Von Willebrand disease is a serious bleeding disorder. Most often, the disease develops over the years, because of which the pathology is diagnosed in the later stages of development. The disease is characterized by an abnormality in the structure and function of von Willebrand factor vWF.
History of the disease
Willebrand's disease was discovered in 1926. At this time, one Finnish doctor observed a tendency to hemorrhages under the skin and mucous membranes of one little girl and her sisters living in the Åland Islands. The child was first examined at the age of five. She died after the fourth menstruation at the age of thirteen.
The doctor made a distinction between hemophilia and a new disease, giving it the name "pseudohemophilia."
What is von Willebrand
Von Willebrand disease is an abnormality of von Willebrand factor. It is represented by a large plasma protein, which is involved in stopping bleeding, activates platelets and stabilizes the eighth coagulation factor . The blood factor synthesizes vascular endothelial cells, in which the factor accumulates in the form of Weibel-Paladi bodies. Also, von Willebrand synthesizes megakaryocins, alpha granules of platelets. The former are maternal platelet cells in the red bone marrow.
When it gets into the blood, von Willebrand is cleaved by a metal protease and new smaller ones appear from the huge molecule.
The von Willebrand factor is one of the few proteins that carries the agglutinogens of the AB0 group. It is the blood group that is responsible for the level of the factor. People with the first group have the least, and people with the fourth have the most.
What function does the factor fulfill?
The factor acts as a stabilizer of antihemophilic globulin, protects it from protease deactivation. Willebrand also localizes antihemophilic globulin at the site of bleeding and the formation of a blood clot. It provides primary hemostasis - gluing platelets together, and also seals the walls of blood vessels.
How often
Von Willebrand disease is common enough. About one percent of the world's population suffers from pathology, but clinical manifestations are found in one person out of forty thousand, and life-threatening bleeding is rare in about two people per million.
Causes of occurrence
Von Willebrand disease occurs due to a loss of factor activity in the blood. As a result, there is a deficiency in the protein responsible for blood coagulation. This may be due to mutations in the gene responsible for the synthesis of von Willebrand protein. Also, pathology can occur due to the following reasons:
- Hypothyroidism
- Nephroblastoma.
- Stromal dysplasia.
- Connective tissue dysplasia.
- Rheumatism.
- Different types of tumors.
The disease is most often inherited in an autosomal dominant manner, and pathology is moderate in the next generation.
Types of ailment
Von Willebrand disease in children and adults is divided into acquired and congenital. The latter is caused by a mutation in the genes responsible for regulating the synthesis and function of von Willebrand factor, its interaction with platelets, endothelium, and the eighth factor. Pathology is equally common in men and women.
To date, more than three hundred species of mutations of the twelfth chromosome in which the vWF molecule is encoded are known. The nature of these changes determines the type of von Willebrand disease.
With an autosomal dominant type of inheritance, the clinical manifestations of pathology are weakly expressed, but in all generations. With the autosomal recessive type, the pathology manifests itself only in a homozygous form and is characterized by severe bleeding.
Pathology classification
Three types of von Willebrand blood disease are distinguished, differing in the degree of insufficiency of the eighth factor.
In the first type, there is a small amount of deficiency of the eighth factor. In this form, the structural model does not change. Clinically, the first type is manifested by small bleeding. Usually patients do not associate them with this type of ailment.
With the second type of violation more pronounced. Here, the formation of multimeric analogues of the coagulation factor structure is observed. Small bruises appear on the skin. With the progression of the disease, a sharp deterioration in the patient's condition is observed.
The third type is considered the most difficult. In a blood test, von Willebrand factor is completely absent.
The second type has several subspecies:
- 2A. It occurs in about ten percent of people with blood disease. With this type of function, vWF is reduced in platelets, there is a violation of the synthesis of macromolecular complexes, and their splitting is accelerated.
- 2B. The platelet count is reduced.
- 2M. By its structure, vWF may be normal, but the affinity for endothelium and platelets is reduced.
- 2N. The vWF affinity for the eighth factor is reduced. The symptoms of this type of von Willebrand disease are similar to hemophilia.
Most often, types 2A and 2B are diagnosed. Other species are rare. The latter type of pathology has been little studied.
An acquired type of von Willebrand disease is diagnosed in approximately one percent of all cases of the disease. Most often, the pathology is the result of other diseases, such as:
- lymphomas
- Waldenstrom disease;
- acute leukemia;
- clonal gammopathy;
- atherosclerosis;
- heart defects;
- Heide syndrome;
- autoimmune pathologies;
- vasculitis, etc.
Also, an ailment can occur due to the intake of certain medications, such as valproic acid, gecodesis, ciprofloxacin.
Clinical manifestations
The main symptom of von Willebrand disease is bleeding. Their severity depends on the degree of manifestation of the pathology. Specific include bleeding from the mucous membranes of the mouth, gums, nose, and also internal organs. The operation also causes severe bleeding. In the postoperative period, relapses may occur.
Special care should be taken by doctors during delivery, since the risk of a woman's death is increased, although such cases have been described little. In most cases, pregnancy has a positive effect on the disease.
Symptoms of von Willebrand disease are manifested by different types of bleeding. Most often observed:
- nosebleeds;
- bleeding after tooth extraction;
- with injuries, injuries;
- heavy menstrual bleeding;
- small point hemorrhages on the skin;
- hematuria;
- gastrointestinal bleeding.
With a mild form, patients usually do not attach importance to increased bleeding, suggesting the usual family tendency to hemorrhage.
Sometimes pathology complications arise: they depend on the severity of the disease and can manifest as petechiae, bruising, hematomas. The danger is hemarthrosis, LCD bleeding. In the most advanced cases, hospitalization is required. With severe gynecological bleeding, when there is no result from conservative therapy, the uterus is extirpated with appendages.
What can say about pathology
The following symptoms may indicate the presence of pathology:
- Epistaxis, in which the blood did not stop more than two times for ten minutes with tamponade.
- Small wounds, scratches, abrasions that bleed.
- Recurrent bleeding from internal organs.
- Subcutaneous hemorrhages that do not disappear during the week.
- Prolonged hemorrhages from the mucous membranes.
- The appearance of feces of a dark color or with blood clots, in which there is no hemorrhoids, gastrointestinal ulcer.
- Bleeding resulting from manipulations on the organs of the oral cavity, nasopharynx and other systems.
- Abundant menstruation without pathologies of the reproductive system. Menstrual irregularities.
- Other types of bleeding that are not associated with other pathologies.
The classic manifestation of the disease is systemic. Hemorrhages occur in those places where there are damaged vessels. Even when positive dynamics are achieved, one cannot talk about full recovery.
Diagnostic Methods
Diagnosis of von Willebrand disease is complicated by the fact that it can be almost asymptomatic. It is difficult for patients to notice its manifestation, since bleeding is felt very rarely. With a severe form, as well as the determination of von Willebrand disease in children, it is much simpler, since patients have severe and frequent bleeding, hemorrhages in the internal organs can occur.
In order to accurately diagnose, you must consult a doctor. He will collect an anamnesis, as well as prescribe tests. It is during communication with a specialist that it always turns out that this pathology is hereditary.
Laboratory diagnostic methods can accurately determine whether the patient has it and what type of violation of the von Willebrand factor is present.
To identify pathology, conduct the following types of tests:
- The duration of bleeding is determined according to the Ivy modification of Shitikova.
- The activity of the eighth factor is being studied.
- The activity of the FB antigen is determined.
- Ristocetin-cofactor activity is fixed.
- Multimeric analysis is being carried out.
If there are any deviations from the norm in the test indices, then this indicates the presence of pathology.
During a survey of patients, doctors pay attention to the following data:
- Have there been any cases of illness in the family, in relatives.
- Has a tendency to bleeding throughout life been observed.
In laboratory conditions, an activity of von Willebrand factor is determined at intervals of two months. Patients have various types of defects.
In addition to the above tests, tests are mandatory. Doctors prescribe:
- General blood analysis. It displays a decrease in platelet count and hemoglobin.
- Increased bleeding time according to Lee-White, Duke. It is observed with type 2A, 2B and 2M.
- The eighth factor is either normal or there is a slight deviation in the form of a decrease.
- The von Willebrand factor function is determined as the ability to bind to activated glycoprotein complexes.
- The binding ability of the von Willebrand factor and the eighth factor is analyzed.
- In perinatal diagnosis, mutations are determined.
As additional methods of examination, blood biochemistry, kidney tests, C-reactive protein, ESR are prescribed. The prothrombin index, INR, fibrinogen, thrombin time, antithrombin, protein C, bleeding time, blood coagulation time, soluble fibrin-monomeric complexes are also evaluated.
Treatment
Mild forms of von Willebrand disease do not require treatment. In other cases, it is necessary to increase the level of von Willebrand factor. This can be done by activating the isolated endogenous vWF or by applying it externally.
For treatment, Desmopressin is used. It is a synthetic analogue of the antidiuretic hormone that releases vWF from the walls of blood vessels. The drug is administered at the rate of 0.3 mg / kg iv, s / c, with an interval of one to two hours. There may be intranasal administration of 150 mcg in each nasal passage (the exact dosage is calculated according to the patient’s weight). Administration of vasopressin increases the level of vWF factor four times.
The effect of treatment of each type of pathology is individual. The highest efficiency is observed with pathology of the first type. In the treatment of 2A and 2M, the effect is not high, and with 2B it reduces the platelet count, which is why the synthetic drug is contraindicated. With the third type of disease, treatment is unsuccessful.
By its standards, “Hemate P” or similar drugs are used in the fight against von Willebrand disease.
Antifibrinolytic agents in the form of traxanoic acid are prescribed at the rate of 25 mg / kg every eight hours with minor hemorrhages in the mucous membranes, nose and menstrual bleeding.
For the treatment of the disease, platelet transfusion is recommended with a decrease in the number of platelets. If there is large blood loss during menstruation, then hormonal contraceptives are prescribed. To stop minor bleeding, Etamzilat is used.
Many believe that by looking at a photo of von Willebrand disease, you can determine this ailment, but this is not so. In order to accurately establish the diagnosis, it is necessary to pass tests, undergo a medical examination. When confirming the diagnosis, its hereditary nature, it is almost impossible to cure the disease. Therapy aims to alleviate symptoms and prevent dangerous effects. The main goal of therapy is to stop bleeding. To do this, you can use various methods: the application of tourniquets, dressings, hemostatic applications, glue, the use of medicines, surgical methods.
Preventive measures for this pathology are aimed only at preventing situations that may lead to bleeding. Also, you can not make injections, carry out dental interventions without first preparing for the upcoming procedure.