Thrombin is a pivotal molecule in acute myocardial infarction (MI) because of its extensive procoagulant and prothrombotic actions. Antithrombin therapy is an important component of the pharmacotherapy for acute MI. The standard agent used in clinical practice, unfractionated heparin (UFH), is associated with the disadvantages of variable anticoagulant effect, inability to inhibit clot-bound thrombin, neutralization by platelet factor 4, and the propensity to cause thrombocytopenic complications. Novel thrombin inhibitors have been developed to overcome these disadvantages. Although possessing the property of inhibiting both fluid-phase and clot-bound thrombin, the direct thrombin inhibitor hirudin has been shown to give marginal benefits over UFH as adjunct to fibrinolysis in ST-elevation MI. Bivalirudin, another direct thrombin inhibitor, is able to reduce reinfarction in patients treated with streptokinase and is a new anticoagulant treatment option in this setting. The pharmacokinetic characteristics of better availability, longer half-life, and dose-independent clearance together with the ability of inhibiting both thrombin generation and activity make the low-molecular-weight heparins (LMWHs) an attractive alternative to UFH. The favorable benefit/risk profile of the LMWHs as adjunct to different generations of fibrinolytic agents is setting the stage for larger clinical trials to confirm their role as the antithrombin agent of choice for STEMI.
Anticoagulants ; therapeutic use ; Electrocardiography ; Heparin, Low-Molecular-Weight ; therapeutic use ; Humans ; Myocardial Infarction ; drug therapy ; physiopathology ; Thrombin ; antagonists & inhibitors

OBJECTIVE: To investigate the proper dosage of heparin and protamin in treating the patients with infective endocarditis (IE) during the operation. METHODS: Activated clotting time (ACT) was measured during and after cardiopulmonary bypass (CPB) in 30 patients with IE and 30 patients with rheumatic heart disease (RHD) respectively. RESULTS: The dosage of heparin before bypass in IE group was significantly higher than that of RHD group (P<0.05); the dosage of protamin for neutralization after bypass in IE group was significantly higher than that of RHD group (P<0.05); the ratio of protamin and heparin were 0.76 +/-0.23 in IE group and 0.74 +/-0.12 in RHD group (P>0.05). CONCLUSION The dosage of protamin should be increased to 3 mg/kg as the heparin is over 400 U/kg before CPB in the patient with IE, but the ratio of protamin and heparin will not be obviously changed.
Adult ; Anticoagulants ; therapeutic use ; Cardiopulmonary Bypass ; Dose-Response Relationship, Drug ; Drug Monitoring ; methods ; Endocarditis ; surgery ; Female ; Heparin ; therapeutic use ; Heparin Antagonists ; therapeutic use ; Humans ; Intraoperative Care ; methods ; Male ; Middle Aged ; Protamines ; therapeutic use ; Whole Blood Coagulation Time

OBJECTIVETo investigate the antithrombotic mechanisms of holothurian glycosaminoglycan (GAG) extracted from sea cucumber.

METHODSHuman endothelial cell line EA. hy926 cells were treated with 10 mg/L GAG or 10U/mL unfractionated heparin (UFH) by short-term (15 min - 2 h) and longer-time incubation (6 h - 48 h). Different doses of GAG were used to stimulate EA. hy926. Released free tissue factor pathway inhibitor(TFPI) was determined by ELISA assay. TFPI expression was investigated by immunofluorescent method and TFPI mRNA level by real-time PCR. In a 96-wells microtitre plate, pooled normal plasma containing different concentrations of GAG was allowed to clot by addition of thrombin and calcium chloride, fibrinolysis was induced by addition of t-PA. TRR (TAFI-related retardation of clot lysis) was used to assess thrombin-activatable fibrinolysis inhibitor(TAFI) functional activity.

RESULTSGAG increased TFPI synthesis, expression and secretion in a dose- and time dependent manner. GAG at low concentrations could lengthen while at intermediate concentrations could shorten clot lysis times significantly as compared to control values. TRR was dose-dependently decreased on addition of GAG.

CONCLUSIONSGAG increases TFPI synthesis, expression and secretion of endothelial cells. GAG at intermediate concentrations significantly affects clot stability of a developing clot by means of diminishing TAFI activation.

Animals ; Carboxypeptidase B2 ; antagonists & inhibitors ; Cell Line ; Dose-Response Relationship, Drug ; Endothelial Cells ; drug effects ; metabolism ; Glycosaminoglycans ; pharmacology ; Heparin ; pharmacology ; Holothuria ; Humans ; Lipoproteins ; biosynthesis ; genetics ; RNA, Messenger ; genetics ; Tissue Extracts ; pharmacology

OBJECTIVETo explore the relationship of airway remodeling with epidermal growth factor receptor (EGFR) and heparin-binding epidermal growth factor-like growth factor (HB-EGF) levels in asthmatic mice and the effect of EGFR tyrosine kinase inhibitor (AG1478) on airway remodeling.

METHODSTwenty-four male BALB/c mice were randomly divided into three groups: normal control, asthma, AG1478-treated. Mice were sensitized and challenged with ovalbumin (OVA) and a mouse mode1 of asthma was prepared. Collagen deposition was determined in Masson-stained lung sections. Periodic acid Schiff (PAS) staining was used to observe the proliferation of goblet cells. Immunohistochemistry was used to determine the protein expression of HB-EGF. RT-PCR was used to determine the mRNA expression of HB-EGF and EGFR.

RESULTSThe characteristic changes of airway remodeling occurred in the asthma group. The expression of HB-EGF and EGFR in the epithelial cells of bronchi in the asthma group was significantly higher than that in the normal control group. Compared with the asthma group, the AG1478-treated group had decreased inflammation reactions, decreased collagen deposition and proliferation of goblet cells and lower expression of EGFR and HB-EGF.

CONCLUSIONSEGFR tyrosine kinase inhibitor (AG1478) ameliorates the progression of airway remodeling in mice with asthma by inhibitions of EGFR and HB-EGF expression and EGFR signal pathway.

Airway Remodeling ; Animals ; Asthma ; drug therapy ; pathology ; Heparin-binding EGF-like Growth Factor ; Immunohistochemistry ; Intercellular Signaling Peptides and Proteins ; analysis ; genetics ; Male ; Mice ; Quinazolines ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; genetics ; physiology ; Tyrphostins ; therapeutic use

The efficacy of low molecular weight heparin (LMWH) with low dose unfractionated heparin (UFH) during percutaneous coronary intervention (PCI) with or without glycoprotein (Gp) IIb/IIIa inhibitor compared to UFH with or without Gp IIb/IIIa inhibitor has not been elucidated. Between October 2005 and July 2007, 2,535 patients with ST elevation acute myocardial infarction (STEMI) undergoing PCI in the Korean Acute Myocardial Infarction Registry (KAMIR) were assigned to either of two groups: a group with Gp IIb/IIIa inhibitor (n=476) or a group without Gp IIb/IIIa inhibitor (n=2,059). These groups were further subdivided according to the use of LMWH with low dose UFH (n=219) or UFH alone (n=257). The primary end points were cardiac death or myocardial infarction during the 30 days after the registration. The primary end point occurred in 4.1% (9/219) of patients managed with LMWH during PCI and Gp IIb/IIIa inhibitor and 10.8% (28/257) of patients managed with UFH and Gp IIb/IIIa inhibitor (odds ratio [OR], 0.290; 95% confidence interval [CI], 0.132-0.634; P=0.006). Thrombolysis In Myocardial Infarction (TIMI) with major bleeding was observed in LMHW and UFH with Gp IIb/IIIa inhibitor (1/219 [0.5%] vs 1/257 [0.4%], P=1.00). For patients with STEMI managed with a primary PCI and Gp IIb/IIIa inhibitor, LMWH is more beneficial than UFH.
Acute Disease ; Aged ; Drug Therapy, Combination ; Female ; Hemorrhage ; Heparin/*therapeutic use ; Heparin, Low-Molecular-Weight/*therapeutic use ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Myocardial Infarction/epidemiology/mortality/*therapy ; Myocardial Revascularization ; Odds Ratio ; Platelet Glycoprotein GPIIb-IIIa Complex/*antagonists & inhibitors/metabolism ; Prognosis ; Registries

Venous thromboembolism (VTE), which is manifested as deep vein thrombosis (DVT) and pulmonary embolism (PE), represents a significant cause of death, disability, and discomfort. They are frequent complications of various surgical procedures. The aging population and the survival of more severely injured patients may suggest an increasing risk of thromboembolism in the trauma patients. Expanded understanding of the population at risk challenges physicians to carefully examine risk factors for VTE to identify high-risk patients who can benefit from prophylaxis. An accurate knowledge of evidence-based risk factors is important in predicting and preventing postoperative DVT, and can be incorporated into a decision support system for appropriate thromboprophylaxis use. Standard use of DVT prophylaxis in a high-risk trauma population leads to a low incidence of DVT. The incidence of VTE is common in Asia. The evaluation includes laboratory tests, Doppler test and phlebography. Screening Doppler sonography should be performed for surveillance on all critically injured patients to identify DVT. D-Dimer is a useful marker to monitor prophylaxis in trauma surgery patients. The optimal time to start prophylaxis is between 2 hours before and 10 hours after surgery, but the risk of PE continues for several weeks. Thromboprophylaxis includes graduated compression stockings and anticoagulants for prophylaxis. Anticoagulants include Warfarin, which belongs to Vitamin K antagonists, unfractionated heparin, low molecular weight heparins, factor Xa indirect inhibitor Fondaparinux, and the oral IIa inhibitor Melagatran and ximelagatran. Recombinant human soluble thrombomodulin is a new and highly effective antithrombotic agent. Prophylactic placement of vena caval filters in selected trauma patients may decrease the incidence of PE. The indications for prophylactic inferior vena cava filter insertion include prolonged immobilization with multiple injuries, closed head injury, pelvic fracture, spine fracture, multiple long bone fracture, and attending discretion. Multiple-trauma patients are at increased risk for DVT but are also at increased risk of bleeding, and the use of heparin may be contraindicated. Serial compression devices (SCDs) are an alternative for DVT prophylaxis. Compression devices provide adequate DVT prophylaxis with a low failure rate and no device-related complications. Immobilization is one of important reasons of VTE. The ambulant patient is far less likely to develop complications of inactivity, not only venous thrombosis, but also contractures, decubitus ulcers, or osteoporosis (with its associated fatigue fractures), as well as bowel or bladder complications.
Anticoagulants ; therapeutic use ; Factor Xa Inhibitors ; Heparin ; therapeutic use ; Heparin, Low-Molecular-Weight ; therapeutic use ; Humans ; Orthopedic Procedures ; adverse effects ; Postoperative Complications ; epidemiology ; Pulmonary Embolism ; prevention & control ; Recombinant Proteins ; therapeutic use ; Risk Factors ; Thrombomodulin ; therapeutic use ; Vena Cava Filters ; Venous Thrombosis ; epidemiology ; prevention & control ; Vitamin K ; antagonists & inhibitors ; Warfarin ; therapeutic use

BACKGROUNDAntithrombotic and antiplatelet therapies have been proposed to treat non-ST elevation acute coronary syndrome (NSTEACS), yet limited information is available about their applications from a multicenter "real-world" clinical procedure, especially in China. This study was undertaken to characterize the use of antithrombotic and antiplatelet agents in relation to the risk levels of the NSTEACS patients who were enrolled in Sino-Global Registry of Acute Coronary Events (GRACEs) registry study.

METHODSWe analyzed the data from 618 Chinese NSTEACS patients stratified into low-(n = 151), intermediate-(n = 233), and high-risk groups (n = 234) based on GRACE risk scores. The baseline characteristics, clinical presentations, antithrombotic and antiplatelet agents were recorded and compared among the three groups.

RESULTSThe administration rates of low-molecular-weight heparins (LMWHs) (86.08%) and thienopyridines (85.92%) were higher whereas the administration rate of glycoprotein IIb/IIIa inhibitor (1.78%) was much lower than those reported previously. Meanwhile, within the first 24 hours of admission, the use of heparin/LMWHs in the high-risk group was more than that in the intermediate- and low-risk groups (73.50% vs 63.09% vs 55.63%, P = 0.001). Furthermore, the combination of antithrombotic and antiplatelet medications showed no significant differences in all groups.

CONCLUSIONSIn the "real world" practice of China, the antithrombotic and antiplatelet therapies on NSTEACS are well adherent to the current guidelines except for several gaps, such as the very low use of glycoprotein IIb/IIIa inhibitor. Moreover, these antithrombotic and antiplatelet treatments usually tend to be underused for the high-risk ones.

Acute Coronary Syndrome ; drug therapy ; Aged ; Coronary Disease ; drug therapy ; Female ; Fibrinolytic Agents ; therapeutic use ; Heparin, Low-Molecular-Weight ; therapeutic use ; Humans ; Male ; Middle Aged ; Platelet Aggregation Inhibitors ; therapeutic use ; Platelet Glycoprotein GPIIb-IIIa Complex ; antagonists & inhibitors ; Pyridines ; therapeutic use ; Registries ; Risk Assessment