We inserted the 0.6 mm caliber graft-heparin (in inner wall) conduits into the tailarteries of 14 mice. The results showed that the graft conduit could be used repeatedly with no blood oozing out in the wound, no massive internal hemorrhage, and no additional coagulative reagent given during the whole experiment. On the other hand, the graft-heparin conduits of variant caliber were inserted into the femur arteries of 4 rabbits and 4 dogs for blood pressure experiment and femur arterio-venous bypass tests. The results showed that the anticoagulative effect of these conduits was markedly improved, but there was a strip of thrombus. There was no thrombus track in the wall of the conduit. The strip of thrombus was formed first in the cone of conduit where caliber changed. The results indicate that the blood flow resistance is in inverse proportion to 4 power of the conduit radius. So the thinner the conduit is, the more sensitive to conduit radius variation the conduit resistance will be. In studying and making the arfificial conduit, one must take notice of the conduit caliber, which should be equal to the caliber of the blood vessel.
Animals ; Anticoagulants ; administration & dosage ; Blood Vessel Prosthesis ; Dogs ; Heparin ; administration & dosage ; Mice ; Rabbits ; Regional Blood Flow

Administration, Oral ; Anticoagulants ; adverse effects ; Aspirin ; adverse effects ; Epistaxis ; chemically induced ; Humans

INTRODUCTIONNovel oral anticoagulants (NOACs) have at least equivalent efficacy compared to standard anticoagulants with similar bleeding risk. Optimal management strategies for bleeding complications associated with NOACs are currently unestablished.

MATERIALS AND METHODSA working group comprising haematologists and vascular medicine specialists representing the major institutions in Singapore was convened to produce this consensus recommendation. A Medline and EMBASE search was conducted for articles related to the 3 available NOACs (dabigatran, rivaroxaban, apixaban), bleeding and its management. Additional information was obtained from the product monographs and bibliographic search of articles identified.

RESULTSThe NOACs still has substantial interactions with a number of drugs for which concomitant administration should best be avoided. As they are renally excreted, albeit to different degrees, NOACs should not be prescribed to patients with creatinine clearance of <30 mLs/min. Meticulous consideration of risk versus benefits should be exercised before starting a patient on a NOAC. In patients presenting with bleeding, risk stratification of the severity of bleeding as well as identification of the source of bleeding should be performed. In life-threatening bleeds, recombinant activated factor VIIa and prothrombin complex may be considered although their effectiveness is currently unsupported by firm clinical evidence. The NOACs have varying effect on the prothrombin time and activated partial thromboplastin time which has to be interpreted with caution. Routine monitoring of drug level is not usually required.

CONCLUSIONNOACs are an important advancement in antithrombotic management and careful patient selection and monitoring will permit optimisation of their potential and limit bleeding events.

Administration, Oral ; Anticoagulants ; therapeutic use ; Benzimidazoles ; Consensus ; Dabigatran ; Hemorrhage ; prevention & control ; Humans ; Singapore ; Thiophenes

Oral anticoagulants play an important role in the prevention and treatment of thromboembolic diseases.Warfarin,a traditional oral anticoagulant,is limited in clinical use due to its limitations such as narrow therapeutic window and requirements on frequent monitoring and dose adjustment.Direct oral anticoagulants(DOACs)such as dabigatran,rivaroxaban,apixaban,and edoxaban are increasingly used to prevent and treat venous thrombosis or thrombus formation.However,recent studies have documented inter-individual variability in plasma drug levels of DOACs.This article summarizes the recent advances in the pharmacogenomics of DOACs.
Administration, Oral ; Anticoagulants ; therapeutic use ; Atrial Fibrillation ; drug therapy ; Dabigatran ; Pharmacogenetics ; Rivaroxaban

Administration, Oral ; Anticoagulants/adverse effects* ; Atrial Fibrillation/drug therapy* ; Humans ; Stroke ; Vascular Calcification/drug therapy* ; Warfarin

BACKGROUNDNon-valvular atrial fibrillation is associated with an increased risk of ischemic stroke; however, the appropriate intensity of anticoagulation therapy for Chinese patients has not been determined. The purpose of this study was to compare the safety and the efficacy of standard-intensity warfarin therapy, low-intensity warfarin therapy, and aspirin therapy for the prevention of ischemic events in Chinese patients with non-valvular atrial fibrillation (NVAF).

METHODSA total of 786 patients from 75 Chinese hospitals were enrolled in this study and randomized into three therapy groups: standard-intensity warfarin (international normalized ratio (INR) 2.1 to 2.5) group, low-intensity warfarin (INR 1.6 to 2.0) group and aspirin (200 mg per day) group. All patients were evaluated by physicians at 1, 3, 6, 9, 12, 15, 18, 21 and 24 months after randomization to obtain a patient questionnaire, physical examination and related laboratory tests.

RESULTSThe annual event rates of ischemic stroke, transient ischemic attack (TIA) or systemic thromboembolism were 2.6%, 3.1% and 6.9% in the standard-intensity warfarin, low-intensity warfarin and aspirin groups, respectively (P = 0.027). Thromboembolic event rates in both warfarin groups were significantly lower than that in the aspirin group (P = 0.018, P = 0.044), and there was no significant difference between the two warfarin groups. Severe hemorrhagic events occurred in 15 patients, 7 (2.6%) in the standard-intensity warfarin group, 7 (2.4%) in the low-intensity warfarin group and 1 (0.4%) in the aspirin group. The severe hemorrhagic event rates in the warfarin groups were higher than that in the aspirin group, but the difference did not reach statistical significance (P = 0.101). The mild hemorrhagic and total hemorrhagic event rates in the warfarin groups (whether in the standard-intensity warfarin group or low-intensity warfarin group) were much higher than that in the aspirin group with the annual event rates of total hemorrhages of 10.2%, 7.6% and 2.2%, respectively, in the 3 groups (P = 0.001). Furthermore, there was no significant difference in all cause mortality among the three study groups.

CONCLUSIONIn Chinese patients with NVAF, the warfarin therapy (INR 1.6 - 2.5) for the prevention of thromboembolic events was superior to aspirin.

Aged ; Aged, 80 and over ; Anticoagulants ; administration & dosage ; therapeutic use ; Aspirin ; administration & dosage ; therapeutic use ; Atrial Fibrillation ; drug therapy ; Female ; Humans ; Male ; Middle Aged ; Warfarin ; administration & dosage ; therapeutic use

Anticoagulation therapy is effective in preventing primary and secondary thromboembolic events due to atrial fibrillation. Warfarin, which was approved by the United States in 1954, was the only long-term oral anticoagulation therapy till the approval of dabigatran in 2010, and of rivaroxaban and other direct factor Xa inhibitors from 2011, forming a group known as novel oral anticoagulants (NOAC). NOAC have fewer food and drug interactions compared to warfarin; hence, the patient will require fewer clinic visits. However, the short half-life of NOAC means that twice-a-day dosing is needed and there is higher risk of a prothrombotic state when doses are missed. Other disadvantages are the lack of long-term data on NOAC, their high cost and the current lack of locally available antidotes.
Administration, Oral ; Anticoagulants ; administration & dosage ; Atrial Fibrillation ; drug therapy ; Cardiology ; methods ; Dabigatran ; administration & dosage ; Family ; Humans ; Professional-Patient Relations ; Rivaroxaban ; administration & dosage ; Stroke ; prevention & control ; Thromboembolism ; prevention & control ; Warfarin ; administration & dosage

OBJECTIVESTo evaluate the safety and define the contraindication of regional citrate anticoagulation treatment on various critically ill patients being treated by continuous blood purification, who also had bleeding tendencies.

METHODSForty critically ill patients being treated by continuous blood purification (CBP) were involved in this study. Due to their bleeding tendencies, regional citrate anticoagulation treatment was given to all of them. Those with hepatic function impairment (n = 10) were classified as Group A, those with hypoxemia were classified as Group B (n = 10), and the others as Group C (n = 20). Blood samples were collected before treatment, and at 4, 12, 24, 36, and 48 hour intervals during CBP. These samples then were used arterial blood gas analysis, whole blood activated clotting time (WBACT) pre- and post-filter, and serum ionized calcium examination.

RESULTSWBACT pre-filter showed little fluctuant through the 48 hr period of CBP, and WBACT post-filter showed obvious prolongation than that of the pre-filter (P < 0.05) at all time points. Metabolic acidosis was found in Group A patients before CBP, and improved during CBP. Normal acid-base conditions of patients were disturbed and deteriorated in Group B during CBP, but not in Group C. Serum ionized calcium was maintained at a normal range during CBP in Group A and C patients, but declined significantly in Group B patients (vs. pre-treatment, P < 0.05).

CONCLUSIONSRegional citrate anticoagulation can be safely used in conjunction with CBP treatment for patients with hepatic function impairment, but may induce acidosis and a decline in serum ionized calcium when used with hypoxemic patients.

Adult ; Aged ; Anticoagulants ; administration & dosage ; Calcium ; blood ; Citric Acid ; administration & dosage ; adverse effects ; Critical Illness ; Female ; Hemofiltration ; Humans ; Male ; Middle Aged

BACKGROUNDObstructive sleep apnea hypopnea syndrome (OSAHS) constitutes an independent factor for high warfarin dose for patients with pulmonary embolism (PE). The aim of this study was to investigate whether the 6-month anticoagulation treatment by warfarin is enough for patients with PE complicated by OSAHS.

METHODSWe investigated 97 PE patients, 32 of them had OSAHS and 65 non-OSAHS. Warfarin was administered for 6-month if no abnormal circumstances occurred. All patients were followed up for 18 months. Adverse events (AE) included death, major bleeding, hospitalization due to heart failure or pulmonary hypertension, and recurrence or aggravation of PE (including deep vein thrombosis). Recurrence rate of PE after warfarin cessation was compared between the two groups.

RESULTSOSAHS patients required a significantly higher dose of warfarin than their non-OSAHS counterparts (4.73 mg vs. 3.61 mg, P < 0.001). During warfarin treatment, no major bleeding and aggravation of PE occurred among OSAHS patients, and the rates of various AE were not significantly different between the OSAHS and non-OSAHS groups. PE recurrence was higher in OSAHS than non-OSAHS groups after withdrawal of warfarin (21.43% vs. 6.78%, P = 0.047). Compared with non-OSAHS patients, OSAHS group had lower international normalized ratio (INR) value but higher plasminogen on baseline and INR resumed to a relatively low level after warfarin discontinuation.

CONCLUSIONSOSAHS patients may present with hypercoagulation and relatively high-risk of recurrence of PE after cessation of 6-month warfarin treatment.

Anticoagulants ; administration & dosage ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Pulmonary Embolism ; drug therapy ; Sleep Apnea, Obstructive ; complications ; Warfarin ; administration & dosage ; therapeutic use

BACKGROUNDWhether an addition of OAC to double antiplatelet therapy for patients with an indication of chronic oral anticoagulation undergoing PCI-S may improve clinical outcomes is still debated. This meta-analysis aimed to update and re-compare the benefits and risks of triple antithrombotic therapy (TT) with double anti-platelet therapy (DAPT) after in patients who requiring oral anticoagulation after percutaneous coronary interventions with stenting (PCI-s).

METHODSTen reports of observational retrospective or prospective studies were retrieved, including a total of 6296 patients, follow-up period ranging from 1 year to 2 years.

RESULTSBaseline characteristics were similar in both groups. The main finding of this study is the overall incidence of major adverse cardiovascular events (MACE), myocardial infarction (MI) and stent thrombosis was comparable between two groups. Patients with TT was associated with significant reduction in ischemic stroke (OR: 0.27; 95%CI: 0.13 - 0.57; P = 0.0006) as compared to DAPT. We reaffirmed triple therapy significantly increased the risk of major bleeding (OR: 1.47; 95%CI: 1.22 - 1.78; P < 0.0001) and minor bleeding (OR: 1.55; 95%CI: 1.07 - 2.24; P = 0.02).

CONCLUSIONSTriple therapy is more efficacious in reducing the occurrence of ischemic stroke in PCI-s patients with an indication of chronic oral anticoagulation (OAC), compared with DAPT. However, it significantly increased major and minor risk of bleeding. It is imperative that further prospective randomized controlled trials are required to defne the best therapeutic strategy for patients with an indication of chronic OAC undergoing PCI-s.

Aged ; Anticoagulants ; therapeutic use ; Drug Therapy, Combination ; Female ; Fibrinolytic Agents ; administration & dosage ; Humans ; Male ; Middle Aged ; Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors ; administration & dosage ; Publication Bias ; Stents