I am writing this report to explain the rare genetic disease of haemophilia causes the abnormality of blood clotting, the symptoms of the disease, the methods of diagnosis and treatment of this disease, modern research aimed at improving the life of patients with haemophilia.
Haemophilia is a hereditary genetic disease. (). Haemophilia is a sex-relative disease. Is transmitted from the X chromosome from the parents. () According to /// the haemophilia gene is the recessive of the disease. Women do not have this disease; however, they are carriers of it.
The cause of the disease is the mutation of the gene responsible for the synthesis in the body of substances for blood clotting (there is no formation of a normal blood clot and the developed bleeding does not stop in the put period). ( Rizza C.R.1997)
Haemophilia has been known since ancient times. The first descriptions of symptoms like haemophilia are found in Hebrew as far back as the 2 ND century BC (traditionally, the boys were circumcised and described that babies were dying from blood loss). The most famous in the history of the carrier of haemophilia was Queen Victoria, one of her sons was sick with haemophilia, and her daughters and granddaughters “distributed” this disease to the reigning houses of Europe. For this reason, the disease was named “Victorian disease or” royal disease “. Since in tsarist surnames, in the political interests, marriages between close relatives were allowed, which made the frequency of haemophilia higher.()
Fig.1 Depending on which of the clotting factors is not enough in the body, 3 types of haemophilia are distinguished.
Types of haemophilia
Currently, medicine distinguishes three types of disease. Classification is carried out to identify a deficit of a certain type of coagulation factor of blood. (Fig.1)
A) The most common type of disease (70-88% of patients with haemophilia). In the blood of the patient there is a deficiency of the ? globulin protein (VIII). This type of disease increases the risk of heavy bleeding during injuries or surgery.()
B) Type B disease is a deficiency of another enzyme – the ? globulin protein occurs in 9-20% of patients. Symptoms of type A and B are very similar and are considered classic.()
C) The third type of disease is very rare, approximately in 1-2% of patients. In the blood of the patient there is a deficiency of the protein ? globulin (factor XI).( Bemtorp E.E 2010)
The genetic principle is the inheritance of haemophilia.
There is a certain probability of genetic combinations, in which the child inherits the disease:
• A healthy father + mother is a carrier of a gene.
Prognosis: 25% chance of having a healthy or affected son, a healthy daughter, or the daughter of a gene carrier.
• Father homophilic + healthy mother.
Prognosis: All sons will be healthy, and all daughters carry the gene.
• Father homophilic + mother is the carrier of the gene.
Prognosis: 25% probability of a healthy or affected son, or daughter of a gene carrier. Getting a healthy girl without a genetic disorder is impossible. (Fig2) ).( Bemtorp E.E 2010)
Hereditary information is transmitted with the help of two sex chromosomes X and X / or Y, (these are haploid chromosomes so we get one of them from the father and the other from the mother). As is known, the haemophilia gene is transmitted only from the X chromosome. This is the reason for the inheritance of this disease. (mysourcecsl.com )
The most famous bearer of the defective gene was the English Queen Victoria. Obviously, the mutation of the haemophilia gene occurred in its genotype, de novo, since in families of her parents, those suffering from haemophilia are not registered .( Potts 1999)
Fig.3 The queen with the altered X chromosome and healthy Prince Albert Saxe-Coburg-Gothsky could have had healthy boys, healthy girls, carrier girls, and homophilic boys.( this scheme was created by me).
One of her sons was a haemophiliac and two daughters were heterozygous carriers of the disease. In the future, thanks to marriages between representatives of the royal family of Europe, this disease spread among the rulers of Germany, Russia and Spain. The example of this family tree shows a typical cross-inheritance.()
• Excessive bleeding with minor injuries or cuts.
• Bruises that do not pass a very long time. In some cases, bruises remain on the body for months, become inflamed and filled with pus.
• Any surgical manipulation, even ordinary, causes strong, long-lasting bleeding.
• Nasal bleeding for no apparent reason.
• Bleeding can occur inside the muscles and joints, blood in the urine may appear.
• Babies experience bleeding and bruising when cutting teeth. (NHS)
The above symptoms do not always mean haemophilia. Analogous symptoms are also characteristic for other diseases, for example, blood coagulability, anaemia, DIC syndrome, chronic leukaemia. Therefore, for the definition of haemophilia, modern science offers tests on the determination of the level of the proteins involved in the process of blood coagulation. The index of ? globulin (VIII), ? globulin (factor Kristmas) or ? globulin (factor XI) in haemophiliacs is below the norm by 50 or more percent. At the same time, a blood coagulability test is performed (pathology – coagulation time is more than 10 minutes) and clinical blood analysis. (NHS)
In the presence of precedents of haemophilia in the family at the present stage it is possible to conduct early or intrauterine diagnosis.
Also tests during pregnancy can diagnose haemophilia in a child. These include:
• choice of chorionic villi (CVS) – a small sample of the placenta (weeks 11-14 of pregnancy)
• amniocentesis – a sample of the amniotic fluid is taken for testing (within 15-20 weeks of pregnancy) (NHS)
At the present stage of the development of medicine, a complete cure for haemophilia is impossible.
However treatment is assigned to support the patient’s health and to prevent complications.
• When haemophilia A treatment is introduced into the patient’s body intravenously with a solution containing the clotting factor (CRYOPRECIPITATE).
• If the patient begins extensive bleeding, he is assigned a blood transfusion of donor blood.
• Haemophiliacs increase the protein content that affects blood coagulation through the introduction of drugs based on donor blood or synthetic substitutes. The clotting factor is maintained at 30-50%. With a higher content of clotting proteins, there is a threat of thromboembolism.
• Operative intervention only in case of acute necessity and with planned surgical interventions, preliminary preparation is carried out. ( Feldman 2017)
This pathology is well treatable. With its timely appointment, the quality of life of patients significantly improves. However, the treatment of this disease is one of the most expensive. According to experts, therapeutic procedures can cost the patient more than 10 thousand dollars a year. (WHO) In the absence of the same treatment, haemophilia quickly leads to disability of the patient, and some of its complications can even become the cause of his death. ( Feldman 2017)
According to statistics provided by the World Health Organization, the incidence of haemophilia A is on average ½-1 per 10,000 new-born boys, the incidence of haemophilia B-½ – by 100,000. It is believed that haemophilia is equally common among different races and nationalities, but there is evidence that among Africans and the Chinese it is found rarely. Currently, there is no possibility of completely curing this disease and patients require lifelong expensive therapy and constant monitoring. However, ongoing research is conducted and some of them give positive predictions for the future. (WHO)
– Specialists of the Medical Centre in Boston developed a technique for electro impulse introduction of a healthy gene into cells isolated from the patient’s body (in 70% this allowed to reduce the doses of substitution therapy drugs)
– Studies on the production of recombinant factors continue to be ongoing.
-The researchers from Queen Mary’s University of London, along with colleagues from the National Health Service of England, announced the first full-fledged victory over Haemophilia A. (Queen Mary University of London).
All this gives the chance to hope for victory over this disease soon.