Fibrin Degradation Products Test

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Fibrin degradation products test

Definition

When injury occurs to a blood vessel wall, thrombin (a coagulation enzyme) is formed in the first stage of a complicated series of steps called the coagulation cascade. In the second phase, fibrinogen, a coagulation protein made by the liver , is converted to fibrin, which results in the formation of a gel-like meshwork at the site. This fibrin mesh is altered by the action of factor XIIIa which cross-links fibrin polypeptides, forming a stable clot. As the site heals, the clot is broken down by the enzyme plasmin. This process, called fibrinolysis, is initiated by a protein called tissue plasminogen activator that is released from blood vessel cells adjacent to the injured site. Plasminogen activator converts plasminogen to an enzyme called plasmin. The plasmin splits polypeptides from the fibrin clot. These fragments are known as fibrin degradation products (FDP).

Fibrin degradation products are fragments (polypeptides) produced when either fibrin or fibrinogen is broken down by the enzyme plasmin. There are four principal fibrin degradation products called X, Y, D, and E that are liberated in various combinations. When a fibrin clot is broken down by plasmin, the last fragment to be degraded is one consisting of two D and one E subunits. This is split, releasing the E fragment and two D fragments that are covalently linked together. This fragment is called D-dimer, and it is produced from fibrin but not from fibrinogen degradation.

Purpose

A test for FDP may be requested by a physician when excessive bleeding occurs and thrombosis or other serious disorder in the coagulation mechanism is suspected. The FDP assay measures amounts of the fibrin and fibrinogen split products in the blood and directly indicates the level of activity of the fibrinolytic system. High levels of FDP will indicate increased fibrinolysis. Excessive fibrin degradation products are released into the plasma in three main conditions: disseminated intravascular coagulation (DIC), thromboembolytic therapy, and primary fibrinogenolysis. Fragments X, Y, E, and D are released whenever either fibrin or fibrinogen is broken down by plasmin. This degradation occurs in all three situations.

Normal blood plasma does not have significant amounts of D-dimer. It is present in the blood in detectable amounts in several conditions, most notably in disseminated intravascular coagulation (DIC), a rare disruption in normal coagulation in which rapid intramicrovascular (within the blood vessels ) coagulation occurs at the same time as fibrinolysis (clot dissolution mechanism). The D-dimer test is used to diagnose DIC. It is also frequently used to help diagnose deep-vein thrombosis (clots in veins); pulmonary embolism (clots in the lungs ); the thrombosis of malignancy; and sickle cell anemia (a form of anemia characterized by bleeding episodes); and to monitor the effects of thrombolytic drugs. Thrombolytic drugs that may increase D-dimer levels are barbiturates, heparin, streptokinase, and urokinase. Levels of D-dimer will be elevated in these conditions.

Description

When functioning normally, coagulation and fibrinolysis maintain hemostasis (the normal fluid state of blood in the circulatory system) by regulating clot formation and dissolution. When bleeding occurs, coagulation results in production of a clot at the site of injury, and subsequent fibrinolysis dissolves the clot as the vessel wall heals. The fibrinolytic system is highly complex. A deficiency of plasminogen will result in increased risk of thrombosis. Plasmin is inactivated by several proteases, which are enzymes that catalyze the breakdown of polypeptides. A deficiency of one of these can result in spontaneous bleeding. FDPs themselves can neutralize the activity of some coagulation factors and interferere with normal clot formation. In three conditions, disseminated intravascular coagulation, thromboembolytic therapy, and primary fibrinogenolysis the fibrinolytic activity of the plasma is increased. When this occurs, depletion of coagulation factors, including fibrinogen, results in uncontrolled bleeding. Measurement of FDP and D-dimer are used to identify these causes of hemorrhage.

DIC results in the formation of circulating small fibrin clots formed by a condition that triggers the coagulation cascade. Coagulation factors become depleted and hemorrhage results. DIC is a rapidly progressing condition caused by an underlying disease or trauma, such as the clinical conditions shown below.

complications of pregnancy , such as toxemia, abortion, cesarean section, placenta previa , and other conditions
tissue trauma, such as major surgery, severe trauma and burns , rejection of transplant, and heatstroke
hemolytic processes (destruction of red blood cells), such as transfusion of mismatched blood, drowning, complications of infection , and certain types of poisoning
malignancies, such as solid tumors, leukemia, and other forms of cancer
infections, such as bacterial infections, septicemia, Rocky Mountain spotted fever , some viral infections, and parasitic infections
miscellaneous clinical conditions, such as diseases of the liver and pancreas , uremia, shock , stroke, severe heart failure , and aortic aneurysm (rupture of the aorta)

Coronary artery disease can result in the formation of a blood clot at the site of blockage in the heart vessels. One alternative form of treatment is the administration of a thrombolytic agent such as streptokinase or tissue plasminogen activator. These drugs act by stimulating fibrinolysis, and consequently they may cause both the fibrin clot and fibrinogen to break down. Fibrinogen depletion and accumulation of FDP can interfere with coagulation, causing spontaneous hemorrhage.

Primary fibrinogenolysis is a condition in which fibrinogen is broken down to fibrin in the absence of a clot. Unlike DIC, the formation of intravascular thrombi does not occur. However, if severe, hemorrhage can result because the body's supply of fibrinogen becomes depleted. Causes include shock, hypoxia, heat stroke, hemorrhage, surgery, and liver disease.

FDP tests will yield abnormal results in all three conditions described above because the fragments detected are produced when either fibrin or fibrinogen is split by plasmin. Therefore, the FDP test is not specific for thrombotic diseases such as DIC or deep vein thrombosis. The FDP test uses latex particles coated with anti-D and anti-E. When mixed with plasma, these antibodies react with D and E fragments of both fibrin and fibrinogen, forming a clump.

The D-dimer test measures only the D fragments of fibrin that are covalently bound together. When a fibrin clot is stabilized by factor XIIIa, the D domains of adjacent molecules become linked together. The action of plasmin causes these to be released from the clot as a dimer, which is a molecule composed of two identical simpler molecules. Therefore, the D-dimer test will be positive only when fibrin degradation has occurred. This happens in DIC, after thromboembolytic therapy, and in such thrombotic conditions as deep vein thrombosis and pulmonary embolism, but does not occur in primary fibrinogenolysis.

D-dimer is detected by a latex agglutination test. Latex particles coated with anti-D that bind only to D-dimer are used. These particles will clump when mixed with serum that has an increased level of D-dimer. Since D-dimer levels parallel the amount of fibrinolytic activity in DIC, a quantitative test is often used to evaluate the severity of the disease. The test used is a two-site double antibody sandwich immunoassay.

Precautions

Blood for FDP testing is collected by venipuncture into tubes containing EDTA, citrate, or heparin anticoagulant. The nurse or phlebotomist performing this procudure should follow universal precautions for the prevention of transmission of bloodborne pathogens. Performing a venipuncture to obtain a blood sample for the D-dimer test may be contraindicated if the patient is exhibiting prolonged bleeding from other sites. In this case the nurse or phlebotomist should consult the testing physician, who will determine an alternate means of obtaining a blood sample (such as placement of a catheter). There are no other notable precautions associated with performing the D-dimer test.

Preparation

There is no special preparation for the D-dimer test. No fasting is required.

Aftercare

Following venipuncture to obtain blood samples for the D-dimer test, the laboratory technologist, nurse, or phlebotomist drawing the sample should apply pressure to the site to stop any residual bleeding. The venipuncture site should then be carefully inspected to make sure that the wound has closed and no bleeding is present. If bleeding continues even after pressure is applied, this event should be reported to the testing physician.

Complications

DIC often involves a rapidly changing hemostatic condition. Patients with DIC or thrombosis may be in serious condition and will likely not be ambulatory; more typically, patients with suspected DIC or thrombosis will be hospitalized. Nurses should be alert to any change in the patient's condition. Noticeable changes in the patient's condition at the time of venipuncture should be reported to the patient's physician. The venipuncture site should be examined for bleeding and any prolonged

KEY TERMS

D-dimer —A fibrin degradation fragment or product that is produced by the action of plasmin on fibrin in the clot dissolution process.

Disseminated intravascular coagulation (DIC) — A disruption in hemostasis in response to an underlying disease or trauma. It is associated with the release of a tissue factor that triggers coagulation and activates rapid thrombin formation and fibrinolysis throughout the vascular system.

Fibrin —A protein formed in the blood as an important component of the coagulation process.

Fibrin degradation products —Known also as fibrin split products, fibrin degradation products are formed when the fibrinolytic system is activated in response to the formation of clots in the vascular system. Fibrin degradation products, including D-dimer, will be present in fibrinolysis or thrombosis.

Fibrinolysis —The dissolution of clots by an activated fibrinolytic system. When clot formation occurs, the fibrinolytic system activates factors that lead to the formation of plasmin, which degenerates the fibrin in the clot.

Hemostasis —A regulating process that maintains blood in a fluid state and prevents the loss of blood through clot formation when the vascular system is compromised.

Plasmin —Plasmin is an enzyme formed in the activation of the fibrinolytic system to dissolve clots. Plasmin breaks down the fibrin in a clot into the fragments that are known as fibrin degradation products.

Thrombolytic drugs —Anticoagulants used to inhibit clotting. Thrombolytic therapy is used when increased fibrin degradation products are present, such as in patients who have had a heart attack or who have a compromised coagulation mechanism or a history of thrombosis.

Thrombosis —The presence of a clot or clots in the vascular system.

bleeding that cannot be stopped by applying pressure should be reported to the physician immediately.

Results

Reference ranges for FDP tests will vary according to the test method used and the laboratory performing the test. Qualitative results may be reported only as positive or negative. Typical FDP results are listed below.

Undiluted plasma is negative (no clumping): FDP is reported as less than 2 micrograms/mL.

A clumping reaction is reported as positive. If plasma is diluted, reporting is as follows:

If the undiluted plasma only is positive: equal to or greater than 2 mcg/mL but less than 10 mcg/mL.
If a 1:5 dilution of plasma is positive: equal to or greater than 10 mcg/mL but less then 80 mcg/mL.
If a 1:20 dilution is positive: equal to or greater than 80 mcg/mL.

D-dimer results are reported as follows.

Qualitative negative: less than 250 nanograms/mL.
Qualitative positive: equal to or greater than 250 ng/mL.
Quantitative: normally less than 250 ng/mL or less than 250 micrograms/L.

Health care team roles

A physician orders the FDP tests and interprets them. The testing physician must obtain an accurate patient history, especially to determine if the patient is taking any drugs that can affect the test results and to learn about any recent illness, trauma, or symptoms that could be related to DIC or thrombosis. The procedure should be explained to the patient by the unit nurse, who should be aware of the degree of seriousness of the patient's condition. FDP tests are performed by clinical laboratory scientists/medical technologists or by clinical laboratory technicians/medical laboratory technicians.

Training

Laboratory technologists performing D-dimer tests will have studied hematology and coagulation, enabling them to understand coagulation and the fibrinolytic system. Hands-on clinical laboratory training will prepare technologists to perform agglutination tests or monoclonal antibody tests for D-dimer. Nursing personnel responsible for patients undergoing D-dimer testing will understand the patient's condition and will be trained to observe changes that may signal a critical hemostatic event.

Resources

BOOKS

Jacobs, David S. Laboratory Test Handbook, 5th ed. Hudson, OH: Lexi-Comp Inc., 2001.

Pagana, Kathleen D., and Timothy J. Pagana. Manual of Diagnostic and Laboratory Tests.St. Louis, MO: Mosby, Inc., 1998.

"Hemostasis and Coagulation Disorders." Sec. 11, Chapter 131, Merck Manual Online, 17th ed. Whitehouse Station, NJ: Merck & Co., Inc. 2001. <http://www.merck.com/pubs>.