Synonyms
Haemophilia, inherited bleeding disorder, blood clotting factor deficiency, factor VIII deficiency, factor IX deficiency, haemophiliacs
Definition
Haemophilia is a hereditary disease of the blood coagulation system: affected patients have impaired blood coagulation, which is manifested by bleeding in the smallest traumas and bleeding is difficult to stop. Coagulation factors cannot be activated, so that the regular course of the coagulation cascade is not possible. Haemophilia is a congenital disease that can exist in two forms, haemophilia A and B. Haemophilia A occurs more frequently (in 85% of cases) than form B (approx.
15%) and is the more serious of the two forms. The activity of the Factor VIII complex is limited in haemophilia A because the formation of Factor VIII-C in the liver cells is reduced. Factor VIII-C is one of the two subunits of the factor VIII complex: von Willebrand factor and factor VIII-C form this coagulation-promoting complex in the coagulation cascade.
The von Willebrand Factor protects Factor VIII-C from rapid degradation. The amount of the functional Factor VIII complex is therefore reduced in Form A. In haemophilia B, the synthesis of coagulation factor IX is less pronounced, so that its effect in the coagulation process is absent and haemostasis is impaired.
Occurrence /Epidemiology
The incidence of hemophilia in the population is 1 in 5,000 for hemophilia A and 1 in 15,000 for form B. The fact that it is mainly men who fall ill is due to the sex-linked X-linked inheritance form of the coagulation defect (see Cause/Genesis).
Basics
Blood coagulation is a finely tuned system: various components of the blood, the so-called coagulation factors, are activated one after the other in cascades to enable haemostasis in the event of an injury. The coagulation system consists of primary and secondary haemostasis, also called plasmatic coagulation. If a vessel wall injury occurs, the affected vessel narrows in a first step (= primary coagulation). A plug (=platelet thrombus) then forms at the injured site, which is formed by blood platelets (= thrombocytes) in order to achieve an initial sealing of the vessel. The formation of the thrombus activates plasma coagulation: The coagulation cascade is set in motion and the interaction of the various coagulation factors results in the formation of a stable wound or vessel seal.
Cause and origin
Hemophilia in both forms of hemophilia is inherited X-linked recessively. In the so-called X-chromosomal mode of inheritance of haemophilia, the genetic information for a gene product is located on the X sex chromosome, which is present in double numbers in women and single numbers in men. For each genetic information there are two gene expressions, the so-called alleles.
If there is a recessive inheritance process, both alleles must be affected by a mutation to cause the disease: Recessive means that the pathologically altered genetic information is suppressed by healthy, i.e. not altered, information and does not lead to disease. A recessive genetic disease therefore only develops if both alleles carry faulty genetic information. If only one gene expression is changed, this does not lead to hemophilia.
In men suffering from haemophilia, the allele carrying the genetic information for coagulation factor VIII-C (haemophilia A) or coagulation factor IX (haemophilia B) is only present in a slightly altered form; women must carry this genetic alteration on both alleles in order to suffer from the disease. If women have one defective and one unmodified allele, they are called carriers of an X-linked disease such as haemophilia. In haemophilia, the faulty genetic information has the effect of reducing the activity of the affected coagulation factor or causes reduced production of the coagulation factor. The X chromosome carries the genetic material for the coagulation factors of secondary haemostasis. Approximately 70% of hemophilia-causing mutations in the genetic material are passed on within the family, 30% of diseases are caused by spontaneous changes (=spontaneous mutations) in the genetic information.
