Should APTT become part of thrombophilia screening?

This first and perhaps most important aspect is that the occasional finding of a prolonged APTT, especially in hospitalized patients, cannot necessarily be attributed to preanalytical problems, whereas APTT values may instead reflect a real ex vivo (sometimes prothrombotic) state. In this context, the question also arises whether we should use the APTT as a screening test to detect elevated levels of coagulation factors (namely FVIII and FIX). The main drawback is that the different reagents used to measure APTT have heterogeneous sensitivity to the concentration of coagulation factors such as FVIII and FIX. Therefore, the detection of shortening (or alternatively prolongations) of clotting times between laboratories may not be readily reproducible, and even a hypothetical “thrombotic risk threshold” would need to be defined locally. The third important aspect relates to the clinical use of this information. In some cases, elevated FVIII levels may be caused by inflammatory diseases, leading to a normalization of FVIII activity (and thus APTT) shortly thereafter. Therefore, repeated measurements at fixed time intervals would be required to clearly determine whether the FVIII elevations are transient or persistent (and thus represent a permanent “risk factor”). The clinical management of elevated FVIII is also an unresolved issue, that would require trials aimed at define whether reductions of elevated FVIII would be associated with a concomitant decrease of the thrombotic risk. To this end, the identification of drugs that are able to lower FVIII without enhancing the risk of bleeding may open interesting therapeutic perspectives.