Standardization of Prothrombin Time/International Normalized Ratio (PT/INR)

The prothrombin time (PT) represents the most commonly used coagulation test in clinical laboratories. The PT is mathematically converted to the international normalized ratio (INR) for use in monitoring anticoagulant therapy with vitamin K antagonists such as warfarin in order to provide test results that are adjusted for thromboplastin and instrument used. The INR is created using two major PT �correction factors�, namely the mean normal PT (MNPT) and the international sensitivity index (ISI). Manufacturers of reagents and coagulometers have made some efforts to harmonizing INRs, for example, by tailoring reagents to specific coagulometers and provide associated ISI values. Thus, two types of ISIs may be generated, with one being a �general� or �generic� ISI and others being reagent/coagulometer-specific ISI values. Although these play a crucial role in improving INR results between laboratories, these laboratories reported INR values are known to still differ, even when laboratories use the same thromboplastin reagent and coagulometer. Moreover, ISI values for a specific thromboplastin can vary among different models of coagulometers from a manufacturer using the same method for clot identification. All these factors can be sources of error for INR reporting, which in turn can significantly affect patient management. In this narrative review, we provide some guidance to appropriate ISI verification/validation, which may help decrease the variability in cross laboratory reporting of INRs. © 2020 John Wiley & Sons Lt

International survey on D-dimer test reporting: a call for standardization

D-dimer is the biochemical gold standard for diagnosing a variety of thrombotic disorders, but result reporting is heterogeneous in clinical laboratories. A specific five-item questionnaire was developed to gain a clear picture of the current standardization of D-dimer test results. The questionnaire was opened online (December 24, 2014-February 10, 2015) on the platform "Google Drive (Google Inc., Mountain View; CA)," and widely disseminated worldwide by newsletters and alerts. A total of 409 responses were obtained during the period of data capture, the largest of which were from Italy (136; 33%), Australia (55; 22%), Croatia (29; 7%), Serbia (26; 6%), and the United States (21; 5%). Most respondents belonged to laboratories in general hospitals (208; 51%), followed by laboratories in university hospitals (104; 26%), and the private sector (94; 23%). The majority of respondents (i.e., 246; 60%) indicated the use of fibrinogen equivalent unit for expressing D-dimer results, with significant heterogeneities across countries and health care settings. The highest prevalence of laboratories indicated they were using "ng/mL" (139; 34%), followed by "mg/L" (136; 33%), and "\ub5g/L" (73; 18%), with significant heterogeneity across countries but not among different health care settings. Expectedly, the vast majority of laboratories (379; 93%) declared to be using a fixed cutoff rather than an age-adjusted threshold, with no significant heterogeneity across countries and health care settings. The results of this survey attest that at least 28 different combinations of measurement units are currently used to report D-dimer results worldwide, and this evidence underscores the urgent need for more effective international joined efforts aimed to promote a worldwide standardization of D-dimer results reporting

International Council for Standardization in Haematology Recommendations for Hemostasis Critical Values, Tests, and Reporting

This guidance document was prepared on behalf of the International Council for Standardization in Haematology (ICSH), the aim of which is to provide hemostasis-related guidance documents for clinical laboratories. The current ICSH document was developed by an ad hoc committee, comprising an international collection of both clinical and laboratory experts. The purpose of this ICSH document is to provide laboratory guidance for (1) identifying hemostasis (coagulation) tests that have potential patient risk based on analysis, test result, and patient presentations, (2) critical result thresholds, (3) acceptable reporting and documenting mechanisms, and (4) developing laboratory policies. The basis for these recommendations was derived from published data, expert opinion, and good laboratory practice. The committee realizes that regional and local regulations, institutional stakeholders (e.g., physicians, laboratory personnel, hospital managers), and patient types (e.g., adults, pediatric, surgical) will be additional confounders for a given laboratory in generating a critical test list, critical value thresholds, and policy. Nevertheless, we expect this guidance document will be helpful as a framework for local practice. © 2020 BMJ Publishing Group. All rights reserved

Recent guidelines and recommendations for laboratory assessment of the direct oral anticoagulants (DOACs): is there consensus?

A new generation of antithrombotic agents, which are conventionally known as direct oral anticoagulants (DOACs), have recently emerged and are continuing to be developed. These provide direct inhibition of either thrombin (factor IIa; FIIa) or activated factor X (FXa) and currently include dabigatran (FIIa inhibitor) and rivaroxaban, apixaban, and edoxaban (FXa inhibitors). The dogma that DOACs do not require laboratory monitoring is countered by ongoing recognition that laboratory testing for drug effects is needed in many situations. In this review, we summarize the background to establishment of DOACs, assess which tests were found to be useful to screen for or quantitate drug effects/levels, and then review published guidelines/recommendations to assess concordance. In brief, (a) for the anti-FIIa agent dabigatran, the recommended screening assays are activated partial thromboplastin time (APTT) and/or thrombin time (TT), and the quantitative assays (using a dabigatran standard) are dilute TT/direct thrombin inhibitor assay (Hemoclot thrombin inhibitor) or an ecarin-based assay such as the ecarin clot time (ECT); (b) for the anti-FXa agent rivaroxaban, the recommended screening assay is the prothrombin time (PT), but this was not endorsed by all guidelines, and the quantitative assay (using a specific rivaroxaban standard) is an anti-FXa assay; (c) for the anti-FXa agent apixaban, the general insensitivity of PT and APTT prevented most groups from providing recommendation, and instead there was generalized support for direct quantitative assessment using anti-FXa assays and specific apixaban standard; (d) there is insufficient data for other direct anti-FXa agents and limited guidance in the literature

Urgent monitoring of dabigatran plasma levels. Less is sometimes more.

Urgent monitoring of dabigatran plasma levels. Less is sometimes more

Article downloads and citations: Is there any relationship?

[no abstract available

Laboratory hemostasis: milestones in Clinical Chemistry and Laboratory Medicine.

Hemostasis is a delicate, dynamic and intricate system, in which pro- and anti-coagulant forces cooperate for either maintaining blood fluidity under normal conditions, or else will prompt blood clot generation to limit the bleeding when the integrity of blood vessels is jeopardized. Excessive prevalence of anticoagulant forces leads to hemorrhage, whereas excessive activation of procoagulant forces triggers excessive coagulation and thrombosis. The hemostasis laboratory performs a variety of first, second and third line tests, and plays a pivotal role in diagnostic and monitoring of most hemostasis disturbances. Since the leading targets of Clinical Chemistry and Laboratory Medicine include promotion of progress in fundamental and applied research, along with publication of guidelines and recommendations in laboratory diagnostics, this journal is an ideal source of information on current developments in the laboratory technology of hemostasis, and this article is aimed to celebrate some of the most important and popular articles ever published by the journal in the filed of laboratory hemostasis

Massive posttraumatic bleeding: epidemiology, causes, clinical features, and therapeutic management.

Bleeding typically results as a consequence of derangements of primary hemostasis, secondary hemostasis, or both, and can be dramatically amplified by the presence of other predisposing conditions, especially inherited bleeding disorders. Life-threatening hemorrhages are, however, almost exclusively caused by penetrating wounds, blunt traumas of chest and abdomen, suicide attempts, amputations, bone fractures with concomitant injury to internal organs and blood vessels, and shearing forces from sudden rotation, violent flexion, extension, or deceleration injuries. The pathogenesis of posttraumatic bleeding is complex and multifaceted. The most dramatic phenomenon that always accompanies major hemorrhages is the abrupt and considerable loss of intravascular volume, that further leads to hypovolemic shock, also known as hemorrhagic shock, culminating with peripheral ischemia, especially in those tissues where oxygen delivery is more critical (i.e., central nervous system and myocardium). The mortality rate of severe posttraumatic bleeding can be as high as 50%, especially when an appropriate treatment is not established in a timely manner. The damage control sequence basically entails a four-step approach including damage control surgery, damage control resuscitation with fluid restoration, and hemocomponents administration, as well as correction of the coagulopathy with platelets, antifibrinolytic (e.g., tranexamic acid), and/or procoagulant agents such as fresh frozen plasma, prothrombin complex concentrate, or recombinant-activated Factor VII

Technical Evaluation of the Novel Preanalytical Module on Instrumentation Laboratory ACL TOP: Advancing Automation in Hemostasis Testing.

Automation in hemostasis testing is entering an exciting and unprecedented phase. This study was planned to assess the performance of the new preanalytical module on the hemostasis testing system Instrumentation Laboratory ACL TOP. The evaluation included interference studies to define reliable thresholds for rejecting samples with significant concentrations of interfering substances; within-run imprecision studies of plasma indices on four different interference degrees for each index; comparison studies with reference measures of hemolysis index, bilirubin, and triglycerides on clinical chemistry analyzers; and calculation of turnaround time with and without automatic performance of preanalytical check. The upper limits for sample rejection according to our interference studies were 3.6 g/L for hemoglobin, 13.6 mg/dL for bilirubin, and 1454 mg/dL for triglycerides. We found optimal precision for all indices (0.6% to 3.1% at clinically relevant thresholds) and highly significant correlations with reference measures on clinical chemistry analyzers (from 0.985 to 0.998). The limited increase of turnaround time (i.e., +3% and +5% with or without cap-piercing), coupled with no adjunctive costs over performance of normal coagulation assays, contribute to make the automatic check of plasma indices on ACL TOP a reliable and practical approach for improving testing quality and safeguarding patient safety