Platelet aggregation with ristocetin (von Willebrand factor )

Reference values (norm) of von Willebrand factor activity are 58-166%.

Von Willebrand factor is synthesized by endothelial cells and megakaryocytes. It is necessary for normal platelet adhesion and has the ability to prolong the half-life of factor VIII. Plasma coagulation factor VIII - antihemophilic globulin A - circulates in the blood as a complex of three subunits designated VIII-k (coagulating unit), VIII-Ag (the main antigen marker) and VIII-vWF (von Willebrand factor associated with VIII-Ag). It is believed that von Willebrand factor regulates the synthesis of the coagulation part of antihemophilic globulin A (VIII-k) and is involved in vascular-platelet hemostasis.

Von Willebrand disease is a hereditary disorder characterized by increased bleeding time, decreased ristocetin cofactor activity, and decreased (to varying degrees) factor VIII coagulant activity. Clinical manifestations of the disease are similar to those of thrombocytopathy. However, patients with significant decreased factor VIII activity may experience hematomas and hemarthrosis.

Based on laboratory studies that allow us to determine the structure and activity of the von Willebrand factor, the following forms of the disease are distinguished.

• Type I (70% of all cases) is characterized by a slight decrease in ristocetin cofactor (von Willebrand factor) and coagulant activity (VIII-k) with a normal macromolecular structure of von Willebrand factor.
• Type II: is based on a selective deficiency of high-molecular polymers of von Willebrand factor due to disturbances in the structure of this protein.
  • Type IIB is caused by increased interaction between von Willebrand factor and platelets, and increased clearance of platelet aggregates leads to thrombocytopenia.
• Type III is characterized by a severe quantitative deficiency of von Willebrand factor, resulting in a clinically significant decrease in factor VIII activity (VIII-k).

The content of von Willebrand factor is determined in cases where bleeding time is increased, the platelet count is within the reference values and there are no obvious causes of platelet dysfunction. To assess the von Willebrand factor, the quantitative content of von Willebrand factor is determined (a study of ristocetin cofactor activity), ristocetin-induced platelet agglutination and the antigenic structure of von Willebrand factor associated with factor VIII (VIII-vWF) are studied.

Determination of platelet aggregation with ristocetin in plasma is used for quantitative assessment of von Willebrand factor. A linear relationship has been established between the degree of ristocetin aggregation and the amount of von Willebrand factor. The method is based on the ability of this antibiotic (ristocetin) to stimulate in vitro interaction of von Willebrand factor with platelet glycoprotein Ib. In most cases of von Willebrand disease, impaired ristocetin aggregation is observed with a normal response to ADP, collagen and adrenaline. Impaired ristocetin aggregation is also detected in Bernard-Soulier macrocytic thrombodystrophy (absence of ristocetin aggregation receptors on the platelet membrane). For differentiation, a test with the addition of normal plasma is used: in von Willebrand disease, ristocetin aggregation normalizes after the addition of normal plasma, while this does not happen in Bernard-Soulier syndrome.

The study can also be used in the differential diagnosis of hemophilia A (deficiency of factor VIII) and von Willebrand disease. In hemophilia, the content of VIII-k is sharply reduced, and the content of VIII-fB is within the normal range. Clinically, this difference is manifested by the fact that in hemophilia, a hematoma type of increased bleeding occurs, and in von Willebrand disease, a petechial-hematoma type.

Ristocetin-induced platelet agglutination is reduced in most cases of von Willebrand disease except type IIB.

The antigenic structure of von Willebrand factor associated with factor VIII (VIII-vWF) is detected by various immunological methods, and the distribution of von Willebrand factor by molecular size is determined by agarose gel electrophoresis. These tests are used to establish the type of von Willebrand disease.

The study of platelet aggregation with various inducers is carried out not only to identify disorders of platelet aggregation functions. This study allows to evaluate the effectiveness of antiplatelet therapy, select individual drug doses and conduct drug monitoring.

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