labour wards around the country.. Despite the catastrophic initial presentation, the long-term prognosis after neonatal ergometrine overdose appears to be favourable. To prevent further cases of this life-threatening drug error, we recommend that administration of vitamin K be deferred until just prior to, or shortly after, transfer of the newborn infant to the postnatal ward.

Topics: Drug Overdose; Ergonovine; Female; Humans; Infant, Newborn; Male; Medication Errors; Oxytocics; Prognosis; Vitamin K

To evaluate the response of 73 patients with antivitamin K (AVK) overdose to 3 different therapeutic regimens.. Seventy three patients were evaluated in 94 occasions: group A (N = 32), consisted of drug withdrawal for 2 days followed by reduced dosage; group B (N = 37), drug withdrawal and reassessment within 4 days; group C (N = 25), oral administration of vitamin K. Therapeutic range was set between INR-values of 2 and 4.. Reversal regimens did not result in differences among 61 patients who had initial INR < 8 (chi 2 = 2.352, p = 0.671). There were more patients bellow therapeutic range in group C (N = 14) than group B (N = 19) (chi 2 = 9.998, p = 0.007). After intervention, 7 patients in group B still had INR > 4, but 5 of them were bellow 4.5, without increased bleeding risk. There were 10 patients in group C bellow therapeutic range, 6 of them with INR < 1.6, with risk of thromboembolism. Thirteen patients bled, but none required transfusion.. Reversal of excessive oral anticoagulation can be safely performed by initial withdrawal of the drug, followed by lower doses. Vitamin K administration may lead to INR bellow the therapeutic range. This should be reserved for patients with high INR or in the presence of bleeding.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Drug Overdose; Female; Hemorrhage; Humans; Male; Middle Aged; Retrospective Studies; Thromboembolism; Vitamin K

Brodifacoum is a 4-hydroxycoumarin derivative that is commonly used as a rodenticide. Human exposures have produced severe coagulopathies resulting in hematuria, gastrointestinal bleeding, intracranial hemorrhage, and death. This is the first report of spontaneous hemoperitoneum secondary to brodifacoum ingestion. The patient was successfully managed with fresh frozen plasma, packed red blood cells, and vitamin K1. No surgical intervention was performed. The patient required ongoing daily vitamin K1 therapy for longer than 6 months.

Topics: 4-Hydroxycoumarins; Adult; Blood Component Transfusion; Drug Overdose; Erythrocyte Transfusion; Female; Hemoperitoneum; Humans; Plasma; Poisoning; Rodenticides; Vitamin K

To determine the outcome of over-anticoagulated patients who were treated with vitamin K and those who were treated conservatively by holding doses and increasing monitoring frequency. A secondary objective was to compare conservative management with American College of Chest Physicians (ACCP) treatment guidelines when followed.. Retrospective chart review of all patients with international normalized ratios (INRs) of 6 or greater and concurrently receiving warfarin between November 1993 and February 1994.. A Veterans Affairs Medical Center providing inpatient and outpatient care. Patients receiving warfarin are managed by an established anticoagulation clinic.. Fifty-one consecutive patients receiving warfarin who had an INR of 6 or greater were reviewed.. Data collection included INR, risks for bleeding, indication for anticoagulation, interventions, and patient outcomes.. INRs ranged from 6.1 to 81.8. Forty-eight patients (94%) did not receive vitamin K; they were treated by withholding doses and increasing monitoring frequency. One developed minor bleeding. Three patients (6%) received vitamin K. Two of these patients died of unrelated problems. The third patient required 47 days of heparin therapy prior to achieving therapeutic oral anticoagulation.. This trial showed that conservative treatment of nonbleeding overanticoagulated patients is safe. A prospective trial comparing the ACCP guidelines with a conservative approach is needed.

Topics: Administration, Oral; Anticoagulants; Drug Monitoring; Drug Overdose; Humans; Retrospective Studies; Vitamin K; Warfarin

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

A man presented with frank haematuria and a grossly prolonged prothrombin time. He was later found to have taken an overdose of difenacoum--a 'superwarfarin' rodenticide. The diagnosis was confirmed by a serum concentration of difenacoum of 0.6 micrograms ml-1. Overdosage with superwarfarins is discussed and the need for prolonged treatment with vitamin K1 highlighted.

Topics: 4-Hydroxycoumarins; Adult; Drug Overdose; Hematuria; Humans; Male; Prothrombin Time; Rodenticides; Vitamin K