Anticoagulant agents are used to reduce the risk of thromboembolic complications in patients with atrial fibrillation or deep vein thrombosis. Several new generation of oral anticoagulants have been approved. These novel oral anticoagulants (NOACs) include direct thrombin inhibitors, dabigatra etexilate, and the direct factor Xa inhibitors, rivaroxaban, apixaban and edoxaban. This review evaluates NOACs-related gastrointestinal bleeding and summarizes the ideal management strategies based on the guideline suggested by American Society for Gastrointestinal Endoscopy.
Anticoagulants* ; Antithrombins ; Atrial Fibrillation ; Endoscopy ; Endoscopy, Gastrointestinal ; Factor Xa Inhibitors ; Gastrointestinal Hemorrhage ; Hemorrhage ; Humans ; Rivaroxaban ; Thromboembolism ; Venous Thrombosis

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

Heparin-induced thrombocytopenia (HIT) is a serious, immune mediated complication of exposure to unfractionated or low-molecular-weight heparin. Though rare, it is a condition associated with high morbidity and mortality that requires immediate change to alternative anticoagulants for the prevention of life-threatening thrombosis. The direct thrombin inhibitors lepirudin and argatroban are currently licensed for the treatment of HIT. Dabigatran, a novel oral anticoagulant (NOAC) with a similar mechanism of action and effective use in other indications, has recently been proposed as another therapeutic option in cases of HIT. This review serves as an introduction to using dabigatran for this purpose, detailing the clinical aspects of its administration, evidence of its performance compared to other anticoagulants, and the preliminary reports of HIT successfully treated with dabigatran. As the literature on this develops, it will need to include clinical trials that directly evaluate dabigatran against the other NOACs and current treatment options.
Anticoagulants ; Antithrombins ; Dabigatran* ; Heparin, Low-Molecular-Weight ; Mortality ; Thrombocytopenia* ; Thrombosis

Adolescent ; Adult ; Antithrombin III Deficiency ; genetics ; Antithrombins ; Female ; Humans ; Male ; Mutation ; Pedigree ; Phenotype

OBJECTIVETo identify the phenotype and the gene mutation in a kindred with antithrombin (AT) deficiency.

METHODSImmuno-nephelometry and chromogenic assay were used to detect the plasma level of AT antigen (AT: Ag) and activity (AT: A), respectively. All the seven exons and intron-exon boundaries of AT gene from the propositus were amplified by PCR and direct sequencing of the PCR pro-ducts was performed. Corresponding PCR fragments from the kindred were also sequenced directly. Megaprimer method was used to construct the mutant AT cDNA expressing vector from normal plasmid pCRII AT cDNA. The normal and mutant AT plasmid were transiently transfected into Cos-7 cells and AT: Ag was detected in supernatant and lysate of transfected cell with ELISA.

RESULTSThe plasma level of AT: Ag and AT: A for the propositus were 179 mg/L and 42.3%, respectively. A heterozygous G13328A missense mutation in exon 6 was identified, which led to the substitution of Thr (ACC) 404 for Ala (GCC). The sequencing results from the pedigree suggested that three other members also had the mutation. The level of AT:Ag in supernatant and lysate from cells transfected with mutant AT cDNA was 40% and 68% of that of normal AT cDNA transfected cells.

CONCLUSIONThis is an unreported AT gene mutation in China, which causes type I hereditary antithrombin deficiency and thrombosis in the proposita.

Antithrombins ; genetics ; Heterozygote ; Humans ; Male ; Middle Aged ; Mutation ; Pedigree ; Thrombosis ; genetics

OBJECTIVEDynamic changes of quality and growth of Whitmania pigra were investigated to provide theoretical basis for quality control and determination of optimal harvest time.

METHODThe contents of moisture, ethanol-soluble extractive, total ash, and acid-insoluble ash, as well as antithrombin activity were determined according to Chinese pharmacopoeia (2005 edition).

RESULTQualities of W. pigra collected from different growth stages met the standards of Chinese pharmacopoeia (2005 edition). The highest amount of ethanol-soluble extract was found in 9-month-old, W. pigra, followed by 6-month-aged ones. And there was significant difference between 9-month-old and 4-month-old, 7 month-old and 11 month-old (P < 0.05). The highest antithrombin activity was detected in 6 month-old W. pigra, followed by 10 month-old. Significant differences of antithrombin activity were found between 6-month-old and 4 month-old ones, and 5 month-old (P < 0.05), however, there were no significant difference between 6 month-old ones with other samples. Eleven-month-old W. pigra got the most dry weight, and there were significant difference between 11 month-old ones with other samples (P < 0.05).

CONCLUSIONNovember, namely for 6 month old artificial cultivated W. pigra was the best harvest time in Jiangsu and Zhejiang provinces.

Animals ; Antithrombin III ; Antithrombins ; analysis ; China ; Leeches ; chemistry ; growth & development ; Medicine, Chinese Traditional ; Peptide Fragments

Abdominal Injuries ; Antithrombins/adverse effects* ; Atrial Fibrillation ; Dabigatran/adverse effects* ; Humans ; Thoracic Injuries

OBJECTIVETo study the molecular mechanisms of inherited antithrombin (AT) deficiency caused by AT L99 mutation.

METHODSWild type (WT), L99V, L99A, L99I and L99S AT were purified from drosophila expression system. The binding capacity of AT and the low molecular weight heparin sodium was analyzed by the heparin binding assay. Surface plasmon resonance (SPR) was used to detect the binding ability of AT to thrombin (FIIa) or AT to coagulation factor Xa (FXa). The activity of AT(AT∶A)was detected by chromogenic assay.

RESULTSThe purified WT and mutant AT were at the same size. No additional band was observed by coomassie blue staining and western blot assay. Compared to the WT AT, the binding abilities of the low molecular weight heparin sodium to the AT L99V, L99A, L99I and L99S were (44.8±3.6)%, (118.9±14.0)%, (15.2±8.8)%, and(23.0±8.2)%, respectively. The binding abilities of FIIa to AT L99V, L99A, L99I and L99S were 13%, 57%, 3%, and 29%, while the binding of FXa to AT L99V, L99A, L99I and L99S were 7%, 51%, 1%, and 25%. The AT∶A of WT, L99V, L99A, L99I and L99S AT were 146.5%, 21.4%, 120.9%, 10.8%, and 39.0%, respectively.

CONCLUSIONThe binding abilities of AT to heparin, FIIa and FXa were damaged by the L99 mutation, which resulted in decreased AT∶A and inherited AT deficiency.

Amino Acids ; genetics ; Animals ; Antithrombin III ; genetics ; Antithrombin III Deficiency ; genetics ; Antithrombins ; Drosophila ; Factor Xa ; genetics ; Genetic Vectors ; Humans ; Mutation

OBJECTIVETo investigate the antithrombin (AT) activity (AT: A) and AT antigen (AT: Ag) level in a Chinese family with type I antithrombin (AT) deficiency, and to explore the molecular mechanism of AT deficiency.

METHODSImmuno-nephelometry and chromogenic assay were used to detect the plasma level of AT: A and AT: Ag, respectively. Genomic DNA was isolated from the peripheral blood, and all the seven exons and exon-intron boundaries of AT gene were amplified by PCR and direct sequencing.

RESULTSThe plasma levels of AT: A and AT: Ag of the proband were 45% and 97 mg/L, respectively, which led to a type I AT deficiency. A heterozygous T to A mutation was found at nucleotide 9833 in exon 5 resulting in a Tyr363Stop nonsense mutation. The sequencing results from the pedigree indicated that four other members also had this mutation.

CONCLUSIONThis heterozygous nonsense mutation of T9833A in exon 5 resulting in venous thrombosis is a novel genetic defect of hereditary AT deficiency, which has not been described before.

Antithrombin III Deficiency ; genetics ; Antithrombins ; genetics ; Blood Coagulation Tests ; Female ; Humans ; Male ; Mutation ; Pedigree ; Polymerase Chain Reaction ; Sequence Analysis, DNA

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