Critical pre-examination variables in the hemostasis laboratory and their quality indicators

doi:10.1016/j.clinbiochem.2016.08.022

Clinical Biochemistry

Volume 49, Issue 18, December 2016, Pages 1315-1320

https://doi.org/10.1016/j.clinbiochem.2016.08.022 Get rights and content

Highlights

•
Laboratory QMS must include a means to identify potential pre-examination errors.
•
The majority of laboratory errors occur in the pre-examination phase of laboratory testing.
•
Common errors include: improper whole blood to anticoagulant ratio and incorrect sample matrix.
•
Incorporation of pre-examination phase quality indicators into a laboratory QMS is recommended.

Abstract

The total testing process comprises a number of phases of laboratory testing, which can be broadly considered as comprising pre-examination, examination and post-examination activities. Although each phase is crucial to providing accurate and meaningful laboratory results, the pre-examination phase of testing is where most laboratory errors currently occur, and thus requires special attention. The activities in this phase include sample collection, handling, transportation, processing and storage, which are frequently outside the control of the laboratory performing the tests. Samples for hemostasis testing are particularly vulnerable to pre-analytical variables, which may ultimately lead to inappropriate test results. We outline here several strategies to mitigate potential problems in the pre-examination phase. We also recommend the implementation of several processes to reduce errors.

Introduction

Pre-examination, examination and post-examination phases of laboratory testing, together comprise the total testing process. Each phase is crucial to providing accurate and meaningful laboratory results. For this reason, each phase must be included in a laboratory total quality management system (QMS) [1]. The implementation of QMS has led to a considerable decrease in analytical errors over the years due to the introduction of effective internal quality control (IQC) systems, external quality assessment (ECA) or proficiency testing programs and well established, automated test methodologies. Greater focus though is still needed in processes associated with the pre-examination phase of testing. Most laboratory errors currently occur in the pre-examination phase, which includes sample collection, handling, transportation, processing and storage [2], [3]. These steps are largely manual, complex in nature, and often outside the control of the laboratory performing the tests. Moreover, samples for hemostasis testing are especially vulnerable to pre-analytical variables compared to samples for clinical chemistry or clinical immunology testing due to the nature of the biological specimen (i.e., citrated plasma) [4]. For these reasons, the pre-examination phase is especially vulnerable to errors, which furthermore tend to be random (or unpredictable). Notably, the laboratory is often unaware that the adverse event has occurred, which makes the control of the entire process even more challenging. To perceive that samples may be affected by a pre-analytical variable, laboratory professionals must be knowledgeable of their likelihood, suspicious of their presence and investigate such possibilities. However, it cannot always be discerned when unsuitable samples have been received in the laboratory, as such samples are not always evidently (i.e., visually) different from appropriate samples [5]. As most pre-analytical errors are preventable, to be proactive against this risk is pivotal. A deepened understanding of the necessary critical steps in the pre-examination phase and the impact of deviations is essential to avoiding these errors. Laboratory QMS must include a means to identify potential pre-examination errors, estimate their impact, determine error frequency and put corrective actions in place whenever possible. This process must also include implementation of written guidelines for blood collection, processing, storage, and transport, along with training of health care professionals on these processes, as well as impressing the importance of following these guidelines [6]. In addition, the activity of specimen collection, processing and transport should be audited periodically to determine if procedures are both correct and followed. The identification and monitoring of errors and non-conformities in the pre-analytical phase can be accomplished by the establishment and use of valid quality indicators [7]. A good quality assessment program should set goals for reduced number of errors and monitor improvements in this phase. In addition, EQA programs should develop schemes to evaluate this phase of testing, as currently such proficiency testing is largely lacking. This review will highlight important variables in the pre-examination phase crucial to hemostasis testing and correlate these to possible quality indicators.

Section snippets

Sample collection, processing, transportation and storage

While appropriate sample collection, processing, transportation and storage is critical to ensure reporting of appropriate and accurate test results, these processes are often poorly applied, unless the important components of the many activities in this phase are thoughtfully appreciated, but also appropriate training and written procedures are put in place and periodically monitored. A summary of common sample processing errors and their impact can be found in Table 1. The characteristics of

Conclusion

The majority of laboratory errors are associated with the pre-examination phase of laboratory testing [53]. Some of the most common errors attributed to this phase include: patient misidentification, improper whole blood to anticoagulant ratio and collection into the incorrect sample matrix. Therefore, the incorporation of pre-examination phase quality indicators into a laboratory QMS for both routine and research testing [54], as well as monitoring these indicators in a regular basis is

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Citation Excerpt :
Laboratory testing is still an important tool for diagnosing patients, developing a treatment plan and monitoring medication, so these tests must be performed under high quality standards. Laboratory diagnostics consist of 3 equally important phases; the pre-analytical, analytical and post-analytical phase, however, most errors occur in the pre-analytical phase [3–8]. The pre-analytical steps, such as patient preparation, sample collection, specimen acquisition, handling and storage of blood samples, all attribute to the occurrence of pre-analytical errors.
Several routine coagulation tests have been developed to give insight in the coagulation pathway. The laboratory diagnostical process consists of 3 phases, the pre-analytical, analytical and post-analytical phase; however, the pre-analytical phase is most sensitive to errors. The amount of time blood is stored, can affect the measurements of these coagulation tests and result in an incorrect conclusion. Therefore, we performed experiments to determine the maximal storage time, centrifuged blood samples can be reliably measured.
Citrated whole blood from hospital patients, who were tested for routine coagulation, was collected in 2.7 mL citrate tubes. These whole blood samples were centrifuged and the plasma was stored on top of the cell pellet at room temperature. After 2 h, 4 h, 6 h, 12 h and 24 h, the prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen concentration, antithrombin activity, D-dimer concentration and thrombin time were measured using Sysmex CS2100 coagulation analysers.
Analytical evaluation of routine coagulation tests resulted in various significant differences and large variations between the various time intervals. Our results indicated that the PT and INR can be measured up till 24 h of storage. Centrifuged blood for measuring the fibrinogen concentration, antithrombin activity, D-dimer concentration and thrombin time can be stored up to 4 h, while 2 h of storage might already be too long for obtaining reliable aPTT measurements.
Proposal for standardized preanalytical and analytical conditions for measuring thrombin generation in hemophilia: communication from the SSC of the ISTH
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Undue clotting is conventionally defined as a coagulation process occurring in blood tubes containing anticoagulants (e.g., sodium citrate, lithium-heparin, EDTA), and presenting with micro or macro-visible clots. A coagulated sample is an overwhelming problem for hematological analysis (i.e., blood cell count, lymphocyte characterization, etc.) and clotting tests [27]. In the latter case, in particular, coagulation factors must be kept in the form of zymogen for producing reliable results of testing.
The extra-analytical phases of the total testing process have substantial impact on managed care, as well as an inherent high risk of vulnerability to errors which is often greater than that of the analytical phase. The collection of biological samples is a crucial preanalytical activity. Problems or errors occurring shortly before, or soon after, this preanalytical step may impair sample quality and characteristics, or else modify the final results of testing.
The standardization of fasting requirements, rest, patient position and psychological state of the patient are therefore crucial for mitigating the impact of preanalytical variability. Moreover, the quality of materials used for collecting specimens, along with their compatibility, can guarantee sample quality and persistence of chemical and physical characteristics of the analytes over time, so safeguarding the reliability of testing. Appropriate techniques and sampling procedures are effective to prevent problems such as hemolysis, undue clotting in the blood tube, draw of insufficient sample volume and modification of analyte concentration. An accurate identification of both patient and blood samples is a key priority as for other healthcare activities. Good laboratory practice and appropriate training of operators, by specifically targeting collection of biological samples, blood in particular, may greatly improve this issue, thus lowering the risk of errors and their adverse clinical consequences.
The implementation of a simple and rapid check-list, including verification of blood collection devices, patient preparation and sampling techniques, was found to be effective for enhancing sample quality and reducing some preanalytical errors associated with these procedures. The use of this tool, along with implementation of objective and standardized systems for detecting non-conformities related to unsuitable samples, can be helpful for standardizing preanalytical activities and improving the quality of laboratory diagnostics, ultimately helping to reaffirm a “preanalytical” culture founded on knowledge and real risk perception.
Managing the patient identification crisis in healthcare and laboratory medicine
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The main drawbacks of labeling blood tubes before venipuncture include the fact that large labels may partially or completely hinder the visibility of the blood inside the tube, so that it cannot be established whether the appropriate filling volume has been achieved, or else the need to detach the labels from the former tubes or print new labels in the case blood drawing had been unsuccessful (e.g., vein missed, tubes with insufficient vacuum). The former issue may be especially critical for those tests needing fulfilment of an accurate ratio between blood and additive (e.g., hemostasis and hematological testing) [42]. On the other hand, labeling collection tubes before blood drawing carries also some important advantages, which include greater assurance of collecting all the correct blood tubes needed for testing (when blood tubes are labeled after blood drawing the phlebotomist may realize that one or more necessary tubes were not filled or that a wrong tube was drawn), the possibility to double check patient and tube identity both before and after blood drawing, and identity check always achievable in the presence of the patient, as for all currently available guidelines (when blood tubes are labeled after venipuncture the patient may be no longer available, especially in the case of outpatients) [18,38,39].
Identification errors have emerged as critical issues in health care, as testified by the ample scientific literature on this argument. Despite available evidence suggesting that the frequency of misidentification in vitro laboratory diagnostic testing may be relatively low compared to that of other laboratory errors (i.e., usually comprised between 0.01 and 0.1% of all specimens received), the potential adverse consequences remain particularly worrying, wherein 10–20% of these errors not only would translate into serious harm for the patient, but may also erode considerable human and economic resources, so that the entire healthcare system should be re-engineered to act proactively and limiting the burden of this important problem. The most important paradigms for reducing the chance of misidentification in healthcare entail the widespread use of more than two unique patient identifiers, the accurate education and training of healthcare personnel, the delivery of more resources for patient safety (i.e., implementation of safer technological tools), and the use of customized solutions according to local organization and resources. Moreover, after weighing advantages and drawbacks, labeling blood collection tubes before and not after venipuncture may be considered a safer practice for safeguarding patient safety and optimizing phlebotomist's activity.
Explaining and reducing the variation in inter-laboratory reported values for International Normalised Ratio
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Pre-analytical issues are now generally known to comprise a large proportion of errors in haemostasis testing, although to our knowledge, this has not been considered substantially within the context of ISI and MNPT, and thus INR resulting. Most known pre-analytical issues arise due to sample collection (e.g., incorrect sample collected, such as wrong patient, tube or anticoagulant), transport (e.g., poor storage temperature) and processing (e.g., inappropriate centrifugation, storage temperature and time to perform the test) [12,13]. However, another important potential source of pre-analytical error for the INR is the incorrect assignment of the ISI and MNPT, due to incorrect values being determined or otherwise used by the laboratory.
Monitoring of vitamin K antagonist (VKA) therapy is usually achieved using the International Normalised Ratio (INR). However, despite international standardisation, there remains considerable concern regarding ongoing high levels of inter-laboratory variation, as generated by different laboratories using the same homogeneous plasma sample. Notably, significant discrepancies continue to be evidenced in external quality assessment (EQA) environments, prompting additional investigations to determine causes and to identify potential inconsistencies of practice.
Several investigations involving all 580 participants in the Haemostasis program of the RCPAQAP Haematology were undertaken from 2009 to 2016, gathering details of methodology, and comparative assessments of INR values differentially obtained directly from participants versus values calculated using raw data for PT, ISI and MNPT provided by the same participants.
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Critical pre-examination variables in the hemostasis laboratory and their quality indicators

Highlights

Abstract

Introduction

Section snippets

Sample collection, processing, transportation and storage

Conclusion

J. Thromb. Haemost.

Chest

Clin. Chim. Acta

J. Thromb. Haemost.

Pathology

J. Lab. Autom.

J. Thromb. Haemost.

Quality management system: a model for laboratory services; approved guideline

Preanalytical and postanalytical variables: the leading causes of diagnostic error in haemostasis?

Semin. Thromb. Hemost.

A review of medical errors in laboratory diagnostics and where we are today

Lab. Med.

Quality standards for specimen collection in coagulation testing

Semin. Thromb. Hemost.

Preanalytical variables in coagulation testing associated with diagnostic errors in hemostasis

Lab. Med.

Training and competence assessment; approved guideline

Harmonization of preanalytical quality indicators

Biochem. Med.

So you're going to collect a blood specimen

Collection, transport, and processing of blood specimens for testing plasma-based coagulation assays and molecular hemostasis assays: approved guideline

Identification errors involving clinical laboratories: a College of American Pathologists Q-probe study of patient and specimen identification errors at 120 institutions

Arch. Pathol. Lab. Med.

Effect of 3.2% vs 3.8% sodium citrate concentration on routine coagulation testing

Am. J. Clin. Pathol.

Procedures for the collection of diagnostic blood specimens by venipuncture. approved standard

Effect of carryover of clot activators on coagulation tests during phlebotomy

Am. J. Clin. Pathol.

Collection of blood specimens by venipuncture for plasma-based coagulation assays: necessity of a discard tube

Am. J. Clin. Pathol.

Discard tubes are sometimes necessary when drawing samples for hemostasis

Am. J. Clin. Pathol.

Minimum specimen volume requirements for routine coagulation testing. Dependence on citrate concentration

Am. J. Clin. Pathol.

Short-term venous stasis influences routine coagulation testing

Blood Coagul. Fibrinolysis

Is phlebotomy part of the dark side in the clinical laboratory struggle for quality?

Lab. Med.

Scaling of hemolysis in needles and catheters

Ann. Biomed. Eng.

Stability of coagulation assays performed in plasma from citrated whole blood transported at ambient temperature

Thromb. Haemost.

Influence of storage time and temperature on International Normalized Ratio (INR) levels and plasma activities of vitamin K dependent clotting factors

Hematology