What the Standard APTT Didn’t Tell You - Dynamic Plasma Clotting Parameters Reveal Hypercoagulation.
Authors: Sørensen Benny , Johansen Peter , Christiansen Kirsten , Norengaard Lisbeth , Larsen Ole H. , Ingerslev Jørgen 
Published: April 2020

Abstract
Patients with a history of venous thrombosis have significantly shorter APTTs as compared with healthy references. The clinical feasibility of a short APTT is hindered because only a small number of patients have APTT values actually below the reference interval of healthy individuals. The APTT merely reflects the very early start of fibrin polymerization; however, clot formation is a continuous dynamic process. It may be speculated that additional prognostic information may be obtained from parameters describing the entire profile of the APTT clotting signal. Hence, we have developed algorithms to derive additional dynamic parameters from a continuous APTT plasma clotting signal, including the maximum velocity of fibrin formation (APTT-MaxVel). The aim of the present study was to characterize dynamic APTT profiles from patients with verified venous thrombosis. We hypothesized that the APTT-MaxVel was significantly accelerated in patients with a history of verified venous thrombosis as compared with healthy controls. A total of 46 patients, 19 males and 27 females, with a verified venous thrombosis were enrolled in the study. Fifty-two percentages of patients had a positive thrombophilia risk factor. Patients with antiphospholipid syndrome were not included. In total 89 healthy individuals, 43 males and 46 females, established a reference group. A standard APTT was recorded using platelet poor plasma, Platelin® as test reagent, and a BCT coagulation analyzer. The digital continuous clotting signal was exported and processed in a software program to derive dynamic coagulation parameters. Comparative statistics and un-paired t-tests were adopted to assess differences between groups and multiple linear regression was performed to predict the value of APTT-MaxVel from levels of FVIII:C and fibrinogen. P-values &lt; 0.05 were considered statistical significant. Patients had a significantly more accelerated mean APTT-MaxVel (193.5 x/sec, SD=57, 95%CI: 176.6–210.4) as compared with healthy controls (137.3 x/sec, SD=21, 95%CI: 126.7–143.8). Patients also had a significantly shorter mean APTT (27.2 sec, SD=3.2, 95%CI: 26.3–28.2) than healthy controls (28.5 sec, SD=2.8, 95%CI: 27.9–29.1). Whereas only 1 of 46 (2.2%) patients had a standard APTT below the lower reference interval, 17 of the 46 (37%) patients had an APTT-MaxVel above the upper reference limit. Regression analysis revealed a linear correlation between FVIII:C, level of fibrinogen, and APTT-MaxVel (R2=0.89, p&lt;0.05). Our data suggest that the APTT-MaxVel of fibrin formation represent a more sensitive marker for hypercoagulation in patients with verified venous thrombosis than standard APTT measures. The APTT-MaxVel may reflect the functional importance of both FVIII:C and level of fibrinogen. Additional studies are required to further assess the possible clinical and laboratory relevance of using dynamic parameters to predict risk of recurrent thrombosis.