title: Maximising the diagnostic potential of APTT-based screening assays for activated protein C resistance.
abstract: BACKGROUND
  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.
authors: Department of Haemostasis and Thrombosis, Viapath Analytics, Guy's & St. Thomas' Hospitals, London, UK.
authors: G W
authors: GW
authors: Moore
authors: Department of Haemostasis and Thrombosis, Viapath Analytics, Guy's & St. Thomas' Hospitals, London, UK.
authors: E
authors: E
authors: Chege
authors: Department of Haemostasis and Thrombosis, Viapath Analytics, Guy's & St. Thomas' Hospitals, London, UK.
authors: A P
authors: AP
authors: Culhane
authors: Department of Haemostasis and Thrombosis, Viapath Analytics, Guy's & St. Thomas' Hospitals, London, UK.|Centre for Haemostasis and Thrombosis, Guy's & St. Thomas' Hospitals, London, UK.
authors: B J
authors: BJ
authors: Hunt
mesh_terms: D020016:Activated Protein C Resistance / Q000097:blood* / Q000175:diagnosis*; D001777:Blood Coagulation; D001780:Blood Coagulation Tests; D005260:Female; D006801:Humans; D008297:Male; D010314:Partial Thromboplastin Time
keywords: Activated protein C resistance; factor V Leiden; screening assays; thrombophilia; thrombosis