Background

Plasma factor XI circulates as a homodimer linked by a disulfide bond complexed to high molecular weight kininogen (HK) in noncovalent form at a molar ratio of 1:2.[1] Each monomer is composed of 607 amino acids and has an apparent MW of 80,000. Most, if not all, of factor XI is synthesized by the liver, although mRNA was also demonstrated in platelets and cell lines with megakaryo-cyte features.[2] Factor XI can be activated by factor XIIa, factor XIa, thrombin, or by autocatalysis through cleavage of a single peptide bond (Arg 369-Ile 370).[3,4]

There is a large body of evidence that under normal conditions, blood coagulation is initiated via the extrinsic pathway. The minute amounts of thrombin formed as a result of exposure of tissue factor will then activate factor XI in a feedback manner, leading to the formation of an amplification loop with continued thrombin generation. Platelets seem to play a central role. They are activated by trace amounts of thrombin, and on the activated platelet surface, thrombin-mediated activation of factor XI is more effective than activation by factor XIa or factor XIIa and directly reflects the occupancy of F XI-binding sites.[3] Furthermore, on the surface of activated platelets, fibrinogen does not inhibit thrombin-mediated factor XI activation, possibly because of colocalization of thrombin and factor XI on a high-affinity binding site.[3] Also, platelet-bound factor XIa, but not factor XIa in solution, is protected from inhibition by protease nexin 2, which is likely to be the most relevant inhibitor of factor XI within the activated platelet environment.1-1,3,4-1

Because thrombin, particularly in the presence of thrombomodulin, activates thrombin activatable fibrinol-ysis inhibitor (TAFI), feedback generation of factor XIa is also regarded to be important for the downregulation of fibrinolysis.[5]

In the laboratory, the diagnosis of factor XI deficiency is usually based on the finding of a prolonged activated partial thromboplastin time (APTT). However, common clotting tests for measurement of factor XI generally rely on factor XI activation via the intrinsic pathway and reflect the contribution of factor XIa for initial fibrin clot formation. Several aspects of factor XI activation and function, in particular the interaction with platelets and the effects of maintained thrombin-mediated factor XI generation, are not adequately measured.

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

Get My Free Ebook


Post a comment