Prekallikrein also known as Fletcher factor, is a 85,000 Mr serine protease that complexes with High-molecular-weight kininogen. PK is the precursor of plasma kallikrein

Kallikrein

Kallikreins are a subgroup of serine proteases, enzymes capable of cleaving peptide bonds in proteins. In humans, plasma kallikrein has no known homologue, while tissue kallikrein-related peptidases encode a family of fifteen closely related serine proteases...

, which is a serine protease that activates kinins

Kinin-kallikrein system

The kinin-kallikrein system or simply kinin system is a poorly understood system of blood proteins that plays a role in inflammation, blood pressure control, coagulation and pain...

. PK is cleaved to produce kallikrein by activated Factor XII

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 class. In humans, factor XII is encoded by the F12 gene.- Function :...

 (Hageman factor).

Prekallikrein deficiency

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

Angioedema or Quincke's edema is the rapid swelling of the dermis, subcutaneous tissue, mucosa and submucosal tissues. It is very similar to urticaria, but urticaria, commonly known as hives, occurs in the upper dermis...

, infection, DIC

Disseminated intravascular coagulation

Disseminated intravascular coagulation , also known as disseminated intravascular coagulopathy or consumptive coagulopathy, is a pathological activation of coagulation mechanisms that happens in response to a variety of diseases. DIC leads to the formation of small blood clots inside the blood...

, and sickle-cell disease

Sickle-cell disease

Sickle-cell disease , or sickle-cell anaemia or drepanocytosis, is an autosomal recessive genetic blood disorder with overdominance, characterized by red blood cells that assume an abnormal, rigid, sickle shape. Sickling decreases the cells' flexibility and results in a risk of various...

.

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.