We studied activated protein C sensitivity ratio (APC-SR), factors V and VIII activity and von Willebrand antigen in control women, women using oral contraceptives, and pregnant women at delivery. The mean APC-SR of 2.4 in pregnant women was significantly lower than the mean APC-SR value of 3.5 for both the other groups and 45% of pregnant women had a ratio below the 5th percentile of the control group. None of them carried the R506-->Q mutation. This decreased ratio at delivery appeared to be connected, at least in part, with increased VIII activity. Thus, APC-SR at delivery should not be used to detect APC resistance.
Activated protein C resistance ratio (APC-Rr), factor VIIIC (FVIIIC) and plasma fibrinogen levels were studied in patients with inflammatory disease. The patient mean APC-Rr was significantly lower than in the control group. This decreased ratio in inflammatory diseases appeared to be connected with increased FVIIIC. Moreover, supplementation of plasmas with purified factor VIII decreased the APC-Rr in plasma from both groups, and suppressed the difference between groups. These data suggest that factor VIIIa and factor Va compete for protein C-catalysed cleavage. Ratios were identical in both groups when FVIIIC level was lowered by dilution in factor V deficient plasma.
In Europe, the ISO 15 189 standard requires uncertainty of measurement to be calculated for all measurands. We calculated the analytical imprecision and bias of our factor VIII coagulometric assay method between 5 and 80 U/dl, using plasmas expected to be at 5, 30 and 80 U/dl of factor VIII. We implemented Meijer et al.'s [Clin Chem 2002; 48:1011-1015] long-term coefficient of variance, bias and also uncertainty of measurement calculations. Assessments used reference plasma diluted in severe haemophilic plasma, in immunodepleted factor VIII-deficient plasma and in bovine serum albumin. With plasmas diluted in severe haemophilic and immunodepleted factor VIII-deficient plasma, calculated uncertainty of measurement was 10% compared with 15% (i.e., 50% greater) for plasma diluted in albumin buffer or as calculated from European Concerted Action on Thrombosis consensus values. It is thus important to approximate the patient sample matrix to obtain as precise an estimation as possible of assay method uncertainty of measurement.
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