PB0325 - Challenges in titration of unfractionated heparin (UFH) using activated partial thromboplastin time (APTT) time in the presence of mild Factor XII deficiency: From Bedside to Bench

Background: The anti-coagulant effect of unfractionated heparin (UFH) is monitored by activated partial thromboplastin time (APTT). APTT however is subjected to interferences.

Aims: We report a case of factor XII (FXII) deficiency which caused challenges in monitoring UFH via APTT due to marked prolongation.

Methods: We performed in-vitro studies to confirm our clinical observation. Serial dilution of normal pooled plasma with FXII deficient plasma was done to obtain FXII plasma 20%. Heparin concentrations at varying levels were added. APTT was measured by Sysmex CS analyzer with Actin FSL as reagent. Anti-Xa (UFH) was measured by chromogenic assay.

Results: A 36 year-old lady, weighing 55kg, underwent major surgery. Post operatively, she suffered cardiac arrest and required extracorporeal membrane oxygenation support (ECMO). UFH was delivered as per protocol and resulted in marked prolongation of APTT. Titration of UFH was challenging as even small amounts of IV UFH (200 units/hr) resulted in marked APTT prolongation (Table 1). Factor assays testing were done and FXII levels were reduced at 7%. We suspected mild FXII deficiency could cause marked prolongation of APTT in the presence of UFH. Anti-Xa (UFH) levels and activated clotting time (ACT), which corroborated well with each other, were subsequently used for heparin titration. Repeat FXII level after cessation of ECMO and UFH was low at 19%.

Table 2 shows results of heparin spiking experiments. Therapeutic range of anti-Xa (UFH) is 0.3 to 0.7 and corresponded to APTT time of 50-70s in control SHP. APTT values however were markedly prolonged in factor XII 20% despite a normal APTT.

Conclusion(s): Mild FXII deficiency may not have a prolonged APTT but can become markedly prolonged in the presence of intravenous UFH. This should be a consideration when evaluating patients with ‘heparin sensitivity’. Heparin titration can subsequently be performed with a combination of ACT and anti-Xa (UFH) measurements.