How is it inherited
The genes for factors VIII and IX are located on the X chromosome. A man has only one, so a breakdown immediately manifests itself as a disease. A woman has two X chromosomes, and the second, healthy one, usually compensates for the defect - the woman becomes a carrier.
- The son of a sick man does not have hemophilia - from his father he receives not an X, but a Y chromosome
- All daughters of a sick man become carriers
- A female carrier has a 50 percent chance of passing on the altered gene to each child: her son may get sick, her daughter may become a carrier
- In about a third of patients, the disease occurs due to a new mutation, and there is no previous case in the family
- The disease often “jumps” generations: the maternal grandfather and grandson are sick, and between them is a healthy-looking carrier daughter.
- The type and severity within the same family usually coincide, because everyone has the same mutation
The practical consequence of this scheme concerns the whole family, and not just the sick person. If the diagnosis is established, it makes sense to examine sisters, daughters, aunts and nieces on the maternal side: some of them will be carriers and will find out about it before the first birth or the first operation, and not after a complication. Genetic counseling when planning a pregnancy provides an opportunity to discuss options early and calmly, without rushing.
Forms and severity
The severity is determined not by the state of health or the number of bleedings suffered, but by a specific figure - the residual activity of the factor, expressed as a percentage of the norm. Literally everything depends on it: the age of first manifestations, the need for constant prevention, the requirements for preparation before interventions.
- Hemophilia A—factor VIII deficiency, the most common form, about 80–85 percent of all cases
- Hemophilia B - factor IX deficiency, is less common, but has a very similar course
- Severe form: factor activity less than 1 percent, hemorrhages occur spontaneously, without trauma, from early childhood
- Moderate severity: 1–5 percent, bleeding usually after minor injuries and interventions
- Mild form: 5–40 percent, may remain unrecognized for years and first appear during tooth extraction, surgery or serious injury
- The severity of the form does not change with age: the percentage of the factor is set genetically and remains the same throughout life
- With a mild form, prophylaxis is usually not constantly needed - the drug is administered before interventions and for injuries
Within the same family, the form and severity are usually the same, because the mutation is the same. This simplifies life: if an older brother has a severe form, the younger brother with the same diagnosis is expected to have the same, and preparation for childbirth, vaccination and the first years of life is planned in advance, and not after the first hemorrhage.
How it manifests itself
The age of first manifestations directly depends on the severity. In severe cases, this is usually the first year of life, when the child begins to crawl and walk.
- Hemarthrosis - hemorrhage in a joint, most often the knee, elbow or ankle: the joint is hot, swollen, painful, movements are limited, the child spares the limb
- Extensive muscle hematomas - deep, tense, with pain and dysfunction
- Prolonged bleeding after tooth extraction, often resuming after a few hours
- Bleeding after operations and injuries, significantly exceeding the expected volume
- Blood in urine without pain
- Heavy and prolonged nosebleeds
- In newborns, prolonged bleeding from the umbilical wound and extensive bruising after injections
- Bleeding when changing primary teeth and after biting the tongue or lip
- Hemorrhage into the muscles of the forearm or lower leg with compression of nerves and blood vessels - a condition requiring urgent help
- Hemorrhages in the neck and throat are a rare but dangerous complication due to the threat to breathing
A characteristic feature of hemophilia is delay. Bleeding after tooth extraction or a cut initially stops as usual: the platelet plug forms normally. But it is not strengthened by a strong clot and after a few hours is destroyed, after which the bleeding resumes. That is why “everything went well” immediately after the intervention does not guarantee anything, and observation continues for 24 hours or longer.
Why joints are the main problem
Blood entering the joint cavity has a destructive effect on the cartilage and synovial membrane. One hemorrhage causes inflammation, the inflamed membrane bleeds again more easily, and a vicious circle closes.
- Первое кровоизлияние: боль, отёк, ограничение движений. При своевременном лечении сустав восстанавливается полностью.
- Повторные кровоизлияния в тот же сустав: он становится целевым, эпизоды учащаются.
- Хроническое воспаление синовиальной оболочки и постепенное разрушение хряща.
- Мышцы вокруг сустава слабеют от вынужденного щажения, и нагрузка на сам сустав растёт ещё больше.
- Гемофильная артропатия: стойкая деформация, ограничение движений, боль, атрофия мышц вокруг сустава.
That is why the modern approach is built not around treating hemorrhage that has already occurred, but around preventing it. Regular preventive therapy, started at an early age, allows the child to grow up without joint damage - and this is fundamentally different from the previous tactics, when the drug was administered only after bleeding.
Diagnostics
The path to diagnosis almost always begins with one line in a routine coagulogram. Next, the doctor’s task is not just to confirm the coagulation disorder, but to determine exactly which factor is missing and to what extent, because the choice of drug depends on this.
- Коагулограмма: удлинённое АЧТВ при нормальном протромбине, МНО, уровне фибриногена и нормальном количестве тромбоцитов.
- Определение активности факторов VIII и IX — устанавливает форму и степень тяжести.
- Исследование фактора Виллебранда: нужно исключить самую частую наследственную коагулопатию, которая встречается у обоих полов и лечится иначе.
- Тест на ингибитор — антитела к вводимому фактору.
- Молекулярно-генетическое исследование: подтверждает диагноз, уточняет тип мутации и позволяет обследовать родственниц.
- Оценка состояния суставов: осмотр, УЗИ, при необходимости МРТ.
- Обследование матери, сестёр и дочерей пациента — определение уровня фактора и носительства.
- Регулярный контроль в динамике: активность фактора, наличие ингибитора и состояние суставов проверяют по графику, а не однократно при постановке диагноза.
Separately, it is worth warning about the typical delay. A prolonged APTT is often perceived as a laboratory error and the test is retaken three or four times in different laboratories, obtaining the same result. The correct next step is not another coagulogram, but determination of the activity of coagulation factors and consultation with a hematologist. This is especially important when the examination is carried out before a planned operation: a few lost weeks here are safer than unexpected bleeding on the table.
Treatment and rules of life
The main shift in recent years has been the transition from treating existing bleeding to preventing it. The drug is administered according to a schedule so that the factor level does not drop to critical levels, and then hemorrhages simply do not occur. Everything else - lifestyle, sports, dentistry, vaccination - is built around this principle.
- Preventive replacement therapy with deficiency factor concentrates on a regular schedule is the basis of modern management
- Long-acting drugs that require less frequent administration
- Non-factorial subcutaneous therapy is a life-changing option for inhibitor patients
- Gene therapy is a direction that has already entered into practice in a number of countries
- Teaching the family how to administer the drug at home at the first sign of hemorrhage
- A supply of the drug at home and when traveling, as well as a pre-known address of the center where to go in an emergency
- Aspirin and anti-inflammatory painkillers, as well as intramuscular injections are strictly excluded
- Swimming, cycling, walking and exercise therapy are beneficial: strong muscles around the joint significantly reduce the incidence of hemorrhages
- Contact and traumatic sports are excluded
- The dentist, surgeon and emergency physician should know about the diagnosis in advance; It is useful to have a document with you indicating the form of the disease and the drug
- Routine vaccination is carried out, but subcutaneously, not intramuscularly
- Regular observation by an orthopedist and assessment of the condition of the joints, even when there have been no hemorrhages for a long time
- Weight control: extra pounds put extra stress on already damaged joints
- Home log of injections and bleeding episodes - it helps the doctor adjust the prophylaxis regimen
Just a few decades ago, severe hemophilia meant disability at a young age. Today, with accessible preventive therapy and proper monitoring, life expectancy is approaching average, people study, work, play sports and start families. The key condition is one - regularity of treatment and observation by a hematologist, and not contacting a doctor only after bleeding.