Description of hemophilia
Genetic linkage, a carrier hemophilia Influence defective gene in blood clotting resulting haemophilia
Hemophilia is among blood clotting disorders (ie. Coagulopathy), manifested as increased bleeding. It is acongenital disease (hereditary) and its genetic background is the reason that the disease is fully manifested only in men (see. Below).
The essence of the disease is the presence of a defective gene on chromosome X. This leads to a lack of (or malfunction) of one of the plasma proteins involved in blood clotting (coagulation). The rate is then expressed lack of severity of the symptoms of the disease.
Discourse about the symptoms of hemophilia and speculation about her inheritance appear in medical writings since the 11th century, but its present name dates back to 1828. The exact nature of the disease was discovered only recently, especially for the huge complexity of the whole set of chemical reactions and blood cells which is a blood clotting (and thus hemostasis) enabled.
Incidence of the disease in some ruling families (eg. In England, Spain and Russia) or related historical-political context is probably the cause of good public awareness about hemophilia, although otherwise this is a relatively rare disease.
The genetic correlation, carrier of hemophilia
A healthy person has in every cell of the body 23 chromosomes, coiled DNA molecules, which are stored all information necessary for the existence of the human body. One of said pairs is responsible except for certain bodily functions, which include the synthesis of blood clotting factors, for determining sex (the sex chromosomes or gonosomes).
In men, this pair consisting of chromosomes X and Y, in women of the two X chromosomes mature gametes (sperm and ova) contain only one of the pair gonosomes: egg female contains one of the two X, the man’s sperm contains either X or Y. their connection for fertilization arises combination determining sex of the child.
Defect causing Haemophilus genetic information is located on the X chromosome. The female has two of these chromosomes, one of which (in the case of hemophilia carrier status) will be one bad, but the presence of other “healthy” chromosome will compensate for this error.
For women, therefore, will not be affected. However, if fertilize sperm carrying a Y chromosome egg that carries the defective X chromosome, then her baby will be male and in his cells will not find the second “healthy” X, which would compensate for the error. For men, therefore, the disease occurs.
Egg with faulty X can also be fertilized with the sperm containing the man’s healthy X. born with a daughter who has a similar genetic makeup, like her mother, and will therefore be more a carrier of hemophilia. When zbávajících two possible combinations (healthy woman’s X with any sex chromosomes from the father), the child will be completely healthy, not carrier and transmission of hemophilia in the family, so stop.
Although it’s very rare, from the above it is clear that even a woman can hemophilia ill, and if along a carrier of hemophilia hemophiliac and beget a daughter who inherits the defective X from the mother and the father. For completeness, it should be noted that slight symptoms of hemophilia can occur even with carriers.
Where did the “defective” X? Error occurred mutation in a gene that was thrown eg. Radiation or viruses, either long generations ago, or is a newly formed mutation in the mother sick boy, without previous history of hemophilia in the family. New mutations are the cause in about 30% of cases.
Effect of the defective gene in blood clotting
Blood coagulation is allowed to very complex interaction of certain plasma proteins (coagulation factors), ions and platelets. These reactions occurring in the Cascades, where one factor influences another factor. Therefore, any error in the chain leads to a significant failure of the whole system.
Hemophilia A is caused by insufficient synthesis or disorder constructions proteins known asFactor VIII (formerly called as antihemophilic factor A), hemophilia B, factor IX deficiency.Previously described more Hemophilia C (factor XI deficiency), but today this name is no longer used because it is not a typical hemophilia.
acquired haemophilia
Rarely, hemophilia can occur even without the genetic background, due to an autoimmune reaction, at a moment when the body starts for some reason produce antibodies against its own molecules of the body. In this case, the antibodies are directed against the aforementioned coagulation factors whose deficiency then causes the same symptoms as with genetically determined hemophilia.
Risk factors for hemophilia
A risk factor is previous incidence of hemophilia in the family and sex (male). Newly created mutations in the gene responsible (see. Above) can not be avoided, since humans constantly active chemical, physical and biological factors suspected of inducing formation of mutations. This action can not be eliminated in the pure nature, let alone in today’s civilization.
Acquired haemophilia may arise in individuals with autoimmune diseases, thus with previously diagnosed disease characterized aggressiveness immune components to part of his own body.Further, it may rise to antibodies occur in old age and after childbirth.
prevention of hemophilia
The disease is genetically determined and as such he can not be prevented. If hemophilia already occurred in the family, the woman should consider the possibility of a symptomless carrier of the danger and handover of the defective X chromosome to his future son.
As will be explained below, the severity of the disease is determined by the level of lack of formation or function of the clotting factor. Prenatal (antenatal) diagnosis in pregnant mothers suspected carrier of hemophilia can be ascertained whether the son healthy, will suffer from a mild form of hemophilia or severe hemophilia significantly reducing the quality of life . When the latter option is given by the mother to consider abortion.
Prenatal diagnosis is carried out from the 10th week of pregnancy, chorionic villus sampling cell and genetic analysis of their DNA. If the finding testifies to the fact that a son will have hemophilia and is withdrawn by about 8 weeks later umbilical cord blood to determine the activity of the clotting factor and determining the severity of hemophilia.
Prevention of acquired hemophilia is not possible.
Signs and symptoms of hemophilia
The severity of disease and the symptoms depend on the activity (quality sufficient) clotting factors in the blood. By Activity distinguishes three forms, ie mild, moderate and severe forms of hemophilia.
Mild can only occur when serious injuries or surgery, where there is a significant intervention into the bloodstream. During life, diseases may be diagnosed at all.
For medium to severe forms of the tolerance to injuries and surgical interventions reduced even more. They may additionally discover the episode called. Spontaneous (spontaneous) bleedingwhere the onrush of blood does not cause a breach in the tissue. If they are injured by the large joints, hemophilia not allow them to heal and in turn causes deterioration of post-traumatic state with lasting consequences in the structure and function of the joint.
The severe form of hemophilia is detected in childhood, usually after childbirth because of the difficult stoppable přestřiženého bleeding from the umbilical cord. In another life are frequent spontaneous bleeding, may be a bleeding of mucous membranes, into the soft tissues (e.g. in muscles) and into body cavities.
Hematomas also arise as a reaction to the utterly banal injury or eg. At the injection site.
Particularly significant are the changes in large joints. Are swollen, warm and clear to them can be dark hematomas. Bleeding into the joint cavity causing oppression of articular cartilage, which is normally nourished only nutrient blending the matter. This prevents interpenetration of oppression and cartilage degenerates. Furthermore, there are changes in the lining of the joints and changes in bone structure. Movement of the joint is painful, sometimes impossible, the joint does not provide sufficient support. Movement disorders, joint disorders lead to flexibility of muscles and tendons.
It can cause a hematoma oppression vessels (and therefore insufficient blood supply and tissue lacking oxygen), nerves (cause pain or numbness), and other structures. Lethal complications is possible bleeding in the brain.
treatment of hemophilia
Treatment by administration of clotting factors derived from blood plasma. Plasma was obtained from healthy donors. Today’s demands on donor possibilities plasma purification and disposal of plasma virus is present at much higher levels than before, when frequent complication in the treatment of hemophilia has been the introduction of viruses (eg. HIV) into the blood hemophiliac.The probability of such complications is small today ..
Nowadays, it is also possible the production of clotting factors using recombinant techniques (not sampling from a living donor), but due to the high costs are thus prepared the factors used for treatment.
Alternatively administration can be called. DDVP, substances having analogous effects of vasopressin, which is a pituitary hormone capable of stimulating short-term increase in plasma factor VIII levels. DDVP is only a short-term effect and therefore can not replace the administration of concentrated clotting factors for severe haemophilia.
Furthermore administered drugs stopping fibrinolysis, thus re-dissolution of already clotted blood.
For mild to moderate hemophilia clotting factors, the dose is administered only during an episode of bleeding condition and applies it mostly by himself sick. The alternative is, of course, the application of the drug in the clinic doctor, but given the time lag is preferred the first option.
Patients with severe hemophilia are placed on a special regime and the clotting factor they must be delivered regularly. They need regular checks orthopedic imaging joints.
complications of hemophilia
Hemophiliacs are at risk of bleeding to death as wounds or invasive medical procedures.Performances, if necessary, they must be planned well in advance and it also relates to dental performances.
Probable degenerative joint disease.
Treatment by administration of clotting factors entails the risk of allergic reactions (and acute) infection or viruses.
Other names: congenital coagulopathies, coagulation disorders, hemophilia A, hemophilia B
