Platelet dysfunction may be acquired, inherited, or induced by platelet-inhibiting agents. It is clinically important to assess platelet function as a potential cause of a bleeding diathesis (epistaxis, menorrhagia, postoperative bleeding, or easy bruising). The most common causes of platelet dysfunction are related to uremia, liver disease, von Willebrand’s disease (vWD), and exposure to agents such as acetyl salicylic acid (ASA, aspirin). Bleeding time (BT) had been the most commonly performed test to evaluate platelet function. However, BT is labor intensive and expensive, and its accuracy depends heavily on operator skills. Its results cannot be reproduced and quantified. Platelet aggregation studies have similar accuracy problems. As a result, more clinical laboratories are using the platelet closure time (CT) to accurately quantify platelet function. This test is often called a Platelet Function Screen. CT can differentiate aspirin effects from other causes of platelet dysfunction.
Platelet closure time is used to identify platelet dysfunction in patients who are suspected of having a bleeding abnormality. This test can identify abnormalities in the ability of platelets to aggregate or instigate the hemostatic cascade. It is used for patients with a family or personal history of acute excessive bleeding.
Closure times are performed on a system (platelet function analyzer) in which the process of platelet adhesion and aggregation following a vascular injury is simulated in vitro. Anticoagulated whole blood is passed over membranes at a standardized flow rate, creating high shear rates that result in platelet attachment, activation, and aggregation on the membrane. A hole in the membrane is occluded when a stable platelet plug develops. The time required to obtain full occlusion of the aperture is reported as the closure time (CT) in seconds.
This test is sensitive to platelet adherence and aggregation abnormalities and allows the discrimination of aspirin-like defects and intrinsic platelet disorder. Two different membranes consisting of collagen/epinephrine (CEPI) and collagen/adenosine-5′-diphosphate (CADP) are used. The CEPI membrane is used to detect platelet dysfunction induced by intrinsic platelet defects. Follow-up testing using the CADP (a potent platelet anti-aspirin stabilizer) membrane enables the discrimination of aspirin effects.
This test can also be used to determine any resistance to the therapeutic effects of aspirin on platelets. While aspirin remains a crucial and cost-effective therapy for the prevention and management of cardiovascular diseases, research suggests that a significant percentage of the 25 million Americans on a chronic aspirin regimen are “aspirin resistant,” or do not achieve sufficient antiplatelet effects from aspirin. Previous studies have shown that aspirin resistance is associated with triple the risk for heart attack, stroke, and death. Once patients are tested and identified as aspirin resistant, physicians may opt for an alternative approach to therapy, which may include increasing the dosage of aspirin or placing the patient on another antiplatelet medication. Up to 27% of patients with coronary artery disease (CAD) who use aspirin are resistant to its antiplatelet effects. Women, the elderly, and those taking lower doses of aspirin are most likely to be aspirin resistant.
There are now quick and easily performed ELISA urine tests to determine the effect of aspirin on the platelets. These aspirin resistance tests measure 11-dehydrothromboxane B2, a stable thromboxane metabolite, in the urine. Aspirin’s protective action is believed to be the result of its ability to inhibit the cyclooxygenase-1 pathway in the platelet that results in the generation of thromboxane A2, initiating the blood clotting process. Early research suggests that a positive test for aspirin resistance raises the possibility that the patient may be clopidogrel (Plavix) resistant as well.
Drugs that case False Measurement of Platelet Closure Time
It is very important to review the patient’s drug history to determine whether the patient has recently had aspirin, anticoagulants, or any other medications that may affect test results. Platelet Closure Time is affected by the following drugs:
- Aspirin and Non-steroidal Antiarthritic Agents (NSAIDS) may increase the Platelet Closure Time and lead to false test results. These medications prevent blood from clotting by blocking the production of thromboxane A2, a chemical that platelets produce that instigates platelet aggregation. Aspirin accomplishes this by inhibiting the enzyme cyclooxygenase-1 (COX-1) that produces thromboxane A2.
- Thienopyridines may also increase Platelet Closure Time leading to false test results. When ADP attaches to ADP receptors on the surface of platelets, the platelets clump. The thienopyridines (e.g., ticlopidine [Ticlid] and clopidogrel [Plavix]) block the ADP receptor, which prevents ADP from attaching to the receptor and the platelets from clumping.
Normal Platelet Closure Time
When Platelets are functioning properly their closure time shouldn’t 175 seconds.
Causes of Prolonged Platelet Closure Time
Intrinsic Platelet defects leads Platelet malfunction which causes abnormally longer Platelet Closure Time. This is usually associated with conditions including:
- Myeloid Leukemia.
- Hereditary Telangiectasia.
- Myeloproliferative Disorders.
- Bernard-Soulier Syndrome.
- Glanzmann Thromboasthenia.
- Hermansky-Pudlak Syndrome.
Defects in the interaction of Platelets and Injured Blood Vessels create an inability of the platelets to aggregate leading to abnormally long Platelet Closure Time. This can be caused by the following diseaes:
- Von Willebrand disease.
- Collagen-vascular disease.
- Cushing Syndrome.
- Henoch-Schönlein Syndrome.
- Connective Tissue Disorder.