Prekallikrein deficiency is a blood condition that usually causes no health problems. In people with this condition, blood tests show a prolonged activated partial thromboplastin time (PTT), a result that is typically associated with bleeding problems; however, bleeding problems generally do not occur in prekallikrein deficiency. The condition is usually discovered when blood tests are done for other reasons.

A few people with prekallikrein deficiency have experienced health problems related to blood clotting such as heart attack, stroke, a clot in the deep veins of the arms or legs (deep vein thrombosis), nosebleeds, or excessive bleeding after surgery. However, these are common problems in the general population, and most affected individuals have other risk factors for developing them, so it is unclear whether their occurrence is related to prekallikrein deficiency.

Prekallikrein deficiency is caused by mutations in the KLKB1 gene, which provides instructions for making a protein called prekallikrein. This protein, when converted to an active form called plasma kallikrein in the blood, is involved in the early stages of blood clotting. Plasma kallikrein plays a role in a process called the intrinsic coagulation pathway (also called the contact activation pathway). This pathway turns on (activates) proteins that are needed later in the clotting process. Blood clots protect the body after an injury by sealing off damaged blood vessels and preventing further blood loss.

The KLKB1 gene mutations that cause prekallikrein deficiency reduce or eliminate functional plasma kallikrein, which likely impairs the intrinsic coagulation pathway. Researchers suggest that this lack (deficiency) of functional plasma kallikrein protein does not generally cause any symptoms because another process called the extrinsic coagulation pathway (also known as the tissue factor pathway) can compensate for the impaired intrinsic coagulation pathway.

Normal Function

The KLKB1 gene provides instructions for making a protein called prekallikrein. Prekallikrein is produced in the liver and circulates in the blood. A molecule called factor XII converts prekallikrein to another protein called plasma kallikrein, and plasma kallikrein helps turn on (activate) more factor XII. Plasma kallikrein and factor XII are involved in the early stages of blood clotting as part of a process called the intrinsic coagulation pathway (also called the contact activation pathway). Blood clots protect the body after an injury by sealing off damaged blood vessels and preventing further blood loss.

The interaction between plasma kallikrein and factor XII also initiates a series of chemical reactions resulting in the release of a protein called bradykinin. Bradykinin promotes inflammation by increasing the permeability of blood vessel walls, allowing more fluids to leak into body tissues. This leakage causes the swelling that accompanies inflammation.

Health Conditions Related to Genetic Changes

Prekallikrein deficiency

At least nine KLKB1 gene mutations have been identified in people with a blood condition called prekallikrein deficiency, which does not generally cause any health problems. The condition is usually discovered when blood tests are done for other reasons.

The KLKB1 gene mutations that cause this condition reduce or eliminate functional plasma kallikrein in the blood of affected individuals and likely impair the intrinsic coagulation pathway. Researchers suggest that this lack (deficiency) of functional plasma kallikrein protein does not generally cause any symptoms because another process called the extrinsic coagulation pathway (also known as the tissue factor pathway) can compensate for the impaired intrinsic coagulation pathway. Either pathway can activate proteins that are needed later in the clotting process.

Other Names for This Gene

• Fletcher factor
• kallikrein B, plasma (Fletcher factor) 1
• kininogenin
• plasma kallikrein
• plasma kallikrein preproprotein
• plasma prekallikrein
• PPK

Genomic Location

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

The prevalence of prekallikrein deficiency is unknown. Approximately 80 affected individuals in about 30 families have been described in the medical literature. Because prekallikrein deficiency usually does not cause any symptoms, researchers suspect that most people with the condition are never diagnosed.