prekallikrein

Prekallikrein is a plasma zymogen of the serine protease kallikrein and a component of the contact activation system that links coagulation, inflammation, and fibrinolysis. In humans, it is encoded by the KLKB1 gene and circulates in the blood, often associated with high-molecular-weight kininogen (HMWK) or factor XII (Hageman factor).

Activation and function: When coagulation factor XII is activated on negatively charged surfaces, it becomes XIIa. XIIa then cleaves and activates prekallikrein to plasma kallikrein, a trypsin-like protease. Plasma kallikrein cleaves HMWK to release bradykinin, a potent vasodilator that increases vascular permeability and promotes inflammation and pain. Kallikrein also participates in a positive feedback loop by further activating more factor XII. The kallikrein–kinin system interacts with other pathways, including aspects of coagulation and fibrinolysis.

Genetics and clinical significance: The KLKB1 gene encodes prekallikrein. Deficiency or dysfunction of prekallikrein is rare and typically results in a prolonged activated partial thromboplastin time (aPTT) in laboratory testing but a minimal or absent bleeding tendency clinically. Dysregulated kallikrein activity, by contrast, can contribute to excessive bradykinin production, as seen in hereditary angioedema due to C1 esterase inhibitor deficiency or dysfunction, where increased bradykinin causes edema.

Other notes: Prekallikrein is a subject of study in laboratory tests of the kallikrein–kinin system and in research on inflammatory and hemostatic pathways.