Protein C inhibitor (plasminogen activator inhibitor‐3) and the risk of venous thrombosis

Summary. Protein C inhibitor (PCI), also known as plasminogen activator inhibitor‐3, is a serine proteinase inhibitor that can inhibit enzymes in blood coagulation, fibrinolysis and fertility. The role of PCI in regulating the blood coagulation mechanism is not known, as it can inhibit both procoagulant (thrombin, factor Xa, factor XIa) and anticoagulant (activated protein C, thrombin‐thrombomodulin, urokinase) enzymes. To determine the relevance of this inhibitor in thrombosis, PCI levels were assessed in the Leiden Thrombophilia Study, a case–control study of venous thrombosis in 473 patients with a first deep‐vein thrombosis and 474 age‐ and sex‐matched control subjects. PCI levels above the 95th percentile of the controls (136·1%) increased the risk 1·6‐fold compared with PCI levels below the 95th percentile (95% confidence interval 0·9–2·8). There was a gradual increase in risk of thrombosis with further increasing levels of PCI. Adjustment for a number of possible confounders led to a reduction of the risk estimates associated with PCI. However, it is unclear whether adjustment for such factors in the risk models is justified. These results indicate that high levels of PCI may constitute a mild risk factor for venous thrombosis.