(Von Willebrand’s disease)

The von Willebrand syndrome is a genetic disease in which a lack of von Willebrand factor (vWF) is leading to a platelet dysfunction. Usually a slight bleeding is present. Screening tests show normal platelet counts and occasionally a slightly prolonged PTT. The diagnosis is made by the detection of low vWF antigen levels and an abnormal ristocetin cofactor activity. The treatment consists in a control of bleeding by replacement of the missing vWF factor with cryoprecipitate or virally inactivated factor VIII concentrates medium Reinhei which contain VWF, t or the administration of desmopressin.

The von Willebrand factor is synthesized by vascular endothelial cells, which form part of the perivascular matrix and secreted. It promotes the phase of platelet adhesion by binding to a receptor on the platelet surface (glycoprotein Ib / IX), whereby the platelets are connected to the vessel wall. VWF is also necessary over it to maintain normal factor VIII levels. The vWF levels may temporarily increase in response to stress, physical stress, pregnancy, inflammation or infection.

The von Willebrand syndrome is a genetic disease in which a lack of von Willebrand factor (vWF) is leading to a platelet dysfunction. Usually a slight bleeding is present. Screening tests show normal platelet counts and occasionally a slightly prolonged PTT. The diagnosis is made by the detection of low vWF antigen levels and an abnormal ristocetin cofactor activity. The treatment consists in a control of bleeding by replacement of the missing vWF factor with cryoprecipitate or virally inactivated factor VIII concentrates medium Reinhei which contain VWF, t or the administration of desmopressin. The von Willebrand factor is synthesized by vascular endothelial cells, which form part of the perivascular matrix and secreted. It promotes the phase of platelet adhesion by binding to a receptor on the platelet surface (glycoprotein Ib / IX), whereby the platelets are connected to the vessel wall. VWF is also necessary over it to maintain normal factor VIII levels. The vWF levels may temporarily increase in response to stress, physical stress, pregnancy, inflammation or infection. The von Willebrand disease is classified into 3 types: Type 1: Quantitative vWF deficiency, which is the most common form and is autosomal dominant Type 2: Qualitative impairment in vWF-formation, which is caused by various genetic anomalies, and autosomal is inherited -dominant type 3: Rare autosomal recessive disease in homozygous patients have undetectable vWF levels. Although the von Willebrand disease is an inherited disease may cause a factor VIII deficiency similar to hemophilia A, and in severe cases, the factor VIII deficiency is usually only moderate. Symptoms and complaints Clinically mostly mild to moderate bleeding. Mucosal bleeding and bleeding from small skin lesions can Nachbluten intermittently for hours. Occasionally stronger menstrual bleeding and more bleeding after surgical procedures are (eg. As tooth extraction, tonsillectomy) to watch. Platelet function is ready yet sufficient that petechiae and purpura not occur. Diagnosis Total plasma vWF antigen, vWF function and plasma factor VIII levels The von Willebrand’s syndrome should be considered in patients with bleeding into consideration, especially when cases of this disease already have occurred in the family. Global coagulation tests show a normal platelet count, normal INR and possibly a slightly prolonged PTT. The determination of bleeding time is unreliable and is no longer carried out. The diagnosis is made by determining the vWF antigen and factor VIII levels in plasma and vWF function. The vWF function is an expression of the ability of the plasma to agglutinate normal platelets by the addition of ristocetin (ristocetin cofactor activity). Since it comes under certain conditions to a temporary increase in vWF levels, false-negative results can be collected from mild forms of von Willebrand syndrome. If necessary, the tests must be repeated. When frequent type 1 von Willebrand syndrome, the results are consistent, d. H. vWF antigen, vWF function and plasma factor VIII levels are equally reduced. The degree of reduction varies between about 15 and 60% of the normal value, and determines the severity of the bleeding tendency. In healthy patients with blood group 0, the vWF antigen level can be 40% below the normal range. The suspicion of von Willebrand syndrome type 2 is for non-matching test results, d. H. the vWF antigen level is higher than expected as compared to the abnormal ristocetin cofactor activity. The vWF antigen is higher than expected, because it is in vWF Type 2 is a qualitative and not a quantitative defect. The diagnosis is made by the detection of a reduced concentration of vWF multimers in the agarose gel electrophoresis. In total there are four different type 2 variants. Their distinction is based on the different functional changes in vWF molecules. Patients with von Willebrand disease type 3 have no detectable von Willebrand factor and a significant factor VIII deficiency. Desmopressin treatment vWF-replacement therapy (if necessary) patients are only treated if active bleeding or be invasive (eg. B. surgery, tooth extraction) are planned. Desmopressin is an analogue of vasopressin (antidiuretic hormone) which stimulates the release of vWF into the plasma and thus leads to an increase of factor VIII levels. The use of desmopressin can be helpful in von Willebrand syndrome type 1 variant. For all other types it has no clinical significance. In certain cases, the use can even be dangerous. Thus, an adequate response is ensured, a test dose is administered to the patient, and the response of the vWF factor measured. Desmopressin at a dose of 0.3 mcg / kg in 50 ml 0.9% sodium chloride solution as an infusion over 15-30 minutes may be sufficient to minor surgery in patients z. As a tooth extraction or to perform without substitution therapy minor surgery. If a replacement therapy is required, the necessary dose can be lowered by desmopressin. A single dose desmopressin acts for the period of 8-10 hours. So another dose of desmopressin is as effective as the first dose, about 48 hours must elapse. Only then can the body’s vWF stores are replenished. In many patients, intranasal desmopressin may be as effective as an i.v. Treatment. For more significant results or in patients with von Willebrand syndrome type 2 or type 3, the treatment from the replacement of vWF by infusion intermediate purity factor VIII concentrates containing vWF components. These concentrates are virus inactivated and therefore does not carry the risk of transmission of infection such. B. HIV or hepatitis viruses. Therefore, they are preferred to cryoprecipitate previously used. High purity factor VIII concentrates are produced by immunoaffinity, contain no vWF and should not be used. A short course of oral-to-use tranexamic acid may decrease in women strong menstrual bleeding due to von Willebrand’s disease. Summary Patients have easy bruising and purpura, mostly on the mucosa; and rare joint bleeding. Screening tests show a normal platelet count, normal INR and possibly a slightly prolonged PTT. The tests are confirmed by the determination of total plasma vWF antigen, vWF function (vWF ristocetin cofactor test) and the plasma factor VIII levels. A treatment, desmopressin, or sometimes moderately pure Factor VIII concentrate, takes place at active bleeding and prior to invasive procedures.

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