Coagulation activation in sickle cell trait: an exploratory study.

Recent epidemiologic data suggest that sickle cell trait (HbAS; AS) is a risk factor for venous thromboembolism. We conducted an exploratory study of healthy subjects with AS under baseline conditions to determine whether a chronic basal hyperactivation of coagulation exists, and if so, what mechanism(s) contribute to this state. Eighteen healthy AS individuals were compared to 22 African-American controls with a normal haemoglobin profile (HbAA; AA) and 17 patients with sickle cell disease (HbSS; SS).

Studies on the mechanism of action of the aptamer BAX499, an inhibitor of tissue factor pathway inhibitor.

Introduction: Promoting thrombin generation by inhibiting tissue factor pathway inhibitor (TFPI) is a potentially viable therapeutic approach to the prevention and/or treatment of bleeding in hemophilia. In this report, we studied the interaction between an aptamer (BAX499; formerly ARC19499) and TFPI that resulted in inhibition of TFPI-mediated regulation of the tissue factor pathway.

Materials And Methods: Enzyme kinetic analyses were performed to study the interaction between BAX499 and recombinant TFPI against factor Xa, the extrinsic Xase and prothrombinase activities.

Membrane microparticles in VTE and cancer.

Microparticles (MPs) are cellular vesicles produced by all cells in response to apoptosis or cellular activation. In this brief review, the evidence that MPs mediate the thrombotic propensity that characterizes patients with cancer is evaluated. It is concluded that while considerable data exist to support a critical pathophysiologic role of host or tumor cell-derived MPs in cancer-associated thrombosis, causality is not yet firmly established.

Tissue factor pathway inhibitor reduces experimental lung metastasis of B16 melanoma.

The importance of tissue factor (TF) in tumor biology has been highlighted by studies suggesting its involvement in cell signaling, metastasis and angiogenesis. Since many animal studies have shown that anticoagulant therapy can reduce experimental metastasis, we studied whether the natural inhibitor of TF-mediated blood coagulation, Tissue Factor Pathway Inhibitor (TFPI), might be similarly effective. Using a murine experimental model, we found that intravenous injection of recombinant murine TFPI immediately before introduction of tumor cells reduced metastasis by 83% (P < 0.