Interference by lupus anticoagulant in a functional assay for tissue factor pathway inhibitor

Tissue factor pathway inhibitor (TFPI) is a three domain Kunitz type inhibitor that regulates the initiation of coagulation by inhibiting tissue factor - activated factor VII (TF - FVIIa) in the presence of activated factor X (FXa) (1). Although the precise role of TFPI has yet to be determined, its ability to inhibit the TF - FVIIa complex in the presence of FXa suggests it does have major physiological significance. Animal studies support this theory and have shown that depletion of TFPI sensitises rabbits to disseminated intravascular coagulation induced by TF (2). TFPI levels have been reported to be normal in a variety of clinical conditions, including patients with lupus anticoagulants (3). Lupus anticoagulants (LA) are acquired inhibitors, generally considered to be immunoglobulins, that interfere with in vitro phospholipid dependent coagulation tests (4). The literature has reported LA to be present in many disorders, but with a particularly high frequency in recurrent pregnancy loss and venous and arterial thrombosis (5–7). In this study two previously reported functional assays for TFPI (8–9) were modified and used to assess TFPI levels in plasma. We assessed TFPI levels in normal and LA positive plasmas using both assays and report an interference by LA in one of these assay systems, which is not evident in the other.