Further investigations of lupus anticoagulant interference in a functional assay for tissue factor pathway inhibitor

Abstract

Tissue factor pathway inhibitor (TFPI) is a natural 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 in haemostasis is yet to be determined, it's ability to inhibit TF - FVIla in the presence of FXa suggests that is does have an important physiological significance. TFPI levels have been reported to be normal in a variety of clinical conditions, including patients with lupus anticoagulants (2,3). Lupus anticoagulants (LA) are acquired inhibitors, generally considered to be immunoglobulins, that interfere with in vitro phospholipid dependent coagulation tests (43). There is current interest in LA due to the associated thrombotic complications as seen in increased risk for venous and arterial thrombosis as well as pregnancy complications (6). We have previously reported decreased functional levels of TFPI in plasma containing LA using a fluid phase assay, but normal levels with a binding assay (7). These low levels of TFPI were shown to be corrected with the addition of excess TF (7). As a continuation of this study, we again assessed TFPI levels in LA plasma using the same fluid assay. The effect of using three different sources of tissue factor (recombinant, human brain and rabbit brain thromboplastins) in the TFPI assay was examined. Of most significance was the apparent correction of TFPI values as thromboplastin levels increased