Laboratory Measurement of the Anticoagulant Activity of the Non–Vitamin K Oral Anticoagulants

AbstractBackgroundNon–vitamin K oral anticoagulants (NOACs) do not require routine laboratory monitoring. However, laboratory measurement may be desirable in special situations and populations.ObjectivesThis study’s objective was to systematically review and summarize current evidence regarding laboratory measurement of the anticoagulant activity of dabigatran, rivaroxaban, and apixaban.MethodsWe searched PubMed and Web of Science for studies that reported a relationship between drug levels of dabigatran, rivaroxaban, and apixaban and coagulation assay results. Study quality was evaluated using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2).ResultsWe identified 17 eligible studies for dabigatran, 15 for rivaroxaban, and 4 for apixaban. For dabigatran, a normal thrombin time excludes clinically relevant drug concentrations. The activated partial thromboplastin time (APTT) and prothrombin time (PT) are less sensitive and may be normal at trough drug levels. The dilute thrombin time (R2 = 0.92 to 0.99) and ecarin-based assays (R2 = 0.92 to 1.00) show excellent linearity across on-therapy drug concentrations and may be used for drug quantification. For rivaroxaban and apixaban, anti-Xa activity is linear (R2 = 0.89 to 1.00) over a wide range of drug levels and may be used for drug quantification. Undetectable anti-Xa activity likely excludes clinically relevant drug concentrations. The PT is less sensitive (especially for apixaban); a normal PT may not exclude clinically relevant levels. The APTT demonstrates insufficient sensitivity and linearity for quantification.ConclusionsDabigatran, rivaroxaban, and apixaban exhibit variable effects on coagulation assays. Understanding these effects facilitates interpretation of test results in NOAC-treated patients. More information on the relationship between drug levels and clinical outcomes is needed

Guidance for the practical management of the heparin anticoagulants in the treatment of venous thromboembolism.

Venous thromboembolism (VTE) is a serious and often fatal medical condition with an increasing incidence. Despite the changing landscape of VTE treatment with the introduction of the new direct oral anticoagulants many uncertainties remain regarding the optimal use of traditional parenteral agents. This manuscript, initiated by the Anticoagulation Forum, provides clinical guidance based on existing guidelines and consensus expert opinion where guidelines are lacking. This specific chapter addresses the practical management of heparins including low molecular weight heparins and fondaparinux. For each anticoagulant a list of the most common practice related questions were created. Each question was addressed using a brief focused literature review followed by a multidisciplinary consensus guidance recommendation. Issues addressed included initial anticoagulant dosing recommendations, recommended baseline laboratory monitoring, managing dose adjustments, evidence to support a relationship between laboratory tests and meaningful clinical outcomes, special patient populations including extremes of weight and renal impairment, duration of necessary parenteral therapy during the transition to oral therapy, candidates for outpatient treatment where appropriate and management of over-anticoagulation and adverse effects including bleeding and heparin induced thrombocytopenia. This article concludes with a concise table of clinical management questions and guidance recommendations to provide a quick reference for the practical management of heparin, low molecular weight heparin and fondaparinux

Similarity in joint function limitation in Type 3 von Willebrand's disease and moderate haemophilia A

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98234/1/hae12119.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98234/2/hae12119-sup-0001-AppendixS1.pd

Structured decision-making drives guidelines panels’ recommendations ‘for’ but not ‘against’ health interventions

Background: The determinants of guideline panels’ recommendations remain uncertain. Objective: To investigate factors considered by members of 8 panels convened by the American Society of Hematology (ASH) to develop guidelines using GRADE system. Study Design and Setting: web-based survey of the participants in the ASH guidelines panels. Analysis: two level hierarchical, random-effect, multivariable regression analysis to explore the relation between GRADE and non-GRADE factors and strength of recommendations (SOR). Results: In the primary analysis, certainty in evidence [OR=1.83; (95CI% 1.45 to 2.31)], balance of benefits and harms [OR=1.49 (95CI% 1.30 to 1.69)] and variability in patients’ values and preferences [OR=1.47 (95CI% 1.15 to 1.88)] proved the strongest predictors of SOR. In a secondary analysis, certainty of evidence was associated with a strong recommendation [OR=3.60 (95% CI 2.16 to 6.00)] when panel members recommended “for” interventions but not when they made recommendations “against” [OR=0.98 (95%CI: 0.57 to 1.8)] consistent with “yes” bias. Agreement between individual members and the group in rating SOR varied (kappa ranged from -0.01 to 0.64). Conclusion: GRADE’s conceptual framework proved, in general, highly associated with SOR. Failure of certainty of evidence to be associated with SOR against an intervention, suggest the need for improvements in the process

Abnormal clot microstructure formed in blood containing HIT-like antibodies

IntroductionThrombosis is a severe and frequent complication of heparin-induced thrombocytopenia (HIT). However, there is currently no knowledge of the effects of HIT-like antibodies on the resulting microstructure of the formed clot, despite such information being linked to thrombotic events. We evaluate the effect of the addition of pathogenic HIT-like antibodies to blood on the resulting microstructure of the formed clot.Materials and methodsPathogenic HIT-like antibodies (KKO) and control antibodies (RTO) were added to samples of whole blood containing Unfractionated Heparin and Platelet Factor 4. The formed clot microstructure was investigated by rheological measurements (fractal dimension; df) and scanning electron microscopy (SEM), and platelet activation was measured by flow cytometry.Results and conclusionsOur results revealed striking effects of KKO on clot microstructure. A significant difference in df was found between samples containing KKO (df = 1.80) versus RTO (df = 1.74; p < 0.0001). This increase in df was often associated with an increase in activated platelets. SEM images of the clots formed with KKO showed a network consisting of a highly branched and compact arrangement of thin fibrin fibres, typically found in thrombotic disease. This is the first study to identify significant changes in clot microstructure formed in blood containing HIT-like antibodies. These observed alterations in clot microstructure can be potentially exploited as a much-needed biomarker for the detection, management and monitoring of HIT-associated thrombosis

Practical management of anticoagulation in patients with atrial fibrillation.

Anticoagulation for atrial fibrillation has become more complex due to the introduction of new anticoagulant agents, the number and kinds of patients requiring therapy, and the interactions of those patients in the matrix of care. The management of anticoagulation has become a team sport involving multiple specialties in multiple sites of care. The American College of Cardiology, through the College\u27s Anticoagulation Initiative, convened a roundtable of experts from multiple specialties to discuss topics important to the management of patients requiring anticoagulation and to make expert recommendations on issues such as the initiation and interruption of anticoagulation, quality of anticoagulation care, management of major and minor bleeding, and treatment of special populations. The attendees continued to work toward consensus on these topics, and present the key findings of this roundtable in a state-of- the-art review focusing on the practical aspects of anticoagulation care for the patient with atrial fibrillation

Statistical Methods Used to Test for Agreement of Medical Instruments Measuring Continuous Variables in Method Comparison Studies: A Systematic Review

BACKGROUND: Accurate values are a must in medicine. An important parameter in determining the quality of a medical instrument is agreement with a gold standard. Various statistical methods have been used to test for agreement. Some of these methods have been shown to be inappropriate. This can result in misleading conclusions about the validity of an instrument. The Bland-Altman method is the most popular method judging by the many citations of the article proposing this method. However, the number of citations does not necessarily mean that this method has been applied in agreement research. No previous study has been conducted to look into this. This is the first systematic review to identify statistical methods used to test for agreement of medical instruments. The proportion of various statistical methods found in this review will also reflect the proportion of medical instruments that have been validated using those particular methods in current clinical practice. METHODOLOGY/FINDINGS: Five electronic databases were searched between 2007 and 2009 to look for agreement studies. A total of 3,260 titles were initially identified. Only 412 titles were potentially related, and finally 210 fitted the inclusion criteria. The Bland-Altman method is the most popular method with 178 (85%) studies having used this method, followed by the correlation coefficient (27%) and means comparison (18%). Some of the inappropriate methods highlighted by Altman and Bland since the 1980s are still in use. CONCLUSIONS: This study finds that the Bland-Altman method is the most popular method used in agreement research. There are still inappropriate applications of statistical methods in some studies. It is important for a clinician or medical researcher to be aware of this issue because misleading conclusions from inappropriate analyses will jeopardize the quality of the evidence, which in turn will influence quality of care given to patients in the future