The incidence of life-threatening anaphylactoid reactions during anesthesia has been increasing. Specific allergic reactions during anesthesia are usually due to muscle relaxants, barbiturates, local anesthetics, narcotics, radiocontrast media, antibiotics, and colloids. Thrombokinase, a hemostatic agent, has been used widely in clinical practice and severe anaphylactoid reactions to thrombokinase can occur rarely. We experienced two cases of anaphylactoid reactions after thrombokinase administration.
Anesthesia ; Anesthetics, Local ; Anti-Bacterial Agents ; Barbiturates ; Colloids ; Contrast Media ; Factor Xa* ; Hypersensitivity ; Incidence ; Narcotics ; Pharmacology

Anticoagulant-related nephropathy (ARN) was initially described in patients on warfarin (as warfarin-related nephropathy) and recently in those using dabigatran. Herein, we report clinical history and kidney biopsy findings in a patient on apixaban (Eliquis). Initiation of treatment with apixaban resulted in aggravation of preexisting mild acute kidney injury (AKI). A few days after apixaban therapy, the patient became oligoanuric, and kidney biopsy showed severe acute tubular necrosis with numerous occlusive red blood cell casts. Only one out of 68 glomeruli with open capillary loops had small segmental cellular crescent. Therefore, there was major discrepancy between the degree of glomerular injury and the glomerular hematuria. Considering that the onset of this AKI was associated with apixaban treatment initiation, we propose that this patient had ARN associated with factor Xa inhibitor (apixaban), which has not previously been described. Monitoring of kidney function is recommended after initiation of anticoagulant therapy.
Acute Kidney Injury* ; Biopsy ; Capillaries ; Dabigatran ; Erythrocytes ; Factor Xa ; Hematuria ; Humans ; Kidney ; Necrosis ; Warfarin

The fine structure of enoxaparin sodium samples with different degree of 1,6-anhydro derivatives were analyzed with polyacrylamide gel electrophoresis, high performance liquid chromatography, ultraviolet spectroscopy, infrared spectroscopy and nuclear magnetic resonance spectroscopy. A further study of anticoagulation activity of enoxaparins was performed, including those on their inhibition activities of coagulation factor Xa (FXa) and thrombin (FIIa). The results showed that the anti-FXa and -FIIa activities of enoxaparins with different degree of 1,6-anhydro derivatives (20.0%-39.7%) with similar structure characteristics, had decreasing tendency when the degree of 1,6-anhydro derivatives increased. Especially, the anti-FXa activity was sensitive to the change of the degree of 1,6-anhydro derivatives.
Anticoagulants ; chemistry ; Enoxaparin ; chemistry ; Factor Xa Inhibitors ; chemistry ; Thrombin ; antagonists & inhibitors

Structure of human blood coagulation factor VIII (FVIII) in relation to its activation process was investigated. FVIII was purified from a commercial FVIII concentrate by immunoaffinity chromatography and its dissociated subunits, heavy and light chains were isolated. The light chain (FVIII-L) was treated with thrombin or factor Xa (FXa) in order to cleave the peptide at Aug(1689) or Arg(1721), respectively, Reassociation of FVIII-H with either of FVIII-L derivatives, FVIII-L-72 (72 kDa) and FVIII-L-65 (65 kDa) brought about the formation of heterodimers which have similar cofactor activity. The association constant of FVIII-H with FVIII-L-72 was about two-fold faster than that with FVIII-L-65, Cleavage of major FVIII-H with thrombin generated two peptides with molecular weights of 50 kDa (A(1)) and 40 kDa (A(2)) Formation of heterotrimer by reassociation of A(1), A(2) and FVIII-L-72-generated FVIII cofactor activity, while the dimers formed from A(1) or A(2) with FVIII-L-72 had no activity, suggesting that both A(1) and A(2) are required for FVIII activity, Heterotrimers formed from A(1) and A(2) with either of FVIII-L-72 or FVIII-L-65 in the presence of CaCl2 (10 mM) revealed cofactor activity, and they were dissociated into subunits with the loss of activity when EDTA (10 mM) was added, indicating that the formation of heterotrimer, the functional unit of FVIII, from A1, A(2) and FVIII-L is calcium dependent and that the cleavage of FVIII-L by FXa does not inactivate FVIII.
Blood Coagulation Factors* ; Blood Coagulation* ; Calcium ; Chromatography ; Edetic Acid ; Factor VIII* ; Factor Xa ; Humans ; Molecular Weight ; Peptides ; Thrombin

Regulatory approvals of non-vitamin K antagonist oral anticoagulants (NOACs) have been based on large randomized phase III trials evaluating dabigatran, rivaroxaban, apixaban, or edoxaban relative to warfarin for atrial fibrillation (AF). The results of the trials showed that all NOACs were at least non-inferior to warfarin in the prevention of stroke/thromboembolism and showed lower rates of intracranial bleeding than those associated with warfarin. However, the trials were designed differently, varied in the inclusion/exclusion criteria, and used either one dose or a low/high dose of the NOAC drug. Some of these differences have challenged the ability to directly compare various NOACs, and comparative data on effectiveness and intracranial bleeding are sparse in “real-world” patients. Real-world data complement data from large randomized phase III trials by providing new aspects of the “real-world” absolute risks of ischemic and hemorrhagic stroke associated with NOACs vs. warfarin. Moreover, “real-world” fragile patients might have been included (e.g., patients with increased risk of bleeding, liver disease, and chronic kidney disease), although these patients would be less represented in trials. This paper introduces recently published real-world data of NOACs and further suggests the recommended dosage of NOACs for Korean patients.
Anticoagulants* ; Atrial Fibrillation ; Complement System Proteins ; Dabigatran ; Factor Xa Inhibitors ; Hemorrhage ; Humans ; Kidney ; Liver Diseases ; Rivaroxaban ; Stroke ; Warfarin

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

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

BACKGROUND: Venous thromboembolism (VTE) is a common and life-threating condition in cancer patients. Low molecular weight heparins (LMWH), such as dalteparin, are recommended in the treatment of VTE. Also, rivaroxaban, an orally administered direct factor Xa inhibitor, was approved for the treatment of VTE. It showed similar efficacy to standard therapy (LMWH or warfarin) and was associated with significantly lower rates of major bleedings. However, in the real world, bleeding has been reported to occur frequently in cancer patient receiving rivaroxaban. The goal of this research was to analyze bleeding risks between rivaroxaban and dalteparin for treatment of VTE in cancer patients. METHODS: Medical records of oncology patients who were treated with rivaroxaban or dalteparin for VTE from July 2012 to June 2014 were retrospectively reviewed. Data collected were as follows: age, sex, weight, height, cancer types and stages, ECOG (eastern cooperative oncology group) PS (performance score), VTE types, concurrently used medications, study drug information (dose and duration of therapy), INR (international normalized ratio), PT (prothrombin time), and platelet counts. Bleeding was classified into major bleedings, clinically relevant non-major bleedings, and minor bleedings. RESULTS: A total of 399 patients were included in the study. Of these patients, 246 were treated with rivaroxaban and 153 with dalteparin. Bleeding rates were significantly higher in the rivaroxaban group than in the dalteparin group (adjusted odds ratio (AOR) 2.09, 95% CI 1.22-3.60) after adjusting for confounders. In addition, rivaroxaban remained independently associated with 1.78-fold (95% CI 1.14-2.76) shorter time to bleeding compared to dalteparin after adjusting other factors known to be associated with poor outcomes. CONCLUSION: This study suggested that rivaroxaban was associated with an increased risk of bleedings in cancer patients.
Dalteparin* ; Factor Xa ; Hemorrhage* ; Heparin, Low-Molecular-Weight ; Humans ; International Normalized Ratio ; Medical Records ; Odds Ratio ; Platelet Count ; Retrospective Studies ; Rivaroxaban* ; Venous Thromboembolism*

Cardioembolic stroke related to nonvalvular atrial fibrillation is associated with a high recurrence rate and high mortality and morbidity. In this population, therefore, optimal anticoagulant therapy is required to prevent the occurrence of second stroke. Oral anticoagulant, warfarin has been traditionally used, but it is greatly limited by its narrow efficacy window, complex pharmacokinetics, and multiple drug interactions, thus requiring frequent blood monitoring. Recently, oral anticoagulants targeted for a specific coagulation component have been newly developed and tested in large clinical trials. Dabigatran, direct thrombin inhibitor, and rivaroxaban, apixaban, and edoxaban, inhibitors of factor Xa harbor great merits of rapid action time, short half-life, stable plasma concentration, and little drug interaction. Recently, large randomized clinical trials and meta-analyses have been published to show the efficacy and safety of the new oral anticoagulants compared with warfarin. Based on the results from recent clinical trials, we revised recommendations to apply optimal anticoagulant therapy in patients with nonvalvular atrial fibrillation and ischemic stroke or transient ischemic attack.
Anticoagulants ; Atrial Fibrillation* ; Drug Interactions ; Factor Xa ; Half-Life ; Humans ; Ischemic Attack, Transient* ; Mortality ; Pharmacokinetics ; Plasma ; Recurrence ; Secondary Prevention ; Stroke* ; Thrombin ; Warfarin ; Dabigatran ; Rivaroxaban

Deep vein thrombosis (DVT) is a relatively common complication of total hip arthroplasty. DVT can accompany symptoms of pain and swelling of the lower leg, and can lead to fatal pulmonary thromboembolism. Surgical procedure is a primary risk factor, and obesity, medical status of disease, or patient's factors could be related. Diagnostic modalities include venography, Doppler ultrasound, CT angiography, and magnetic resonance venography. Mechanical prophylaxis, such as compression stocking and use of an intermittent pneumatic compression device or a pharmacological agent, such as Warfarin, low molecular weight heparin, thrombin inhibitors, and factor Xa inhibitor can be useful. Neurovascular injury after total hip arthroplasty is an uncommon complication, but can be disastrous and fatal. To prevent this complication, the surgeon must be well acquainted with the anatomy and proper surgical skill is needed.
Angiography ; Arthroplasty ; Factor Xa ; Heparin, Low-Molecular-Weight ; Hip ; Leg ; Magnetic Resonance Spectroscopy ; Obesity ; Phlebography ; Pulmonary Embolism ; Risk Factors ; Stockings, Compression ; Thrombin ; Venous Thrombosis ; Warfarin