The APTTCan Monitor for Increased Thrombotic Risk.
Authors: Mengshol Sarah , Lefkowitz Jerry B. 
Published: October 2019

This laboratory has been interested in the significance of short activated partial thromboplastin times (APTT) and has published work suggesting that short APTTs are associated with an increased thrombotic risk (Am J Clin Path113:123–127, 2000). Since our original publication, other workers have shown that increased levels of coagulation factor II (FII), factor VIII (FVIII), factor IX (FIX), or factor XI (FXI) are associated with an increased risk of thrombosis. Therefore, this study was designed to determine if elevated levels of FII, FVIII, FIX, or FXI might predictably result in a shortened APTT. Using a set of 30 normal plasma samples, APTT reference ranges were determined on a Stago ST4 analyzer for the following APTT reagents--Stago PTTA5, Dade Behring Actin FSL, Hemosil Synthasil, and Biomèrieux Platelin L. For this study, a short APTT was defined as being below the value of the reference range lower limit. FII, FVIII, FIX, and FXI levels were determined on a pool normal plasma in the clinical laboratory and these levels were used as a baseline to add purified factor to increase a factor activity level. The amount of factor level increase was based upon literature reports of factor levels associated with an increased thrombotic risk. A normal baseline APTT control was run for each set of assays. The coefficient of variation for control APTTs ranged from 1%–3.4% and seemed to be dependent on the specific APTT reagent. Differences were noted in the sensitivity between different APTT reagents to elevated factor levels, but all APTT reagents demonstrated the same overall trend to higher factor levels. In addition to raising individual factor concentrations, several plasmas were spiked with combinations of FVIII and FIX or FVIII, FIX, and FXI. Increasing concentrations of FVIII showed a significant decrease in the APTT, up to 3.5 seconds below the lower limit reference range at 2.2 units (U)/mL. Increasing [FIX] was associated with a trend towards a shorter APTT, but no decrease below the lower limit APTT reference range was found even with a [FIX] of 1.8 U/mL. When compared to control APTTs, increases in [FXI]<1.2 U/mL were associated with a shortening of the APTT but with [FXI]>1.4 U/ml the APTT prolonged compared to control. In no case did increases in FXI level cause the APTT to be outside of the reference range. Increasing concentrations of FII were associated with prolongations of the APTT compared to control. At the highest [FII] of 1.9 U/mL 3 of the 4 APTT reagents gave results up to 1.4 seconds above the upper limit of the reference range. When both [FVIII] and [FIX] were increased, minimal difference was seen in the APTT compared to only increased [FVIII]; however, when the concentrations of FVIII, FIX, and FXI were increased, the APTT was shortened up to 5.7 sec below the lower APTT reference range when compared to samples which had only a single factor concentration raised. These data show an association with increasing [FVIII] in plasma and shortening of the APTT. They also show that increased [FVIII] in combination with elevated levels of FIX and FXI cause a significant shortening of the APTT that exceeds a simple additive effect. These findings suggest that the APTT could be used as a screening test for elevated plasma coagulation factors, especially elevated [FVIII] which has been previously associated with an increased risk of thrombosis.