[2014] High Factor VIII Can Falsely Increase Factor IX and XI Levels Due to the Shortening of aPTT

Rabia Shafi, Vadim Kostousov, Kim Nguyen, Shiu-Ki Rocky Hui, Jun Teruya. Baylor College of Medicine, Houston, TX

Background: The acute phase response is followed by an elevation of proteins in the plasma, including coagulation factor VIII (FVIII) levels. High FVIII levels cause a shortening of the activated partial thromboplastin time (aPTT), and may also affect the measurement of aPTT-based coagulation factor levels, including those of factors IX (FIX) and XI (FXI). This may mask a deficiency of these factors, a situation which can lead to hazardous bleeding risks. The purpose of this study is to determine if high FVIII levels will affect the measurement of FIX and FXI during the acute phase response.
Design: Testing samples with mild deficiency were prepared from citrated FIX and FXI deficient plasmas mixed with normal pooled plasma. Then recombinant FVIII was added in order to increase FVIII activity by 100; 300 and 500% from baseline. FIX, FXI, FVIII and aPTT were measured by a coagulation analyzer using commercially available reagents. All experiments and measurements were run in triplicate and data are reported as mean ± SD. Statistical analysis was performed using ANOVA test and significance was set up at p<0.05.
Results: Elevated FVIII activity in plasma significantly shortened aPTT. Although the FIX and FXI levels were not significantly changed, the FIX level was overestimated by 1%, and FXI level by 0.8% in average with each +100% of FVIII increment.

Factor IX Deficient Plasma
Factor VIII LevelsFVIII,%FIX,%aPTT,sec
Baseline Level104+/-720+/-636.3+/-1.7
+ 100%199+/-721+/-533.5+/-1.3
+ 300%428+/-724+/-631.0+/-1.2
+ 500%655+/-3326+/-429.5+/-1.2

Factor XI Deficient Plasma
Factor VIII LevelsFVIII, %FXI,%aPTT,sec
Baseline Level119+/-415+/-437.5+/-1.7
+ 100%212+/-715+/-434.7+/-1.4
+ 300%415+/-2417+/-331.7+/-1.7
+ 500%630+/-2319+/-330.5+/-1.5

Conclusions: Elevated FVIII levels cause a meaningful shortening of the aPTT that is associated with a mild increase of FIX and FXI activity. Further studies are warranted to evaluate if high FVIII levels compromise these factor activity measurements in cases of severe factor deficiency.
Category: Quality Assurance

Tuesday, March 5, 2013 9:30 AM

Poster Session III # 301, Tuesday Morning


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