Hemophilia A

Hemophilia is a disease associated with a recessive mutation in the X chromosome . It occurs in men and in homozygous women. However, mild hemophilia A (and B) occurs in heterozygous women due to inactivation of the X chromosome, therefore, it is recommended to determine the level of factor VIII and IX in all carriers and potential carriers before surgery and in case of clinically significant bleeding ^[3] .

Hemophilia occurs in about 1 out of 5,000 men ^[3] . Of these, 85% have hemophilia A and 15% have hemophilia B ^[3] . In 5-10% of patients with hemophilia, the problem is with factor VIII protein dysfunction (qualitative insufficiency), and in the rest, with an insufficient amount of produced factor VIII (quantitative deficiency) ^[3] . Among those who have a serious deficiency (defined as <1% of factor VIII activity), 45-50% have the same mutations, inversions within the factor VIII gene, which leads to the complete elimination of protein production. However, both forms of hemophilia can be caused by different mutations, and the initial diagnosis and classification is made by measuring the activity of the protein, and not using genetic tests, although genetic tests are recommended for a single test of members of a family having one known case of hemophilia B ^[3] . Approximately 30% of patients do not have a family history of the disease, their disease is presumably caused by a new mutation ^[4] .

There are many different mutations that lead to hemophilia A. Due to differences in changes in the genes involved (and as a result in the resulting protein), patients with hemophilia may experience different levels of active coagulation factor. Cases with less than 1% of the active factor are classified as severe hemophilia, 1-5% of the active factor refers to moderate hemophilia, and mild hemophilia is characterized by a range of 5-40% of the normal level of active blood coagulation factor ^[5] .

Characteristic symptoms depend on the severity of the disease. In general, cases of internal or external bleeding, which are called "bleeding" ^{[6] [7]} , are characteristic. Patients with a more severe form of hemophilia suffer more severe and more frequent bleeding, while patients with a mild form of hemophilia are characterized by smaller symptoms, with the exception of the postoperative period or serious injuries. Patients with mild hemophilia have variable symptoms that manifest in the range between severe and mild.

If forceps or vacuum extraction are used in vaginal delivery, the first sign of hemophilia may be severe bruising or head bruising, or even intracranial hemorrhage ^[8] . Prolonged bleeding from a circumcision wound or after a vein puncture or a sample of the heel of a newborn is another common early sign of hemophilia. These symptoms can lead to blood tests that indicate hemophilia. In other patients, especially in cases of moderate or mild hemophilia, the first serious bleeding will occur in the first serious injury. Hemophilia greatly increases the risk of prolonged bleeding with common injuries, and in severe cases, bleeding can be spontaneous and not have an obvious reason. Bleeding can occur in any part of the body. Superficial bleeding, for example as a result of abrasion, a small or lacerated wound, can last for a long time, and the resulting crust can be easily damaged due to the absence of fibrin , which will lead to repeated bleeding. While superficial bleeding can cause some inconvenience, the most serious today are the following groups of dangerous hemorrhages:

• in the joints
• in the muscles
• gastrointestinal tract
• in the brain

Hemorrhages in the muscles and joints indicate hemophilia, while hemorrhages in the digestive tract are also observed with other disorders of blood coagulation. Joint hemorrhages are one of the most serious symptoms of hemophilia, although they usually do not threaten life. Repeated bleeding into the joint capsule can lead to permanent damage to the joints, chronic arthritis and disability. Damage to the joint is not the result of hemorrhage in the capsule, but occurs during the healing process. When blood in the joint is broken down by enzymes, the bones in this area also deteriorate. This in turn leads to severe pain.

Standard blood tests (general and biochemical) do not allow us to judge the number of coagulation factors. Various laboratory methods are used to diagnose hemophilia. A diagnosis of hemophilia may be suspected if coagulological tests show an increase in Activated Partial Thromboplastin Time (APTT), prothrombin time, and bleeding time. APTT test - this is the first blood test that is indicated for suspected hemophilia. The diagnosis is made if there is a very low (<10 IU) level of factor VIII. Family history data are often taken into account, although they are not critical. Recently, genetic testing has become available to determine the likelihood of the presence or transmission of hemophilia. The diagnosis of hemophilia A also includes determining the severity of the disease, which can vary from mild to severe, depending on the amount and activity of factor VIII found in the blood. The level of factor VIII in the blood usually does not change throughout a person's life.

Differential diagnosis is most often required by the two most common diagnoses: hemophilia B (also known as Christmas disease), which is characterized by a deficiency of factor IX, and von Willebrand disease , which is characterized by a deficiency of von Willebrand factor, necessary for the proper functioning of factor VIII. Hemophilia C also sometimes requires differential diagnosis.

Patients with the most severe form of hemophilia require regular intravenous administration of a plasma or recombinant factor VIII concentrate. The prophylactic treatment regimen is determined individually. In addition to “conventional” nutritional supplements, an additional factor concentrate is given during surgical procedures and after an injury.

A particular therapeutic problem is the development of factor “VIII” inhibitor antibodies caused by its frequent infusion. This is manifested by the fact that the body accepts the “normal” factor VIII as alien, since it does not have its own “copy”. In such patients, the infusion of factor VIII becomes ineffective. Recently activated factor VII (NovoSeven) has become available for the treatment of bleeding in patients with hemophilia and factor inhibitors.

• Hemophilia

Coagulological tests:

• Thromboelastography
• Thrombin generation test (thrombin potential, endogenous thrombin potential)
• Prothrombin time test (or Prothrombin test, INR, PV)
• Activated Partial Thromboplastin Time (APTT)
• Thrombodynamics