Lack of rivaroxaban influence on a prothrombinase-based assay for the detection of activated C protein resistance: an Italian ex vivo and in vitro study in normal subjects and factor V Leiden carriers.
BACKGROUND
Activated protein C resistance (APCr) leads to hypercoagulability and is due, often but not exclusively, to Factor V Leiden (FVL). The aim of this study was to assess the ex vivo and in vitro interference of the direct factor Xa inhibitor rivaroxaban (RIV) on a prothrombinase-based assay for APCr detection.


METHODS
An ex vivo study was performed on fresh plasma samples obtained from 44 subjects with FV wild-type and seven with FVL heterozygous, all treated with RIV. An in vitro study was performed on 15 plasma samples (six from normal subjects, six from heterozygous, and three from homozygous FVL carriers, all frozen specimens) spiked with RIV. RIV concentration was evaluated using a chromogenic assay, and APCr was evaluated by a prothrombinase-based assay.


RESULTS
No significant interference of RIV on APCr results obtained by a prothrombinase-based assay was observed for drug concentrations up to 400 ng/mL in FV wild-type and FVL carriers (homozygous and heterozygous). These results were confirmed both ex vivo and in vitro.


CONCLUSIONS
RIV did not significantly interfere with the prothrombinase-based assay used for the assessment of APCr, and this was observed to occur independently of FV status. However, only concentrations up to 400 ng/mL were tested and, therefore, what occurs in the presence of higher doses remains to be investigated.
Trasfusional Deptartment of Venetian District, Ospedale dell'Angelo, Mestre, Venice, Italy.
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http://orcid.org/0000-0002-9272-4211
G
Gessoni
Laboratory Medicine, Ospedale Madonna della Navicella, Chioggia, Venice, Italy.
S
S
Valverde
Cardiology and Intensive Coronary Unit, Ospedale Madonna della Navicella, Chioggia, Venice, Italy.
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L
Valle
Laboratory Medicine, Ospedale Madonna della Navicella, Chioggia, Venice, Italy.
F
F
Gessoni
DASIT SpA, Milan, Italy.
P
P
Caruso
Cardiology and Intensive Coronary Unit, Ospedale Madonna della Navicella, Chioggia, Venice, Italy.
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R
Valle
D020016:Activated Protein C Resistance / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D016903:Drug Monitoring; D005165:Factor V / Q000235:genetics*; D005166:Factor V Deficiency / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007558:Italy; D008297:Male; D000069552:Rivaroxaban / Q000494:pharmacology* / Q000627:therapeutic use; D013925:Thromboplastin / Q000378:metabolism*
C095381:factor V Leiden; D005165:Factor V; D013925:Thromboplastin; D000069552:Rivaroxaban
APC resistance; factor V Leiden; prothrombinase-based assay; rivaroxaban