Laboratory Diagnosis of Activated Protein C Resistance and Factor V Leiden

Abstract

The factor V Leiden (FVL) polymorphism is known as the most common inherited risk factor for venous thrombosis. In turn, FVL is the leading cause of an activated protein C resistance (APCR) phenotype, in which the addition of exogenous activated protein C to plasma does not result in the expected anticoagulant effect. In the routine laboratory approach to the formal diagnosis of FVL, an initial positive screening plasma-based method for APCR is often performed, and only if needed, this is followed by a confirmatory DNA-based assay for FVL. Multiple methods with accepted sensitivity and specificity for determining an APCR/FVL phenotype are commonly categorized into two separate groups: (1) screening plasma-based assays, including qualitative functional clot-based assays, for APCR, and (2) confirmatory DNA-based molecular assays, entailing several tests and platforms, including polymerase chain reaction-based and non-PCR-based techniques, for FVL. This review will describe the methodological aspects of each laboratory test and prepare suggestions on the indication of APCR and FVL testing and method selection.

Laboratory Diagnostics for Thrombosis and Hemostasis Testing—Part 3

“…2 Specific issue content follows, with the first review of this issue from Bahraini et al, exploring laboratory diagnosis of activated protein C resistance and factor V Leiden; this review details technical aspects of the methodologies used, emphasized in informative figures, as well as approaches for resolving challenges such as genotype-phenotype discrepancy. 3 In the next manuscript, Reilly-Stitt and colleagues address internal quality control in hemostasis assays, where they report results of survey data from participants in the UKNE-QAS (United Kingdom National External Quality Assessment Scheme) for Blood Coagulation. 4 The survey questions and responses help the reader understand best practices, but also highlight the between-laboratory variability that exists and opportunities for improvement.…”

Celebrating 50 Years of Seminars in Thrombosis and Hemostasis—Part III

“…The venom entered a new chapter when it started to be used to investigate hemostasis in research laboratories, culminating in current use in a variety of laboratory assaysmost notable, the dilute RVV time, [15][16][17] as used to investigate lupus anticoagulant, but also within the activated protein C resistance landscape. 18 Also notable is that RVV has had an interesting comeback to clinical medicine this year. A group from China engineered Staidson protein-0601 (STSP-0601), a factor X activator from RVV and showed that it has the potential to be used as a hemostatic treatment of patients with hemophilia and inhibitors.…”