vitamin-k-semiquinone-radical and Substance-Related-Disorders

Oral vitamin K antagonists are highly efficacious in the prevention and treatment of thromboembolic disease. Optimal use of these agents in clinical practice is challenged by their narrow therapeutic window. The proportion of time spent in the International Normalized Ratio (INR) range of 2.0-3.0 [time in the therapeutic range (TTR)] has been closely associated with adverse outcomes, i.e., stroke, hemorrhage, mortality. Although TTR is a validated marker, it has several limitations. TTR does not capture short-term risks associated with highly variable periods or periods characterized by extreme deviations in INR. Because TTR measurement is limited to consecutive periods of warfarin exposure, it does not inform the risks associated with gap periods of 56 days or greater as these time intervals are excluded from end-point rate calculations. Because individuals with gaps in monitoring represent a different patient population than those without gaps, e.g., less adherent, more acutely ill, more frequent transitions in health status, TTR analyses are likely most valid and informative for individuals with uninterrupted monitoring of the INR. Duration of warfarin therapy and patient-specific factors have also been shown to influence TTR. Younger age, female sex, lower income, black race, frequent hospitalizations, polypharmacy, active cancer, decompensated heart failure, substance abuse, psychiatric disorders, dementia, and chronic liver disease have all been associated with lower TTR. Targeted strategies to improve TTR are urgently needed.

Topics: Age Factors; Anticoagulants; Chronic Disease; Female; Heart Failure; Hemorrhage; Humans; International Normalized Ratio; Liver Diseases; Male; Neoplasms; Sex Factors; Stroke; Substance-Related Disorders; Thromboembolism; Vitamin K; Warfarin

We present the case of a 19-year-old male athlete with protein C deficiency who developed proximal deep venous thrombosis and pulmonary embolism while abusing anabolic-androgenic steroids. Anabolic-androgenic steroids have been reported to have anticoagulatory and profibrinolytic effects in patients with protein C deficiency. Despite these antithrombotic effects, the patient developed repeated venous thromboembolism during treatment with low-molecular-weight heparin. The net effect of anabolic-androgenic steroids on the haemostatic system may change from antithrombotic to prothrombotic in male abusers of anabolic steroids with protein C deficiency.

Topics: Anticoagulants; Blood Coagulation Factors; Dalteparin; Doping in Sports; Enoxaparin; Hematoma, Subdural; Humans; Male; Methandrostenolone; Pleural Effusion; Protein C Deficiency; Pulmonary Embolism; Substance-Related Disorders; Thrombophilia; Thrombophlebitis; Vena Cava Filters; Vitamin K; Young Adult

Topics: Buspirone; Humans; Lactation; Metronidazole; Neoplasms; Nicotine; Paclitaxel; Substance-Related Disorders; Vitamin K

Because of the emergence of warfarin resistance, new potent long-acting anticoagulants are now readily available in several over-the-counter rodenticide products. The availability of these "superwarfarin" compounds has led to accidental and purposeful human ingestions, one of which has resulted in a death. We summarize the prior case reports and report a second death. In addition, we report the availability of an assay to detect the presence of brodifacoum (a superwarfarin compound) in human plasma and tissues.

Topics: 4-Hydroxycoumarins; Adult; Female; Humans; Kidney; Liver; Osmolar Concentration; Rodenticides; Substance-Related Disorders; Vitamin K; Warfarin

Twenty-five patients with covert ingestion of oral anticoagulant drugs were studied. Most of the patients were women who were either connected with the medical profession or were previously treated with antigoagulants. The most common findings were ecchymoses, hematuria, and a markedly prolonged prothrombin time. The anticoagulant drug was identified in the plasma of all 25 patients. Most patients responded promptly to administration of vitamin K1. The most common motives were malingering and suicide. The world literature was reviewed for covert ingestion of oral anticoagulant drugs and 48 other cases were found. The correct diagnosis is important to focus the physician's attention on the psychiatric rather than the somatic aspects of the disorder.

Topics: Adult; Aged; Anticoagulants; Canada; Diagnosis, Differential; Europe; Female; Hemorrhagic Disorders; Humans; Hysteria; Male; Malingering; Medical Staff; Middle Aged; Prothrombin Time; Substance-Related Disorders; United States; Vitamin K

A young woman presented with a 2 year history of a severe bleeding disorder and marked deficiencies in all four vitamin-K-dependent factors. Metabolic studies with tracer doses of tritium-labelled vitamin K1 suggested that the patient might be taking an oral anticoagulant; and subsequently her plasma was found to contain a substance identical to phenindione in its spectrophotometric and chromatographic properties. The half-disappearance times of factors II, IX, X were measured after the administration of a concentrate of these factors and were found to conform with published figures. The concentrate controlled the patient's excessive bruising and prolonged skin and gingival bleeding. It would therefore seem that factor VII may not be essential in reversal of the bleeding disorder induced by anticoagulant overdose.

Topics: Adult; Anemia; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Chromatography, Gas; Chromatography, Thin Layer; Diabetes Complications; Female; Glucosephosphate Dehydrogenase; Hematemesis; Hematuria; Humans; Menorrhagia; Phenindione; Self Medication; Spectrum Analysis; Substance-Related Disorders; Vitamin K; Warfarin

Topics: Abortion, Spontaneous; Adult; Dicumarol; Disseminated Intravascular Coagulation; Female; Hemorrhage; Humans; Personality Disorders; Pregnancy; Prothrombin Time; Spectrophotometry; Substance-Related Disorders; Vitamin K

Topics: Adult; Blood Coagulation Disorders; Cathartics; Factor VII; Female; Humans; Infusions, Parenteral; Prothrombin; Substance-Related Disorders; Vitamin K

Topics: Humans; Substance-Related Disorders; Vitamin A; Vitamin K; Vitamins