Prekallikrein (PK), also known as Fletcher factor, is an 85,000 Mr

serine protease Serine proteases (or serine endopeptidases) are enzymes that cleave peptide bonds in proteins. Serine serves as the nucleophilic amino acid at the (enzyme's) active site. They are found ubiquitously in both eukaryotes and prokaryotes. ...

that complexes with

high-molecular-weight kininogen High-molecular-weight kininogen (HMWK or HK) is a circulating plasma protein which participates in the initiation of blood coagulation, and in the generation of the vasodilator bradykinin via the kallikrein-kinin system. HMWK is inactive until it ...

. PK is the precursor of plasma

kallikrein Kallikreins are a subgroup of serine proteases, enzymes capable of cleaving peptide bonds in proteins. In humans, plasma kallikrein (encoded by ''KLKB1 gene'') has no known paralogue, while tissue kallikrein-related peptidases (''KLKs'') encode a f ...

, which is a serine protease that activates kinins. PK is cleaved to produce kallikrein by activated

Factor XII Coagulation factor XII, also known as Hageman factor, is a plasma protein. It is the zymogen form of factor XIIa, an enzyme () of the serine protease (or serine endopeptidase) class. In humans, factor XII is encoded by the ''F12'' gene. Struct ...

(Hageman factor).

Structure

Prekallikrein is homologous to

factor XI Factor XI or plasma thromboplastin antecedent is the zymogen form of factor XIa, one of the enzymes of the coagulation cascade. Like many other coagulation factors, it is a serine protease. In humans, Factor XI is encoded by the ''F11'' gene. ...

, and similarly consists of four apple domains and a fifth, catalytic

domain. The four apple domains create a disk-like platform around the base of the catalytic domain. However, unlike factor XI, prekallikrein does not form dimers. Prekallikrein is activated to form

factor XII Coagulation factor XII, also known as Hageman factor, is a plasma protein. It is the zymogen form of factor XIIa, an enzyme () of the serine protease (or serine endopeptidase) class. In humans, factor XII is encoded by the ''F12'' gene. Struct ...

cleavage of a bond homologous to the corresponding bond cleaved during factor XI activation.

Prekallikrein deficiency

Hereditary deficiencies in PK are very rare. They can cause a prolonged

APTT The partial thromboplastin time (PTT), also known as the activated partial thromboplastin time (aPTT or APTT), is a blood test that characterizes coagulation of the blood. A historical name for this measure is the kaolin-cephalin clotting time ( ...

, which can be corrected by incubation of the patient’s plasma. Deficiencies in PK can also be acquired due to some disease states, such as

angioedema Angioedema is an area of swelling ( edema) of the lower layer of skin and tissue just under the skin or mucous membranes. The swelling may occur in the face, tongue, larynx, abdomen, or arms and legs. Often it is associated with hives, which ...

, infection, DIC, and

sickle-cell disease Sickle cell disease (SCD) is a group of blood disorders typically inherited from a person's parents. The most common type is known as sickle cell anaemia. It results in an abnormality in the oxygen-carrying protein haemoglobin found in red blo ...

. Although most cases of prekallikrein deficiency are asymptomatic, a few reports link severe prekallikrein deficiency with thrombotic phenomena and recurrent pregnancy loss. More recently, a case of prekallikrein deficiency was shown to be associated with severe mucosal bleeding.

Discovery of prekallikrein

PK was initially described by Hathaway et al. in 1965 after encountering a Kentucky family who exhibited strikingly abnormal APTT results, but showed no bleeding symptoms. The family appeared to have a hereditary deficiency in an unknown coagulation factor, dubbed “Fletcher factor” after the family. In 1973 Kirk Wuepper determined that Fletcher factor and prekallikrein were the same.

References

{{Coagulation Coagulation system Kinin–kallikrein system