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International Workshop on the Standardization of Whole Blood Coagulation Devices

Presented By

The United States Food and Drug Administration
Center for Devices and Radiological Health
and
The College of American Pathologists

The Washington Plaza Hotel
10 Thomas Circle N.W.
Washington, D.C.
20005
Ph:  202-842-1300 Fax: 202-371-9602

August 13, 1999
1:00 PM to 6:00 PM

Introduction

Whole blood clotting assays are employed increasingly in the near-patient testing environment. The calibration of these assays is achieved through a variety of approaches. Consequently, test results between different devices may have limited comparability. Traceability of results to plasma methods may also be variable. Limited correlation between test systems can be problematic, particularly when these devices are used for the monitoring of anticoagulant drugs.

The standardization of whole blood clotting assays is a challenging task. The development of a standard calibration approach requires the broad consensus of industry, government regulators, coagulation experts and end-users.

The International Workshop on the Standardization of Whole Blood Coagulation Devices was held to develop recommendations for standardizing the calibration of whole blood clotting assays. Draft standardization proposals were prepared in advance by workshop presenters specifically for use as a starting point for workshop discussions (see Draft Standardization Proposal). Workshop participants were encouraged to review these documents in advance of the meeting. Comments were also volunteered by a small number of individuals for consideration by participants prior to the workshop date (see Comments Received).

The workshop was well attended by individuals representing the manufacturing industry, coagulationists, clinicians, as well as proficiency testing and standards development organizations. A full transcript of workshop presentations and plenary session discussions is available for review (Transcript of Meeting).

Recommendations were established to guide the development of standardized calibration methods for whole blood clotting assays. These recommendations were presented at the meeting of the International Society on Thrombosis and Haemostasis Scientific Subcommittee on Control of Anticoagulation in Washington, D.C., on August 15, 1999. A summary is provided below under the title of Summary of Workshop Recommendations.

We welcome your comments and questions. Please direct all email correspondence to Dr. Ginette Y. Michaud, of the U.S. Food and Drug Administration at GYM@CDRH.FDA.GOV.

Agenda

Summary of Workshop Recommendations

Presented at the XVII Congress of the ISTH, Subcommittee on Control of Anticoagulation, Part II
Washington, D.C.

August 15, 1999

Presented by
Ginette Y. Michaud, M.D.
US Food and Drug Administration

The US Food and Drug Administration and the College of American Pathologists recently co-sponsored the International Workshop on the Standardization of Whole Blood Coagulation Devices. The meeting was held on the afternoon of August 13, 1999 in Washington, D.C. at the Washington Plaza Hotel.

The focus of the workshop was the calibration of whole blood clotting assays. Whole blood test systems, manufactured by different companies, often give results of limited comparability when testing identical samples of blood. Therefore, the workshop was intended to facilitate discussions on this topic and take a first step towards the establishment of standards for the calibration of these devices.

The workshop was attended by close to one hundred international participants representing a broad cross-section of interested parties. Participants included industry, government regulatory and non-regulatory staff, professional groups, academic researchers, clinicians, standards development organizations, and proficiency testing organizations. Discussions focused on three principal whole blood coagulation assays: the Prothrombin Time, the activated Partial Thromboplastin Time, and the Activated Clotting Time.

Several areas of consensus emerged from workshop discussions. It was determined that the calibration issue is an important one that should be the subject of a standardization effort.

RECOMMENDATIONS:

I. The magnitude of the calibration problem needs to be defined.

II. The concept of harmonization may be more appropriate than calibration because these test systems measure processes rather than distinct analytes.

III. The degree of bias or "miscalibration" considered acceptable, when comparing two different test systems, must be established.

IV. Good clinical outcomes are the priority. The goal of standardization is to obtain comparable patient management regardless of the test system used.

V. A standard should be specific to the test's clinical application (e.g. monitoring of oral anticoagulation therapy).

VI. Calibration standardization should primarily be the responsibility of the manufacturer.

VII. Standardizing the calibration of the whole blood PT test systems may be more easily achieved in view of the current existence of material standards (international reference preparations) and a widely accepted reagent calibration method (ISI calibration according to WHO recommendations). The standardization of the whole blood aPTT and the ACT is likely to be more problematic in view of their multiple clinical uses and the lack of existing standards.

VIII. Whole blood should be considered as a possible matrix for new reference methods. While decades of experience based on plasma test systems should not be abandoned, whole blood methods may more closely mimic physiological coagulation pathways.

IX. Standardization should be accompanied by educational efforts in order to optimize the proper use and interpretation of test results.

A working group is being formed to develop, through a consensus process, a standardized approach for the calibration of whole blood coagulation devices. All individuals willing to participate in this process are invited to send an email to Ginette Y. Michaud, MD of the US Food and Drug Administration at GYM@CDRH.FDA.GOV.

Updated 12/17/99

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