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Maximising the diagnostic potential of APTT ‐based screening assays for activated protein C resistance
Author(s) -
Moore G. W.,
Chege E.,
Culhane A. P.,
Hunt B. J.
Publication year - 2015
Publication title -
international journal of laboratory hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.705
H-Index - 55
eISSN - 1751-553X
pISSN - 1751-5521
DOI - 10.1111/ijlh.12419
Subject(s) - thrombophilia , protein c , medicine , lupus anticoagulant , clotting time , protein s , thrombin generation , immunology , gastroenterology , coagulation , thrombin , thrombosis , platelet
Summary Introduction Activated protein C resistance ( APC ‐R) due to FV Leiden is the most common hereditary thrombophilia. Rarer FV mutations can also confer APC ‐R, and acquired APC ‐R is encountered in a number of conditions. APC ‐R screening with clotting tests is common, yet they are prone to interferences and elevated baseline clotting times can invalidate testing. Methods APTT ‐based classic APC ‐R ( CAPC ‐R) screening, and modified screening ( MAPC ‐R) employing dilution in FV ‐deficient plasma were performed on an automated analyser. Baseline clotting times and APC ‐R ratios of 1340 patients being screened for hereditary and acquired thrombophilia were assessed for analytical and diagnostic validity. Results Most patients (1117/1340) had normal baseline clotting times, and in 270 of these cases, this was despite the presence of a lupus anticoagulant ( LA ). FV Leiden was genetically confirmed in all patients with reduced CAPC ‐R and MAPC ‐R ratios. A subgroup with normal CAPC ‐R but reduced MAPC ‐R also identified FV Leiden, but also other patients with minimally reduced MAPC ‐R ratios not due to FV Leiden. Reduced CAPC ‐R and normal modified APC ‐R identified possible acquired APC ‐R in 49 patients. LA ‐positive patients with elevated baseline clotting times did not affect distinction between APC ‐R and normality, although therapeutic anticoagulation did invalidate CAPC ‐R, and occasionally MAPC ‐R too. Conclusions Many departments only screen with MAPC ‐R to detect just FV mutations. Concurrent performance of CAPC ‐R and MAPC ‐R increases diagnostic capability by detecting acquired APC ‐R. Elevated baseline clotting times can invalidate APC ‐R ratios, although prolongation by LA alone may not.