Fletcher factor

Fletcher factor, also known as prekallikrein or Factor XII (Hageman factor) activator, is a protein that plays a crucial role in the blood coagulation system and kinin-kallikrein system. It is named after Dr. John H. Fletcher, who discovered the factor's role in blood coagulation. The Fletcher factor is essential for the initiation of the intrinsic pathway of blood coagulation and is involved in the formation of bradykinin, a peptide that contributes to inflammation and blood pressure regulation.

Function

The primary function of the Fletcher factor is to act as a precursor to kallikrein, an enzyme that cleaves kininogen to produce bradykinin. This process is part of the kinin-kallikrein system, which is closely related to the mechanisms of blood coagulation and inflammation. In the coagulation cascade, the Fletcher factor is activated by Factor XII (Hageman factor) and, in turn, helps to activate Factor XII, thus playing a critical role in the initiation of the intrinsic coagulation pathway.

Genetic and Biochemical Aspects

The Fletcher factor is encoded by the KLKB1 gene located on chromosome 4 in humans. It is synthesized in the liver and circulates in the blood plasma as a zymogen, which is an inactive enzyme precursor. Upon activation, it converts into an active serine protease, initiating the cascade of reactions leading to blood clot formation and inflammation.

Clinical Significance

Alterations in the activity or levels of the Fletcher factor can lead to bleeding disorders or thrombotic conditions. Deficiency in this factor is rare but can result in a prolonged activated partial thromboplastin time (aPTT), a diagnostic test used to assess the intrinsic pathway of coagulation. However, individuals with Fletcher factor deficiency typically do not exhibit abnormal bleeding, which suggests that other pathways can compensate for its absence in blood coagulation.

Research and Therapeutic Potential

Research into the Fletcher factor and its role in coagulation and inflammation has potential therapeutic implications. Inhibitors of the kinin-kallikrein system, including those targeting the Fletcher factor, may be beneficial in treating conditions characterized by excessive inflammation or unwanted blood clot formation.