What Are Platelets?
Platelets (thrombocytes) are cells in the blood that clump together to begin the clotting process. They are usually one of the first responders when there is injury and help initiate the inflammatory response of the innate immune system.
The four main platelet functions are:
- Adherence to each other
- Taking part synergistically with other coagulation factors
As necessary as platelets are, also necessary is their proper functioning, neither under-active nor hyperactive:
- Decreased platelet activation impairs clotting and results in bleeding
- Increased platelet activation results in their aggregating together to obstruct blood flow in veins risking pulmonary emboli, or in arteries risking ischemia to tissues beyond the clot
There are conditions when decreasing platelet function is desirable and for which antiplatelet medication is indicated:
- Acute coronary syndrome
- Myocardial infarction
- Secondary prevention of stroke
- Coronary artery stenting
- Deep vein thrombosis
- Congenital platelet disorders that cause arterial and venous thromboembolic events
- Non-steroidal Anti-inflammatory Drugs (NSAIDs)
- P2Y12 receptor antagonists, which block the platelet activation receptor
- Nitrates, which reduce platelet aggregation and adhesion
- Calcium channel blockers, which reduce platelet aggregation and adhesion
- Heparin, which reduces platelet adhesion
Other anticoagulants work other than by affecting platelets directly. An example is warfarin, which interferes with vitamin K, important in clotting.
Testing for platelet dysfunction usually doesn’t change the therapy used, since the end result is the dissolution or prevention of clots. However, it is important to know why a patient experiences blood clots that are life-threatening.
- Complete Blood Count (CBC): a manual or automated platelet count from a peripheral smear of blood on a slide.
- Bleeding time is determined by making a small cut and timing how long hemostasis takes. These tests the interaction of platelets with blood vessel wall injury
- Platelet Function Analyzer: commercially available, this has largely replaced the cumbersome bleeding time test
- PTT and PT: the prothrombin time (PT) is a measure of one of the pathways (extrinsic) of the clotting cascade in which platelets take part. Activated partial thromboplastin time (aPTT) tests another pathway, the intrinsic clotting cascade
- Genetic testing of blood DNA: To identify gene mutations
Platelet Function Testing
The evaluation of platelet function inside the body has always been a challenge until recently. New technology has made it possible to test platelet aggregation, adhesion, and circulating properties. These use light to measure the amount of opaqueness there is due to clots or non-clotting in platelet-rich plasma or whole blood, or they use the time it takes for clots to form:
- Platelet Aggregometry: The VerifyNow Assay is the latest technology in aggregometry
- Whole Blood Aggregometry
- Light Scattering methods
- Clot Signature Analyzer: uses a tube of blood to measure platelet function via platelet “plugs” observed
- Thrombotic Status Analyzer: measures platelet activation via capillary tube occlusion. The Platelet Function Analyzer measures the drop in flow rate through a capillary tube due to platelet plugs
- High Shear Filterometer: measures the time it takes for a filter to stop allowing blood through
Diagnosis of inherited platelet dysfunction can be made from genetic testing and platelet aggregometry.
Other Testing for Platelet Hyperfunction
The end result of platelet hyperfunction is clotting. In this regard, confirmation is done via ultrasound of blood vessels, or when more accuracy is needed, CT or MRI of arteries or veins suspected to harbor thrombi (clots).
Testing Used After Antiplatelet Medicines are Begun
Anticoagulation using antiplatelet drugs is challenging, in that the effect must be enough to discourage clot formation but not so much to provoke bleeding. Once antiplatelet medications are begun, it is necessary to do interval testing to ensure the patient’s clotting tendencies fall into the narrow range of what is considered ideal anticoagulation. For this purpose, the following interval blood tests are used:
- PT (prothrombin time): Measures the time for plasma to clot when exposed to tissue factor.
- INR (the international normalized ratio): A PT ratio applied to a world-wide standard and measures how well the PT is affected by anticoagulants. It is expressed in the multiples of decreased speeds from normal clotting. The therapeutic goal for anticoagulation is an INR of 2-3 (ideally, 2.5). Because it is an international standard, it is especially useful for travelers.
- aPTT (activated partial thromboplastin time): measures the time for plasma to clot after exposure to contact factors.
Treatment of Thrombosis with Antiplatelet Therapy
An overreaction of the clotting process with premature, unprovoked, or exaggerated platelet initiation can be managed using medications that interfere with this, called antiplatelet agents:
- Aspirin: in doses of 50-100 mg/day
- Non-aspirin NSAIDs: non-steroidal anti-inflammatory drugs. Complications can include upper gastrointestinal bleeding and gastritis
- Platelet receptor site antagonists: interfere with platelet activation ,P2Y12 receptor blockers (e.g., clopidogrel, prasugrel, ticagrelor), glycoprotein IIb/IIIa inhibitors (e.g., abciximab, tirofiban, eptifibatide).
- Nitrates: Reduce platelet reactivity, adhesion, and aggregation.
- Calcium channel blockers: Reduce platelet aggregation and adhesion.
- Heparin: reduces platelet adhesion.
- Warfarin: not a true antiplatelet medication but a vitamin K antagonist, it is used for long term anticoagulation in those who prefer pills or who have recurrent embolic events.
Oral antiplatelet preparations include aspirin, NSAIDs, calcium channel blockers, warfarin, rivaroxaban, apixaban, edoxaban, and dabigatran.
Non-Medical Antiplatelet Treatment
If patients fail to achieve ideal anticoagulation or who have recurrent thrombosis or thromboembolic events, a filter can be placed in the vena cava to catch venous migratory clots before they reach the right-sided heart circulation to the lungs.
Prevention of Platelet Dysfunction
Prevention of platelet dysfunction relies on screening methods involving blood work and platelet function testing in those at risk, such as patients with a strong history of venous thrombosis and pulmonary emboli, stroke, atherosclerosis, and myocardial infarction. A family history positive for platelet dysfunction is a major risk that calls for preventative measures.
Platelet dysfunction may remain dormant until the sudden appearance of venous clots or arterial plaques. Identification of those as risk is the best strategy for preventing venous, arterial, and cardiac thromboembolic disease. Those with an increased tendency toward clotting (i.e., previous thrombosis, strong family history, previous stroke, venous stasis, or atherosclerosis) may benefit from anti-platelet therapy.
Antiplatelet Therapy as Preventative Medicine
Antiplatelet therapy is used to prevent serious complications from many thrombotic and atherosclerotic conditions:
- Coronary artery disease: Especially those with stents.
- Acute coronary syndromes.
- Previous or current myocardial infarction.
- Atrial fibrillation: Which can throw clots to distal sites that can cause ischemia or tissue death (infarction) in the lungs (from the right atrium), or in the kidneys, liver, spleen, intestines, or other organs (from the left atrium).
- Carotid artery thrombosis: Ischemic stroke and transient ischemic attack (TIA).
- Pre-operative or perioperative prophylaxis against postoperative pulmonary emboli: “Mini-dose” heparin.
- Prolonged immobilization.
- Severe extremity trauma.
- Chronic deep venous thrombosis.
- Diabetics with end-organ damage.
- Disseminated intravascular coagulopathy (DIC): An over-clotting phenomenon due to infection, trauma, hemorrhage, surgery, or pregnancy that results in exhausting all of the coagulation factors, ultimately leading to fatal hemorrhage; antiplatelet therapy is given with the intention of stopping the consumption of platelets before all of the coagulation factors are gone.