A blood sample drawn from a vein in your arm
When an injury occurs and bleeding begins, the body begins to form a clot at the injury site to help stop the bleeding. Small cell fragments called platelets adhere to, aggregate, and are activated at the injury site. At the same time, the coagulation cascade begins and proteins called coagulation factors, including fibrinogen, are activated. Fibrinogen is then converted by thrombin into insoluble threads called fibrin that crosslink together to form a fibrin net that adheres to the injury site. Along with the platelets adhering, this forms a stable blood clot and prevents additional blood loss, remaining in place until the injury has healed.
For a stable clot to form, there must be enough normally functioning platelets and coagulation factors. If there are dysfunctional factors or platelets, or too few of them, it can lead to bleeding episodes and/or to inappropriate blood clotting (thrombosis).
The thrombin time evaluates that part of the hemostatic process where soluble fibrinogen is changed into fibrin threads. It measures the time required for a fibrin clot to form following the addition of a standard amount of thrombin to plasma. It is affected by the level and/or function of fibrinogen and the presence of inhibitors (e.g., heparin, fibrinogen/fibrin degradation products, direct thrombin inhibitor). With the addition of thrombin to the test sample, the thrombin time bypasses the rest of the coagulation factors and focuses on the function of fibrinogen.
It is now understood that blood coagulation tests are based on what happens artificially in the test setting (in vitro) and thus do not necessarily reflect what actually happens in the body (in vivo). Nevertheless, there are several laboratory tests used to evaluate specific components of the hemostasis system. (For more on this, see the explanation of the Coagulation Cascade).
How is the test used?
The thrombin time may sometimes be used as part of an investigation of a possible bleeding disorder or inappropriate blood clot formation (thrombotic episode), particularly to evaluate the level and function of fibrinogen.
The clotting-based functional fibrinogen assay is now routinely available in clinical laboratories and has largely replaced the need for thrombin time for evaluation of fibrinogen.
This test is very sensitive to the anticoagulant heparin. Because of this, it was once used to monitor unfractionated heparin therapy and to detect heparin contamination in a blood sample. While it is still sometimes used for these purposes, other tests and heparin neutralization procedures have largely replaced it.
When is it ordered?
A thrombin time may be ordered by itself or along with a combination of other tests when you have bleeding or clotting episodes, experience recurrent miscarriages, or have unexplained prolonged results on primary coagulation tests such as prothrombin time (PT) or partial thromboplastin time (PTT).
This test may be ordered when your healthcare practitioner suspects that you may have a disorder associated with decreased or dysfunctional fibrinogen. However, as mentioned previously, the functional fibrinogen assay (with or without a fibrinogen antigen assay) has largely replaced thrombin time for evaluating fibrinogen.
A thrombin time may sometimes be ordered when heparin contamination of a sample is suspected or when you are receiving heparin therapy, although these uses have declined.
What does the test result mean?
Significantly prolonged thrombin times are most commonly found when there is contamination of the blood sample by the anticoagulant heparin, direct thrombin inhibitor (such as dabigatran), and may be seen with heparin-like substances and inhibitors (e.g., fibrinogen/fibrin degradation products). Contamination can occur when you are on heparin therapy and/or when heparin is used as a periodic flushing agent to keep intravenous catheters from clotting.
A prolonged thrombin time may indicate decreased fibrinogen level (hypofibrinogenemia or afibrinogenemia) and/or abnormal fibrinogen function (dysfibrinogenemia). Conditions such as disseminated intravascular coagulation (DIC) or abnormal fibrinolysis impair fibrin formation and can also lead to a prolonged thrombin time, as can conditions such as end stage liver disease or malnutrition.
If thrombin time is abnormal, additional tests may be needed, including fibrinogen activity assay (now routinely available in clinical laboratories), fibrinogen antigen assay, and liver function tests.
Is there anything else I should know?
A significant percentage of people with decreased or dysfunctional fibrinogen will have no symptoms or mild symptoms and may only be diagnosed if the abnormality is discovered during testing for another reason, or because they have unexpected or prolonged bleeding following a surgical procedure or trauma.
Fibrinogen is one of several blood factors that are called acute phase reactants. Blood levels of fibrinogen along with other acute phase reactants rise sharply with conditions causing acute tissue inflammation or damage.
Genetic molecular testing is occasionally performed on those with inherited dysfibrinogenemia, hypofibrinogenemia, or afibrinogenemia to identify the genetic mutation responsible. Testing for this mutation may also be performed on other family members.
Some recurrent miscarriages are thought to be related to inappropriate clotting in placental blood vessels.
Can the thrombin time be performed in my doctor's office?
Can I have decreased or abnormal fibrinogen and not know it?
Yes. For many people, the clotting process functions relatively normally even when fibrinogen concentrations and/or activity are decreased. Your condition may not be identified unless pre-surgery screening identifies a potential problem or you bleed longer than expected after a surgical procedure or trauma.
Are there treatments available for decreased or dysfunctional fibrinogen?
Treatment is not needed in most cases, but people with significant bleeding may be given fibrinogen replacements like cryoprecipitate or fresh frozen plasma on a short-term basis to replace fibrinogen. Those who have recurrent inappropriate clotting may require anticoagulation therapy with anticoagulants such as warfarin (Coumadin) or heparin. See the article on Transfusion Medicine for more about these treatments.
What is a reptilase time (RT) and how is it used?
If heparin is suspected as the cause of a prolonged thrombin time, heparin assays or reptilase time (RT) can be used to confirm heparin presence. Reptilase time measures the time it takes for a clot to form after reptilase has been added to plasma. Thrombin time may be ordered with a reptilase time to investigate a prolonged clotting time. Since thrombin time, but not reptilase time, is affected by the anticoagulant heparin, prolongation of both thrombin time and reptilase time indicates decreased fibrinogen level and/or abnormal function of fibrinogen. If thrombin time is prolonged but reptilase time is normal, heparin contamination or presence of an interfering substance is likely the cause. The clotting-based functional fibrinogen assay is now routinely available in clinical laboratories and has largely replaced the need for thrombin time and reptilase time for evaluation of fibrinogen.
Can thrombin time be used for monitoring dabigatran therapy?
Dabigatran, a direct thrombin inhibitor, is one of the newly approved oral anticoagulants. Routine therapeutic monitoring is not required; however, monitoring may be needed in certain clinical conditions. Thrombin time or a modified plasma-diluted thrombin time (dTT) has been advocated for monitoring dabigatran therapy, but it has not been widely accepted as the standard practice. Instead, direct measurement of dabigatran level should be used if monitoring is indicated.