To help determine the cause of or potential for excessive bleeding and/or to diagnose a platelet function disorder; to monitor and evaluate platelet function; to monitor the presence and effectiveness of anti-platelet medications
Platelet Function Tests
When you bruise easily or experience excessive or prolonged bleeding from minor cuts, nose or gums, or excessive menstrual bleeding; when you are taking medications that can alter platelet function; prior to or during certain surgeries; if you have a family member with a history of excessive bleeding
A blood sample drawn from a vein in your arm
You may be instructed to refrain from taking drugs that can affect the results of these tests, such as aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), or any over-the-counter medications that contain drugs such as these, anti-histamines, and certain antibiotics. The most common NSAIDs include ibuprofen, naproxen and COX-2 inhibitors. However, do not stop taking your medications unless instructed to do so by your healthcare practitioner.
Platelets (also known as thrombocytes) are small, round cellular fragments that are vital for normal blood clotting. Platelet function tests indirectly evaluate how well a person's platelets work in helping to stop bleeding within the body.
Platelets are produced in the bone marrow and circulate in the blood. When there is an injury to a blood vessel and bleeding begins, platelets are the first elements to help to stop bleeding. They do so in three ways. They:
- Adhere to the injury site
- Clump together (aggregate) with other platelets, forming a temporary plug
- Release compounds that stimulate further aggregation and the eventual formation of a blood clot
These reactions result in the formation of a loose platelet plug in a process called primary hemostasis. At the same time, activated platelets support the coagulation cascade, a series of steps that involves the sequential activation of proteins called clotting factors. This is called secondary hemostasis and the two processes result in the formation of a stable clot that remains in place until the injury has healed.
If there are insufficient platelets or if they are not functioning normally in any of the three main ways, a stable clot may not form and a person may be at an increased risk of excessive bleeding. The number of platelets in blood can be determined with a platelet count and can help diagnose disorders having to do with too many or too few platelets. However, the overall ability of platelets to function properly in the body is more difficult to measure.
Platelet function tests are a group of assays that use specialized equipment to measure the ability of platelets to aggregate and promote clotting in a sample of blood. There are a variety of tests available but no one test that identifies all problems with platelet function. Also, there is no widespread agreement on which test(s) is best for each circumstance.
In addition to evaluating people for excessive bleeding, platelet function tests may be used in other situations. There are situations in which it is desirable to decrease the ability of platelets to aggregate, as in for people who are at an increased risk of developing a dangerous blood clot or at increased risk for heart attacks. These people may be prescribed medications that reduce platelet activation or reduce their ability to aggregate. People on these types of anti-platelet medications, such as low-dose aspirin or clopidogrel, may have platelet function tests done as a way of monitoring their treatment. However, there is currently no consensus among medical experts on the usefulness of platelet function tests in anti-platelet therapy.
In the past, the primary screen for platelet dysfunction was the bleeding time or the standardized bleeding time. This was the only test that directly measured platelet function within the body. It involves making two small, shallow, standardized cuts on the inner forearm and measuring the amount of time for bleeding to stop. The bleeding time procedure has fallen from favor in recent years. Many hospitals no longer offer it and several national organizations have issued position statements against its routine use. The bleeding time is not sensitive or specific and it does not necessarily reflect the risk or severity of surgical bleeding. It is poorly reproducible, can be affected by aspirin use and by the skill of the person performing the test, and frequently leaves small, thin scars on the forearm.
Closure time assays
This test measures the time required for the platelets in a sample of blood to plug a small hole in a tiny tube after being exposed to various activating substances. This is called the closure time. Prolonged closure times indicate lower platelet function but do not identify the cause. This test may be abnormal if the platelet count is low, if platelet function is reduced, if other proteins needed for platelet function are reduced, or if anti-platelet medications are present. This type of assay can be used to screen for von Willebrand disease and some platelet function disorders, but it will not detect all platelet function disorders, particularly the milder forms. This test is relatively simple to perform and is available in many healthcare facilities. Further testing would need to be performed in order to identify the exact cause of any abnormal results.
Viscoelastometry (or Thromboelastometry)
Blood clots have to be strong to stop bleeding and prevent new bleeding until healing can occur. This type of testing is designed to determine the strength of a blood clot as it forms. It is most often performed in larger hospitals, either in the operating room as a point-of-care test or in the clinical laboratory.
Endpoint bead or endpoint platelet aggregation assays
These assays determine the number of coated beads or platelets that aggregate after substances are added to activate platelets in a sample of blood. They provide a single measure of aggregation (an endpoint) rather than a measure of aggregation over time. More platelets aggregating or sticking to beads indicates better platelet function. These tests may be abnormal if the platelet count is low, if platelet function is reduced, or if anti-platelet medications are present.
Platelet count ratio
The number of platelets are measured in an initial sample. A substance is added to the sample to activate the platelets and cause them to aggregate. The number of platelets is measured again – only those that have not aggregated will be counted the second time. The difference between the first measurement and the second measurement is an indication of platelet function.
Many different substances can activate a platelet, including proteins in the wound, factors released from other activated platelets, and factors produced by the coagulation system that aids platelets in forming a strong plug to stop bleeding. Many different platelet abnormalities have been described due to problems with one or more of these activating systems. Platelet aggregometry consists of 4 to 8 separate tests. In each test, a different platelet activating substance (agonist) is added to blood, followed by measurement of platelet aggregation over several minutes. When complete, the entire panel of tests is reviewed and interpreted to determine if there is any evidence of abnormal platelet function. Platelet aggregation testing is the gold standard in platelet function testing and can diagnose a variety of inherited and acquired platelet function disorders. It is typically performed at academic medical centers or large hospitals due to the complexity of the testing and interpretation.
Similar to platelet aggregometry, lumiaggregometry simultaneously measures the release of certain organic agents from platelet granules (little sacs within the platelet) utilizing a luminescence technique. This technique measures the amount of light emitted when activating substances are added, that results in the conversion of ADP (adenosine diphosphate) to ATP (adenosine triphosphate). This measurement reflects any abnormalities that may be present in platelet granules, a problem with patients with 'storage pool defects' that are often seen in grey platelet syndrome, Hermansky-Pudlak syndrome, and Chediak-Higashi syndrome.
Platelets can be evaluated for functional defects using flow cytometry. This test uses lasers to determine proteins that are present on the platelet surface and how they change when the platelet is activated. Platelet flow cytometry is a highly specialized procedure available only in a few university hospital and reference laboratories to diagnose inherited platelet function disorders.
A blood sample is drawn though a needle from a vein in the arm. Due to critical time constraints related to platelet activation/ function, you may be sent directly to the laboratory performing the tests. If you have a history of excessive bleeding, you should inform the healthcare practitioner drawing your blood.
In general, no test preparation is needed. However, you may be instructed to refrain from taking drugs that can affect the results of these tests, such as aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), or any over-the-counter medications that contain drugs such as these. The most common NSAIDs include ibuprofen, naproxen, and COX-2 inhibitors. (See MedlinePlus Drugs & Supplements for more information on drugs, drug ingredients, and brand names.) However, do not stop taking your medications unless instructed to do so by your healthcare practitioner.
- How is it used?
Various platelet function tests are used to evaluate the ability of platelets to clump together and begin to form a clot. They may be used for a variety of reasons. Examples of some of the situations in which they may be used include:
- To identify and help diagnose platelet dysfunction in those with a history of excessive bleeding. It is in this area that platelet function tests are of the most use. They can be used to screen for dysfunction and, along with other bleeding disorder tests, to help diagnose inherited and acquired platelet dysfunctions. von Willebrand disease, for instance, is the most common inherited disorder that is assoicated with platelet dysfunction. Decreased production or dysfunction of von Willebrand factor (VWF) results in reduced platelet adherence to the injured blood vessel and increased blood loss.
- To monitor platelet function during complex surgical procedures, including cardiopulmonary bypass surgery, cardiac catheterization, liver transplantation, and trauma surgery. For example, those undergoing cardiopulmonary bypass surgery are given anticoagulants to reduce blood clotting, resulting in an increased risk of excessive bleeding. At the same time, bypassing the heart and mechanically circulating the blood activates large numbers of platelets and causes them to become dysfunctional. Monitoring the number of platelets in blood (platelet count) during cardiac surgery also helps the healthcare practitioners maintain a delicate balance between bleeding and clotting.
- To screen at-risk pre-surgical patients who have a personal or family history of bleeding. Healthcare practitioners currently evaluate a person for known risk factors and rely on the person's clinical history and results of other coagulation tests such as PT and PTT to determine the overall risk of excessive bleeding. There is no single platelet function screening test that will definitively predict which people are likely to bleed during surgery. Interestingly, studies have shown that platelet function tests are not useful for predicting bleeding risk in people taking anti-platelet medications such as aspirin, clopidogrel, or non-steroidal anti-inflammatory drugs (NSAIDs).
- To monitor anti-platelet therapy given to some people after a stroke or heart attack to help inhibit blood clotting. Currently, most anti-platelet therapies are not routinely monitored with platelet function testing. As more anti-platelet therapies are created, it is anticipated that additional methods will be developed to monitor them.
- To detect aspirin resistance. Low-dose aspirin is being prescribed as an anti-platelet therapy to many people who have had a cardiovascular incident, such as a heart attack or stroke. Some people on this therapy who have another heart attack are thought to have aspirin resistance. At present, aspirin resistance is a somewhat vague term, with no consensus on its definition, how many people are affected by it, or on how to measure it. There are questions as to whether testing can predict what will happen in an individual person, whether the resistance will persist or be transient, and whether it is also associated with resistance to other anti-platelet therapies such as clopidogrel. While these tests are becoming more widely available and easy to perform, there is still lack of agreement on how to alter therapy based on the results. Most agree that there is still much work to be done on determining its clinical relevance.
Platelet function testing may include one or more of the following:
- Closure time assay
- Bleeding time
- Platelet aggregometry/Lumiaggregometry
- Flow cytometry
For a more detailed explanation of these tests, read the "What is being tested?" section.
Some other tests that may be done in conjunction with or as follow up to platelet function tests to evaluate platelet disorders include complete blood count (CBC), platelet count, PT, PTT, D-dimer, and von Willebrand factor (vWF).
- When is it ordered?
One or more platelet function tests are ordered whenever a healthcare practitioner wants to evaluate platelet function. This may be:
- When a person is experiencing symptoms of platelet dysfunction, such as excessive bleeding; these include easy bruising, frequent nosebleeds, heavy menstrual bleeding, bleeding gums, excessive bleeding during dental procedures, etc.
- Prior to surgery or other invasive procedure
- During surgery, especially prolonged procedures
- When a person is taking a medication that can have an effect on platelet function
- What does the test result mean?
The interpretation of results of the various types of platelet function tests depends on why the tests were performed.
In the investigation of excessive bleeding or the potential for bleeding during surgery, abnormal results may indicate the presence of a platelet disorder. Testing for coagulation factor deficiencies or abnormalities (bleeding disorder tests) in addition to clinical evaluation is often necessary to identify an inherited disorder or acquired condition as the cause of the dysfunction. Often, family studies may be required to determine if the abnormality is inherited or acquired.
Examples of inherited platelet function disorders include:
- Von Willebrand disease – decreased production or dysfunction of von Willebrand factor results in reduced platelet adherence to the injured blood vessel and increased blood loss
- Glanzmann's thrombasthenia – affects platelets' ability to aggregate
- Bernard-Soulier syndrome – characterized by reduced platelet adhesion
- Storage pool disease – can affect platelets' ability to release substances that promote aggregation
Acquired platelet dysfunction – those that are not inherited – may be due to chronic conditions such as:
- Kidney failure (uremia)
- Myelodysplastic syndrome (MDS)
- Certain leukemias (chronic myeloid leukemia or CML; acute myeloid leukemia or AML)
Some acquired platelet disorders that are temporary include:
- Decreased function due to medications like aspirin and non-steroidal anti-inflammatory drugs
- Abnormal function after prolonged cardiac bypass surgery
When a person is on an anti-platelet medication, such as aspirin, the results of testing reflect the platelet response to the medication.
- Is there anything else I should know?
Platelet function testing is not a perfect reflection of the clotting process in the body (in vivo). A person with normal platelet function test results may still experience excessive bleeding or inappropriate clotting during and after a surgery.
Most samples for platelet function testing are only stable for a very short period of time. Testing choices are often limited to what is locally available.
There are several drugs that can affect the results of platelet function tests. Some of these include:
- Aspirin and aspirin-containing compounds (salicylates)
- Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and any over-the-counter medications that contain NSAIDs
- Tricyclic antidepressants
- Some antibiotics
- Some supplements (including garlic, turmeric, cumin, gingko biloba)
- Should everyone have platelet function tests?
Many people will never need to have platelet function testing performed. It is generally only indicated when someone is experiencing bleeding, on specific medications, or having certain surgeries. The tests are not indicated for general screening.
- Can my healthcare practitioner choose from a variety of platelet function tests?
Typically, a hospital or laboratory will offer one or more tests but not a wide variety. Since the sample must be tested promptly, your healthcare practitioner will choose from what is available. Rarely, if a healthcare practitioner wanted a particular type of test done, then it might be necessary for you to go to a clinic, hospital, or another city where that test is performed.
- Will my platelet function change over time?
It could. While some conditions associated with platelet dysfunction are inherited, others are acquired and may occur at any point in your life. Platelet dysfunction that is due to a chronic disease may persist but can generally be managed. Dysfunction due to medication will typically resolve once the medication is discontinued.