Description:

ChromogenixCoatest®APC™ResistanceControlPlasmaLevel2 isforcontrolofaccuracywhenusingChromogenixCoatest®ActivatedProteinCResistanceassaykits.

Composition:

Packaging: ChromogenixCoatest®APCControlPlasmaLevel2isalyophilizedpreparationofcitratedhumanplasma.

StorageandStABIlity:hoursat20-25°C,6hoursat2-8°Cor3monthsat-20°Corbelow.Thefrozenreagentshouldbethawedat37°Candgentlymixedbeforeuse.Donotrefreeze.

Procedure:

Reconstituteeachvialwith1.0mLdeionizedwater,filteredthrough0.22µmorNCCLStypeIIwater1.Allowtostandatroomtemperaturefor30minutes.Swirlgentlybeforeuse.

Differentclottingtimeswillbeobtainedwithdifferenttypesofinstrumentsdependingontheclotdetectionprinciple.

Background:

ProteinC,apartofthenaturalanticoagulantsystem,isavitaminK-dependentproteinzymogen(molecularweight=62,000da)thatissynthesizedintheliverandcirculatesataplasmaconcentrationofapproximately5mcg/mL.ProteinCisactivatedtoactivatedproteinC(APC)viaproteolyticcleavagebythrombinboundtothrombomodulin,anendothelialcellsurfacemembraneprotein.APCdownregulatestheprocoagulantsystembyproteolyticallyinactivatingprocoagulantfactorsVaandVIIIa.ProteinS,anothervitaminK-dependentcoagulationprotein,catalyzesAPCinactivationoffactorsVaandVIIIa.APCinteractswithandproteolysesfactorsV/VaandVIII/VIIIaatspecificAPCbindingandcleavagesites,respectively.ResistancetoactivatedproteinC(APCresistance)isatermusedtodescribeabnormalresistanceofhumanplasmatotheanticoagulanteffectsofhumanAPC.APCresistanceischaracterizedbyareducedanticoagulantresponseofpatientplasmaafteraddingastandardamountofAPC.Forthisassay,theactivatedpartialthromboplastintimeclottingtestfailstoprolongsignificantlyaftertheadditionofAPC.

ThevastmajorityofindividualswithfamilialAPCresistancehaveaspecificpointmutationintheprocoagulantfactorVgene(1691G-A,factorVLeiden)encodingforaglutamine(Q)substitutionforarginine(R)-506intheheavychainoffactorV(factorVR506Q).ThisaminoacidchangealtersanAPCcleavagesiteonfactorVsuchthatfactorV/VaispartiallyresistanttoinactivationbyAPC.ThecarrierfrequencyforthefactorVLeidenmutationvariesdependingonthepopulation.

TheChromogenixCoatest®APC™ResistanceControlPlasmascanbeusedwithCoatestAPCResistancecat#K823120(823120),CoatestAPCResistanceVcat#K823120(823120)andCoatestAPCResistanceVScat#K823138(823138)kits.