Contents
When on the July night of 1918, Nicholas II and his family went down to the basement of Ipatiev’s house in Yekaterinburg, where the fate of the Romanov dynasty was to be fulfilled, he was carrying his nearly 14-year-old son in his arms. The Tsarevitch could not walk because of his swollen and stiff joints. These ailments were caused by a disease that was a medical mystery at the beginning of the XNUMXth century. Doctors only knew that the person affected must be extremely careful, because even the smallest injury or fall can turn into a serious threat to life …
- Haemophilia is an X-linked, or sex-linked, hereditary disease
- It almost always affects men, while women are carriers of the abnormal gene
- The heir to the throne was handed over by his mother, granddaughter of the Queen of the United Kingdom of Great Britain and Ireland – Victoria. Victoria’s daughters were married to the descendants of European ruling families, and as a result, hemophilia appeared at the courts of Spain, Our Country, and POur Country. Interestingly, the disease did not occur in the families of the mother and father of the British queen, so scientists speculate that it was the result of a genetic mutation
- More information can be found on the Onet homepage
A life marked by hemophilia
When Tsarina Alexandra Feodorovna gave birth to a son on July 30, 1904, the dream came true not only of the tsarist family, but also of their subjects, because finally, after four girls, the heir to the throne was born.
Meanwhile, Fr.symptoms of haemophilia in the form of sudden and difficult to control navel bleeding occurred in Tsarevich Alexei when he was only six weeks old. Although they had completely stopped after three days, in the years that followed, each time the boy stumbled and fell, his arms and legs were bruised and turned into blue swelling.
- Read also: The causes of the appearance of bruises. They can be a sign of diseases
The disease was kept a secret for a long time, as the future tsar should be free from all defects, but rumors could not be avoided …
The boy was often unable to move on his own, he was bedridden and was brought to official events by the servants. This was because the blood, instead of clotting, seeped into the joints, destroying bones and tendons. Pierre Gillard, the Tsarevich’s Swiss tutor, recalled that the atmosphere at court changed with the health and mood of the heir to the throne. Besides, Alexei was fully aware of the fact that he might die. During attacks of hemophilia, he repeatedly spoke of death as a deliverance from suffering.
He grew up under the close supervision of nurses, and when he turned five he was placed in the care of two seafarers, tasked with keeping him from injuries. The heir to the throne had missed most of the pleasures of his childhood. He was not allowed to ride a bicycle as there was a risk of falling. His room was filled with elaborate toys, which, however, did not compensate for playing in the fresh air.
Powerless doctors most often gave massages and exercises, but they too were burdened with the risk of injuries and bleeding.
The tsar’s and his wife’s constant fears for their son’s life elevated the self-proclaimed monk and mystic Rasputin, who was the only one who was able to soothe pain and stop bleeding. The Tsarina believed that he could heal remotely by talking to Alexei on the phone or sending a telegram. In fact, Rasputin calmed a suffering and sometimes hysterical child without even touching him, standing at the foot of his bed and praying.
Over the years, the attacks of hemophilia have somewhat lessened. The most serious one took place in the fall of 1912. A bruise in the abdominal cavity led to internal bleeding, which was accompanied by swelling and severe pain. The legs were immobilized, the child was confined to the bed and in terrible pain. The fever had risen to 39 degrees Celsius and would not come down, and cries and groans echoed throughout the palace. The pain grew so strong that the tsarevich did not allow the swelling to be touched. He slept on his side, cross-legged, pale as he continued to moan.
He was in pain for 11 days, and doctors began to prepare his parents for the worst. Even an official statement about the health of the heir to the throne was published. However, he miraculously recovered after Rasputin’s remote intervention, who advised: “Don’t let the doctors worry him too much, let him rest.”
The treatment he stopped was to administer aspirin, the then new wonder drug (appeared in 1910). Since it is an anticoagulant (these properties were discovered in 1971), it further increased the bleeding, causing swelling and pain in the joints. No wonder the boy felt better after weaned it.
When the tsarevich’s burial site was discovered in 2007, and American scientists conducted DNA tests. The genetic mutation responsible for haemophilia B has been revealed.
The rest of the text below the video.
The types of hemophilia depend on various clotting factors
The earliest references to haemophilia come from ancient Egypt, while the oldest descriptions are found in the Talmud. The first modern description of the disease dates back to the beginning of the XNUMXth century.
Haemophilia is a congenital plasma disorder caused by an abnormal structure of the genes responsible for the production of factor VIII or IX of clotting. These genes are located on the X sex chromosome. Men who have only one such chromosome, when the damaged gene is there – get sick. Women who have two X chromosomes, if the gene is damaged on one of them, they have the other in spare and do not get sick. Haemophilia will only affect them if both forms of the factor VIII or IX gene are defective, that is, when they inherit the abnormal X chromosome from the affected father and the abnormal X chromosome from the carrier mother.
There are two main types of haemophilia – A (the disease is caused by a deficiency of clotting factor VIII) and B (caused by a factor IX deficiency), which are clinically indistinguishable. Hemophilia A accounts for 80% of all cases. One in 10 people worldwide suffers from it. men. One in 20–30 people has hemophilia B. men. In 50-60 percent patients have a severe form.
There is also type C, resulting from a deficiency of coagulation factor XI (Rosenthal factor) and acquired hemophilia A, which affects the elderly (aged 60–80 years), both men and women.
The cause of acquired haemophilia A is usually difficult to establish. It sometimes occurs in the course of autoimmune diseases or cancer as a reaction to drugs. Autoantibodies to factor VIII appear in the blood, neutralizing its activity. On the other hand, type C hemophilia is caused by an autosomal recessive mutation within chromosome 4 (the trait is inherited in conjunction with non-sex chromosomes and is revealed only in a homozygous recessive system, which means that both alleles of a gene must encode a given trait). It occurs mainly in the Ashkenazi Jewish population, is milder, and affects both men and women.
Factors VIII and IX as plasma proteins are essential for proper blood clotting and the functioning of the human body. In healthy people, the activity of most clotting factors is within the range of 0,5-1,5 IU / ml (50-150% of the norm).
Symptoms of hemophilia
The symptoms of hemophilia include:
- intra-articular and intramuscular bleeding – characteristic of the severe form of the disease. Bleeding episodes, 30–40 per year, lead to joint destruction – haemophilic arthropathy. After each bleeding, some blood remains in the joint, causing it to stiffen. Frequent intra-articular haemorrhages damage the synovium in the joint, which begins to limit the production of synovial fluid, which leads to cartilage damage. Bleeding usually occurs spontaneously, and the joints most frequently affected are the ankles, knee joints, and elbows;
- prolonged bleeding from minor cuts, as well as after an injury and tooth extraction. Very heavy secondary bleeding after surgery, starting a few hours or days after the surgery;
- tendency to bruise easily;
- bleeding gums;
- frequent or prolonged nose bleeds;
- gastrointestinal bleeding.
Symptoms are related to the amount of coagulation factor present in the blood, so in patients with a slight decrease in it, they occur rarely or only during injuries. Bleeding in hemophilicists is not more intense or faster, it just lasts longer.
The first symptoms of hemorrhagic diathesis in haemophilia A usually appear in children at the turn of the first and second year of life, and in patients with type B, the activity of factor IX may increase with age, therefore the symptoms of the disease lessen.
In 30 percent patients had no family history of haemophilia, the males were not ill, and the females were not carriers. A spontaneous mutation (the so-called de novo mutation) that occurred before birth is responsible for the appearance of the disease.
What should worry us?
It is necessary to consult a specialist if you notice:
- unexplained bleeding into soft tissues
- prolonged bleeding after surgery
- extensive bruising and bleeding in children.
Clinical classification:
Depending on the degree of deficiency or the type of factor VIII or IX defect, three forms of the disease are distinguished:
- mild form; factor concentration is 5-49%. standards. Major bleeding may not happen at all and is caused by trauma;
- moderate form; concentration is 2–5 percent. standards. Symptoms are moderate. Bleeding happens about once a month, rarely for no apparent reason;
- severe form; plasma concentration of the factor is less than 1%. standards. It is the most common form – around 50% of patients suffer from it. hemophiliacs. Symptoms of hemorrhagic diathesis are always severe, there may be bleeding in the joints and muscles for no specific reason.
Hemophilia B is also called Christmas disease, after the American boy Stephen Christmas, who was first diagnosed with factor IX deficiency.
People with type B haemophilia experience prolonged bleeding after an injury, surgery, or tooth extraction. In severe cases, they can bleed once or twice a week, often for no obvious reason. Bleeding in the joints, muscles, brain, or other internal organs can cause serious complications. In mild cases of haemophilia B, the disorder may not become apparent until after surgery or major trauma.
Inheritance
Unfortunately, hemophilia is a disease that cannot be prevented. A gene mutation can result in a complete lack of clotting factor synthesis, a reduction in its level, or the synthesis of an abnormal protein. In haemophilia A and B, the inheritance is the same.
In the case of parents where the man is ill and the woman is healthy – boys will be healthy, while girls will be carriers.
For parents where the male is healthy and the female is a carrier, boys will be healthy or sick and girls will be carriers or healthy.
For parents where the male is sick and the female is a carrier, boys will be sick or healthy and girls will be sick or carriers.
Risk factors
The risk factors include:
- in the case of haemophilia type A and B, a close relationship with the patient;
- in the case of acquired haemophilia A – comorbidities: neoplastic disease, rheumatoid arthritis, systemic lupus; multiple transfusions of blood products; skin diseases (psoriasis, pemphigus); drug reaction: penicillin, methyldopa, phenytoin, sulfonamides, interferon-alpha.
RESEARCH
The diagnosis of hemophilia consists of an interview, physical and laboratory tests. The interview includes establishing a family history of the disease, especially from the mother’s side. Physical examination involves the doctor looking for symptoms of hemorrhagic diathesis, i.e. hematomas, bruises, petechiae and traces of bleeding, determining their location and size.
Laboratory tests:
- screening tests: blood count with platelet count; homeostasis testing: APTT, bleeding time (BT), prothrombin time (PT);
- tests for suspected haemophilia: plasma factor VIII concentration – haemophilia A; plasma factor IX concentration – haemophilia B; plasma concentration of factor XI – haemophilia C; quantitative assessment of factor VIII inhibitor – acquired haemophilia.
Screening tests will neither confirm nor exclude the disease, but they are important in the diagnosis of bleeding disorders. The morphology allows you to assess the work of the hematopoietic system. In the case of studies on the homeostasis system, APTT prolonged, normal platelet count and normal PT are observed in patients.
Genetic testing for haemophilia is best done before pregnancy, as factor VIII levels increase during pregnancy and the results may be misleading.
- What is life like with hemophilia?
Treatment
Now we have effective treatments for haemophilia that enable people with the condition to live almost normal lives. The mainstay of treatment is replacement therapy, in which the clotting factor is administered intravenously as needed: prophylactically to prevent bleeding, or after bleeding for immediate treatment.
Pharmacological treatment:
- Desmopressin – it works by stimulating the release of factor VIII from tissue reserves, which enables the proper clotting mechanism to be used. These reserves are depleted after five or seven days, and the drug is mainly used in patients with mild hemophilia.
- Preparation containing factor VIII or IX, used prophylactically before planned physical exercise, in the perioperative period, before tooth extraction, regularly from the earliest years of life in severe haemophilia, where the risk of spontaneous bleeding is high.
- The clotting factor concentrates used in Poland are produced from human plasma. The dosage of the clotting factor concentrate depends on the type and extent of the bleeding, as well as the patient’s weight. Currently, patients can administer the factor concentrate themselves at home.
- Antifibrinolytic drugs – inhibiting the activity of the fibrinolytic system and supporting the stabilization of the clot. Useful in the treatment of minor mucosal bleeding and after tooth extraction, they are used in combination with other preparations.
In patients with acquired haemophilia A, the following are used:
- high doses of desmopressin and preparations containing factor VIII,
- recombinant factor VIIa (rVIIa),
An important element of treatment is elimination of the factor VIII inhibitor. It is carried out with the use of immunosuppressive drugs (prednisone, cyclophosphamide).
- Hemophilia – what is the treatment of patients in Poland?
New treatment regimens are constantly being searched and developed because the recommended therapy turns out to be ineffective or insufficient in over 30% sick.
Though hemophilia has long ceased to be a mysterious “royal disease”, still almost 75 percent patients do not have access to modern treatments and die before adulthood or live with joint deformities.
We encourage you to listen to the latest episode of the RESET podcast. This time we devote it to yoga. How to start your yoga adventure? How to benefit from it not only because of pain in the spine, joints or muscles? Check what non-obvious benefits this practice brings and what are the contraindications for practicing it. Listen.
This may interest you:
- Seven genetic diseases that mainly affect men
- Ten sex-linked genetic diseases. How do we inherit them?
- Atypical diseases of rulers. Some were embarrassing to say the least