Thrombin is the most important factor in hemostasis. In recent years, it has been found that thrombin is a potent mitogen capable of inducing cellular functions. Therefore, it is proved to be of importance in promoting the growth, metastasis and angiogenesis of cancer. Anticoagulant therapy not only reduce the characteristic hypercoagulability of cancer, but also inhibits growth and metastasis of cancer, and alters the fundamental biology of cancer. In this paper thrombin and its receptor, relationship of thrombin and its receptor with cancer growth, metastasis and angiogenesis, the mechanisms of thrombin influence on cancer angiogenesis, as well as application prospects on anti-angiogenesis and anti-coagulation therapy were reviewed.
Angiogenesis Inhibitors ; therapeutic use ; Animals ; Anticoagulants ; therapeutic use ; Antithrombins ; therapeutic use ; Humans ; Neoplasms ; blood supply ; drug therapy ; Neovascularization, Pathologic ; Receptors, Thrombin ; physiology ; Thrombin ; physiology

INTRODUCTIONDirect oral anticoagulants (DOACs) are establishing themselves as principle choices for the treatment of a variety of thrombotic disorders. DOACs are also known to affect common coagulation tests which are routinely performed for patients in clinical practice. An understanding of their varied effects is crucial for the appropriate ordering of coagulation tests and their interpretation.

MATERIALS AND METHODSLaboratories in public and private healthcare institutions and commercial sectors were surveyed on coagulation tests offered and their methods. A Medline and bibliography search, including a search on search engines, was performed for publications reporting the effects of dabigatran, apixaban and rivaroxaban on these coagulation tests. These papers were reviewed and summarised for consensus recommendations.

RESULTSProthrombin time (PT) and activated partial thromboplastin time (aPTT) are variably affected by the DOACs and dependent of the coagulation assays used. Clinicians must know which laboratory has performed these tests to logically interpret test results. A normal PT or aPTT does not exclude the presence of residual DOACs effect. The thrombin time is sensitive to dabigatran but not apixaban or rivaroxaban. Specialised coagulation tests such as thrombophilia tests are also variably affected by the DOACs. All laboratories in Singapore however, employ similar test methods permitting a common set of recommendations for specialised coagulation testing.

CONCLUSIONKnowledge of the effects of DOACs on coagulation testing is essential to determine the appropriateness of performing such tests and interpreting them coherently. Practical recommendations which are tests and location-specific are set out in this paper.

Antithrombins ; therapeutic use ; Blood Coagulation Tests ; Dabigatran ; therapeutic use ; Factor Xa Inhibitors ; therapeutic use ; Humans ; Partial Thromboplastin Time ; Practice Guidelines as Topic ; Prothrombin Time ; Pyrazoles ; therapeutic use ; Pyridones ; therapeutic use ; Rivaroxaban ; therapeutic use ; Singapore

Anticoagulants ; Antithrombins/therapeutic use* ; Coronary Disease ; Heparin ; Hirudins ; Humans ; Peptide Fragments ; Percutaneous Coronary Intervention ; Recombinant Proteins ; Treatment Outcome

In recent years, pharmacoeconomic studies have drawn increasing attention from experts in clinical medicine, pharmacy, health economics and health management. Their findings play an important role in drug pricing, drafting of the List of Essential Medicines and rational selection of clinical drugs. The essay summarizes the literatures published in recent years concerning pharmacoeconomics of traditional Chinese medicines on stroke, in order to make clear the current development of the latest studies on traditional Chinese medicines on treating stroke and rehabilitation methods and provide basis for further studies on pharmacoeconomics of traditional Chinese medicines on stroke and reference for rational clinical drug use.
Animals ; Antithrombins ; economics ; therapeutic use ; Drug Therapy ; economics ; Drugs, Chinese Herbal ; economics ; therapeutic use ; Economics, Pharmaceutical ; Humans ; Medicine, Chinese Traditional ; economics ; Stroke ; drug therapy ; economics

OBJECTIVETo assess the role of direct thrombin inhibitor argatroban in the renal replacement therapy.

METHODSElectronic databases including Cochrane library, PubMed, EMBASE, Highwire, MEDLINE, CBM, CNKI, and CSJD were searched using keywords including "Argatroban", "hemodialysis", "renal function", "renal failure", and "renal replacement therapy". A meta-analysis of all randomized controlled trials(RCTs)comparing argatroban with controls in renal replacement therapy was performed. Both the study selection and the meta-analysis were conducted according to the Cochrane Handbook for systematic reviews. Data were extracted from these trials and analyzed by RevMan 5.0 software.

RESULTSCompared with the control group, argatroban in renal replacement therapy showed no significant difference in mortality(RR=0.97, 95%CI: 0.48-1.97, P=0.93)and bleeding rate(RR=0.71, 95%CI: 0.37-1.34, P=0.29). Argatroban significantly decreased the incidence of new thrombosis in renal replacement therapy for patients with heparin-induced Thrombocytopenia(RR=0.40, 95%CI: 0.21-0.75, P=0.004). Also, argatroban significantly decreased the clotting events in extracorporeal circuit during the renal replacement therapy(RR=0.06, 95%CI: 0.01-0.23, P<0.0001). CONCLUSION Argatroban applied in renal replacement therapy can decrease the incidences of new thrombosis and clotting events in extracorporeal circuit and meanwhile will not increase the mortality and bleeding.

Antithrombins ; therapeutic use ; Hemorrhage ; epidemiology ; Humans ; Incidence ; Pipecolic Acids ; therapeutic use ; Renal Dialysis ; Renal Insufficiency ; Renal Replacement Therapy ; methods ; Thrombosis ; drug therapy

OBJECTIVEThe study was designed to compare the antithrombotic property and safety between nadroparin and unfractionated heparin during percutaneous coronary intervention (PCI).

METHODSA prospective, single blind, randomized study was performed. A total of 98 patients (aged 65.1 +/- 8.6 years, female, 28.6%, diabetes, 7.1%) undergoing selective PCI were randomized to be administered intravenously either nadroparin (0.075 ml/10 kg) or unfractionated heparin (100U/kg) for procedural anticoagulation, in whom stable angina was 42.9%, unstable angina, 27.6%, myocardial infarction, 29.6%, two or three-vessel disease, 23.5%, stent, 100%. Blood samples for anti-Xa level were assayed in the first 22 patients of the nadroparin group before and after administration at the following intervals: 8 min, 1 h, 2 h and 4 h. Bleeding complications were classified according to Thrombolysis In Myocardial Infarction (TIMI) criteria. The bleeding index (change in hemoglobin) was calculated. All patients were monitored for adverse clinical events (i.e. death, myocardial infarction, need for revascularization) during the period of 30 days after PCI.

RESULTS(1) There were no significant differences in baseline characteristics between the two randomized groups. (2) Plasma anti-Xa activities were 0.10 +/- 0.00 IU/ml at the time just before the administration of nadroparin, 1.89 +/- 0.24 IU/ml, 0.96 +/- 0.24 IU/ml, 0.47 +/- 0.13 IU/ml, and 0.30 +/- 0.12 IU/ml at the time of 8 min, 1 h, 2 h and 4 h after the use of nadroparin (and the rate of > 0.5 IU/ml were 100%, 100%, 45% and 9% patients), respectively. (3) There were no significant differences in the mean bleeding index, post-PCI hemoglobin and hematocrit between nadroparin and unfractionated heparin group [(1.16 +/- 5.80) g/L vs (0.90 +/- 6.50) g/L, P = 0.858; (129.5 +/- 13.6) g/L vs (125.5 +/- 14.9) g/L, P = 0.175; (39.0 +/- 3.9)% vs (37.9 +/- 4.6)%, P = 0.205]. (4) None of the patients in two randomized groups were observed hemorrhagic events, which including TIMI major or minor bleeding complications, gross or microscopic hematuria, melena, positive stool occult blood. There were no blood transfusions and no hematoma at the vascular access site in either of the group. (5) No death, no recurrent angina pectoris, and no urgent revascularization occurred within 30 days in both groups. One patient in nadroparin group was observed "no reflow" phenomenon that was accompanied with an elevated ST segment and a risen serum level of cTnI. This patient was diagnosed as non-Q-wave myocardial infarction. Though no myocardial infarction was found in unfractionated heparin group, there was no significant difference in the rate of myocardial infarction between the two groups of the study (P = 0.970).

CONCLUSIONSThe administration of nadroparin before PCI seems effective and safe. Compared with unfractionated heparin, nadroparin was associated with neither an excess of bleeding nor an increase of clinical complications in this study.

Adult ; Aged ; Aged, 80 and over ; Angioplasty, Balloon, Coronary ; methods ; Antithrombins ; adverse effects ; therapeutic use ; Female ; Heparin ; adverse effects ; therapeutic use ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; therapy ; Nadroparin ; adverse effects ; therapeutic use ; Prospective Studies ; Single-Blind Method ; Treatment Outcome

BACKGROUNDBivalirudin was widely used as an anticoagulant during coronary interventional procedure in western countries. However, it was not available in China before this clinical trial was designed. This randomized, single-blind and multicenter clinical trial aimed to evaluate the efficacy and the safety of domestic bivalirudin during percutaneous coronary intervention (PCI).

METHODSA randomized, single-blind, multicenter trial was designed. Elective PCI candidates in five centers were randomized into a bivalirudin group and a heparin group, which were treated with domestic bivalirudin and non-fractional heparin during the PCI procedure. The efficacy was evaluated by comparing the activated coagulation time (ACT), the procedural success rate (residual stenosis < 20% in target lesions without any coronary artery related adverse events within 24 hours after PCI), and the survival rate without major adverse cardiac events at 30 days after PCI between the two groups. Safety was evaluated by the major/minor bleeding rate.

RESULTSA total of 218 elective PCI patients were randomized into a bivalirudin group (n = 110) and heparin group (n = 108). Except for two patients needing additional dosing in the heparin group, the ACT values of all other patients in both groups were longer than 225 seconds at 5 minutes after the first intravenous bolus. Procedural success rates were respectively 100.0% and 98.2% in the bivalirudin group and heparin group (P > 0.05). Survival rates without major adverse cardiac events at 30 days after PCI were 100.0% in the bivalirudin group and 98.2% in the heparin group (P > 0.05). Mild bleeding rates were 0.9% and 6.9% (P < 0.05) at 24 hours, and 1.9% and 8.8% (P < 0.05) at 30 days after PCI in the bivalirudin group and heparin group respectively. There was one severe gastrointestinal bleeding case in the heparin group.

CONCLUSIONSDomestic bivalirudin is an effective and safe anticoagulant during elective PCI procedures. The efficacy is not inferior to heparin, but the safety is superior to heparin.

Aged ; Antithrombins ; adverse effects ; therapeutic use ; Female ; Heparin ; therapeutic use ; Hirudins ; adverse effects ; Humans ; Male ; Middle Aged ; Peptide Fragments ; adverse effects ; therapeutic use ; Percutaneous Coronary Intervention ; Recombinant Proteins ; adverse effects ; therapeutic use ; Single-Blind Method ; Survival Rate ; Whole Blood Coagulation Time

Endoscopic hemostasis is the first-line treatment for upper gastrointestinal bleeding (UGIB). Although several factors are known to be risk factors for rebleeding, little is known about the use of antithrombotics. We tried to verify whether the use of antithrombotics affects rebleeding rate after a successful endoscopic hemostasis for peptic ulcer disease (PUD). UGIB patients who underwent successful endoscopic hemostasis were included. Rebleeding was diagnosed when the previously treated lesion bled again within 30 days of the initial episode. Of 522 UGIB patients with PUD, rebleeding occurred in 93 patients (17.8%). The rate of rebleeding was higher with aspirin medication (P=0.006) and after a long endoscopic hemostasis (P<0.001). Of all significant variables, procedure time longer than 13.5 min was related to the rate of rebleeding (OR, 2.899; 95% CI, 1.768-4.754; P<0.001) on the logistic regression analysis. The rate of rebleeding after endoscopic hemostasis for PUD is higher in the patients after a long endoscopic hemostasis. Endoscopic hemostasis longer than 13.5 min is related to rebleeding after a successful endoscopic hemostasis for PUD.
Antithrombins/*therapeutic use ; Aspirin/adverse effects ; Female ; Gastrointestinal Hemorrhage/drug therapy/*surgery ; Hemorrhage/*drug therapy ; Hemostasis, Endoscopic/methods ; Humans ; Male ; Middle Aged ; Peptic Ulcer/*surgery ; Recurrence ; Upper Gastrointestinal Tract/pathology

PURPOSE: Comparisons of rhythm and rate control strategies for stroke prevention in patients with atrial fibrillation (AF) are still inconclusive. We compared differences in clinical outcomes between the rhythm and rate control strategies. MATERIALS AND METHODS: The COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation (CODE-AF) registry prospectively enrolled 6000 patients who were treated for AF using real-world guideline adherence at multiple referral centers. In total, 2508 (41.8%) patients were clinically followed up for over six months. Of these, 1134 (45.2 %) patients treated by rhythm control and 1374 (54.8 %) patients treated by rate control were analyzed for clinical outcomes, including stroke and cardiovascular outcomes. RESULTS: Among all patients (age, 68±10 years; male, 62.4%), those treated with the rhythm control strategy were significantly younger, had more symptomatic paroxysmal AF, and a shorter AF duration, and were less likely to have diabetes, renal dysfunction, and heart failure, compared to those treated with the rate control strategy (CHA₂DS₂-VASc score 2.4±1.5 vs. 3.1±1.7, p < 0.001). Even though oral anticoagulation was similarly prescribed in both groups, occurrence of stroke was less likely to occur in the rhythm control strategy group (0.0% vs. 0.7%, p=0.015). Multivariate Cox hazard regression showed that only age, especially more than 75 years old, were significantly correlated with the occurrence of stroke, regardless of the strategy used for treatment. CONCLUSION: In this prospective AF cohort, compared with the rate control strategy, the rhythm control strategy was associated with fewer cardiovascular events and strokes in a short-term period.
Administration, Oral ; Aged ; Antithrombins/administration & dosage/therapeutic use ; Atrial Fibrillation/drug therapy/*physiopathology ; Female ; Heart Rate/*physiology ; Humans ; Kaplan-Meier Estimate ; Male ; Proportional Hazards Models ; Prospective Studies ; Stroke/drug therapy/*etiology/*physiopathology ; Treatment Outcome