College of American Pathologists
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CAP Today



Coagulation quality assessment review

July 2010

The CAP has 30 official liaisons to various organizations who attend scientific meetings or designate others to do so. They report to the Standards Committee, which reports to the Council on Scientific Affairs. We began last month to publish on a periodic basis bits of what the CAP’s outbound liaisons hear and see in their liaison roles.

Elizabeth M. Van Cott, MD
Charles S. Eby, MD

UK NEQAS for Coagulation is part of the United Kingdom National External Quality Assessment Service, an organization founded in 1969 that coordinates a network of “schemes” (external challenges designed by experts within the various professions) whose primary aim is educational (participants with persistent problems are offered advice and assistance). UK NEQAS for Coagulation organizes an annual meeting for participants, and the CAP provides a liaison to this meeting.

At last year’s gathering, all of the presentations were informative and timely, but there were a few highlights. Dianne Kitchen, a fellow of the Institute for Biomedical Sciences who is with UK NEQAS for Coagulation, reviewed proficiency testing product evaluations for a variety of point-of-care hemostasis tests, including prothrombin time, activated clotting time, and D-dimer. This was instructive for current and future CAP whole blood Surveys. NEQAS’ evaluation of a proposed new proficiency test for International Normalized Ratio using point-of-care testing for prothrombin time revealed an interesting phenomenon. All of the volunteer laboratories observed significantly higher imprecision for the second sample. Suspecting that labs were reconstituting both specimens and then testing them sequentially, NEQAS altered the instructions to require sequential reconstitution followed by immediate testing and found that both samples showed the same low imprecision.

Marco Cattaneo, MD, of the University of Milano in Italy, reviewed in vitro methods to assess platelet function, including a patient’s response to aspirin and clopidogrel (Plavix) therapy. He favors urinary thromboxane B2 levels for monitoring aspirin inhibition, and flow cytometry measurement of vasodilator stimulated phosphoprotein (VASP) phosphorylation to monitor clopidogrel inhibition of platelet ADP receptor P2Y12. However, he concluded that laboratory monitoring to determine if patients are “resistant” to aspirin or clopidogrel remains an active research topic and should not be introduced at this time for routine patient management.

Steve Kitchen, PhD, of the Royal Hallamshire Hospital in England, and David Keeling, MD, of Churchill Hospital in England, conducted a spirited and humorous debate on determining reference intervals for hemostasis tests. Dr. Kitchen, who stressed that reference intervals are guidelines rather than definitive limits, defended local calculation based on a small sample size of healthy adults (25 to 30 subjects). Dr. Keeling, who noted that many hemostasis tests (such as factor assays) do not require definitive reference ranges, countered that the uncertainty (95 percent confidence interval) surrounding reference interval limits is very large until a sample size of at least 100 is obtained. A majority of attendees favored local reference intervals before the debate; a second show of hands after the debate showed a small shift toward adopting external reference intervals, but supporters of local ranges were still in the majority.

Finally, Dorothy Funk, MD (a member of the CAP Coagulation Resource Committee), of Esoterix Inc., talked about how to evaluate prolonged screening coagulation tests. She reviewed clinical signs and symptoms associated with hemostasis disorders, congenital (hemophilia, von Willebrand disease) and acquired (lupus anticoagulant, specific factor inhibitors) causes of prolonged activated partial thromboplastin time, and causes of prolonged PT and thrombin time. Dr. Funk concluded with a discussion of the different approaches to performing mixing studies for a prolonged aPTT. She emphasized that interpretation remains an art, since minimally prolonged aPTTs may correct completely despite the presence of a weak inhibitor, and markedly prolonged aPTTs due to severe deficiency of an intrinsic pathway factor may incompletely correct.

Dr. Van Cott, a member of the CAP Standards Committee, is in the Department of Pathology, Massachusetts General Hospital. Dr. Eby, of Washington University School of Medicine, is chair of the CAP Coagulation Resource Committee and was the CAP’s liaison to the 2009 meeting of UK NEQAS for Coagulation.