Effect of platelet phospholipid exposure on activated protein C resistance: implications for thrombophilia screening

Abstract
The effect of platelet contamination and freeze‐thawing on the activated protein C sensitivity ratio (APCsr) was determined. With increasing platelet count there was a progressive reduction in the ratio. Filtration of samples through a 0.2 μm filter before or after freeze‐thawing abolished the development of resistance to the addition of activated protein C indicating that the phenomenon is due to the presence of a particulate factor. Contamination of normal plasma with platelets from a patient with homozygous factor V (FV) deficiency was also associated with the same development of resistance to activated protein C, indicating that the phenomenon was not due to exposure of platelet‐derived factor V that might be inaccessible to APC.82% (96/117) of FVQ506 and 32% (138/430) of FV R506 individuals had APC resistance on analysis of unfiltered plasma. However, 85% (42/50) of FVQ506 individuals had APC resistance on analysis of filtered plasma, whilst only 1/50 FV R506 individuals had APC resistance after filtration. For the purpose of identifying individuals at increased risk of venous thromboembolism due to the presence of the FVQ506 and associated APC resistance a PCR‐based genotypic analysis is recommended.

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