Von Willebrand's disease in adults

Von Willebrand disease is a congenital deficiency of vWF, which leads to platelet dysfunction.

It is usually characterized by mild bleeding. Screening shows an increase in bleeding time, a normal number of platelets and, possibly, a slight increase in partial thromboplastin time. The diagnosis is based on a low level of antigen of von Willebrand factor and a deviation from the norm of activity of the ristocetin cofactor. Treatment includes monitoring of bleeding with replacement therapy (cryoprecipitate or factor VIII concentrate of medium purification) or desmopressin.

Causes of von Willebrand disease

The von Willebrand factor (PV) is synthesized and secreted by the vascular endothelium in the area of the perivascular matrix. The von Willebrand factor promotes the adhesion phase of hemostasis, connecting to the receptor on the surface of platelets (glycoprotein Ib-IX), which adheres platelets to the vascular wall. The von Willebrand factor is also necessary to maintain a normal level of factor VIII in the blood plasma. The level of vWF can temporarily increase in response to stress, physical activity, pregnancy, inflammation or infection.

Von Willebrand's disease (BV) includes quantitative (types 1 and 3) or qualitative (type 2) violation of vWF synthesis. Type 2 von Willebrand disease can be the result of various genetic abnormalities. The inheritance of von Willebrand disease occurs in an autosomal dominant type. Although Willebrand's disease, like hemophilia A, is an inherited pathology and can cause a deficiency of factor VIII, the deficit is usually moderately expressed.

[1], [2], [3], [4], [5]

Symptoms of Willebrand's Disease

The manifestation of bleeding in von Willebrand disease is mild or moderately pronounced and includes a tendency to subcutaneous hemorrhages; dinitelnoe bleeding from small cutaneous cuts, which can stop and then again resume after a few hours; sometimes prolonged menstrual bleeding; abnormal bleeding after surgical procedures (eg, tooth extraction, tonsillectomy).

Diagnosis of von Willebrand disease

Von Willebrand's disease is suspected in patients with hemorrhagic diseases, especially those with a family history of the disease. Screening of the hemostasis system reveals normal platelet count, normal MHO, increased bleeding time and, in some cases, a slight increase in partial thromboplastin time. However, during stimulation, a temporary increase in the level of von Willebrand factor may occur, which can lead to false negative results of studies with mild von Willebrand disease, so a repeat of screening tests is necessary. For the diagnosis, it is necessary to determine the level of the plasma total antigen of von Willebrand factor, a function of vWF, determined by the ability of the plasma to maintain normal platelet agglutination caused by ristocetin (activity of the ristocetin cofactor); plasma level of factor VIII.

In general, with the first type of von Willebrand disease, the results of the studies are concordant, i.e. Von Willebrand factor antigen, von Willebrand factor function and plasma level of von Willebrand factor are equally reduced. The degree of depression varies from about 15 to 60% of the norm, which determines the severity of bleeding in patients. It should be borne in mind that in healthy people with blood group 0 (I) there is a decrease in antigen of von Willebrand factor below 40%.

In the second type of von Willebrand disease, the results of the studies are discordant, i.e. Willebrand factor antigen is above the degree of activity of the ristocetin cofactor (vWF antigen is higher than expected because the Willebrand factor anomaly in the second type is qualitative, not quantitative). The diagnosis is confirmed by the detection of a decrease in the concentration of large Willebrand factor multimers by agarose gel electrophoresis. There are four variants of the second type of Willebrand disease, differing in functional deviations of the vWF molecule.

Type 3 Willebrand disease is a rare autosomal recessive disease in which the von Willebrand factor is not determined in homozygotes with a significant decrease in factor VIII. They have a combined anomaly of platelet adhesion and blood coagulation.

[6], [7], [8], [9], [10]

Treatment of von Willebrand disease

The need for treatment of von Willebrand disease occurs only if there is active bleeding or invasive procedures (eg, surgery, extraction of teeth). Treatment consists in replacement of von Willebrand factor by infusion of a factor VIII concentrate of medium degree of purification, in which the von Willebrand factor is contained. These concentrates undergo viral inactivation and do not transmit HIV or hepatitis, so they are more preferable than the widely used cryoprecipitate. High purity factor VIII concentrates are prepared by immunoaffinity chromatography and do not contain the von Willebrand factor.

Desmopressin is an analogue of vasopressin, stimulating the release of von Willebrand factor into the blood plasma and capable of increasing the level of factor VIII. Desmopressin can be effective in type 1 von Willebrand disease, but it is ineffective in other types and even with some can cause harm. To ensure an adequate response to the drug, the doctor should give a test dose and measure the response according to the level of antigen of von Willebrand factor. Desmopressin 0.3 μg / kg in 50 ml of a 0.9% NaCl solution intravenously for 15 to 30 minutes can provide the patient with hemostasis for small interventions (eg, tooth extraction, small surgery) without the need for substitution therapy. If, however, replacement therapy is necessary, desmopressin may lower the dose required. One dose of desmopressin is effective for 8-10 hours. To resume VF stores, it takes about 48 hours, which allows a second injection of desmopressin to have the same efficacy as the initial dose of the drug.