Low levels of heparin-releasable tissue factor pathway inhibitor in young patients with thrombosis

An association between deficiency of tissue factor pathway inhibitor (TFPI) and thrombosis has not been clearly demonstrated in humans, but previous s tudies have focused on the measurement of plasma TFPI, which is only a smal l part of the total body TFPI. The major fraction of this natural anticoagu lant can be measured in plasma after release by heparin injection. To inves tigate if deficiency of heparin-releasable TFPI is associated with thrombos is, we measured TFPI activity in plasma before and 10 min after intravenous injection of 7500 IU unfractionated heparin in 64 young patients with veno us thrombosis, 49 young patients with arterial thrombosis and 38 healthy in dividuals. Post-heparin TFPI activity levels were significantly lower in th e group of patients with venous thrombosis than in controls (mean +/- SD: 2 30% +/- 39 vs 260% +/- 34, p = 0.0002), whereas there was no difference for patients with arterial thrombosis. Defining the normal range as the mean /- 2 SD of TFPI activity in controls, twelve patients had low post-heparin TFPI activity levels, seven with venous and five with arterial thrombosis. Low levels of TFPI activity were confirmed by immunoassay in six of the sev en patients with venous thrombosis and two of the five patients with arteri al thrombosis, and were present also in at least one first degree relative of six patients, suggesting that the defect might be inheritable. However, the causative role of low heparin-releasable TFPI remains uncertain, becaus e co-segregation of the defect with thrombotic symptoms could not be demons trated in the small number of families studied.