Apc resistance

Term (APC = acronym for activated protein C), which denotes the resistance of activated factor V to activated protein C APC resistance is a blood coagulation disorder characterized, among other things, by thrombophilia. Most common thrombophilic coagulation disorder. Occurs in approx. 5-8% of the population or in approx. 15-65% of thrombosis patients (depending on the source).

APC resistance is based on a point mutation discovered by Dahlbäck in 1993, which is based on an exchange of arginine 506. Dahlbäck and his colleagues have put forward the thesis that the factor VQ-506 variant in Western society is the result of a so-called founder effect, i.e. that the mutation occurred in a single person. Dahlbäck postulates that this mutation occurred in a single human being after our ancestors had already branched out into Europeans, Asians and Africans. This explains why the Factor V mutant is frequently found in Europe among the European population and only minimally among the Japanese, Chinese and Native Americans in Africa, Australia and America.

Dahlbäck's colleague Lindqvist has put forward the hypothesis that the factor V mutation has a potential survival advantage, since women have a reduced risk of bleeding after birth compared to the normal population. Lindqvist assumes that the factor V-Q-506 allele has not had a negative effect on the survival of the species, since thromboses usually occur in middle and old age and do not affect fertility. Furthermore, Lindqvist argues that many of our risk factors such as inactivity, lifestyle and operations, and the use of anticonceptives did not play a role for our ancestors.

In addition to the factor V mutation described by Dahlbäck, a factor V mutation Hong Kong and an F-V Cambrigde have been described.

• The most frequent cause is an autosomal-dominantly inherited genetic structural defect (mutation in the factor V gene in approx. 90% of cases), which alters the blood coagulation factor V, the so-called factor V Leiden mutation (Leiden = Dutch city in which the first description of the mutation was successful). The mutation in the "docking site" of the activated protein C results in significantly reduced degradation of the activated coagulation factor V, i.e. thrombophilia.
• In approx. 10% of cases, the phenotype APC resistance does not correspond to a factor V gene mutation. Pathological APC resistance can also be caused by a deficiency or dysfunction of protein S, an increased concentration of factor VIII or the presence of a lupus anticoagulant. In particular, the influence of protein S leads to gender-specific differences and the influence of oral contraceptives in the determination of APC resistance, as has been reported many times before. Theoretically, other defects in factor V protein or defects in factor VIII protein are also conceivable.

1. HA Neumann (2014) The coagulation system. ABW-Wissenschaftsverlag GmbH Berlin S. 212ff.