Время свертывания крови (ВСК)

Thrombin time (TT), also known as thrombin clotting time (TCT), measures the conversion of fibrinogen to fibrin after exogenous thrombin is added to plasma. The assay is used to detect both quantitative and qualitative abnormalities of fibrinogen, supporting evaluation of acquired dysfibrinogenemia in liver disease and autoimmune conditions as well as hereditary dysfibrinogenemia, hypofibrinogenemia, and afibrinogenemia. Clinicians order TT to investigate recurrent pregnancy loss, to estimate risk for disseminated intravascular coagulation (DIC), to assist in DIC diagnosis, and to monitor therapy in DIC. Because fibrinogen biology is linked to atherothrombosis, TT may also contribute to assessment of arterial thrombosis risk.

Thrombin time quantifies the interval required for a fibrin clot to form when purified thrombin is added to patient plasma. Thrombin (factor IIa) catalyzes the terminal step of the coagulation cascade by cleaving fibrinogen to insoluble fibrin, which then polymerizes and stabilizes the clot together with platelets and red cells. Alterations in fibrinogen concentration or structure change the efficiency of this step; as a result, thrombin time increases or, less commonly, decreases in parallel with functional impairment of fibrin formation. Fibrinogen is a hepatocyte-derived glycoprotein (coagulation factor I) that also participates in fibrinolysis by binding excess thrombin (historically termed antithrombin I) and promoting plasminogen activation. Disorders of fibrinogen include hypofibrinogenemia and afibrinogenemia (quantitative deficiency) and dysfibrinogenemia (qualitative defect); each may be inherited or acquired. Acquired causes encompass liver disease, disseminated intravascular coagulation, primary fibrinolysis, and drug effects (for example, thrombolytic agents and l-asparaginase). Liver disease is a frequent cause of acquired dysfibrinogenemia: in cirrhosis, chronic active hepatitis, acute hepatic failure, obstructive cholestasis, and hepatoma, secreted fibrinogen carries excessive sialic acid, increasing negative charge and impairing fibrin polymerization, which contributes to bleeding. Functionally abnormal fibrinogen may also be produced by certain tumors (selected squamous cell carcinomas of the cervix, breast adenocarcinoma, hypernephroma, hepatoma). In conditions with antibodies that bind fibrinogen, such as systemic lupus erythematosus and multiple myeloma, fibrinogen activity falls and thrombin time is prolonged. Disseminated intravascular coagulation is the most common cause of acquired hypofibrinogenemia. DIC is a secondary, systemic thrombohemorrhagic process characterized by widespread fibrin microthrombi with consumption of platelets and coagulation factors. Acute DIC is associated with severe infections (including Escherichia coli sepsis, HIV, cytomegalovirus, and malaria), acute myeloblastic leukemias, obstetric complications (abruptio placentae, eclampsia, and amniotic fluid embolism), extensive burns, and massive transfusion; chronic DIC occurs with solid tumors, chronic leukemias, pregnancy complications such as intrauterine fetal demise, myeloproliferative disorders, rheumatoid arthritis and Raynaud disease, myocardial infarction, and inflammatory bowel disease (ulcerative colitis and Crohn disease). Excess entry of tissue factor (factor III) into the circulation drives microthrombus formation in the kidneys, brain, liver, and lungs, leading to multiorgan failure. Ongoing consumption of fibrinogen and other factors produces secondary deficiency with a shift from hypercoagulability to hypocoagulability and disseminated bleeding; hyper- and hypocoagulability may coexist in a single patient. Because clinical manifestations are heterogeneous, diagnosing DIC is challenging; serial thrombin time, interpreted with other coagulation assays, supports risk assessment, early recognition, and treatment monitoring. Inherited fibrinogen disorders are uncommon. Approximately 80 pathogenic variants cause quantitative deficiency or absence of fibrinogen, often by halting synthesis or preventing secretion from hepatocytes. Afibrinogenemia, the most severe quantitative defect, is autosomal recessive with a frequency near 1:1,000,000 and typically presents in the neonatal period with umbilical stump bleeding, cutaneous hemorrhage, gastrointestinal or genitourinary bleeding, and intracranial hemorrhage; it can also first appear later in childhood or adulthood. Women may have menorrhagia, metrorrhagia, recurrent miscarriage, and postpartum hemorrhage. Despite bleeding liability, some patients experience thrombosis, more often venous than arterial. Hypofibrinogenemia is far more prevalent (about 1:500) and is frequently asymptomatic because residual fibrinogen supports hemostasis in small-vessel injury and pregnancy; however, major trauma, surgery, or coexisting coagulopathy can precipitate life-threatening bleeding. Dysfibrinogenemia comprises a heterogeneous set of qualitative defects with normal or slightly reduced fibrinogen concentration (hypodysfibrinogenemia). Roughly 400 missense mutations have been described that diminish activity, impair thrombin interaction, or prevent fibrin polymerization. Most patients (about 55%) are asymptomatic and identified through abnormal laboratory results or family studies; 25% have bleeding episodes (often after trauma, surgery, or delivery), 20% develop thrombosis (predominantly venous), and 27% exhibit both phenotypes. In some families, abnormal fibrinogen deposits in renal tissue as amyloid, leading to early-onset chronic kidney failure. Beyond its central role in clot formation, fibrinogen contributes to inflammation, angiogenesis, and wound repair, and elevated plasma fibrinogen is associated with increased risk of arterial thrombosis.