warfarin 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

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

Topics: Anticoagulants; Child; Child, Preschool; Consumer Product Safety; Dicumarol; Drug Overdose; Humans; Infant; Infant, Newborn; Rodenticides; Warfarin; Washington

The use of anticoagulant drugs requires a knowledge of the essential elements of their pharmacology and mechanisms of action. This article illustrates the marked differences for the drugs warfarin, heparin and aspirin.

Topics: Algorithms; Aspirin; Blood Coagulation; Dose-Response Relationship, Drug; Drug Overdose; Family Practice; Hemostasis, Surgical; Heparin; Humans; Preoperative Care; Tooth Extraction; Warfarin

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

Guidelines exist on the management of supratherapeutic/subtherapeutic international normalized ratio (INR) values for patients on warfarin. However, there is a paucity of the literature relating to an acute overdose of warfarin. This is a retrospective cohort study for all acute and acute-on-chronic (AOC) warfarin overdoses reported to the Maryland Poison Center in patients ≥12 years between January 1st, 2000, until October 31st, 2019, managed in a health care facility. The primary outcome was to determine the time after presentation to peak INR. Secondary outcomes included risk factors associated with INR >10 and describing patient characteristics. A total of 163 overdoses were included, 68 acute and 95 AOC. In patients who did not receive reversal therapies, INR peaked at a median value of 3.8 (interquartile range 2.6-5.5) between 24 and 36 hours. The median time to phytonadione was 22.0 hours. Most patients received phytonadione (62.0%), with fewer receiving blood products (16.6%). The median warfarin dose ingested was 75 mg. The AOC group had a greater mean age (56 vs. 43 years), median INR value (2.4 vs. 1.4), and men (62.1% vs. 41.2%). Factors associated with an INR > 10 included initial INR and reported quantity ingested. Peak INR was greater in the AOC than the acute overdose group (6.1 vs. 3.4), although the bleeding rate was similar. Peak INR values after warfarin overdose occur between 24 and 36 hours after presentation. Initial INRs and reported quantity ingested may be useful to predict those needing treatment.

Topics: Adult; Aged; Anticoagulants; Antidotes; Antifibrinolytic Agents; Blood Coagulation; Drug Overdose; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Maryland; Middle Aged; Poison Control Centers; Predictive Value of Tests; Retrospective Studies; Time-to-Treatment; Vitamin K 1; Warfarin

Splenic infarction is a rare clinical condition seen in the emergency department and can mimic acute abdomen. Hematologic, vascular, and thromboembolic events are considered in the etiology. Treatment options vary between symptomatic treatment and splenectomy. Warfarin is a vitamin K antagonist used for the prevention and treatment of thromboembolic disorders. In overdose situations, there is a possibility of bleeding in every part of the body. Prothrombin complex concentrates, vitamin K, and fresh-frozen plasma are used in the treatment of warfarin overdose. We describe a case of splenic infarction coexistent with warfarin overdose treatment, which has never been published in literature. Prothrombin complex concentrate was administered to the patient because of warfarin overdose. A spleen infarction was detected in computerized tomography of the patient after the occurrence of abdominal pain, and there was no infarction three days before hospitalization. The patient was monitored with symptomatic treatment in the general surgery clinic and discharged without the need for operation. In the pathogenesis, it was thought that prothrombin complex concentrates might be caused by early thrombosis or by warfarin not affecting the existing clot. Emergency physicians should not forget spleen infarction in the differential diagnosis of abdominal pain.

Topics: Abdominal Pain; Aged; Anticoagulants; Blood Coagulation Factors; Coagulants; Conservative Treatment; Diagnosis, Differential; Drug Overdose; Female; Humans; International Normalized Ratio; Predictive Value of Tests; Splenic Infarction; Tomography, X-Ray Computed; Treatment Outcome; Warfarin

Pulmonary embolism is a relatively common clinical presentation of venous thromboembolism, which develops in relation to acute pulmonary arterial occlusion mostly caused by thrombi of the lower limbs.. 29year old female admitted to emergency department with pulmonary thromboembolism due to an ingestion of 17 Diana 35 pills (2 mg cyproterone acetate and 0.035mg ethinyl estradiol) in a suicide attempt without any previously known predisposing factors. After thrombolytic therapy, the patient was discharged with oral warfarin treatment.. We know that exogenous estrogen increase the risk of venous thromboembolism in therapeutic use. It should be kept in mind that even single ingestion of a single high-dose exogenous estrogen intake may induce pulmonary thromboembolism.

Topics: Adult; Anticoagulants; Contraceptives, Oral, Hormonal; Drug Overdose; Female; Humans; Pulmonary Embolism; Suicide, Attempted; Thrombolytic Therapy; Treatment Outcome; Warfarin

Topics: Adult; Aneurysm, False; Aneurysm, Ruptured; Drug Overdose; Dyspnea; Echocardiography, Doppler, Color; Humans; Leg Ulcer; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Male; Treatment Outcome; Venous Thrombosis; Ventricular Dysfunction, Left; Warfarin

Aortic false aneurysm is life-threatening with high morbidity and mortality rates. Surgical treatment varies according to the pathologic process, infection status, and site of origin of the aneurysm. We presented a case of false aneurysm of the ascending aorta, developing after type A acute aortic dissection repair. The operation was performed with the use of deep hypothermia and circulatory arrest to avoid massive uncontrollable hemorrhage.

Topics: Acute Disease; Aneurysm, False; Anticoagulants; Aortic Aneurysm; Aortic Dissection; Aortography; Blood Vessel Prosthesis Implantation; Circulatory Arrest, Deep Hypothermia Induced; Debridement; Drug Overdose; Fatal Outcome; Humans; Intracranial Hemorrhages; Male; Middle Aged; Reoperation; Stroke; Suture Techniques; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Warfarin

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

Topics: Anticoagulants; Antidotes; Drug Overdose; Emergency Service, Hospital; Factor VIIa; Female; Humans; International Normalized Ratio; Middle Aged; Recombinant Proteins; Suicide, Attempted; Vitamin K 1; Warfarin

New portable devices for the measurement of the prothrombin time and the international normalized ratio (INR) from capillary blood samples have demonstrated to have good correlation with classic laboratory methods in multiple clinical settings. In this study, we evaluated the performance of the point-of-care device CoaguChek XS (CoaguChek XS; Roche Diagnostics, Basel, Switzerland), comparing the INR results with the standard laboratory method (automatic coagulometer) in an outpatient anticoagulation clinic. Results were compared by linear regression and Bland-Altman plot. Two hundred paired results were collected from 170 patients in a period of 90 days. The main indications for anticoagulation were prophylaxis of venous thromboembolic events, atrial fibrillation and prosthetic heart valves. Mean INR results obtained with the portable device and with the standard laboratory method were 2.22 ± 0.70 and 2.30 ± 0.77, respectively. The proportion of patients with supratherapeutic INRs was 13.5%. The CoaguChek XS monitor tended to underestimate the INR on average by 0.08 U. The correlation coefficient (R) between the two methods was 0.91 (P < 0.0001). The CoaguChek XS device is suitable for INR monitoring in patients in outpatient oral anticoagulation clinics.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Drug Overdose; Humans; International Normalized Ratio; Middle Aged; Point-of-Care Systems; Prothrombin Time; Warfarin; Young Adult

Introduction of warfarin use in prevention and treatment of thromboembolic diseases resulted in lower rates of thromboembolic complications, however, on the other hand, it has been associated with increased incidence of hemorrhagic complications,which often require surgical management. AIM, MATERIAL, METHODS: The aim of the study was a retrospective analysis of hemorrhagic complications in 184 patients, hospitalized in the FNKV (Královské Vinohrady Faculty Hospital) Surgical Clinic during 2000-2008, following warfarin overdose. The following diagnostic or treatment methods were used: endoscopy of the upper or lower GIT in GIT hemorrhages and spiral CT when peritoneal bleeding was suspected.. GIT bleeding, such as hematemesis, melena, enterorrhagy, was the commonest complication observed in 147 patients, ie. 79.9%. Upper GIT was identified as the source of bleeding in 76 subjects, i.e. 51.7%, lower GIT was the identified source in 26 subjects, ie. 17.7%, and the source remained unidentified in 45 patients, ie. in 30.6%. 10 patients suffered from soft tissue bleeding, m. rectus abdominis hematoma was detected in 7 subjects, hemoperitoneum and/or retrohemoperitoneum was identified in 8 subjects. Intestinal wall or its intestinal peritoneum was affected in 3 subjects and 3 patients suffered from liver or splenic intraparenchymal hematoma. Out of the total of 184 patients, 165 subjects were treated conservatively (89.7%), 19 subjects underwent surgery (10.3%), including 14 laparotomies for acute abdomen symptoms and 5 incisions with removal of hematomas. Overall lethality rate was 7/184, ie. 3.8%, 5 subjects undergoing conservative treatment and 2 subjects undergoing surgery exited.. Uncontrolled warfarin administration may cause serious, even life- threatening complications. Therefore, patients undergoing warfarin therapy should be adequately informed about potential complications and regular INR monitoring is required.

Topics: Aged; Anticoagulants; Drug Overdose; Female; Hemorrhage; Humans; Male; Thromboembolism; Warfarin

Plasma transfusion is standard therapy for urgent warfarin reversal in the United States. "Four-factor" prothrombin complex concentrate (PCC), available in Europe, has advantages over plasma therapy for warfarin reversal; however, only "three-factor" PCCs (containing relatively low Factor [F]VII) are available in the United States.. The efficacy of a three-factor PCC for urgent warfarin reversal was evaluated in 40 patients presenting with supratherapeutic international normalized ratio (ST-INR > 5.0) with bleeding (n = 29) or at high risk for bleeding (n = 11). In 13 patients, pre- and posttherapy vitamin K-dependent factors were assayed. Historical controls (n = 42) treated with plasma alone were used for rate of ST-INR correction comparison.. Treatment with plasma alone (mean, 3.6 units) lowered the INR to less than 3.0 in 63 percent of historical controls. Low-dose (25 U/kg) and high-dose (50 U/kg) PCC alone lowered INR to less than 3.0 in 50 and 43 percent of patients, respectively. Additional transfusion of a small amount of plasma (mean, 2.1 units) increased the rate of achieving an INR of less than 3.0 to 89 and 88 percent for low- and high-dose PCC therapy, respectively. FII, F IX, and FX increments were similar for PCC-treated patients with or without supplemental plasma; FVII was significantly higher in the PCC plus plasma group compared to the PCC-only group (p = 0.001).. Three-factor PCC does not satisfactorily lower ST-INR due to low FVII content. Infusion of a small amount of plasma increases the likelihood of satisfactory INR lowering.

Topics: Adult; Aged; Anticoagulants; Blood Coagulation Factors; Drug Combinations; Drug Overdose; Factor IX; Factor VII; Factor X; Female; Humans; International Normalized Ratio; Male; Middle Aged; Prothrombin; Retrospective Studies; Warfarin

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

To study the characteristics of patients admitted with drug overdose caused either by accidental overdose of the prescribed medications or as an act of deliberate self harm (DSH) at a tertiary care hospital in Karachi, Pakistan.. A retrospective case series review was conducted at the Aga Khan University Hospital from January 2002 to October 2006. Three hundred and twenty four adult patients admitted with drug overdose were included in the study.. Our sample group revealed mean age of 36.2 +/- 17.0 years, more females (59%), housewives (34%), and students (20%). Fifty six percent of patients committing DSH were married (p = 0.001), 81% needed in-patient psychiatric services (p = 0.016) of whom a significantly high number (38%) refused it. Domestic and social issues were rated highest among DSH group (p = 0.003), depression among females was common (p = 0.028) and Benzodiazepines (41%) was the most frequently used drug (p = 0.021). Sub-group analysis of accidental overdoses revealed mean age of 45.6 +/- 19.6 years, single (75.4%) and males (54.1%). Drugs used were mainly Benzodiazepines (18%) followed by Opioids (11%), Antiepileptics (10%) and Warfarin (10%).. Our study showed that depressed housewives are at greater risk for DSH. Domestic and social issues were rated highest and Benzodiazepines were the most commonly used agents. Most of our patients refused inpatient psychiatric treatment leading us to believe that general awareness of psychiatric illnesses is imperative in our community. High number of accidental overdoses is alarming in older, single males convincing us to believe that existing pharmacy system needs further evaluation and modification.

Topics: Accidents, Home; Adult; Analgesics, Opioid; Anticonvulsants; Benzodiazepines; Drug Overdose; Female; Humans; Male; Middle Aged; Pakistan; Retrospective Studies; Risk Factors; Warfarin

Topics: Aged; Aryl Hydrocarbon Hydroxylases; Drug Overdose; Genotype; Humans; International Normalized Ratio; Male; Mixed Function Oxygenases; Pharmacogenetics; Steroid Hydroxylases; Vitamin K Epoxide Reductases; Warfarin

We reported an 80-year-old Chinese woman on chronic stable dose of warfarin who experienced two episodes of an elevated international normalized ratio (INR) after drinking herbal tea containing Lycium barbarum L. Our case illustrated the potential herbal-drug interaction between warfarin and L. barbarum L. in keeping with a previous case report. Enquiry about herbal intake may be a crucial part in the management of anticoagulation in this locality.

Topics: Aged; Aged, 80 and over; Anticoagulants; Drug Overdose; Humans; International Normalized Ratio; Lycium; Warfarin

Topics: Acquired Immunodeficiency Syndrome; Anticoagulants; Drug Overdose; HIV Protease Inhibitors; Humans; Lopinavir; Male; Middle Aged; Pyrimidinones; Ritonavir; Warfarin

We report here the successful treatment of a 16-year-old female who ingested 20 tablets of digoxin each containing 0.25 mg (total dose ingested equivalent to 0.1 mg/kg), 32 tablets of warfarin each containing 5mg (equivalent to 3.2 mg/kg), and approximately 15 tablets of propafenone each containing 300 mg (equivalent to 90 mg/kg). The patient developed hypotension and sinus bradycardia necessitating external cardiac pacing 17 hours after drug ingestion. In addition to gastric lavage, activated charcoal, blood alkalinisation, administration of vitamin K and temporary cardiac pacing, the authors performed plasma exchange for drug removal and administered rifampicin in order to increase the metabolism of digoxin, propafenone and warfarin. The patient was discharged without any sequelae. Plasma exchange may be lifesaving in drug ingestions where there is a low volume of distribution and high plasma protein binding. Rifampicin, an inducer of cytochrome p450, may be used in intoxications for elimination of drugs with inactive metabolites.

Topics: Adolescent; Anti-Arrhythmia Agents; Anticoagulants; Bradycardia; Cytochrome P-450 Enzyme System; Digoxin; Drug Overdose; Enzyme Induction; Female; Humans; Hypotension; Plasma Exchange; Propafenone; Rifampin; Warfarin

Warfarin reversal is frequently required in day to day haematology practice. Prothrombin complex concentrates (PCC) have replaced fresh frozen plasma as the agent of choice in warfarin reversal due to its safety profile. Ideal dose of PCC is still not known and many centres have local guidelines on using the product. We have successfully used PCC (Beriplex) at a fixed dose in our hospital, but we still need randomised control trials to identify the ideal dose of PCC which can result in rapid reversal of warfarin with minimum risk of thrombosis.

Topics: Antidotes; Blood Coagulation Factors; Clinical Audit; Dose-Response Relationship, Drug; Drug Overdose; Humans; International Normalized Ratio; Treatment Outcome; Warfarin

Topics: Aged, 80 and over; Anticoagulants; Drug Overdose; Erythrocyte Transfusion; Fatal Outcome; Female; Hemorrhage; Humans; Lung Diseases; Pulmonary Alveoli; Pulmonary Edema; Respiratory Distress Syndrome; Respiratory Insufficiency; Warfarin

Topics: Blood Coagulation Disorders; Combined Modality Therapy; Drug Overdose; Humans; Male; Middle Aged; Suicide, Attempted; Warfarin

Conventionally warfarin therapy is initiated using a loading dose given over several days. Daily international normalised ratio (INR) monitoring is recommended to prevent overdose; however, with a large proportion of patients with deep vein thrombosis now receiving treatment out of hospital daily blood tests are inconvenient. We introduced a low-dose protocol for starting anticoagulant therapy that only required INR testing on days 4 and 6 and audited the results to assess safety and efficacy.. Two-hundred and forty-eight patients with confirmed deep vein thrombosis were started on warfarin therapy at 5 mg daily for 3 days. INR measurements were taken at day 4 and day 6.. Of these patients, 21% had an INR within the therapeutic range on day 4 and 52% had a therapeutic INR on day 6. The risk of overdose was small with only one case with an INR above 4.0 on day 4 and nine cases on day 6. There were no reported cases of bleeding.. The low-dose protocol with infrequent testing is safe and convenient for outpatient management. However, our results suggest that patients on this protocol take between 6-10 days to achieve a stable INR.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Child; Drug Overdose; Female; Humans; International Normalized Ratio; Male; Middle Aged; Retrospective Studies; Venous Thrombosis; Warfarin

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

We investigated the effect of prothrombin complex concentrate (PCC) on the international normalized ratio (INR) and blood coagulation system in two emergent patients treated with warfarin for secondary prevention of cardioembolic stroke due to nonvalvular atrial fibrillation. An 80-year-old woman developed massive subcutaneous hemorrhage and swelling on her right upper extremity with weak pulsation of the right radial artery and had an INR above 10. An 83-year-old man had pleural effusion with an INR value of 6.69 and pleural puncture was immediately required. We administered 500 IU of PCC to the two patients (17.2 IU/kg and 12.5 IU/kg) with 10 mg of vitamin K. The INR decreased to 1.12 and 1.85, respectively, with an increase of plasma levels of protein C and coagulant factors IIa, VIIa, IXa, and Xa 10 min after administration. The plasma levels of the thrombin-antithrombin III complex increased (from 4.0 to 12.0 micro g/l and from 0.5 to 28.9 micro g/l, respectively, normal value <3.0), but prothrombin fragment 1+2 increased minimally 10 min after administration (from 0.4 to 1.1 nmol/ml and from 0.4 to 0.7 nmol/ml, respectively, normal value 0.4-1.4 nmol/ml). Plasma levels of D-dimer remained unchanged. The massive subcutaneous hemorrhage in the former patient improved in 14 days. Anticoagulation was restarted in the latter patient after 14 days of PCC administration. There were no embolic episodes during the month after PCC administration. In conclusion, a small amount of PCC may be effective in immediately correcting increased INR levels with increased plasma levels of protein C and coagulant factors IIa, VIIa, IXa, and Xa and may partially activate the coagulation system without any effects on plasma levels of D-dimer.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Biomarkers; Blood Coagulation; Blood Coagulation Factors; Drug Overdose; Emergency Medical Services; Female; Hemorrhage; Humans; International Normalized Ratio; Stroke; Warfarin

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

Intramural hematoma of the intestine is a rare complication of anticoagulant therapy. We evaluated 7 nontrauma patients with intramural hematoma of the intestine diagnosed at our institution between May 1998 and June 2001. All of the patients were receiving long-term anticoagulant therapy for previous diseases. All 7 patients had abdominal pain, 6 had additional symptoms of nausea and vomiting, and 4 had melanotic stools at admission. Six of the patients had abnormal coagulation parameters. Both abdominal ultrasonography (US) and computerized tomography (CT) showed the exact pathology in all patients. Five of the 7 patients were treated, nonoperatively, and the other patients underwent surgery. All of the patients were followed with abdominal US and CT (mean 12 = months), with complete resolution of their intramural hematomas. Abdominal US and CT evaluation performed together will help the accuracy of diagnosis of intramural hematoma, but nonoperative therapy is the treatment of choice, with surgery indicated if generalized peritonitis or intestinal obstruction develops.

Topics: Abdomen; Abdomen, Acute; Abdominal Pain; Adult; Aged; Anticoagulants; Diagnosis, Differential; Drug Overdose; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Hematoma; Humans; Male; Middle Aged; Radiography, Abdominal; Treatment Outcome; Ultrasonography; Warfarin

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

Warfarin toxicity is common and usually results from dose changes or drug interactions. There are few reported cases of intentional overdose. The management of warfarin overdose is usually complicated by the patient using warfarin therapeutically, often for a mechanical heart valve or pulmonary embolus prophylaxis. Untreated patients have a significant bleeding risk, but treatment carries a significant risk of complete reversal of anticoagulation and consequent risk of thrombosis. The objective of this study was to describe warfarin overdoses and complications of treatment and develop a safe approach to management. Three patients are described. Two patients received a single 10-mg dose of vitamin K. Both required anticoagulation, and in one, warfarin resistance persisted for 2 weeks. In a third patient serial INR, factor levels and warfarin concentrations were measured, and incremental doses of vitamin K (up to 7.5 mg) were given based on INR. This patient did not require anticoagulation, and regular warfarin therapy was recommenced after 4 days. Patients intentionally overdosing on warfarin can be classified into three groups based on preexisting indications for warfarin: nontherapeutic, moderate risk, and major risk for thromboembolic complications. All patients should have regular INR measurements (6-hourly) to catch rapid rises. Patients not on warfarin therapeutically can be given 10 mg of vitamin K1 and repeat INRs as an outpatient. Titrating intravenous vitamin K with doses of 0.5 to 2.0 mg when INR > 5 is appropriate to reduce INR without causing warfarin resistance. The high-risk group must be kept anticoagulated, and warfarin resistance avoided.

Topics: Adult; Anticoagulants; Drug Overdose; Humans; Male; Warfarin

All pharmaceutical drugs have the potential to be misused or wrongly administered, which can result in toxic amounts of drug being ingested. To help you keep up-to-date with the latest data on outcomes and management of overdoses, both accidental and intentional, we have selected the following case reports recently published in the international medical literature and summarised in Reactions Weekly. Any claim of first report has been verified by a search of the Adisbase (a proprietary database of Adis International) and Medline. In addition, the World Health Organization (WHO) Adverse Drug Reaction database is also searched. This database, maintained by the Uppsala Monitoring Centre in Sweden, is the largest and most comprehensive adverse drug reaction source in the world, with information obtained from the National Centres of over 70 affiliate countries.

Topics: Acetaminophen; Adolescent; Adult; Aged; Amlodipine; Child, Preschool; Diphenhydramine; Dizocilpine Maleate; Drug Overdose; Female; Humans; International Normalized Ratio; Lithium; Male; Middle Aged; Paroxetine; Salicylates; Valproic Acid; Warfarin

Some drugs are known to induce pleural effusion. Drug-induced pleural effusion is often associated with pleural fluid eosinophilia. Anticoagulant therapy may induce pleural effusion by at least two different mechanisms: bleeding complication (haemothorax) and allergic or toxic reaction. Authors describe 76-yr-old male with warfarin-induced pleural effusion. Since INR was 15.5, and the value of pleural effusion Hct exceeded significantly 50% of Hct value in blood, spontaneous haemothorax due to warfarin overdose was diagnosed. Pleural fluid analysis revealed relatively high percentage of eosinophils (13%), but it was probably secondary to the presence of numerous red blood cells in the effusion. The authors discuss different mechanisms of drug-induced pleural effusion, with special attention to eosinophilic pleural effusion and review the literature on the spontaneous haemothorax as a complication of anticoagulant therapy.

Topics: Aged; Anticoagulants; Drug Overdose; Hemothorax; Humans; Male; Pleural Effusion; Pulmonary Eosinophilia; Time Factors; Warfarin

Topics: Adolescent; Allopurinol; Anticoagulants; Antimetabolites; Drug Interactions; Drug Overdose; Humans; International Normalized Ratio; Male; Warfarin

A medication order for warfarin sodium was sent by facsimile transmission with a decimal point and trailing zero. The order was incorrectly transcribed as a ten-fold overdose and would almost certainy have been fatal if administered as transcribed. Other hazardously written medication orders are presented with guidelines for safer ordercomposition.

Topics: Anticoagulants; Colchicine; Drug Overdose; Fatal Outcome; Gout Suppressants; Guidelines as Topic; Handwriting; Humans; Medication Errors; Pharmaceutical Services; Telefacsimile; Warfarin

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

Topics: Adult; Anticoagulants; Drug Overdose; Hemorrhage; Humans; Kidney Diseases; Male; Ureteral Diseases; Urothelium; Warfarin

To describe an episode of inadvertent and excessive anticoagulation caused by mistaken substitution of medication by a pharmacy outside the US.. A 57-year-old white woman was found to have profound prolongation of her prothrombin time (56.9 sec) and international normalized ratio (22.18), with other coagulation parameters relatively normal. She had no prior history of bleeding diatheses and was not taking any prescribed anticoagulants. Her coagulopathy rapidly corrected with the administration of fresh frozen plasma and vitamin K. After her medications were visually inspected, it was discovered that she had purchased her prescription medications from a pharmacy in Mexico and that she inadvertently had been taking a preparation of warfarin (proprietary name in Mexico, "Romesa") instead of the prescribed ramipril for her hypertension (proprietary name in Mexico, "Ramace"). After removal of the incorrect medication, she experienced no further prolongation of her coagulation parameters.. Medication errors contribute significantly to adverse events for patients. The frequency of different types of medication errors is reviewed, and problems specific to the use of warfarin are detailed. Circumstances that might lead to a patient seeking prescription medication outside of the US are also discussed.. The acquisition of prescription medications from pharmacies outside of the US can have adverse consequences, especially if the foreign name of the medication is different from its American name, while sounding similar to other medications that also might be dispensed in foreign pharmacies.

Topics: Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Blood Pressure; Drug Overdose; Female; Heart Rate; Humans; Medication Errors; Mexico; Middle Aged; Pharmacies; Ramipril; United States; Warfarin

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

Topics: Drug Overdose; Factor IX; Humans; Infarction; Male; Middle Aged; Testis; Warfarin

A retrospective review of over-anticoagulated patients with critical international normalized ratios (INRs) was undertaken in a large outpatient laboratory. In the six-month study period, 85 prothrombin times (PTs) were identified with an INR of > or = 6.0, an overall incidence of elevated PTs of 0.2% or two per 1,000 INR tests. Complete follow-up data was available on 65 patients. When compared to an age- and gender-matched control group without INR > or = 6.0, high-INR patients were significantly more likely to manifest the presence of alcoholism or liver disease, to have been anticoagulated for less than six months, to have experienced more frequent warfarin dosage changes, and to have had the addition of a medication known to interact with warfarin. In the high-INR group, a likely cause for the specific critical INR was identified in 44 patients (68%). Drug interactions followed by compliance problems were the most common factors identified. The 13 patients (20%) who received vitamin K therapy experienced no difference in the clinical outcome compared with those managed conservatively. Conservative management of critically high INR values appeared to be as efficacious as intervention with vitamin K therapy.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Drug Interactions; Drug Overdose; Female; Hemorrhage; Humans; Incidence; International Normalized Ratio; Male; Medical Audit; Middle Aged; Outpatients; Patient Compliance; Prothrombin Time; Retrospective Studies; Risk Factors; Warfarin

Topics: Anticoagulants; Drug Overdose; Humans; Malpractice; Pennsylvania; Professional-Family Relations; Surgical Procedures, Operative; Warfarin

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

Coumadin is a coumarin anticoagulant that induces a state similar to vitamin K deficiency and is routinely used for chronic oral anticoagulation. Intramural hematoma of the bowel is a rare complication of anticoagulant therapy. In this paper, we describe such a case of an anticoagulated patient who had complaints of abdominal pain and who had inadvertently been taking higher dose of coumadin. Although the diagnosis can usually be made by history and plain abdominal x-ray, we report here some radiographic signs that can be seen on a CT-scan of the abdomen and are relatively specific for this diagnosis. We stress the importance of recognizing the disorder because the management is conservative and surgery is reserved for cases in which no improvement is seen.

Topics: Drug Overdose; Female; Hematoma; Humans; Intestinal Diseases; Intestinal Obstruction; Intestine, Small; Middle Aged; Warfarin

Topics: Colchicine; Drug Overdose; Drug Prescriptions; Fatal Outcome; Humans; Medication Errors; Metric System; Vincristine; Warfarin; Writing