Quantification of apixaban in human plasma using ultra performance liquid chromatography coupled with tandem mass spectrometry

Apixaban, an inhibitor of direct factor Xa, is used for the treatment of venous thromboembolic events or prevention of stroke. Unlike many other anticoagulant agents, it does not need periodic monitoring. However, monitoring is still required to determine the risk of bleeding due to overdose or surgery. Usually, apixaban concentrations are indirectly quantified using an anti-factor Xa assay. However, this method has a relatively narrow analytical concentration range, poor selectivity, and requires an external calibrator. Therefore, the goal of current study was to establish an analytical method for determining plasma levels of apixaban using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). To this end, apixaban was separated using 2.5 mM ammonium formate (pH 3.0) (A) and 100% methanol containing 0.1% formic acid (B) using the gradient method with a Thermo hypersil GOLD column. The mass detector condition was optimized using the electrospray ionization (ESI) positive mode for apixaban quantification. The developed method showed sufficient linearity (coefficient of determination [r² ≥ 0.997]) at calibration curve ranges. The percentage (%) changes in accuracy, precision, and all stability tests were within 15% of the nominal concentration. Apixaban concentration in plasma from healthy volunteers was quantified using the developed method. The mean maximum plasma concentration (C(max)) was 371.57 ng/mL, and the median time to achieve the C(max) (T(max)) was 4 h after administration of 10 mg apixaban alone. Although the results showed low extraction efficiency (~16%), the reproducibility (% change was within 15% of nominal concentration) was reliable. Therefore, the developed method could be used for clinical pharmacokinetic studies.

Epidural hematoma after total knee arthroplasty in a patient receiving rivaroxaban: A case report

Rivaroxaban, a factor Xa inhibitor, is one of the newly developed direct oral anticoagulants (DOAC). In recent times, it has been increasingly used in the prevention of pulmonary embolism in patients undergoing orthopedic surgery. This report describes a case of epidural hematoma in an elderly patient who underwent combined spinal epidural anesthesia for total knee arthroplasty; the patient received rivaroxaban postoperatively for 7 days to prevent pulmonary embolism. Additionally, the epidural hematomas developed on the 5th postoperative day but the patient recovered well with conservative treatment. Although rivaroxaban has a low need for monitoring and is easily administered, the guidelines should be carefully checked for the postoperative administration schedule in patients undergoing regional anesthesia. In addition, rivaroxaban should be used with caution, especially in elderly patients.

Arritmias cardíacas na sala de emergência e UTI. Anticoagulação do paciente com FA aguda submetido a cardioversão: já podemos contar com os novos anticoagulantes orais? / Cardiac arrhythmias in the emergency room and ICU. Anticoagulation of the patient with acute af undergoing cardioversion: can we rely on the new oral antioagulants?

A fibrilação atrial (FA) é a arritmia cardíaca mais comum na população com uma prevalência de 1-2%, além disso, está associada a um risco, aproximadamente cinco vezes maior de acidente vascular cerebral do que na população em geral. A anticoagulação é a melhor maneira de prevenir os eventos tromboembólicos. A varfarina é utilizada há décadas como uma droga segura e eficaz, desde que rigorosamente controlada. Nos últimos anos, foram desenvolvidas novas classes de anticoagulantes orais: inibidores diretos da trombina e inibidores do fator Xa, conhecidos como anticoagulantes orais de ação direta (DOACs). Tanto a cardioversão elétrica quanto a cardioversão farmacológica estão associadas a um maior risco de eventos tromboembólicos durante o primeiro mês após o procedimento (5-7%). No entanto, com a utilização de nticoagulantes essa taxa é inferior a 1%. No presente artigo, faremos uma revisão das principais evidências científicas relacionadas ao uso da dabigatrana, rivaroxabana, apixabana e edoxabana durante a cardioversão e uma abordagem prática com o manejo antitrombótico em diferentes cenários clínicos (cardioversão em pacientes com uso prévio de DOACs, cardioversão em pacientes com FA com duração maior ou menor que 48 horas sem anticoagulação)

Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice with a prevalence of 1-2%, and is associated with an almost 5-fold increase in the risk of stroke compared to the general population. Anticoagulation is the best way to prevent thromboembolic events. Warfarin has been used for decades as a safe and effective drug, provided it is strictly controlled. In recent years, new classes of oral anticoagulants have been developed: direct thrombin inhibitors and factor Xa inhibitors, known as direct oral anticoagulants (DOACs). Both electrical and pharmacological cardioversion are associated with an increased risk of thromboembolic events during the first month after the procedure (5-7%). However, with the use of anticoagulants, this rate is less than 1%. In this article, we will review the main scientific evidence related to the use of dabigatran, rivaroxaban, apixaban and edoxaban during cardioversion and a practical approach with antithrombotic management in different clinical scenarios (cardioversion of patients in previous use of DOACs, cardioversion of patients not using oral anticoagulants with episodes of AF longer or shorter than 48 h)

Uso de inhibidores directos del factor Xa en síndrome antifosfolípido: una serie de 7 casos / Use of factor Xa inhibitors in antiphospholipid antibodies syndrome: A serie of 7 cases

RESUMEN Introducción: El síndrome antifosfolípido se caracteriza por la presencia de anticuerpos contra fosfolípidos de membrana y manifestaciones clínicas, principalmente trombóticas y obstétricas. Su tratamiento se basa en la anticoagulación indefinida, generalmente con warfarina, la cual, por diversos factores, no siempre es factible por lo que es necesario el uso de terapias alternativas. Objetivo: Describirla experiencia con rivaroxabán en pacientes con síndrome antifosfolípido. Materiales y métodos: Estudio descriptivo en el que se evaluaron pacientes que cumplieron los criterios de Sydney de 2006 para síndrome antifosfolípido y que recibieron anticoagulación con rivaroxabán a dosis de 20 mg día en 2 hospitales de referencia en Medellín (Colombia), entre enero de 2012 y abril de 2015. Resultados: Se incluyeron 7 pacientes con una media de edad de 36,6 ± 10,8 arios (rango: 2355). De estos, 4 individuos tenían trombosis venosa, 5 trombosis arteriales, 5 anticuerpos anticardiolipinas positivos, 3 anticoagulante lúpico positivo, 2 pacientes tenían anti-f32 glicoproteína positivo y un paciente triple positividad de anticuerpos. La mediana de utilización de la warfarina fue de 15 meses (rango: 1-36). Las razones para el inicio de rivaroxabán fueron: sangrado (n = 2), rango subterapéutico de anticoagulación (n = 2), toxicodermia (n = 1), intolerancia gastrointestinal (n = 1) y retrombosis (n = 1). El tiempo de uso fue 17,9 ± 13,4 meses (rango: 3-34) y durante el periodo de seguimiento no se presentaron eventos adversos, pero sí 2 episodios nuevos de trombosis. Conclusión: El uso de inhibidores del factor Xa en una serie de pacientes con síndrome antifosfolípido e imposibilidad para el uso de warfarina mostró un adecuado perfil de seguridad; no obstante, hubo 2 episodios recurrentes de trombosis.

ABSTRACT Background: Antiphospholipid syndrome is an autoimmune disease with antibodies against membrane phospholipids with mainly thrombotic and/or obstetric manifestations. Its treatment is generally based on indefinite anticoagulation, usually with warfarin, and which, for various factors, is not always feasible, making it necessary to use alternative therapies. Objective: To describe the experience with rivaroxaban in patients with antiphospholipid syndrome. Materials and methods: A descriptive study was conducted on subjects that met the 2006 Sydney criteria for antiphospholipid antibodies syndrome and received anticoagulation with rivaroxaban at 20mg daily dose in 2 reference hospitals in Medellin, Colombia, between January 2012 and April 2015. Results: The study included 7 patients, with a mean age of 36±10.8 years (range 23-55). Four patients had venous thrombosis, 5 arterial, 5were positive for anticardiolipin antibodies, 3 reactive to lupus anticoagulant, 2 anti-β2 glycoprotein positive subjects, and one patient had triple antiphospholipid antibody positivity. The median time of warfarin use was 15 months (RIQ 1-36). The reasons for starting rivaroxaban were: bleeding (n = 2), sub-therapeutic coagulation ranges (n = 2), toxicoderma, gastrointestinal intolerance, and re-thrombosis (n = 1, each). The time of use was 17.9±13.4 months (range: 3-34). There were 2 recurrent cases of thrombosis during follow-up, and no adverse events. Conclusion: The use of factor Xa inhibitors in a series of patients with antiphospholipid syndrome and unable to use warfarin showed an adequate safety profile; however, 2 recurrent episodes of venous thrombosis occurred.

Acute kidney injury aggravated by treatment initiation with apixaban: Another twist of anticoagulant-related nephropathy

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.

Evaluación de la anticoagulación con rivaroxaban, en pacientes con fibrilación auricular no valvular de reciente diagnóstico / Evaluation of oral anticoagulation with rivaroxaban, in patients with new onset non valvular atrial fibrillation

Background: Atrial fibrillation (AF) generates a hypercoagulable state with an increased thrombin generation and raised levels of thrombin-antithrombin complexes, which results in a high risk of stroke and thromboembolism. Aim: To evaluate the anticoagulant effect of rivaroxaban by anti-Xa factor activity and its correlation with thrombin-antithrombin complexes, thrombin generation and prothrombin time in patients newly diagnosed with non-valvular AF. Patients and Methods: Prospective study in patients with indication of anticoagulation. Demographic variables, cardiovascular risk factors, CHA2DS2-VASc and HAS-BLED scores were recorded. Blood samples were taken at baseline, at 3 and 24 hours after the administration of the drug and at 30 days. Rivaroxaban levels, anti-Xa activity, prothrombin time, thrombin generation and plasma levels of thrombin-antithrombin complexes were determined. Results: We studied 20 patients aged 76.3 ± 8.0 years (60% female) with a CHA2DS2-VASc score > 2 points. The anti-Xa factor activity correlated with rivaroxaban plasma levels at 3 hours (r = 0.61, p < 0.01), at 24 hours (r = 0.85, p < 0.01) and at 30 days (r = 0.99, p < 0.01), with prothrombin time at 3 hours (r = -0.86, p = 0.019) and at 30 days (r = -0.63, p = 0.02) and with a sustained decrease in thrombin generation at 30 days of follow-up (r = -0.74, p < 0.01). There was no correlation with thrombin-antithrombin complexes (r = -0.02, p = 0.83). Conclusions: Rivaroxaban consistently inhibited the mild pro-coagulant state found in newly diagnosed non-valvular AF patients through the first 24 hours and this effect was maintained at 30 days. Plasma levels of the drug correlated with anti-Xa factor activity, thrombin generation and prothrombin time

Factor Xa Promotes Differentiation of Meg-01 Cell Line / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect and mechanism of Factor Xa on the differentiation of Meg-01 cells into platelet-like particles.</p><p><b>METHODS</b>The Meg-01 cells were used as experimental object, Factor Xa was used as agonist. Cell proliferation was detected by CCK-8 assay. The viability of platelet-like particles was analyzed by AlamaBlue kit. MAPK/ERK pathway and PI3K/AKT pathway were assayed by Western blot. The expression of CD41b was analyzed by Western blot and flow cytometry. Cell cycle and apoptosis were detected by flow cytometry.</p><p><b>RESULTS</b>The Factor Xa (1 µg/ml) inhibited cell viability, induced apoptosis. Factor Xa triggered cell arrest at the G(2)/M stage and down-regulated the expression of SKP2. After Meg-01 cells were stimulated by Factor Xa, the expression of CD41b was up-regulated and the MAPK/ERK pathway and PI3K/AKT pathway were activated. The platelets-like particles stimulated by FXa activation were viable.</p><p><b>CONCLUSION</b>The Factor Xa maybe display some effect on the differentiation of megakaryocytes into platelets.</p>

Prophylaxis for Venous Thromboembolism Following Total Knee Arthroplasty: A Survey of Korean Knee Surgeons

PURPOSE: The purpose of this study is to provide information on the actual status and prevailing trend of prophylaxis for venous thromboembolism (VTE) following total knee arthroplasty (TKA) in South Korea. MATERIALS AND METHODS: The Korean Knee Society (KKS) developed a questionnaire with 6 clinical questions on VTE. The questionnaire was distributed to all members of KKS by both postal and online mail. Participants were asked to supply details on their specialty and to select methods of prophylaxis they employ. Of the total members of KKS, 27.9% participated in the survey. RESULTS: The percentage of surgeons who routinely performed prophylaxis for VTE was 60.4%; 19.4% performed prophylaxis depending on the patient's health condition; and the remaining 20.2% never implemented prophylaxis after surgery. The common prophylactic methods among the responders were compression stocking (72.9%), pneumatic leg compression (63.3%), perioral direct factor Xa inhibitor (46.9%), and low-molecular-weight heparin (39.5%). For the respondents who did not perform prophylaxis, the main reason (51.5%) was the low risk of postoperative VTE considering the low incidences in Asians. CONCLUSIONS: The present study involving members of the KKS will help to comprehend the actual status of VTE prevention in South Korea. The results of this study may be useful to design VTE guidelines appropriate for Koreans in the future.

Comparisons of Bleeding Risks between Rivaroxaban and Dalteparin for Treatment of Venous Thromboembolism in Cancer Patients

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.

New Oral Anticoagulants: General Features and Review of Pivotal Clinical Trials

For the last half century, vitamin K antagonists (VKAs) have been used for treatment and prevention of venous thromboembolism and stroke prevention in patients with atrial fibrillation. However, their fragile pharmacokinetics, need for routine laboratory monitoring and dose adjustments complicated the use of these drugs. Recently, new oral anticoagulants (NOACs) have overcome the limitation of VKA therapy and shows favorable outcomes and better safety, especially for patients with intracranial hemorrhage, both in phase III clinical trials and real-world registry. Currently available NOACs are one thrombin inhibitor, dabigatran, and three Xa inhibitors, rivaroxaban, apixaban, and edoxaban. This review covers the pharmacokinetics, published pivotal clinical trials, and dose adjustments in chronic kidney disease. The reimbursement criteria, discontinuation during elective surgical procedure, issues on reversal agents are also discussed.

Antithrombotic Management of Patients with Nonvalvular Atrial Fibrillation and Ischemic Stroke or Transient Ischemic Attack: Executive Summary of the Korean Clinical Practice Guidelines for Stroke / 대한뇌졸중학회지

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.

The functional study of antithrombin L99 mutation / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the molecular mechanisms of inherited antithrombin (AT) deficiency caused by AT L99 mutation.</p><p><b>METHODS</b>Wild 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.</p><p><b>RESULTS</b>The 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.</p><p><b>CONCLUSION</b>The 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.</p>

Effect of Rivaroxaban on Fibrinolytic Therapy in Massive Pulmonary Embolism: Two Cases / 결핵및호흡기질환

The risk of dying from a pulmonary embolism (PE) is estimated to be about 30% if inotropic support is required and no cardiopulmonary arrest occurs. Fibrinolysis in massive PE is regarded as a life-saving intervention, unless there is a high risk of bleeding following the use of the fibrinolytic therapy. Rivaroxaban is an oral factor Xa inhibitor, however its anticoagulation effects before or after administration of fibrinolytics in massive PE are still unknown. Two patents were admitted: 61-year-old woman with repeated syncope, and a 73-year-old woman was admitted with dyspnea and poor oral intake. Systemic arterial hypotension with radiologic confirmation led to a diagnosis of massive PE in both patients. Rivaroxaban was administered before in one, and after firbrinolytic therapy in the other. One showed similar efficacy of rivaroxaban with currently used anticoagulants after successful fibrinolysis, and the other one without antecedent administration of the fibrinolytic agent showed unfavorable efficacy of rivaroxaban.

Leishmania amazonensis exhibits phosphatidylserine-dependent procoagulant activity, a process that is counteracted by sandfly saliva

Leishmania parasites expose phosphatidylserine (PS) on their surface, a process that has been associated with regulation of host's immune responses. In this study we demonstrate that PS exposure by metacyclic promastigotes of Leishmania amazonensis favours blood coagulation. L. amazonensis accelerates in vitro coagulation of human plasma. In addition, L. amazonensis supports the assembly of the prothrombinase complex, thus promoting thrombin formation. This process was reversed by annexin V which blocks PS binding sites. During blood meal, Lutzomyia longipalpis sandfly inject saliva in the bite site, which has a series of pharmacologically active compounds that inhibit blood coagulation. Since saliva and parasites are co-injected in the host during natural transmission, we evaluated the anticoagulant properties of sandfly saliva in counteracting the procoagulant activity of L. amazonensis . Lu. longipalpis saliva reverses plasma clotting promoted by promastigotes. It also inhibits thrombin formation by the prothrombinase complex assembled either in phosphatidylcholine (PC)/PS vesicles or in L. amazonensis . Sandfly saliva inhibits factor X activation by the intrinsic tenase complex assembled on PC/PS vesicles and blocks factor Xa catalytic activity. Altogether our results show that metacyclic promastigotes of L. amazonensis are procoagulant due to PS exposure. Notably, this effect is efficiently counteracted by sandfly saliva.

Anticoagulant and factor Xa-like activities of Tityus discrepans scorpion venom

Tityus discrepans venom (TdV) produces a variety of haemostatic manifestations including alveoli fbrin deposition and/ or prothrombin and partial thromboplastin time (PT, PTT) alterations in mammals. In vitro studies have demonstrated that TdV contains tissue plasminogen activator-like (t-PA), fbrinolytic and plasmin inhibitory compounds and produces platelets activation through GPVI and a novel Src-dependent signalling pathway. The aim of this study is to describe the initial characterization of procoagulant and anticoagulant components from TdV. This venom was fractionated by exclusion molecular chromatography on a Sephadex G-50 column. The eluted material was collected as fve fractions called S1 to S5. These fractions and the whole venom were used to evaluate factor Xa- and thrombin-like activities, fbrinogen degradation, furthermore thrombin- and factor Xa-inhibitory activities. The results demonstrated that TdV contain components with factor Xa-like activity (procoagulants) as well fbrinogenolytic compounds present in the fraction S1 and components with factor Xa inhibitory activity in the fractions S4 and S5 (anticoagulants).

El veneno de Tityus discrepans (TdV) produce en mamíferos una variedad de manifestaciones hemostáticas tales como depósitos de fbrina en alveolos y/o alteración en los tiempos de protrombina y tromboplastina parcial (PT, PTT). Estudios in vitro han demostrado que el TdV contiene componentes semejantes al activador del plasminógeno tipo tisular (t-PA), fbrino-líticos, compuestos que inhiben la actividad de plasmina y además componentes que promueven la activación de plaquetas a través del receptor GPVI y por una nueva vía de señalización dependiente de las Src kinasas. El objetivo de este estudio es describir la caracterización inicial de componentes procoagulantes y anticoagulantes a partir del TdV. Este veneno fue fraccionado por cromatografía de exclusión molecular sobre una columna Sephadex G-50. El material eluido fue colectado en cinco fracciones denominadas S1 a S5. Estas fracciones y el veneno completo fueron usados para evaluar actividades semejantes a factor Xa y trombina, degradación de fbrinógeno, como también la inhibición de la actividad del factor Xa y de la trombina. Los resultados demostraron que TdV contiene componentes con actividad semejante al factor Xa (procoagulantes) y compuestos fbrinogenolíticos presentes en la fracción S1, además de componentes con actividad inhibitoria del factor Xa presentes en la fracción S4 y S5 (anticoagulantes).

Antifactor Xa Levels in Critically Ill Korean Patients Receiving Enoxaparin for Thromboprophylaxis: A Prospective Observational Study

The aim of this study was to investigate antifactor Xa (aFXa) levels after once daily dose of 40 mg of enoxaparin and to evaluate factors influencing aFXa levels among Korean intensive care unit (ICU) patients. This prospective observational study was conducted between August and December 2011 in medical ICUs at Samsung Medical Center. AFXa levels between 0.1 and 0.3 U/mL were considered to be effective for antithrombotic activity. Fifty-five patients were included. The median aFXa levels were 0.22 (IQR 0.17-0.26) at 4 hr, 0.06 (IQR 0.02-0.1) at 12 hr, and 0 U/mL (IQR 0-0.03) at 24 hr. The numbers of patients showing effective antithrombotic aFXa levels were 48 (87.3%), 18 (32.7%), and 0 (0%) at 4, 12 and 24 hr, respectively. At 12 hr, higher sequential organ failure assessment (SOFA) scores and hyperbilirubinemia were significantly associated with low aFXa levels (OR, 0.58; 95% CI, 0.36-0.93; P = 0.02 and 0.06; 0.003-0.87; 0.04, respectively). Once daily dose of 40 mg of enoxaparin is inadequate for maintaining effective antithrombotic aFXa levels, and the inadequacy is more salient for patients with high SOFA scores and hyperbilirubinemia.

La importancia de la determinación del factor X activado para la anticoagulación con heparinas de bajo peso molecular: experiencia en el hospital san juan de dios, 2009-2011 (primer reporte) / The importance of the determination of factor X acivated for anticoagulation with low molecularweight heparins experience at the hospital san juan de dios. (first report) 2009-2011

La anticoagulación con heparinas de bajo peso molecular (HBPM) es una herramienta terapéutica fundamental para el tratamiento de la enfermedad tromboembólica. En el presente reporte se evidencia la importancia de cuantificar la actividad del anticuerpo antifactor X activado (Xa) para el monitoreo de la enoxaparina y analizar los grupos de pacientes en riesgo de tener niveles inferiores al terap‚utico. M‚todos: se estudiaron 34 pacientes adultos, anticoagulados con enoxaparina durante el periodo 2009-2011. Asimismo, se realizó un análisis descriptivo de las características demográficas y clínicas de todo los pacientes, en donde se indicaron las causas de la anticoagulación, la comorbilidades y el tipo de anticoagulación. Se midió la actividad anti-Xa 4 horas después de la administración de enoxaparina. Resultados: El promedio de edad de los pacientes fue de 62,3+17,7 años. Un 72,71 por ciento de los pacientes utilizaron enoxaparina como indicación para el síndrome coronario agudo. La comorbilidad más importante fue la combinación con la hipertensión arterial. El aclaramiento renal promedio fue de 62,47 ml/min, solamente tres pacientes tuvieron un aclaramiento menor a 30 ml/min; un 44,1 por ciento de los pacientes eran obesos. El 55,9 por ciento de los pacientes tuvo niveles anti-factor Xa dentro del rango terapéutico y un 35,3 por ciento tuvo valores de anti factor Xa profilácticos. Conclusión: El manejo del paciente adulto que recibe terapia anticoagulación con HBPM presenta una alta complejidad, hecho que se ve reflejado tanto a su perfil demográfico como clínico. También, se considera importante contar con la determinación del factor anti Xa para el monitoreo de HBPM para cierto grupo de pacientes vulnerables y con ello lograr el efecto deseado con esta terapia, debido a que existe un alto porcentaje de pacientes con niveles fuera del rango terapéutico.

Anticoagulation is an important therapeutic tool for patients with thromboembolic disease who receive therapy with lowmolecular weight heparins (LMWH). This report gives evidence about the importance of determining the activity of Anti-Xaactivity for monitoring enoxaparin and for identifying those patients who need this analysis based on some risk factors.Methods: We studied 34 adult patients who received enoxaparin as anticoagulation therapy during the period 2009-2011. We performed a descriptive analysis of demographic and clinical characteristics of all patients, indicating thereasons for anticoagulation, comorbidities and type of anticoagulation. We determined the anti-Xa activity 4 hours afteradministration of enoxaparin.Results: The mean age of patients was 62,3 + 17,7 years, regardless of gender. 72,7% of patients received enoxaparin astherapy for an acute coronary syndrome. The most frequent comorbidity was hypertension. The average of renal clearancewas 62,47 ml/min, only three patients had a renal clearance below 30 ml/min. 44,1% of the patients were obese. 55, 9%of patients were within therapeutic levels of anti-Xa activity and 35,3% of patients had an anti-Xa activity considered asprophylactic.Conclusion: The management of adult patients receiving anticoagulation therapy with LMWH is complex and it isreflected in their demographic and clinical characteristics. It is important to determine Anti-Xa activity to monitor the useof enoxaparin as anticoagulant therapy because of the high variability found in certain groups of patients.

Deep Vein Thrombosis and Neurovascular Injury after Total Hip Arthroplasty / 대한고관절학회지

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.

Stroke Update 2011: New Antithrombotics / 대한뇌졸중학회지

Several new antithrombotic drugs have been developed and approved to use in clinical practice recently. Dabigatran, a direct thrombin inhibitor, and rivaroxaban, a factor Xa inhibitor, have been approved in many countries including Korea to prevent stroke in patient with atrial fibrillation. Apixaban, another factor Xa inhibitor, showed good results in clinical trial and is waiting for approval for clinical use. New antiplatelet agent, terutroban, selective thromboxane A2 receptor inhibitor, failed to prove the efficacy over the aspirin in secondary stroke prevention. Vorapaxar, a new antiplatelet agent that inhibits thrombin through PAR-1 antagonism, showed a high incidence of intracranial hemorrhage in patient with a history of stroke.