PK

PK Full Name

Prekallikrein

PK Introduction

Prekallikrein (PK), historically known as Fletcher factor, is a vital single-chain glycoprotein and serine protease zymogen synthesized primarily by the liver. In human blood plasma, the majority of PK circulates in a non-covalent complex with high-molecular-weight kininogen (HMWK). It serves as a fundamental building block in both the contact activation system (the intrinsic pathway of coagulation) and the kallikrein-kinin system (KKS), acting as a biochemical bridge between blood coagulation, blood pressure regulation, and inflammatory responses.

Figure 1. The contact activation and kallikrein/kinin systems (KKS) have two mechanisms, whereby they influence thrombosis risk in the intravascular compartment. (Source: Schmaier AH. 2016)

The primary physiological function of PK is realized when it is converted into its active enzymatic form, plasma kallikrein. This activation process is typically initiated when coagulation Factor XII (FXII) comes into contact with negatively charged surfaces (either artificial or biological), undergoing autoactivation to become FXIIa. FXIIa then cleaves PK to generate plasma kallikrein. In a powerful positive feedback loop, plasma kallikrein reciprocally activates additional FXII, rapidly amplifying the cascade. Beyond its role in the contact activation of coagulation, plasma kallikrein plays a critical role in vascular inflammation by cleaving its carrier protein, HMWK, to release bradykinin. Bradykinin is a potent pro-inflammatory peptide and vasodilator that increases vascular permeability, modulates blood pressure, and induces localized edema and pain.

Clinically, anomalies involving PK are linked to several distinct pathologies. Prekallikrein deficiency, also known as Fletcher trait, is a rare autosomal recessive disorder. Interestingly, while it presents in laboratory settings with a markedly prolonged activated partial thromboplastin time (aPTT), patients are typically asymptomatic and do not suffer from spontaneous bleeding tendencies, as the hemostatic balance in vivo remains largely unaffected. On the other end of the spectrum, the dysregulation of PK and the subsequent overproduction of bradykinin are heavily implicated in severe inflammatory and vascular conditions. The most notable of these is hereditary angioedema (HAE), where uncontrolled plasma kallikrein activity leads to recurrent, potentially life-threatening episodes of severe localized tissue swelling.

Alternate Names for PK

Fletcher factor; Glandular kallikrein; kallikrein 1 related peptidase b1; Kallikrein B plasma; Kallikrein B plasma (Fletcher factor) 1; Kallikrein B, plasma 1; Kininogenin; KLK3; Klkb1; nerve growth factor gamma; Plasma kallikrein; Plasma kallikrei

• 1. Schmaier AH. A Novel Antithrombotic Mechanism Mediated by the Receptors of the Kallikrein/Kinin and Renin-Angiotensin Systems. Front Med (Lausanne). 2016 Nov 28;3:61.
  2. Quail MT. Prekallikrein deficiency. J Pediatr Oncol Nurs. 2013 Jul-Aug;30(4):198-204.