Тромбиновое время (TT)

Thrombin Time (TT), also called Thrombin Clotting Time (TCT), assesses the final step of coagulation by measuring the time to fibrin clot formation after exogenous thrombin is added to plasma. The test is used to identify qualitative or quantitative fibrinogen abnormalities, including acquired dysfibrinogenemia related to liver disease or autoimmune disorders and hereditary dysfibrinogenemia. It supports evaluation of recurrent pregnancy loss where fibrinogen defects are suspected and is applied to risk assessment, diagnosis, and treatment monitoring of disseminated intravascular coagulation (DIC). In selected patients, TT may contribute to evaluating arterial thrombosis risk in the context of prothrombotic profiles.

Thrombin Time measures the interval required for fibrin formation after adding thrombin (factor IIa) to patient plasma, thereby recreating the terminal phase of the coagulation cascade. Because the assay isolates the conversion of fibrinogen to fibrin, alterations in fibrinogen concentration or molecular structure typically prolong, and occasionally shorten, the measured time. Fibrinogen is a hepatocyte-derived glycoprotein (factor I). In addition to its central role in clot formation, it binds excess thrombin (historically termed antithrombin I) and promotes plasminogen activation, linking coagulation and fibrinolysis. Consequently, abnormalities in fibrinogen level or function can manifest as bleeding, thrombosis, or a combination of both. Deficiency states include hypofibrinogenemia and afibrinogenemia, whereas structural defects are termed dysfibrinogenemia; each may be inherited or acquired. Acquired causes encompass liver disease, disseminated intravascular coagulation (DIC), primary fibrinolysis, and drug effects (for example, thrombolytic agents and l‑asparaginase). Liver disease is the most frequent cause of acquired dysfibrinogenemia: excess sialylation of the fibrinogen molecule increases its negative charge and impairs fibrin polymerization, contributing to bleeding in the context of multifactorial hepatic coagulopathy. TT serves as a primary screening test when dysfibrinogenemia is suspected in bleeding assessments. Abnormal fibrinogen may also be produced by certain tumors (such as squamous cell carcinoma of the cervix, breast adenocarcinoma, renal cell carcinoma, and hepatoma). Autoantibodies in systemic lupus erythematosus and multiple myeloma can diminish fibrinogen activity, prolonging TT. DIC is the most common cause of acquired hypofibrinogenemia and represents a systemic thrombohemorrhagic disorder characterized by widespread fibrin microthrombi with consumption of clotting factors and platelets. DIC is always secondary to an underlying condition and may be acute or chronic. Acute triggers include infections (E. coli sepsis, HIV, cytomegalovirus infection, malaria), acute myeloblastic leukemias, obstetric complications (placental abruption, eclampsia, amniotic fluid embolism), extensive burns, and massive transfusion. Chronic DIC is associated with solid tumors, chronic leukemias, pregnancy complications such as intrauterine fetal demise, myeloproliferative neoplasms, rheumatoid arthritis and Raynaud disease, myocardial infarction, and inflammatory bowel disease (ulcerative colitis and Crohn disease). Excess tissue factor (factor III) initiates intravascular clotting with microthrombi formation in the kidneys, brain, liver, and lungs, producing multiorgan dysfunction. Progressive consumption of fibrinogen and other factors leads from hypercoagulability to hypocoagulability with disseminated bleeding, and both states may coexist in the same patient. Given its complex presentation, DIC remains diagnostically challenging; TT, interpreted alongside other hemostasis assays, aids risk evaluation, early detection, and therapeutic monitoring. Inherited fibrinogen disorders are uncommon. Approximately 80 mutations cause absent or reduced fibrinogen due to failure of synthesis or impaired secretion with hepatic retention. Afibrinogenemia (no detectable plasma fibrinogen) is autosomal recessive with an estimated frequency of 1:1,000,000 and often presents in the neonatal period with umbilical stump bleeding, skin, gastrointestinal or genitourinary hemorrhage, or intracranial bleeding, though later onset is possible. Affected women may have menorrhagia or metrorrhagia, recurrent spontaneous miscarriage, and postpartum hemorrhage; paradoxical venous thrombosis can occur in some cases. Hypofibrinogenemia is more common (about 1:500), frequently asymptomatic, but may result in life‑threatening bleeding with major trauma, surgery, or concomitant coagulation defects. Hereditary dysfibrinogenemia comprises a heterogeneous group with roughly 400 reported mutations that substitute amino acids within the fibrinogen molecule. Plasma fibrinogen concentration is normal or mildly reduced (hypodysfibrinogenemia), but functional activity is decreased because of impaired thrombin interaction or defective fibrin polymerization. Clinical expression varies: about 55% are asymptomatic; approximately 25% have bleeding episodes, often after trauma, surgery, or childbirth; roughly 20% experience thrombosis, more commonly venous; and 27% exhibit both bleeding and thrombotic events. In some families, abnormal fibrinogen deposits as amyloid in the kidney, leading to early chronic kidney failure. Beyond hemostasis, fibrinogen participates in inflammation, angiogenesis, and wound repair, and it may contribute to atherogenesis through smooth muscle proliferation and macrophage uptake of oxidized lipids. Elevated fibrinogen levels correlate with increased risk of arterial thrombosis.