Coagulation factor VIII

General Information

coagulation factor VIII (antihemophilic factor A), a non-enzymatic cofactor that is synthesized in the liver and circulates in plasma together with Willebrand factor. The ratio of factor 8 and Willebrand factor molecules is 1:50.

The coagulation factor VIII protein is called the FVIII antigen. Von Willebrand factor regulates plasma concentration of factor VIII and stabilizes it by prolonging its half-life to 8-12 hours. Through the cleavage of procofactor FVIII, activated factor VIII is obtained, which in turn interacts with serine protease with the participation of calcium ions and forms a complex similar to prothrombinase. This complex is involved in the next step of the coagulation process and is an activator of coagulation factor X.

The gene encoding factor VIII is located on the long arm of the X (sex) chromosome and is one of the largest genes, accounting for 0.1% of the total X chromosome.

Hemophilia A, or classic hemophilia, is a congenital deficiency of factor VIII. After von Willebrand disease, classical hemophilia is the most common congenital hemorrhagic disease. (Approximately 5000 case per 1 male newborns).

Hemophilia A is an X-linked recessive disease. Hemophilia A accounts for 85% of all hemophiliacs. The factor VIII gene can contain multiple mutations in the nucleotide sequence. The most common intron 22 mutation is associated with 45% of all hemophilia cases. As a result of this mutation, a protein is synthesized that has no immunological and functional activity.

Most cases of the disease occur in boys who receive the defective gene from their mother along with the X chromosome.

Diagnosing hemophilia is also possible prenatally, through the study of fetal DNA at 11-12 weeks of pregnancy.

30% of cases of factor VIII deficiency are due to de novo mutations (newly formed mutations), with no family history.

According to the severity of the disease, three clinical forms of hemophilia A are distinguished:

• severe - with spontaneous bleeding (factor VIII level in plasma <1%);
• Medium – bleeding occurs against the background of minor injuries (factor VIII level in plasma 1-5%);
• mild - bleeding occurs against the background of mass trauma or surgical intervention (factor VIII level in plasma 5-40%);

The clinical picture of the disease is represented by bleeding from early childhood. Hemarthrosis (intra-articular bleeding) is the most frequent (up to 60%) manifestation of the disease, although it does not appear until the child begins to walk.

Repeated intra-articular bleedings lead to degenerative changes in the joint tissues, limitation of movement and hypotrophy of muscles surrounding the joint.

Intramuscular hematomas develop at injection sites. In 10% of cases, bleeding from the digestive tract is observed.

Patients with hemophilia A who are on replacement therapy often develop factor VIII inhibitors due to the development of autoantibodies.

Diagnosis of the disease is based on both clinical and laboratory data.

Activated partial thromboplastin time (APTT) is significantly prolonged and returns to normal with normal plasma transfusion. Whereas, prothrombin time and bleeding time are within normal limits.

preliminary preparation – The study is conducted on an empty stomach.

Research material – venous blood

Interpretation of results

As we mentioned, the severity of the course of the disease depends on the degree of factor 8 deficiency.

factor in patients with von Willebrand disease VIIIThat level is usually low because Willebrand factor is a "carrier" for factor 8 in the plasma.

A combination of factor 8 and Willebrand factor deficiency has been described in several dozen families in Mediterranean countries.

An increase in factor VIII is observed at birth and during pregnancy. Factor VIII is an acute phase reactant, the level of which increases during acute stress, inflammation and postoperative periods.

An increase in factor VIII indicators is also observed under the influence of some medications, such as: epinephrine, desmopressin, estrogens, other hormones. Also in conditions: hemolytic anemias, deep vein thrombosis, myocardial infarction, diabetes, liver and kidney diseases, leukemia and carcinomas.