Anticoagulation Monitoring Part 1: Warfarin and Parenteral Direct Thrombin Inhibitors

2005 ◽  
Vol 39 (6) ◽  
pp. 1049-1055 ◽  
Author(s):  
Sarah A Spinler ◽  
Edith A Nutescu ◽  
Maureen A Smythe ◽  
Ann K Wittkowsky
Keyword(s):  
Clinical Application ◽  
Web Sites ◽  
English Language ◽  
Point Of Care ◽  
Anticoagulation Therapy ◽  
Thrombin Inhibitors ◽  
Care Utilization ◽  
Direct Thrombin Inhibitors ◽  
Reference Laboratory ◽  
Medline Search

OBJECTIVE: To review the availability, mechanisms, limitations, and clinical application of point-of-care (POC) devices used in the management of warfarin and parenteral direct thrombin inhibitors. DATA SOURCES: Scientific articles were identified through a MEDLINE search (1966–August 2004), manufacturer Web sites, additional references listed in articles and Web sites, and abstracts from scientific meetings. STUDY SELECTION AND DATA EXTRACTION: English-language literature from clinical trials was reviewed to evaluate the accuracy, reliability, and clinical application of POC monitoring devices. DATA SYNTHESIS: The prothrombin time expressed as the international normalized ratio (PT—INR) is a well-established test for monitoring warfarin anticoagulation. Multiple devices are available for POC testing. Because there is no universally accepted standard, the performance of each device is typically tested against a standard test performed in a reference laboratory. Performance of currently available devices, as measured by correlations to a standard reference laboratory PT—INR, may be considered very good and acceptable for use in patient care. Utilization of patient self-testing and patient self-monitoring of warfarin anticoagulation using POC devices is increasing. Parenteral direct thrombin inhibitors are typically monitored using a standard laboratory activated partial thromboplastin time. Some research has shown that POC monitoring of direct thrombin inhibitors using the ecarin clotting time is helpful for patients undergoing cardiopulmonary bypass surgery, although that test is not readily available. CONCLUSIONS: POC testing for anticoagulation therapy has been available for >20 years. Multiple POC devices are available to monitor warfarin. There is some variability in results between devices and between reagents used in the same device. Despite these limitations, POC monitoring of warfarin via the PT—INR is an integral part of clinical practice. Additional research evaluating POC monitoring of direct thrombin inhibitors is necessary.

Anticoagulation Monitoring Part 2: Unfractionated Heparin and Low-Molecular-Weight Heparin

2005 ◽  
Vol 39 (7-8) ◽  
pp. 1275-1285 ◽  
Author(s):  
Sarah A Spinler ◽  
Ann K Wittkowsky ◽  
Edith A Nutescu ◽  
Maureen A Smythe
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Clinical Application ◽  
Therapeutic Range ◽  
Web Sites ◽  
English Language ◽  
Point Of Care ◽  
Low Molecular Weight ◽  
Medline Search ◽  
Heparin Concentration

OBJECTIVE To review the availability, mechanisms, limitations, and clinical application of point-of-care (POC) devices used in monitoring anticoagulation with unfractionated heparin (UFH) and low-molecular-weight heparins (LMWHs). DATA SOURCES Articles were identified through a MEDLINE search (1966–August 2004), device manufacturer Web sites, additional references listed in articles and Web sites, and abstracts from scientific meetings. STUDY SELECTION AND DATA EXTRACTION English-language literature from clinical trials was reviewed to evaluate the accuracy, reliability, and clinical application of POC monitoring devices. DATA SYNTHESIS The activated partial thromboplastin time (aPTT) and activated clotting time (ACT) are common tests for monitoring anticoagulation with UFH. Multiple devices are available for POC aPTT, ACT, and heparin concentration testing. The aPTT therapeutic range for UFH will vary depending upon the reagent and instrument employed. Although recommended by the American College of Chest Physicians Seventh Conference on Antithrombotic and Thrombolytic Therapy, establishing a heparin concentration–derived therapeutic range for UFH is rarely performed. Additional research evaluating anti-factor Xa monitoring of LMWHs using POC testing is necessary. CONCLUSIONS Multiple POC devices are available to monitor anticoagulation with UFH. For each test, there is some variability in results between devices and between reagents used in the same device. Despite these limitations, POC anticoagulation monitoring of UFH using aPTT and, more often, ACT is common in clinical practice, particularly when evaluating anticoagulation associated with interventional cardiology procedures and cardiopulmonary bypass surgery.

Ximelagatran: A new type of oral anticoagulant

2005 ◽  
Vol 21 (4) ◽  
pp. 480-486
Author(s):  
Lisa Kwok ◽  
Dana Molckovsky ◽  
Michel Boucher
Keyword(s):  
Atrial Fibrillation ◽  
Venous Thromboembolism ◽  
Web Sites ◽  
Liver Toxicity ◽  
Oral Anticoagulants ◽  
Bleeding Risk ◽  
Thrombin Inhibitors ◽  
Cochrane Library ◽  
Direct Thrombin Inhibitors ◽  
Elevated Liver Enzymes

Objectives: This assessment sought to evaluate the comparative benefit and adverse effect profile of ximelagatran, as well as the clinical issues surrounding its potential use.Methods: We performed a Dialog OneSearch across BIOSIS Previews, EMBASE, MEDLINE, PASCAL, and ToxFile to identify published literature. PubMed and The Cochrane Library were also searched. Gray literature was identified by searching a variety of Web sites of health technology assessment and related agencies and their associated databases. The manufacturer's Canadian office, AstraZeneca, was invited to submit information.Results: Ximelagatran is the first oral agent from a new class of anticoagulants called direct thrombin inhibitors. Other oral anticoagulants require routine blood monitoring; ximelagatran does not. Ximelagatran has been evaluated in the areas of venous thromboembolism management, particularly after orthopedic surgery, and stroke prevention in patients with atrial fibrillation. Overall, ximelagatran's efficacy appears comparable to other anticoagulants in these clinical settings. Also, bleeding rates were generally similar between ximelagatran and comparators but, as for warfarin, bleeding risk increases with higher ximelagatran doses. In addition, there is no specific antidote to help manage ximelagatran-induced bleeding. Finally, significantly more patients exposed to long-term ximelagatran developed elevated liver enzymes more than three times the upper normal limit, compared with patients on comparator anticoagulants.Conclusions: Given its apparent simplicity of use, ximelagatran carries the potential to replace, at least in part, anticoagulants currently used in the management of venous thromboembolism or for preventing stroke in atrial fibrillation patients. However, the safety of ximelagatran will not be fully known without further evaluation and surveillance for potential liver toxicity. There is also a need to evaluate its use in special populations such as patients with renal failure and patients using several concurrent medications.

Thrombophilia and New Anticoagulant Drugs

Hematology ◽  
2004 ◽  
Vol 2004 (1) ◽  
pp. 424-438 ◽  
Author(s):  
Jeffrey I. Weitz ◽  
Saskia Middeldorp ◽  
William Geerts ◽  
John A. Heit
Keyword(s):  
Clinical Trials ◽  
Venous Thromboembolism ◽  
Phase Ii ◽  
Anticoagulation Therapy ◽  
Factor Xa ◽  
Thrombin Inhibitors ◽  
First Episode ◽  
Direct Thrombin Inhibitors ◽  
Risk Of Recurrence ◽  
Phase Ii And Iii

Abstract Venous thromboembolism, which includes deep vein thrombosis and pulmonary embolism, is the result of an imbalance among procoagulant, anticoagulant and profibrinolytic processes. This imbalance reflects a complex interplay between genetic and environmental or acquired risk factors. Genetic thrombophilic defects influence the risk of a first episode of thrombosis. How these defects influence the risk of recurrence in patients whose first episode of venous thromboembolism was unprovoked is less certain. Thus, when anticoagulants are stopped, patients with unprovoked venous thromboembolism have a risk of recurrence of at least 7% to 10% per year, even in the absence of an underlying thrombophilic defect. Consequently, there is a trend toward longer durations of anticoagulation therapy for these patients, which is problematic given the limitation of existing anticoagulants. This chapter provides an overview of the thrombophilic defects and how they influence the risk of venous thromboembolism. The chapter also details advances in anticoagulant therapy, focusing on new inhibitors of factor Xa and thrombin. In Section I, Dr. Saskia Middeldorp describes the various thrombophilic defects and reviews their relative importance in the pathogenesis of a first episode of venous thromboembolism. She then discusses the influence of these defects on the risk of recurrent thrombotic events in patients with unprovoked venous thromboembolism and in those whose thrombosis occurred in association with a known risk factor, such as surgery. In Section II, Dr. William Geerts reviews the pharmacology of new parenteral and oral factor Xa inhibitors and describes the results of the Phase II and III clinical trials with these agents. He then provides perspective on the potential advantages and drawbacks of these drugs for the prevention and treatment of venous thromboembolism. In Section III, Dr. John Heit focuses on direct thrombin inhibitors. He discusses their mechanism of action and compares and contrasts their pharmacological profiles prior to describing the results of Phase II and III clinical trials. Dr. Heit then provides perspective on the potential advantages and limitations of these drugs relative to existing anticoagulants.

Review of the Target-Specific Oral Anticoagulants in Development for the Treatment and Prevention of Venous Thromboembolism

2016 ◽  
Vol 29 (4) ◽  
pp. 392-405 ◽  
Author(s):  
Sandeep Devabhakthuni ◽  
Connie H. Yoon ◽  
Kathleen J. Pincus
Keyword(s):  
Venous Thromboembolism ◽  
Clinical Decision Making ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Bleeding Risk ◽  
Clinical Decision ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Treatment And Prevention

Anticoagulation therapy is often indicated for the treatment and prevention of venous thromboembolism (VTE). Despite advances in anticoagulant management with parenteral anticoagulants and vitamin K antagonists, limitations to their use still exists, leading to investigation of alternative anticoagulants such as factor Xa inhibitors and direct thrombin inhibitors. To date, 3 target-specific oral anticoagulants (TSOACs) are Food and Drug Administration approved; several other agents are currently in development to optimize VTE management and minimize bleeding risks. The objective of this systematic review article is to provide clinicians an overview of the clinical evidence on the investigational TSOACs for the treatment and prevention of VTE. Of the agents in development, edoxaban holds the most promise due to robust data supporting its clinical benefit with a similar bleeding risk to currently approved agents. Clinicians should understand the TSOACs under investigation, since differences in pharmacokinetics and pharmacodynamics may influence clinical decision making and agent selection for management of VTE. Currently, no direct comparisons between TSOACs have been conducted. Agents under investigation have yet to overcome the major limitations of the currently existing TSOACs. Further studies are necessary to clarify which TSOAC agent is best for management of VTE in clinical practice.

Accuracy of point of care coagulometers compared to reference laboratory measurements in patients on oral anticoagulation therapy

2016 ◽  
Vol 140 ◽  
pp. 66-72 ◽  
Author(s):  
Jean-Guillaume Dillinger ◽  
Thiziri Si Moussi ◽  
Natacha Berge ◽  
Claire Bal Dit Sollier ◽  
Patrick Henry ◽  
...  
Keyword(s):  
Oral Anticoagulation ◽  
Point Of Care ◽  
Anticoagulation Therapy ◽  
Reference Laboratory ◽  
Laboratory Measurements ◽  
Oral Anticoagulation Therapy

Quality of Pharmacist-Managed Anticoagulation Therapy in Long-Term Ambulatory Settings: A Systematic Review

2017 ◽  
Vol 51 (12) ◽  
pp. 1122-1137 ◽  
Author(s):  
Beenish S. Manzoor ◽  
Wei-Han Cheng ◽  
James C. Lee ◽  
Ellen M. Uppuluri ◽  
Edith A. Nutescu
Keyword(s):  
Systematic Review ◽  
Emergency Department ◽  
English Language ◽  
Anticoagulation Therapy ◽  
Emergency Department Visits ◽  
Care Utilization ◽  
Thromboembolic Events ◽  
Anticoagulation Management ◽  
Anticoagulation Control

Objective: To perform a systematic review to evaluate the quality of warfarin anticoagulation control in outpatient pharmacist-managed anticoagulation services (PMAS) compared with routine medical care (RMC). Data Sources: MEDLINE, SCOPUS, EMBASE, IPA, CINAHL, and Cochrane CENTRAL, from inception to May 2017. Search terms employed: (“pharmacist-managed” OR “pharmacist-provided” OR “pharmacist-led” OR “pharmacist-directed”) AND (“anticoagulation services” OR “anticoagulation clinic” OR “anticoagulation management” OR “anticoagulant care”) AND (“quality of care” OR “outcomes” OR “bleeding” OR “thromboembolism” OR “mortality” OR “hospitalization” OR “length of stay” OR “emergency department visit” OR “cost” OR “patient satisfaction”). Study Selection and Data Extraction: Criteria used to identify selected articles: English language; original studies (comments, letters, reviews, systematic reviews, meta-analyses, editorials were excluded); warfarin use; outpatient setting; comparison group present; time in therapeutic range (TTR) included as a measure of quality of anticoagulant control; study design was not a case report. Data Synthesis: Of 177 articles identified, 25 met inclusion criteria. Quality of anticoagulation control was better in the PMAS group compared with RMC in majority of the studies (N = 23 of 25, 92.0%). Clinical outcomes were also favorable in the PMAS group as evidenced by lower or equal risk of major bleeding (N = 10 of 12, 83.3%) or thromboembolic events (N = 9 of 10, 90.0%), and lower rates of hospitalization or emergency department visits (N = 9 of 9, 100%). When reported, PMAS have also resulted in cost-savings in all (N=6 of 6, 100%) of studies. Conclusions: Compared with routine care, pharmacist-managed outpatient-based anticoagulation services attained better quality of anticoagulation control, lower bleeding and thromboembolic events, and resulted in lower health care utilization.

High Incidence of Thromboembolic Complications and PF4 Positivity in Patients with Ventricular Assist Devices.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4083-4083
Author(s):  
Brandon J. McMahon ◽  
Jainulabdeen J. Ifthikharuddin ◽  
Elie Dib ◽  
Leway Chen ◽  
Charles W. Francis ◽  
...  
Keyword(s):  
Anticoagulation Therapy ◽  
High Rate ◽  
Thrombin Inhibitors ◽  
Ventricular Assist Devices ◽  
Direct Thrombin Inhibitors ◽  
Thromboembolic Complications ◽  
Ventricular Assist ◽  
Full Dose ◽  
Assist Devices ◽  
High Incidence

Abstract Patients with ventricular assist devices (VAD) are at high risk for thromboembolic complications (TEC) probably due to platelet activation and excessive thrombin generation once the device is implanted. This warrants prophylactic use of full dose anticoagulation, usually with unfractionated heparin (UFH), which increases the risk for development of heparin-induced thrombocytopenia (HIT). We retrospectively evaluated the incidence of TEC and PF4 positivity in 50 sequential patients who underwent VAD placement for severe ventricular dysfunction between November 2002 and April 2005. Median age at VAD placement was 52 years (range 18–72), 68% were men, and all patients were on full dose UFH post-VAD insertion. TEC were observed in 22/50 patients (44%), with 8 patients experiencing >1 event. CNS embolic phenomena occurred in 11/22 (50% of TEC), with watershed/non-embolic CNS infarcts being identified in 2 additional patients. Splenic infarcts were identified in 6/22 (27%). Two patients had lower extremity deep vein thromboses (DVT), and two patients had pulmonary emboli. One patient died from complications of multiple infarcts involving his spleen and gut that were attributed to HIT. All patients became thrombocytopenic (<150K) at some point during VAD/UFH use. 44 patients (88%) dropped the platelet count below 100K with an average nadir of 56K. Antibodies to the PF4/heparin complex were checked using a standard enzyme immunoassay (EIA) in 38 (76%) patients, and found to be positive in 17 (44.7%). PF4 antibodies were detected using the EIA in 50% of patients with TEC and in 25% of patients with no documented TEC. A functional antibody assay was checked in a total of 17 patients, the serotonin release assay (SRA) in 13 and heparin-induced agglutination (HIA) in 4 cases. The SRA was only positive in 2/13 cases, and concordant with the PF4 result both times. The HIA was positive once, and concordant with the PF4 result. These results highlight the high incidence of TEC in patients with a VAD, despite anticoagulation therapy. There is a particularly high rate of embolic stroke in this patient population, and better ways of preventing this complication need to be explored. Thrombocytopenia is also extremely common post-VAD placement, prompting evaluation of HIT in over ¾ of the patients, often necessitating use of direct thrombin inhibitors. The frequent detection of PF4 antibodies in this patient group and lack of correlation with functional assays illustrates the need for more specific laboratory means to quickly confirm those patients with HIT.

Advances in antithrombotic therapy as adjunct to reperfusion therapies for ST-segment elevation myocardial infarction

2008 ◽  
Vol 100 (08) ◽  
pp. 184-195 ◽  
Author(s):  
Paolo Marino ◽  
Giuseppe De Luca
Keyword(s):  
Myocardial Infarction ◽  
Antithrombotic Therapy ◽  
Anticoagulation Therapy ◽  
Primary Angioplasty ◽  
Thrombin Inhibitors ◽  
Bleeding Complications ◽  
Direct Thrombin Inhibitors ◽  
St Segment Elevation ◽  
Segment Elevation Myocardial Infarction ◽  
St Segment

SummaryThe treatment of ST-segment elevation myocardial infarction (STEMI) has improved over the past decades, mainly due to reperfusion therapies. The aim of this article is to provide an updated review of adjunctive antithrombotic therapy to reperfusion strategies for STEMI. As compared to unfractionated heparin (UFH), among patients treated with thrombolysis, low-molecular- weight heparins (LMWHs),mainly enoxaparin, fonda-parinux and clopidogrel have been shown to improve outcome in terms of death and reinfarction, whereas GP IIb-IIIa inhibitors, mainly abciximab, and direct thrombin inhibitors have reduced reinfarction, but not mortality. Among patients undergoing primary angioplasty, early UFH should still be regarded as the gold standard in anticoagulation therapy. In addition to ASA, early GP IIb-IIIa inhibitors, especially abciximab, should be considered since it has been shown to provide further benefits in terms of preprocedural recanalization. Despite the positive results observed in the HORIZONS trial, additional studies are needed to investigate the role of bivalirudin as compared to abciximab administration. In our opinion, bivalirudin may be considered instead of GP IIb-IIIa inhibitors among STEMI patients at high risk for bleeding complications. Due to the very low mortality currently achieved by primary angioplasty, a further reduction in short- or medium-term mortality would be quite improbable to be observed. Thus, additional endpoints, such as infarct size and myocardial perfusion, may be considered in future randomized trials among patients undergoing mechanical revascularization for STEMI.

scholarly journals Old and new oral anticoagulants for secondary stroke prevention in atrial fibrillation

2015 ◽  
Vol 9 (4) ◽  
pp. 314
Author(s):  
Tommaso Sacquegna ◽  
Anna Zaniboni ◽  
Andrea Rubboli ◽  
Gaetano Procaccianti ◽  
Michela Crisci ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Secondary Prevention ◽  
Stroke Prevention ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
New Oral Anticoagulants ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Significant Difference

Vitamin K antagonists, such as warfarin, used in oral anticoagulation therapy currently represent the standard drugs for the primary and secondary prevention of stroke in non-valvular atrial fibrillation (AF), with a relative risk reduction close to 70%. Newer oral anticoagulants, such as direct thrombin inhibitors (<em>i.e</em>., dabigatran) and direct factor Xa inhibitors (<em>i.e</em>., apixaban and rivaroxaban) have been recently compared with warfarin in large randomized trials for stroke prevention in AF. The new oral anticoagulants showed, compared with warfarin, no statistically significant difference in the rate of stroke or systemic embolism in secondary prevention (patients with previous transient ischemic attack or stroke) subgroups. With regard to safety, the risk of intracranial bleeding was reduced with new anticoagulants compared with warfarin. Indirect treatment comparisons of clinical trials on secondary prevention cohorts showed no significant difference in efficacy among apixaban, rivaroxaban, and dabigatran; but dabigatran 110 mg was associated with less intracranial bleedings than rivaroxaban.

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