Antiphospholipid Syndrome: Clinical Features and Genetics of Thrombotic Manifestations

Pathogenetic mechanisms of the development of antiphospholipid syndrome (APS) are presented in the article, which is the basis for the development of clinical manifestations and laboratory markers of APS. The modern literature data are analyzed, according to which the presence of antiphospholipid antibodies is a hypercoagulable background, and the formation of thrombi occurs under the influence of other allowing procoagulation factors. The basis of the pathogenesis of APS development is the permanent activation of the hemostatic system, caused by the intensification of thrombotic processes with simultaneous weakening of antithrombotic processes in the body, which inevitably leads to a relapse of thrombogenesis. Herewith, antiphospholipid antibodies (APL-antibodies) interacts with phospholipids forming the vascular and thrombocytes' endothelium, thereby provoking activation of thrombocytic cells, loss of antithrombogenic properties of the vascular endothelium and violation of fibrinolytic processes. Depending on the method of detection, APL-antibodies are conventionally divided into three groups: detectable with the help of immunoenzymatic methods using cardiolipin, less often than other phospholipids; antibodies detected by functional tests (lupus anticoagulant); antibodies that are not diagnosed by standard methods (antibodies to proteins C, S, thrombomodulin, heparin sulfate, endothelium, etc.). The clinical significance of APL-antibodies depends on whether their presence in blood serum is associated with the development of characteristic symptoms. Thus, APS manifestations are observed only in 30% of patients with positive lupus anticoagulant and in 30-50% of patients who have a moderate or high level of antibodies to cardiolipins. The disease develops mainly at young age, meanwhile APS can be diagnosed in children and even in newborns. Like other autoimmune rheumatic diseases, this complex of symptoms is more common for women than for men (5: 1 ratio). The classification of the main types of hereditary thrombophilia is given, which is the primary disorder, against the background of which an autoimmune thrombosis APS develops: a deficiency of natural anticoagulants (protein C, protein S, antithrombin III), disorders in genes encoding blood coagulation factors (primarily factor V and prothrombin) and the enzymes of folate cycle participating in the processes of homocysteine remethylation and transfusion (MTR, MTRR, MTHFR). But in practice, to determine the correct diagnosis of a specific nosological form of thrombophilia, it is often necessary to investigate other factors of hemostasis. A clinical observation of a young age patient is given. Heterozygous carriage of mutations in the genes is responsible for blood coagulation (F VII, PAI-1 and ITGB3-β-integrin), as well as homozygous carriage of a mutation in the MTRR gene associated with a violation of homocysteine methylation, APS was developed, which led to the processes of thrombosis. Timely diagnosis and individually developed pathogenetic therapy allows avoiding life-threatening complications of APS and improving the patients' quality of life. A conclusion about the need for APS and hereditary thrombophilias' examination to all patients of young age with unprovoked thrombosis of deep veins of lower extremities and pulmonary embolism was made.