Coagulation tests are blood tests that measure the time it takes for an individual’s blood to clot under standardized conditions. When the body has been injured, blood clots form to stem bleeding. Without blood clots to stop the bleeding, a person would bleed to death.
By measuring how well and how long it takes a patient’s blood to clot, coagulation tests can help diagnose illness. Some conditions can prevent blood from clotting properly, whereas others may cause the blood to clot too easily or cause clots to remain in the body too long.
In addition, coagulation tests can be used to monitor patients taking anticoagulants (medications that decrease the ability of the blood to clot). Anticoagulant medications are often prescribed to patients after they have suffered a heart attack or stroke. Those with arrhythmia (irregular heart beats) may also take anticoagulants to prevent a first or recurrent stroke. Coagulation tests may also be ordered to evaluate a patient’s risk of excessive bleeding before surgery.
There are many types of coagulation tests. Some are general and tell only whether or not a person’s blood is clotting normally. Other tests can identify which element within the blood is causing abnormal clotting. There are also tests to measure how well the body destroys blood clots that are no longer needed.
About coagulation tests
Coagulation tests are blood tests that measure the time it takes for an individual’s blood to clot under standardized conditions. The clotting of blood is a necessary and life-sustaining function. Without it, excessive and potentially life-threatening amounts of blood would be lost from simple cuts or scrapes. However, clots that form too easily or stay in the body too long can cause a variety of health concerns. They may:
Obstruct blood flow in the deep veins embedded in the muscles, usually in the lower leg and sometimes in the lower abdomen or groin (deep vein thrombosis). While deep vein thrombosis may cause no symptoms, there is a high risk of either the whole blood clot or a piece of the blood clot breaking off and traveling through the bloodstream. If the traveling material lodges in one of the arteries of the lungs, then a potentially fatal pulmonary embolism could result.
Obstruct blood flow in one of the arteries, causing tissue death (necrosis) from a lack of oxygen-rich blood supply to the body’s tissues.
Break off and travel to the heart (causing a coronary embolism) or the brain (causing a cerebral embolism). If the resulting obstruction of blood flow to these vital organs is severe, it could trigger a heart attack or stroke.
Coagulation tests are designed to identify any of these types of clotting problems. There are three main reasons coagulation tests may be ordered:
To monitor patients on regular anticoagulant medications and make changes to the dosages as needed. Patients taking anticoagulants generally have regular blood coagulation tests to guide the physician in managing the dosages of anticoagulant medication.
To diagnose bleeding disorders. For example, thrombotic thrombocytopenic purpura is a condition in which the formation of small blood clots throughout the body can cause widespread damage to many organs.
To test patients before surgery to evaluate their risk of bleeding problems either during or after the procedure.
Coagulation tests are performed on samples of the patient’s blood that are sent to a clinical laboratory for analysis. The results are compared with the “normal range” established for each laboratory. “Normal ranges” may vary slightly from lab to lab.
Types and differences of coagulation tests
Coagulation tests fall into three categories: general tests, factor-specific tests and tests that measure the destruction (lysis) of blood clots.
General coagulation tests provide a basic indication of the blood’s ability to clot. These tests cannot determine the exact nature of a clotting problem, but some can indicate whether a clotting problem is due to an intrinsic (inside the body) or extrinsic (outside the body) factor. These tests are used for a variety of purposes, including screening for a coagulation problem and monitoring the treatment of patients on anticoagulants. The most common general coagulation tests are the following:
INR/prothrombin time. This test is frequently used to monitor patients taking warfarin, a powerful anticoagulant. Because of variability from lab to lab and different clotting agents used during the test, results are usually expressed as the International Normalized Ratio (INR). This measure was developed by the World Health Organization so physicians could compare results among labs.
Prothrombin is a protein substance that must be converted to thrombin in order for clotting to occur. The time this process takes to form a clot is called the prothrombin time. A normal range is from 10 to 20 seconds. Besides warfarin therapy, an abnormal prothrombin time may indicate vitamin K deficiency, severe liver disease or a deficiency in various blood clotting factors.
Activated partial thromboplastin time (APTT or PTT). This test measures all the coagulation reactions that occur inside the body (intrinsic), except for platelet aggregation. It measures the time it takes for a blood clot to form after an aggregating agent has been added to the blood sample. Normal time ranges from 25 to 36 seconds. This test is used to monitor patients on heparin therapy. Heparin is an anticoagulant.
Bleeding time. A test in which three small scratches are made on the patient’s skin and then the time it takes for the bleeding to stop is recorded. It is used to assess the integrity of platelet function.
Activated clotting time (ACT). This test is used to measure a patient’s clotting time before or during surgeries in which a slower clotting rate is desired. It has also become an important replacement test for the APTT test to monitor patients on heparin therapy. The normal range is from 94 to 120 seconds. During operations such as bypass surgery, physicians give their patients anticoagulants to slow their ACT to between 400 and 600 seconds.
Platelet aggregation. Platelets (thrombocytes) are the smallest type of blood cells. When an injury occurs, platelets clump together (aggregate) to form a blood clot that will stop the bleeding. The platelet aggregation test is one of several coagulation tests used to measure the rate and degree to which the platelets (in a sample of blood plasma) form clumps after the addition of a material that stimulates aggregation.
Plasma thrombin time (also called thrombin time or thrombin clotting time). This is the time that it takes for clots to form in the blood sample when a set amount of bovine (cattle) thrombin is added to a sample of the patient’s blood that has very few platelets. Thrombin changes fibrinogen (Factor I) to fibrin, the active component of blood clotting. Measuring the conversion of fibrinogen to fibrin, allows for a quick analysis of how much fibrinogen is in the blood. Normal thrombin time ranges from 10 to 15 seconds. A prolonged result will usually lead to additional and more specific testing, such as the one-stage factor assays.
Plasma fibrinogen. This test directly measures the levels of fibrinogen in the blood. Normal ranges are from 195 to 365 milligrams per deciliter.
Factor-specific coagulation tests can help physicians pinpoint which coagulation factor is causing a clotting problem. Deficiencies of a particular clotting factor are often inherited, but some can be the result of other illnesses. Factor-specific coagulation tests include:
One-stage factor assay. This test can determine which factor is the cause of a coagulation problem. The actual testing procedure can vary according to which clotting factor is being evaluated. The patient’s plasma is diluted and then mixed with another sample of plasma in which the factor being tested is not present. The activity of the mixture is then compared to the activity of the patient’s blood. Normal ranges vary from 50 to 150 percent. If the clotting time for the mixture is longer than for the patient’s blood then the patient has a deficiency of that blood factor. This would be indicated by a test result of less than 50 percent. The results of the PT and APTT tests determine which additional clotting factors need to be tested, as shown below:
When both PT and APTT are abnormally long, then factors in the extrinsic coagulation system will be tested. These include factors II, V or X.
When PT is normal, but APTT is abnormal, factors in the intrinsic coagulation system will be tested. These include factors VIII, IX, XI or XII.
Thromboplastin generation test (TGT). This test is used to differentiate between factor VIII clotting problems (as seen in hemophilia A) and factor IX clotting problems (as seen in hemophilia B).
Fibrinopeptide A. This substance is released as a part of the normal clotting process. This test is used to indicate the severity of a clotting condition called disseminated intravascular coagulation (DIC), a serious bleeding disorder in which the clotting and clot-dissolving properties in the body are activated not just at the site of an injury, but throughout the entire body. It may also indicate leukemia, cellulitis or certain infections. Normal ranges vary from 0.6 to 1.9 milligrams per milliliter.
Lysis tests evaluate the process by which blood clots are destroyed. Blood clots provide a temporary but vital service in the body – they inhibit the loss of blood through a wound so the body has a chance to heal. Since a blood clot is not needed forever, the body eventually releases a substance called plasmin to break it up. The following tests are used to evaluate this destruction process (lysis):
Plasma plasminogen. Plasminogen is the inactive form of plasmin, the substance that breaks up blood clots. Plasmin can only be measured in its inactive form. Normal plasminogen levels range from 10 to 20 milligrams per deciliter. The value is sometimes expressed in units per deciliter, in which case the normal ranges are from 80 to 120.
Fibrin split products (or fibrin degradation products). The products that are created during the break up of clots are called fibrin split products. The presence and levels of fibrin split products in the blood can give physicians valuable information about the patient’s coagulation status. Normal levels are 3 to 10 micrograms per milliliter.
Protein C. This substance is produced in the liver and inhibits blood clotting by suppressing factors V and VIII. This test is made only if others have not been able to determine the reason why patients are prone to repeated blood clots. A deficiency of this protein is rare, but may be the cause of unexplained blood clots. Normal ranges from 70 to 140.
Euglobulin lysis time (or lysis time). This test measures the time interval between when a clot is formed to when it is dissolved. Normal lysis time is at least two hours, but normal values may range between 90 minutes and six hours. Abnormally brief lysis time indicates that the body is destroying blood clots too quickly, and abnormally long lysis time indicates that the body is destroying blood clots too slowly.
Factors that may affect coagulation test results
Patients may be asked to avoid eating or to eat only nonfat foods for eight to 12 hours prior to testing. They may also be asked to stop taking certain medications that could interfere with the accuracy of the test. These medications include some types of:
Nonsteroidal anti-inflammatory drugs (NSAIDs). Medications that reduce pain and inflammation by inhibiting the production of certain chemicals in the body.
Aspirin. While typically used as a pain-reliever (analgesic), aspirin is also an NSAID and an antiplatelet that inhibits the formation of blood clots.
Inotropes. Medications that strengthen the contractions of the heart so that the heart can circulate more blood with fewer beats.
Diuretics. Medications that promote the formation of urine in the kidneys, causing the body to flush out fluids and minerals.
Antibiotics. Medications that harm or kill microorganisms and are commonly used to treat infections.
Antihistamines. Medications used to treat histamine releases such as those that cause nasal congestion, allergic skin rashes and hives.
Sedatives. Medications used to promote relaxation or to induce sleep.
Progestin-estrogen combinations. This combination of synthetic hormones is often used in birth control pills and hormone replacement therapies.
Antidepressants. Medications used in the treatment of depression.
Vitamin K. Vitamin K is necessary to the natural formation of blood clots. Use of supplements could potentially lead to elevated coagulation test levels.
Abnormal coagulation test results
Longer than normal (prolonged) results for a coagulation test means that the patient's blood is taking more time to coagulate (clot) than it should or is not clotting at all. Additional testing will usually be ordered to determine the cause. For patients taking anticoagulants, an abnormal coagulation test will usually result in a change in the dosage or type of anticoagulant medication prescribed.
Clotting times can be affected by a deficiency in certain clotting factors in the blood or by the presence of:
Anticoagulants. Medications that inhibit clotting.
Fibrin split products.
Fibrinolysins.
Clotting factor antibodies. Substances that attack and destroy certain clotting factors. These can be produced in the body or be introduced by certain medications. Deficiencies in one or more clotting factors can cause a variety of health concerns, including:
Liver disease.
Vitamin K deficiency.
Disseminated intravascular coagulation (DIC). A serious bleeding disorder in which the clotting and clot-dissolving properties in the body are activated not just at the site of an injury, but throughout the entire body.
Fibrinogenolysis. A condition in which plasma fibrinogen degrades, making the blood unable to clot.
Hemophilia. A hereditary bleeding disorder caused by a deficiency of coagulation factor VIII (hemophilia A) or factor IX (hemophilia B).
Platelet disorders.
Cancer of the prostate, pancreas, kidney, breast, lung or bone marrow.
Pregnancy complications.
Inflammatory disorders. Conditions that cause body tissues to become inflamed, usually resulting in pain or stiffness in the joints, back or shoulders.
13 coagulation factors
Scientists have identified 13 distinct coagulation factors involved in clot formation. They are referred to by the Roman numerals I to XIII. Many of the factors can also be broken down into sub factors that are indicated with a letter (e.g., Factor Xa). The factors are not listed in the order they occur, but in the order they were discovered. For example, scientists learned about Factor I before Factor II, but Factor II actually causes Factor I.
Scientists are learning how these coagulation factors relate to cardiovascular disease. For instance, Factor V Leiden and Factor II prothombin (see below) each plays a major role in the risk of deep vein thrombosis (DVT), a condition in which a blood clot in the larger veins interferes with circulation. Other inherited clotting abnormalities have been associated with heart attack in some patients.
It is not important for most people to understand the complex reactions that result in blood clots. However, it may be helpful for people to know the different terms that are used to describe the coagulation factors involved:
Factor I (Fibrinogen). A substance that is converted to fibrin, one of the main components of blood clotting.
Factor II (Prothrombin). A substance that is converted to thrombin, which converts fibrinogen to fibrin.
Factor III (Tissue factor or tissue thromboplastin). A part of the blood cell that causes the primary reaction that initiates coagulation.
Factor IV (Calcium). Factors VII, IX, X and XIII can only be activated in the presence of calcium.
Factor V Leiden (Proaccelerin, accelerator globulin, labile factor). A substance that activates prothrombin and is also involved with platelets and protein C.
Factor VI (Accelerin). This is the same as a subset of Factor V (Factor Va). Some sources disregard Factor VI and list only 12 coagulation factors.
Factor VII (Proconvertin, cothromboplastin, serum prothrombin conversation accelerator). A substance that binds to Tissue Factor then forms Factor VIIIa and activates factors IX and X.
Factor VIII (Antihemophilic globulin). A substance that is similar to Factor V and activates other parts of the coagulation process.
Factor IX (Christmas factor). A substance that reacts with other factors to activate Factor X.
Factor X (Stuart-Prower factor). A substance that reacts with other factors to activate Prothrombin.
Factor XI (Plasma thromboplastin antecedent, Fletcher factor [or prekallikrein] and high molecular weight kininogen). A complex chain reaction that catalyzes other parts of the coagulation process.
Factor XII (Hageman Factor or contact factor). A substance that reacts with other factors to activate Factor XI.
Factor XIII (Fibrin stabilizing factor and protein C). A complex chain reaction that stabilizes the blood clot, basically halting new coagulation.
Questions for your doctor
Preparing questions in advance can help patients have more meaningful discussions with their physicians regarding their conditions. Patients may wish to ask their doctor the following questions about coagulation tests:
Why do I need coagulation tests?
What, specifically, are you testing for?
Do I have any conditions that put me at increased risk of cardiovascular conditions that should be monitored with coagulation tests?
Do I take any medication that should be monitored with coagulation tests?
How often should I have a coagulation test?
Do I need to alter my medication usage or do anything else to prepare for the test?
What can I expect during the test?
When and how will I be informed of my test results?
What do my test results indicate?
Is any follow-up testing needed?
Do my results show a need for treatment? If so, what are my treatment options?
Frequency of coagulation testing
Patients taking anticoagulants may need to undergo coagulation testing on a regular basis to monitor their medication dosage. Traditionally, these tests have required the patient to visit a hospital, doctor's office or laboratory on a monthly or bimonthly basis. However, coagulation clinics are now available at various medical centers in large cities to manage the long-term treatment of people taking anticoagulants. Furthermore, the Food and Drug Administration recently approved a coagulation test that can be self-administered at home. Patients interested in these at-home tests should consult their physician for more information.
