Humans ; Vitamins/therapeutic use* ; Iron, Dietary ; Diabetes Mellitus, Type 2 ; Nutrition Surveys ; Diet ; Vitamin A ; Vitamin K

Object We aimed to compare the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOAC) and vitamin K antagonist (VKA) in the prevention and treatment of thrombotic diseases in patients with active cancer. Methods: To find randomized controlled trials (RCT) in which NOACs were compared VKAs in active cancer, we searched the electronic databases (PubMed, Web of Science and Clinical Trials) up to May 2019 and and languages restricted to Chinese and English. According to the screening strategy, two researchers independently screened and extracted literature, evaluated the quality of literature, the suitability of collected cross study data for analysis, and tested the heterogeneity. The relative risk (RR) and 95% confidence interval (95%CI) of major bleeding, clinically related non-major bleeding, VTE, stroke and all-cause mortality in active cancer patients with VTE, active cancer patients with non-valvular atrial fibrillation (NVAF) was calculated and the results were compared between NOAC with VKA. Results: A total of 9 RCTs were included, including 5 cancers with VTE (5/9) and 4 cancers with NVAF (4/9). A total of 5 867 patients were included. After excluding 1 818 (30.99%) patients with cancer history, 4 049 (68.86%) patients with active cancer were statistically analyzed. Among them, 2 278 (56.26%) received NOAC treatment, 1 771 patients (43.74%) received VKA treatment. The quality of the included documents was high (all scores were>5 points), and the data of each included document could be summarized and analyzed (P>0.05). The heterogeneity of main outcome events was very low (I² = 0). In VTE patients with active cancer, NOACs were more effective in reducing recurrence of VTE （RR=0.55, 95%CI 0.36 -0.84; P = 0.005) and clinically related non-major bleeding (RR=0.77, 95%CI 0.60 -0.98; P = 0.03) than VKAs. In NVAF patients with active cancer, efficacy of NOACs and VKAs was similar in terms of reducing VTE, stroke, clinically related non-major bleeding, major bleeding and all-cause mortality events (P>0.05). Conclusions: For patients with active cancer accompanied by VTE, NOAC may has more advantages in efficacy and safety compared to VKA in the prevention and treatment of thrombotic diseases.
Administration, Oral ; Anticoagulants/therapeutic use* ; Atrial Fibrillation/drug therapy* ; Humans ; Neoplasms/drug therapy* ; Randomized Controlled Trials as Topic ; Venous Thromboembolism/prevention & control* ; Vitamin K/therapeutic use*

OBJECTIVETo compared the therapeutic effect of a Chinese patent medicine Naoxintong Capsule (, NXT) and aspirin with adjusted-dose warfarin in Chinese elderly patients (over 65 years) with nonvalvular atrial fibrillation (NVAF) and genetic variants of vitamin K epoxide reductase (VKORC1), who are at high-risk of thromboembolism.

METHODSA total of 151 patients, with NVAF and AA genotype of VKORC1-1639 (a sensitive genotype to warfarin) and a CHADS-VASc clinical risk score of 2 or above, were chosen for this study. Patients were randomized into two groups and orally treated with a combination of aspirin (100 mg/day) and NXT (1.6 g thrice a day) or adjusted-dose warfarin [international normalized ratio 2.0-3.0). The primary end points including ischemic stroke and death as well as the secondary end points including hemorrhage events were followed up for at least 1 year.

RESULTSBaseline clinical data and the rates of primary end points were similar between groups. However, the rate of serious bleeding (secondary event) in the combination therapy group was lower than that in the adjusted-dose warfarin group (0% vs. 7.9%, odds ratio: 0.921, 95% confidence interval: 0.862-0.984, P=0.028).

CONCLUSIONSAspirin combined with NXT and warfarin displayed comparable rates of primary end point including ischemic stroke and all-cause death during the 1-year follow-up. However, as compared with warfarin, the combination therapy reduced the rate of serious bleeding. Therefore, aspirin combined with NXT might provide an alternative pharmacotherapy in preventing ischemic stroke for elderly patients with NAVF who cannot tolerate warfarin. (No. ChiCTR-TRC-13003596).

Aged ; Aspirin ; therapeutic use ; Atrial Fibrillation ; drug therapy ; enzymology ; genetics ; Base Sequence ; Capsules ; Drugs, Chinese Herbal ; therapeutic use ; Endpoint Determination ; Female ; Genetic Variation ; Humans ; Male ; Risk Factors ; Treatment Outcome ; Vitamin K Epoxide Reductases ; genetics ; Warfarin ; therapeutic use

Pharmacogenetic testing for clinical applications is steadily increasing. Correct and adequate use of pharmacogenetic tests is important to reduce unnecessary medical costs and adverse patient outcomes. This document contains recommended pharmacogenetic testing guidelines for clinical application, interpretation, and result reporting through a literature review and evidence-based expert opinions for the clinical pharmacogenetic testing covered by public medical insurance in Korea. This document aims to improve the utility of pharmacogenetic testing in routine clinical settings.
Anticoagulants/therapeutic use ; Antidepressive Agents/therapeutic use ; Antimetabolites, Antineoplastic/therapeutic use ; Antitubercular Agents/therapeutic use ; Arylamine N-Acetyltransferase/genetics ; Coronary Artery Disease/drug therapy/genetics ; Cytochrome P-450 CYP2C19/genetics ; Cytochrome P-450 CYP2C9/genetics ; Cytochrome P-450 CYP2D6/genetics ; Depressive Disorder/drug therapy/genetics ; Genotype ; Isoniazid/therapeutic use ; Laboratories, Hospital/standards ; Methyltransferases/genetics ; Pharmacogenomic Testing/*methods/standards ; Platelet Aggregation Inhibitors/therapeutic use ; Pulmonary Embolism/drug therapy/genetics ; Ticlopidine/analogs & derivatives/therapeutic use ; Tuberculosis/drug therapy/genetics ; Vitamin K Epoxide Reductases/genetics ; Warfarin/therapeutic use

PURPOSE: The genes for cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) have been identified as important genetic determinants of warfarin dosing and have been studied. We developed warfarin algorithm for Korean patients with stroke and compared the accuracy of warfarin dose prediction algorithms based on the pharmacogenetics. MATERIALS AND METHODS: A total of 101 patients on stable maintenance dose of warfarin were enrolled. Warfarin dosing algorithm was developed using multiple linear regression analysis. The performance of all the algorithms was characterized with coefficient of determination, determined by linear regression, and the mean of percent deviation was used to predict doses from the actual dose. In addition, we compared the performance of the algorithms using percentage of predicted dose falling within ±20% of clinically observed doses and dividing the patients into a low-dose group (≤3 mg/day), an intermediate-dose group (3-7 mg/day), and high-dose group (≥7 mg/day). RESULTS: A new developed algorithms including the variables of age, body weight, and CYP2C9 and VKORC1 genotype. Our algorithm accounted for 51% of variation in the warfarin stable dose, and performed best in predicting dose within 20% of actual dose and intermediate-dose group. CONCLUSION: Our warfarin dosing algorithm may be useful for Korean patients with stroke. Further studies to elucidate clinical utility of genotype-guided dosing and find the additional genetic association are necessary.
Aged ; *Algorithms ; Anticoagulants/*administration & dosage/therapeutic use ; Cytochrome P-450 CYP2C9/*genetics ; Dose-Response Relationship, Drug ; Female ; Genotype ; Humans ; International Normalized Ratio ; Linear Models ; Male ; Middle Aged ; Multivariate Analysis ; Pharmacogenetics ; Regression Analysis ; Republic of Korea ; Stroke/*drug therapy/ethnology ; Vitamin K Epoxide Reductases/*genetics ; Warfarin/*administration & dosage/therapeutic use

A 73-yr-old Korean man with permanent atrial fibrillation visited outpatient clinic with severely increased International Normalized Ratio (INR) values after taking a usual starting dosage of warfarin to prevent thromboembolism. We found out later from his blood tests that he had hyperthyroidism at the time of treatment initiation. His genetic analysis showed CYP2C9*1/*3 and VKORC1+1173TT genotypes. We suspect that both hyperthyroidism and genetic variant would have contributed to his extremely increased INR at the beginning of warfarin therapy. From this case, we learned that pharmacogenetic and thyroid function test might be useful when deciding the starting dosage of warfarin in patients with atrial fibrillation.
Aged ; Anticoagulants/blood/metabolism/therapeutic use ; Aspirin/therapeutic use ; Atrial Fibrillation/*diagnosis ; Chromatography, High Pressure Liquid ; Cytochrome P-450 CYP2C9/*genetics ; Genotype ; Humans ; Male ; Polymorphism, Single Nucleotide ; Tandem Mass Spectrometry ; Thromboembolism/prevention & control ; Thyrotoxicosis/*diagnosis ; Vitamin K Epoxide Reductases/genetics ; Warfarin/*blood/metabolism/therapeutic use

OBJECTIVETo summarize the clinical characteristics of secondary coagulation disorders caused by exposure to poison (raticide) in children and to investigate the diagnosis and corresponding treatment.

METHODThe process of diagnosis, clinical characteristics, response to treatment and the prognosis were analyzed.

RESULTSThe main clinical manifestation was mucosal bleeding (66.6%), including epistaxis, gingival bleeding, hematomas and so on. All these children were previously well and had no history of bleeding. Activated partial thromboplastin time (APTT) and prothrombin time (PT) were prolonged, factor II was undetectable and the levels of factors VII, IX, and X were lower. The fibrinogen was normal. A raticide was detected in blood and urine of 13 children although 12 of the patients had no definite history of raticide ingestion. Prothrombin complex, fresh frozen plasma and vitamin K(1) were effective in these cases. However, 2 - 3 weeks later, 6 patients presented with recurrent bleeding.

CONCLUSIONFor children with secondary coagulation disorders of unknown cause, intoxication of raticide should be considered. The administration of blood coagulation factors and vitamin K(1) are effective in early treatment, and the treatment period should be more than 2 months. The PT and APTT should be followed up. Vitamin K(1) should be stopped when PT and APTT are normal.

Blood Coagulation Disorders ; chemically induced ; diagnosis ; therapy ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Rodenticides ; poisoning ; Vitamin K 1 ; administration & dosage ; therapeutic use

A 71-year-old man was stable on warfarin (2.25 mg daily) therapy with an international normalized ratio (INR) of 1.8-2.2 after a heart valve replacement surgery. Recently, he consumed the liquid-like herbal product called shengmai-yin (10 mL daily) against medical advice. Seven days after the daily consumption of shengmai-yin, he was admitted to the intensive care unit because of consciousness disturbance [Glasgow Coma Scale (GCS) score 7] with an INR of 5.08. Head computed topography revealed intracerebral hematoma in the left temporoparietal region. Both warfarin therapy and the herbal product were withdrawn. At the same time, therapy with intravenous vitamin K1 40 mg was started. On the second day of admission, craniectomy was performed to remove the intacerebral hematoma under general anesthesia. He remained confused and restless for 2 days, but then showed progressive recovery in the consciousness level as well as motor and verbal functions. Shengmai-yin contains herbal ingredients that can interact with warfarin. The Drug Interaction Probability Scale (DIPS) indicated that warfarin and shengmai-yin were highly probable causes of intracerebral hematoma. Patients on warfarin therapy should be discouraged from taking herbal medicines, especially preparations that are already known to have antiplatelet and antithrombotic effects.
Aged ; Anticoagulants/*adverse effects/therapeutic use ; Cerebral Hemorrhage/*chemically induced/drug therapy/surgery ; Drug Interactions ; Drugs, Chinese Herbal/*adverse effects ; Hematoma/*chemically induced/drug therapy/surgery ; Humans ; Male ; Treatment Outcome ; Vitamin K 1/therapeutic use ; Warfarin/*adverse effects/*therapeutic use

A 71-year-old man was stable on warfarin (2.25 mg daily) therapy with an international normalized ratio (INR) of 1.8-2.2 after a heart valve replacement surgery. Recently, he consumed the liquid-like herbal product called shengmai-yin (10 mL daily) against medical advice. Seven days after the daily consumption of shengmai-yin, he was admitted to the intensive care unit because of consciousness disturbance [Glasgow Coma Scale (GCS) score 7] with an INR of 5.08. Head computed topography revealed intracerebral hematoma in the left temporoparietal region. Both warfarin therapy and the herbal product were withdrawn. At the same time, therapy with intravenous vitamin K1 40 mg was started. On the second day of admission, craniectomy was performed to remove the intacerebral hematoma under general anesthesia. He remained confused and restless for 2 days, but then showed progressive recovery in the consciousness level as well as motor and verbal functions. Shengmai-yin contains herbal ingredients that can interact with warfarin. The Drug Interaction Probability Scale (DIPS) indicated that warfarin and shengmai-yin were highly probable causes of intracerebral hematoma. Patients on warfarin therapy should be discouraged from taking herbal medicines, especially preparations that are already known to have antiplatelet and antithrombotic effects.
Aged ; Anticoagulants/*adverse effects/therapeutic use ; Cerebral Hemorrhage/*chemically induced/drug therapy/surgery ; Drug Interactions ; Drugs, Chinese Herbal/*adverse effects ; Hematoma/*chemically induced/drug therapy/surgery ; Humans ; Male ; Treatment Outcome ; Vitamin K 1/therapeutic use ; Warfarin/*adverse effects/*therapeutic use

This observational study aimed at evaluating recent superwarfarin intoxication of Korean patients. Ten patients were diagnosed as or highly suspicious for superwarfarin intoxication. Case report forms described by attending hematologists of the patients were collected and analyzed. Bleeding symptoms were varied among the patients. Patients uniformly showed prolonged prothrombin time (PT) and activated thromboplastin time (aPTT) with decreased activity of vitamin K dependent coagulation factors. Positive serum brodifacoum test results in 4 of 5 requested patients contributed to confirmatory diagnosis. Psychiatric interview revealed an attempted ingestion in one patient. High dose vitamin K1 therapy promptly corrected prolonged PT and aPTT, but hasty discontinuation caused repeated bleeding diathesis in 6 patients. Route of intoxication was unknown or not definite among 8 of 10 patients. Three patients had a possibility of environmental exposure considering their occupations: there might be intoxication by transdermal absorption or inhalation. Therefore, high dose and prolonged use of vitamin K1 therapy is necessary for effective detoxification. Further detailed investigation on environmental exposure and efforts to improve availability of the blood level test in clinic are requested.
4-Hydroxycoumarins/*poisoning ; Adult ; Aged ; Aged, 80 and over ; Anticoagulants/*poisoning ; Antifibrinolytic Agents/therapeutic use ; Environmental Exposure ; Female ; Hemorrhage/*chemically induced/diagnosis/drug therapy ; Humans ; Male ; Middle Aged ; Partial Thromboplastin Time ; Prothrombin Time ; Republic of Korea ; Treatment Outcome ; Vitamin K 1/therapeutic use