Prekallikrein (Fletcher Factor) Assay

Prekallikrein is a single-chain serine protease synthesized in the liver that circulates in two forms having molecular weights of 85 and 88 kilodaltons.⁶ Prekallikrein's plasma concentration is 35 to 45 mg/mL. It circulates in an equimolar complex with high molecular weight kininogen (HMWK), and has a plasma half-life of 24 hours. Kallikrein liberates kinins from kininogens, activates factor XII and plasminogen, converts protein to renin, destroys C₁ components, and interacts with leukocytes.

Factors VIII, IX, XI, XII, prekallikrein, and high molecular weight kininogen (HMWK) are the coagulation factors of the intrinsic coagulation pathway. Factor XII, high molecular weight kininogen, and prekallikrein are also called the “contact” factors. Factor XI is sometimes included in this designate of “contact” factors because of its interaction with others listed. Factor XI is activated by factor XIIa formed through activation of XII by a HMWK-prekallikrein complex on endothelial cells. With production of XIIa and kallikrein, activation of kinin, fibrinolytic, and complement systems occur. The major inhibitor of XIIa and kallikrein is C1 inhibitor. Other inhibitors include antithrombin (AT), plasminogen activator inhibitor (PAI), and α₂-macroglobulin.

Contact factor deficiencies have no hemorrhagic consequence; however, the contact factors are necessary for normal aPTT clot formation in the laboratory. Deficiency of prekallikrein produces markedly prolonged aPTT results. Hereditary prekallikrein deficiency conditions are inherited through an autosomal recessive pattern. Although the aPTT is prolonged in deficiencies of factor XII, prekallikrein, and high molecular weight kininogen, there is generally no clinical evidence of bleeding unless other contributing factors are present. These deficiencies are generally diagnosed when evaluating a prolonged aPTT with no other explanation (ie, other screening test) and clinical history is negative for a bleeding disorder.