High Molecular Weight Kininogen (HMWK / Fitzgerald Factor)

High molecular weight kininogen (HMWK) is a 110 kilodalton single-chain nonenzymatic cofactor synthesized in the liver which is central to contact activation reactions.⁶ It forms a complex with prekallikrein and factor XI. HMWK's plasma concentration is 70 mg/mL and its plasma half-life is approximately 144 hours. Factors VIII, IX, XI, XII, prekallikrein, and 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 HMWK-prekallikrein complex on endothelial cells. HMWK proteolysis leads to the production of bradykinin, a mediator of vasodilation, smooth muscle contractions, and increased vascular permeability. Other functions of HMWK include inhibition of thrombin-induced platelet aggregation, participant in fibrinolysis, as well as having surface-binding antiadhesive properties. Contact factor deficiencies have no hemorrhagic consequence; however, the contact factors are necessary for normal aPTT clot formation in the laboratory. Deficiency of HMWK produces markedly prolongs aPTT results. Hereditary HMWK 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 tests) and clinical history is negative for a bleeding disorder.

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