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To cite this article: Dahm AEA, Andersen TO, Rosendaal F, Sandset PM. A novel anticoagulant activity assay of tissue factor pathway inhibitor 1 (TFPI). J Thromb Haemost 2005; 3: 651-8.See also Arië ns RAS. The quest for the Holy Grail of tissue factor pathway inhibitor deficiency has just begun. This issue, pp 649-50.Summary. Tissue factor (TF) pathway inhibitor I (TFPI) is the physiological inhibitor of TF-induced blood coagulation. Circulating blood contains full-length TFPI and TFPI truncated at the C-terminal end. Previous studies have shown that full-length TFPI exerts a stronger anticoagulant effect on diluted prothrombin time (DPT) than truncated TFPI, and it has been suggested that full-length TFPI is biologically more important in vivo. The objective of this study was to develop and validate an assay of TFPI anticoagulant activity. TFPI anticoagulant activity was assayed using a modified DPT assay. Plasmas were incubated in the absence and the presence of TFPI-blocking antibodies. Results were expressed as a ratio with the clotting time in the presence of anti-TFPI as the denominator. The ratio was normalized against a ratio obtained with a reference plasma. The assay was compared with assays of TFPI free antigen, total antigen, and bound TFPI, and TFPI chromogenic substrate activity. We performed all tests in 436 healthy individuals. The normalized TFPI anticoagulant ratio was strongly associated with TFPI free antigen (r ¼ 0.73) but was weakly associated with TFPI chromogenic substrate activity (r ¼ 0.46), TFPI total antigen (r ¼ 0.48), and bound TFPI (r ¼ 0.30). TFPI chromogenic substrate activity was strongly associated with TFPI total antigen (r ¼ 0.73). We have developed a novel assay of TFPI anticoagulant activity in plasma, which may be considered a functional assay of fulllength TFPI. Further studies are needed to establish the role of TFPI anticoagulant activity for thrombotic disorders.

Summary. Spinal cord injured patients are at increased risk of developing deep vein thrombosis (DVT). Whether these patients have increased blood levels of prothrombotic markers remains to be clarified. In general, the risk of developing DVT is highest in the morning hours. In healthy humans, several haemostatic and fibrinolytic parameters exhibit circadian variations, but it is not known whether this also applies to those with spinal cord injury. The aim of the present study was to examine possible circadian variations in prothrombotic markers in tetraplegic patients. We studied six patients with complete tetraplegia and eight control subjects with repetitive blood sampling over a 24 h period. While the control subjects showed marked circadian variations in factor VIII activity, prothrombin fragments 1+2 and D-dimer levels, the tetraplegic patients did not (P < 0AE05). Circadian variation in plasminogen activator inhibitor type-1 was present in both groups, being most marked (P < 0AE05) in tetraplegia. We conclude that the circadian variations of several factors of the haemostatic and fibrinolytic systems are impaired in spinal cord injury. This could possibly reflect a deregulated autonomic nervous system, leading to a dysfunctional link between central and peripheral circadian oscillators.

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