Effect of platelet phospholipid exposure on activated protein C resistance: implications for thrombophilia screening.
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 microm 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 FVR506 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.
Luddington
R
R
Department of Haematology, Addenbrooke's NHS Trust, Cambridge.
Brown
K
K
Baglin
T
T
D001483:Base Sequence; D001792:Blood Platelets / Q000378:metabolism*; D001796:Blood Protein Disorders / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010743:Phospholipids / Q000378:metabolism*; D011486:Protein C / Q000235:genetics / Q000378:metabolism*; D012680:Sensitivity and Specificity; D013923:Thromboembolism / Q000175:diagnosis* / Q000235:genetics
D010743:Phospholipids; D011486:Protein C