New Normal Ranges Measuring APC Resistance on a New Coagulation Analyzer (COAG360)

Background: The well-established activated protein C resistance (APC-R) clotting assay, Pefakit APC-R Factor V Leiden (DSM Nutritional Products AG, Branch Pentapharm, Basel, Switzerland), is used to detect an increased resistance of factor V against inactivation by the presence of activated protein C. This resistance is caused by the presence of functional active factor V mutations (e.g factor V Leiden, factor V Cambridge, i.a.). So far control material may give APC-R results between 3.6 and 6.8 for control samples without active factor V polymorphisms (wild-type or non-mutated). This assay fitted to a new generation of coagulation analyzers needs re-evaluation of the expected results of the commercially provided control material (i.e. new reference ranges for the normal control material).

Material and Methods: Heterozygous and wild-type samples for the factor V Leiden (F5 R506Q) polymorphism were tested with Pefakit APC-R Factor V Leiden (DSM Nutritional Products AG, Branch Pentapharm, Basel, Switzerland) on 40 consecutive on two Atellica COAG 360 Systems (Siemens Healthineers, Marburg, Germany).

Results: Homozygous control samples for factor V Leiden give APC-R results of 1.00

Heterozygous control samples for factor V Leiden give APC-R results of 1.70±0.07 and 1.73±0.07, respectively. Wild-type control samples for factor V Leiden give APC-R results of 8.0±0.36 and 8.43±0.33, respectively. Based on stored samples of patients with known non-functional factor V Leiden polymorphisms due to further factor V polymorphisms (i.e. factor V Graz F5 G1718S[1]) an adopted cut-off for normal ranges was be established: APC-R ≥3.8. So far a cut-off ≥3.0 was used to discriminate between wild-type and pathologic APC-R results using the above mentioned APC-R assay on BCS XP coagulation analyzers (Siemens Healthineers, Marburg, Germany). The cut-offs for pathologic results are not affected at all.

Conclusion: Adopting assays on open coagulation analyzers needs adjustment of reference ranges of the available control material and re-adapted cut-offs for correct reporting of patient samples.

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• References

• 1 BJH 2013; A novel factor V mutation causes a normal activated protein C ratio despite the presence of a heterozygous F5 R506Q (factor V Leiden) mutation. Prüller et al.; PMID: 23957718