von Willebrand disease is a serious bleeding disorder. Most often, the disease develops over the years, which is why the pathology is diagnosed in the later stages of development. The disease is characterized by an anomaly in the structure and function of the von Willebrand factor vWF.
History of the onset of the disease
Willebrand disease was discovered in 1926. At this time, one Finnish doctor observed a tendency to hemorrhages under the skin and mucous membranes in one little girl and her sisters living in the Aland Islands. The child was examined for the first time at the age of five. She died after her fourth period 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 anomaly of the von Willebrand factor. It is a large plasma protein that is involved in stopping bleeding, activating platelets and stabilizing the eighth factor of blood clotting. Blood factor synthesizes vascular endothelial cells, inwhich the factor accumulates in the form of Weibel-Palady bodies. Willebrand also synthesizes megakaryocins, platelet alpha granules. The former are the mother cells of platelets in the red bone marrow.
When it enters the bloodstream, von Willebrand is cleaved by metaloprotease and new, smaller molecules appear from a huge molecule.
Von Willebrand factor is one of the few proteins that carries AB0 group agglutinogens. It is the blood type that is responsible for the level of the factor. People with the first group have the least of them, and people with the fourth have the most.
What is the function of the factor
The factor performs the function of a stabilizer of antihemophilic globulin, protecting it from deactivation by proteases. Willebrand also localizes antihemophilic globulin at the site of bleeding and thrombus formation. It provides primary hemostasis - gluing platelets together, and also seals the walls of blood vessels.
How common
Willebrand disease is quite common. About one percent of the world's population suffers from the pathology, but clinical manifestations occur in one person in forty thousand, and life-threatening bleeding is rare, about two people in a million.
Causes of occurrence
Von Willebrand disease occurs due to the loss of factor activity in the blood. As a result, there is a lack of a protein responsible for blood clotting. This may be due to a mutation in the gene responsible for protein synthesis. Willebrand. Also, pathology may 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 the next generation is mildly affected.
Types of illness
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 the von Willebrand factor, its interaction with platelets, endothelium, and the eighth factor. Pathology is equally common in men and women.
Today, more than three hundred types 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 mild, but in all generations. In the autosomal recessive type, the pathology manifests itself only in the homozygous form and is characterized by severe bleeding.
Classification of pathology
There are three types of von Willebrand blood disease, differing in the degree of insufficiency of the eighth factor.
In the first type, there is a small amount of insufficiency 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 notassociate them with this type of ailment.
In the second type, the violations are more pronounced. Here, the formation of multimeric analogues of the clotting 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. The von Willebrand factor is completely absent on a blood test.
The second type has several subtypes:
- 2A. It occurs in about ten percent of people suffering from blood disease. With this type, the vWF function is reduced in platelets, there is a violation of the synthesis of macromolecular complexes, their cleavage is accelerated.
- 2B. The platelet count is decreasing.
- 2M. Structurally, vWF may be normal, but affinity for endothelium and platelets is reduced.
- 2N. The affinity of vWF for the eighth factor is reduced. This type of von Willebrand disease is similar in symptoms to hemophilia.
The most commonly diagnosed types are 2A and 2B. Other species are rare. The latter type of pathology has been little studied.
Acquired type of von Willebrand disease is diagnosed in about one percent of all cases of the disease. Most often, pathology is the result of other diseases, such as:
- lymphomas;
- Waldenström's disease;
- acute leukemia;
- clonal gammopathy;
- atherosclerosis;
- heart defects;
- Heide's syndrome;
- autoimmune pathologies;
- vasculitis, etc.
Also, the disease can occur due to taking certain medications.drugs such as valproic acid, hecodese, 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 internal organs. The operation also causes severe bleeding. Relapses may occur in the postoperative period.
Particular care should be taken by doctors during delivery, as the risk of a woman's death increases, although such cases are rarely described. In most cases, pregnancy has a positive effect on the disease.
Von Willebrand disease symptoms are manifested by different types of bleeding. Most commonly seen:
- nosebleeds;
- bleeding after tooth extraction;
- for injuries, injuries;
- heavy menstrual bleeding;
- small petechial hemorrhages on the skin;
- hematuria;
- GI bleeding.
In mild cases, patients usually do not attach importance to increased bleeding, suggesting a normal family tendency to hemorrhage.
Sometimes complications arise in pathology: they depend on the severity of the disease and can manifest as petechiae, bruising, hematomas. The danger is caused by hemarthrosis, LC bleeding. In the most advanced cases, hospitalization is necessary. With severe gynecological bleeding, when there is no result from conservative therapy, the uterus is extirpated withappendages.
What can indicate pathology
The following symptoms may indicate the presence of pathology:
- Nosebleeds in which more than two times the bleeding did not stop within ten minutes with tamponade.
- Small wounds, scratches, abrasions that bleed.
- Recurrent bleeding from internal organs.
- Subcutaneous hemorrhages that do not disappear within a week.
- Prolonged hemorrhages from the mucous membranes.
- The appearance of dark-colored feces or with blood clots, in which there is no hemorrhoids, peptic ulcer of the gastrointestinal tract.
- 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 speak of a complete recovery.
Diagnostic Methods
Diagnosis of von Willebrand disease is difficult because it can be almost asymptomatic. It is difficult for patients to notice its manifestation, since bleeding makes itself felt very rarely. In severe form, as well as the definition of von Willebrand disease in children is much easier, since patients have strong and frequentbleeding, hemorrhages may occur in the internal organs.
In order to accurately diagnose, you need to see a doctor. He will collect an anamnesis, and also 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 a patient has it and what type of von Willebrand factor disorder is present.
To detect pathology, the following types of tests are carried out:
- Determine the duration of bleeding according to Shitikova's Ivy modification.
- The activity of the eighth factor is being studied.
- The activity of the FB antigen is determined.
- Ristocetin-cofactor activity is fixed.
- Multivariate analysis in progress.
If there are any deviations from the norm in the test results, then this indicates the presence of pathology.
When interviewing patients, doctors pay attention to the following data:
- Have there been cases of illness in the family, relatives.
- Has there been a tendency to bleed throughout life.
In laboratory conditions with an interval of two months, the determination of the activity of the von Willebrand factor is carried out. Patients show different types of defects.
In addition to the above tests, tests are required. Doctors prescribe:
- Complete blood count. It displays a decrease in the number of platelets and hemoglobin.
- Increased bleeding time according to Lee-White, Duke. Seen in type 2A, 2B and 2M.
- Eighthfactor is either normal or there is a slight deviation in the form of a decrease.
- The function of the von Willebrand factor is determined in the form of the ability to attach to activated glycoprotein complexes.
- The binding ability of the von Willebrand factor and the eighth factor is analyzed.
- Mutations are detected in perinatal diagnostics.
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 clotting time, soluble fibrin-monomer 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 the von Willebrand factor. This can be done by activating a dedicated endogenous vWF or by supplying it externally.
Desmopressin is used for treatment. 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). The introduction of vasopressin increases the level of factor vWF four times.
Effect of treatment of each type of pathology is individual. The highest efficiency is observed in the pathology of the first type. In the treatment of 2A and 2M, the effect is low, and with 2B it reduces the number of platelets, due tofor which a synthetic drug is contraindicated. With the third type of disease, treatment is unsuccessful.
By his standards, von Willebrand disease is treated with Hemate P or similar drugs.
Antifibrinolytic agents in the form of trexanoic acid are prescribed at the rate of 25 mg/kg every eight hours for minor hemorrhages in the mucous membranes, nasal and menstrual bleeding.
For the treatment of the disease, thromboconcentrate transfusions are recommended with a decrease in the number of platelets. If there is a large blood loss during menstruation, then hormonal contraceptives are prescribed. To stop minor bleeding, "Etamzilat" is used.
Many people think that by looking at a photo of von Willebrand disease, you can determine this disease, but this is not so. To accurately establish the diagnosis, it is necessary to pass tests, undergo a medical examination. When the diagnosis is confirmed, its hereditary nature, it is almost impossible to cure the disease. Therapy is aimed at relieving symptoms and preventing dangerous consequences. The main goal of therapy is to stop bleeding. For this, various methods can be used: the application of tourniquets, bandages, 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 prior preparation for the upcomingprocedure.
