Anticoagulants ; pharmacology ; therapeutic use ; Cardiovascular Diseases ; drug therapy ; Humans

Lung cancer is the first leading cause of morbidity and mortality in the world. Venous thromboembolism (VTE) is a recognized complication in patients with lung cancer, which is one of the leading cause of death in lung cancer patients. The cancer-related, patient-related and treatment-related factors are the main causes of VTE in lung cancer patients. Malignant cells can directly activate blood coagulation by producing tissue factor (TF), cancer procoagulance (CP), inflammatory factors and cytokines; And the one of predominant mechanisms in cancer-related thrombosis is the overexpression of TF. The 10th edition of the antithrombotic therapy guidelines for VTE with cancer patients (AT-10) published in 2016 by American College of Chest Physicians (APCC) recommended that anticoagulant therapy is the basic treatment for patients with lung cancer complicated with VTE; And low molecular-weight-heparin (LMWH) is preferred as an anticoagulant drug, but can be use with caution due to increasing risk of bleeding.
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Anticoagulants ; pharmacology ; therapeutic use ; Humans ; Lung Neoplasms ; complications ; Risk Factors ; Venous Thromboembolism ; complications ; drug therapy

OBJECTIVE: This study assessed the outcomes of using vascular closure devices following percutaneous transfemoral endovascular procedures in the patients who were treated with heparin, abciximab or thrombolytics (urokinase or t-PA) during the procedures. MATERIALS AND METHODS: From March 28, 2003 to August 31, 2004, we conducted a prospective and randomized study in which 1,676 cases of 1,180 patients were treated with one of the two different closure devices (the collagen plug device was Angio-SealTM; the suture-mediated closure device was The Closer STM) at the femoral access site after instituting percutaneous endovascular procedures. Among the 1,676 cases, 108 cases (the drug group) were treated with heparin only (n = 94), thrombolytics only (n = 10), heparin and thrombolytics (n = 3), or abciximab and thrombolytics (n = 1) during the procedures; 1,568 cases (the no-drug group) were treated without any medication. We compared the efficacy and complications between the two groups. Of the drug group, 42 cases underwent arterial closures with the collagen plug devices and 66 cases underwent arterial closures with the suture-mediated closure devices. We also compared the efficacy and complications between these two groups. RESULTS: The immediate hemostasis rates were 92.9% (1,456/1,568) in the no-drug group and 91.7% (99/108) in the drug group. Early complications occurred in four cases of the drug group. These included two episodes of rebleeding with using the Closer S, which required manual compression for at least 10 minutes, and two episodes of minor oozing with using one Angio-Seal and one Closer S, which required two hours of additional bed rest. There was no late complication. So, the total success rates were 90.8% (1,423/1,568) in the no-drug group and 88.0% (95/108) in the drug group. These results were not significantly different between the two groups (p = 0.34). In the drug group, the difference of the successful hemostasis rate between the collagen plug devices and the suture-mediated devices was also not statistically significant (92.9% vs. 84.8%, respectively; p = 0.21). CONCLUSION: Arterial closure of the femoral access site with using vascular closure devices is both safe and effective, even in the patients who received heparin, abciximab or thrombolytics.
Sutures ; Prospective Studies ; Postoperative Complications ; Middle Aged ; Male ; Immunoglobulin Fab Fragments/pharmacology/*therapeutic use ; Humans ; Hemostatic Techniques/*instrumentation ; Hemostasis/*drug effects ; Fibrinolytic Agents/pharmacology/*therapeutic use ; Femoral Artery/*surgery ; Female ; Collagen ; Anticoagulants/pharmacology/*therapeutic use ; Antibodies, Monoclonal/pharmacology/*therapeutic use

OBJECTIVETo investigate the protective effect and anticoagulation effect of polysaccharides from the sea cucumber (PSU) on acute incomplete cerebral ischemia (AICI).

METHODSAdult SD rats were randomly divided into 5 group (n = 12): sham operation group, model group, low-dose (30 mg/(kg x d)), middle-dose (60 mg/(kg x d)) and high-dose (120 mg/(kg x d)) groups. The cerebral ischemia rat model was established by permanently ligating the common carotid arteries on both sides of rats. We observed the change of behavior disturbance, brain water content, the levels of serum C-reactive protein (CRP) as well as the effects on prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen(FIB).

RESULTSDue to the use of polysaccharides, the behavioral disturbance was improved, brain water content and the levels of serum CRP were significantly decreased. Also PSU significantly prolonged APTT, TT and reduced the content of FIB (P < 0.05).

CONCLUSIONPSU has protective effect on acute incomplete cerebral ischemia injured rats and significant anticoagulation effect.

Animals ; Anticoagulants ; pharmacology ; therapeutic use ; Brain ; metabolism ; Brain Ischemia ; drug therapy ; metabolism ; physiopathology ; Male ; Polysaccharides ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Sea Cucumbers ; Thrombin Time

OBJECTIVETo investigate the association of the polymorphisms of cytochrome P450 2C9 (CYP2C9) exon 4 608T/G, 561A/C, 537A/C and 527A/C, and -65G/C with warfarin sensitivity.

METHODSA total of 102 patients under warfarin anticoagulant therapy were selected. During follow-up, warfarin dosage and associated Prothrombin Time-International Normalized Ratio (P-INR) values were recorded. Simultaneous monitoring of incidence of bleeding and thrombosis adverse effect was recommended. Genetic polymorphisms of the above mentioned loci were identified by polymerase chain reaction and DNA sequencing.

RESULTSThe average age of the 102 patients was (62.1+/-10.5) years. The body mass index (BMI) was (24.7+/-3.8) kg/m2. Mean daily warfarin requirement was from 1.250 to 5.077 mg/day when therapeutic PT-INR (1.5-2.5) was maintained. DNA sequencing showed no polymorphisms of 608T/G, 561A/C, 537A/C, 527A/C in CYP2C9 exon 4. Warfarin daily dosage in CYP2C9 exon 4 -65C carriers was 3.106+/-0.619 mg/d, while it was (2.555+/-0.708) mg/d in individuals with wild-type -65G (P=0.020). Receiver operating characteristic (ROC) analysis showed that warfarin daily dosage of more than 2.5 mg/d can be used to predict the CYP2C9 exon 4 -65GC genotype (AUC: 0.770, P=0.005, 95%CI:0.626-0.915). Logistic regression indicated that BMI was an independent factor of bleeding during anti-coagulation therapy (OR=0.794, 95%CI: 0.651-0.970, P=0.024).

CONCLUSIONThe Chinese population are, generally, warfarin-sensitive. Exon 4 of the CYP2C9 gene is highly conserved in this population. The warfarin maintenance dosage in CYP2C9 exon 4 -65CG carriers was significantly higher than those with wild-type -65GG. The clinical significance needs further investigation with more large-scale, multi-center trials.

Adult ; Alleles ; Anticoagulants ; pharmacology ; therapeutic use ; Aryl Hydrocarbon Hydroxylases ; genetics ; Cytochrome P-450 CYP2C9 ; Exons ; genetics ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Middle Aged ; Point Mutation ; Polymorphism, Genetic ; Thrombosis ; drug therapy ; Warfarin ; pharmacology ; therapeutic use

To observe the protective effect of heparin-coated circuits (HCC) on the platelet function during cardiopulmonary bypass (CPB), 23 patients with heart valve replacement were studied. The system heparin dose was 3 mg/kg in the control group (n = 15) and heparin-coated circuits in the HCC group (n = 8). Platelet count, alpha-granule membrane protein-140 (GMP-140) concentrations were determined before CPB, at 60 min of CPB, 30 and 60 min after protamine administration, first 12 h after CPB, respectively. At end of CPB the arterial filters in the circuits were observed by electron microscopy. The amount of first 12-h postoperative blood loss was measured. There was significant reduction in platelet loss during and after CPB in the HCC group in contrast to the control group during CPB (P<0.05). During the first 12 h, postoperative blood loss was reduced in the HCC group as compared with that in the control group (218+/-61 ml, vs. 332+/-118 ml, P<0.05). Electron microscopy showed that in the HCC group the filter meshes and their fringes were clear and fragments of floccules were occasionally seen, without adherent cells or only few adherent cells on their surfaces, whereas several cellular and fibrous components were found to adhere to the surfaces of the filter meshes in the control group. This study indicates that heparin-coated circuits might reduce the platelet loss and activation during CPB and improve hemocompatibility of cardiopulmonary bypass equipment.
Adult ; Anticoagulants ; metabolism ; pharmacology ; therapeutic use ; Blood Coagulation ; drug effects ; Blood Platelets ; metabolism ; Cardiopulmonary Bypass ; instrumentation ; Coated Materials, Biocompatible ; therapeutic use ; Extracorporeal Circulation ; Female ; Fibrinolytic Agents ; metabolism ; pharmacology ; therapeutic use ; Heart Valve Prosthesis Implantation ; Heparin ; metabolism ; pharmacology ; therapeutic use ; Humans ; Male ; Middle Aged ; Mitral Valve Insufficiency ; surgery ; P-Selectin ; metabolism ; Platelet Activation ; drug effects

BACKGROUND: Oral anticoagulation with warfarin requires routine monitoring of prothrombin time to maintain the international normalized ratio (INR) within the appropriate therapeutic range. Coagu- Chek XS (Roche Diagnositic, Germany) is a portable coagulometer that measures the INR. We evaluated the precision and accuracy of CoaguCheck XS by comparing it with CA-1500 (Sysmex, Japan). METHODS: We analyzed the CV and the correlation of all INR results measured in 68 samples obtained from patients treated with warfarin and 10 samples from control subjects with no history of anticoagulant therapy with CoaguChek XS and CA-1500. We compared the turn-around time between two instruments and evaluated the differences between the results obtained with venous and capillary blood samples and those obtained with different lots of the test strip. We also evaluated the precision of the two instruments in 5 repeated tests with samples of normal and increased INR. RESULTS: Mean INR values of 5 repeated tests with the same samples were similar. The correlation of INR values between two instruments was excellent (r2=0.97, P=0.001), and the difference in the values between the two instruments was mostly within the 95% limit of agreement, but was shown to increase in direct proportion to INR values. The turn-around time of CoaguChek XS was shorter than that of CA-1500. The differences between venous and capillary blood and between different lots of the test trip were not significant (P>0.05). CONCLUSIONS: CoaguChek XS showed a good precision and correlation with CA-1500 with a very short turn-around time. This instrument should be clinically useful in monitoring INR of patients with oral anticoagulation.
Administration, Oral ; Anticoagulants/administration & dosage/pharmacology/*therapeutic use ; Drug Monitoring ; Humans ; International Normalized Ratio/*instrumentation ; Prothrombin Time/*instrumentation/methods ; Reproducibility of Results ; Self Care/instrumentation/methods ; Warfarin/administration & dosage/*therapeutic use

EDTA-dependent pseudothrombocytopenia (PTCP) is the phenomenon of a spurious low platelet count due to EDTA-induced aggregation of platelets. Since the failure to recognize EDTA-dependent PTCP may result in incorrect diagnosis and inappropriate treatment, the recognition of this phenomenon is very important. We report an insidious case of EDTA-dependent PTCP confirmed by supplementation of kanamycin to anticoagulant in a 53-year-old women. Although sodium citrate and heparin usually prevented the aggregation of platelets in EDTA-dependent PTCP patients, these anticoagulants failed in preventing PTCP in our case. EDTA-dependent PTCP was confirmed by the findings that the clumping of platelets on microscopic evaluation was found in EDTA-anticoagulated blood samples, whereas thrombocytopenia and platelet aggregation were not revealed in the sample supplemented with kanamycin.
Antibiotics, Aminoglycoside/*pharmacology ; Anticoagulants/*adverse effects/pharmacology ; Case Report ; Edetic Acid/*adverse effects ; Female ; Human ; Kanamycin/*pharmacology ; Middle Age ; Platelet Aggregation/*drug effects ; Platelet Aggregation Inhibitors/*therapeutic use ; Platelet Count ; Thrombocytopenia/*blood/chemically induced

Since the late 1980s, low dose aspirin has been used to prevent stroke and ischemic heart disease. However, prophylactic effect of antiplatelets against venous thromboembolism (VTE), in patients who undergo hip fracture surgery (HFS) is controversial. Our purpose was to determine the incidence of symptomatic VTE after HFS and to evaluate whether antiplatelets reduce the development of symptomatic VTE following HFS. We retrospectively reviewed 858 HFS in 824 consecutive patients which were performed from May 2003 to April 2010 at an East Asian institute. We compared the incidence of symptomatic VTE in antiplatelet users and non-users using multivariate logistic regression analyses. Overall incidences of symptomatic pulmonary embolism including fatal pulmonary embolism, and symptomatic deep vein thrombosis in this study were 2.4% (21/858), and 3.5% (30/858), respectively. The incidence of symptomatic VTE was 4.8% (12/250) in antiplatelet users and 4.3% (26/608) in non-users (P = 0.718). It is suggested that antiplatelet agents are not effective in prevention of symptomatic VTE after HFS.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anticoagulants/therapeutic use ; Aspirin/administration & dosage/pharmacology/*therapeutic use ; Female ; Hip Fractures/complications/*surgery ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Platelet Aggregation Inhibitors/*therapeutic use ; Postoperative Complications/drug therapy/*epidemiology/*prevention & control ; Regression Analysis ; Venous Thromboembolism/complications/*epidemiology/*prevention & control

OBJECTIVETo investigate potential contributions of genetic variants of cytochrome P-450 2C9 (CYP2C9) and vitamin K expoxide reductase (VKORC1) to the anticoagulation response during the initiation of warfarin therapy in the Han Chinese population.

METHODSA total of 798 Han Chinese patients received long-term warfarin anticoagulant therapy orally after valve replacement in our hospital between 2000 and 2008 were included in this study. Nine single nucleotide polymorphism (SNP) loci [rs12572351 G > A, rs9332146 G > A, rs4917639 G > T, rs1057910 A > C (CYP2C9(*)3), rs1934967 G > T, rs1934968 G > A, rs9923231 C > T (VKORC1-1639 G > A), rs2359612 G > A and rs10871454 C > T] in 2 genes including CYP2C9 and VKORC1, which were possibly correlated with warfarin pharmacokinetics and pharmacodynamics through literature retrieval, were selected and analyzed. Warfarin steady-state dose requirement, time to the INR (the international normalized ratio) within the therapeutic range and percent of the INR of more than 3.5 were compared among genotype subgroups. SNaPshot technique was used to detect gene SNPs; Hardy-Weinberg genetic equilibrium test was used to test population representativeness.

RESULTSCYP2C9(*)3 genotype did not affect the required warfarin dose while it was associated with increased risk of bleeding when treated with routine dosage regimen during the initiation of treatment. The allelic mutation frequency at VKORC1 gene rs10871454G > A and VKORC1-1639G > A SNP loci was 92.04% and 88.03%, respectively and rs10871454 was in perfect linkage disequilibrium with-1639. Patients with VKORC1 rs10871454 genetic mutation required lower warfarin dose in the first 28 days of therapy. VKORC1-1639 genetic polymorphism was also associated with shorter time to the INR within the therapeutic range and increased risk of over-anticoagulation.

CONCLUSIONDetecting genetic polymorphism of CYP2C9 and VKORC1 could guide clinical use of warfarin to reduce the risk of adverse reactions including bleeding in patients receiving chronic anticoagulation therapy.

Aged ; Anticoagulants ; pharmacology ; therapeutic use ; Aryl Hydrocarbon Hydroxylases ; Cytochrome P-450 CYP2C9 ; genetics ; Gene Frequency ; Genes ; Genetic Variation ; Genotype ; Hemorrhage ; Humans ; International Normalized Ratio ; Linkage Disequilibrium ; Mixed Function Oxygenases ; Polymorphism, Single Nucleotide ; Vitamin K Epoxide Reductases ; genetics ; Warfarin ; pharmacology ; therapeutic use