Platelet Function Assays Menu

What Are Platelet Function Assays?

platelet function assays help diagnose blood disordersPlatelets (“thrombocytes”) are cells in the blood that circulate freely until there is an injury, which attracts them to accumulate at that site as one of the first steps in the clotting process. Healing begins with hemostasis, and the platelets play a crucial initial role in a clotting/clot-dissolving cycle that is part of healing.

The four main platelet functions are

  • Adherence to each other
  • Activation
  • Aggregation
  • Taking part synergistically with other coagulation factors

When circulating platelets are exposed to tissue, as happens when injury interrupts the lining that separates them, they adhere to the tissue, which activates them to secrete factors which attract other platelets to do the same. Next, circulating fibrinogen begins to bind, and this prompts further platelet aggregation, which stabilizes the growing clot. Meanwhile, the tissue exposed to the vascular circulation signals other processes which begin additional cycles in the clotting process.

When one fails to clot effectively or when there is over-functioning of platelets that produces clots that could obstruct blood flow or embolize, one or more of the four functions above are abnormal, and platelet testing is an important tool in investigating the cause so that appropriate interventions can be made.

Although merely counting the platelets within a certain volume of blood is helpful in identifying thrombocytopenia (i.e., too few platelets, leading to bleeding), this does nothing to measure their successful function or identify their dysfunction within the body. The difficulty in evaluating platelet function as it occurs inside the body, which makes the platelet count insufficient for dysfunctional diagnoses, has been solved with recent technologies.

Platelet function assays are not only helpful in diagnosing bleeding disorders or thrombosis, but also determine the efficacy of therapy when antiplatelet drugs are used to treat a tendency toward clotting in abnormal situations.

Diagnosis of Platelet Function Assays

A bleeding or clotting disorder, called “bleeding diathesis,” is an abnormal hemostatic process. It can be a delay in clotting after injury, leading to hemorrhage, or a tendency to develop thrombi in blood vessels. Disorders of platelets is a major consideration in a bleeding diathesis, and the diagnosis of abnormal platelet function begins with an in-depth history and a thorough physical exam.

A bleeding history can reveal problems a patient may have had with bleeding after surgery, tooth extractions, and in women, menstrual flow. The patient can be asked about bloody urine, blood in the stool, or persistent bleeding beyond what was expected after minor trauma. Aspirin consumption, the most common cause of platelet dysfunction, can be identified. A history of transfusions is obtained. Family history of clotting or bleeding abnormalities can identify those at risk for congenital clotting dysfunction.

The physical exam can readily identify suspicious, unprovoked (by history) bruises (“ecchymoses”), petechiae (small hemorrhagic blood spots under the skin), or “splinter hemorrhages” (small bloody streaks under the nails). Large, spreading soft tissue hematomas can be documented.

Initial Testing

  • Platelet counting: From a peripheral smear of blood on a slide can allow manual counting, totaling how many platelets are there in one high-power field of magnification; platelets can also be counted with an automated process that flags samples with unusual abundance or sparsity of platelets.
  • Bleeding time: Is determined by making a small cut and timing how long hemostasis takes. This tests the interaction of platelets with a blood vessel wall, but is invasive and uncomfortable.
  • Platelet Function Analyzer: commercially available, this has largely replaced the cumbersome bleeding time test.
  • Prothrombin time (PT): Tests one of the pathways (extrinsic) of the clotting cascade which platelets impact.
  • Activated partial thromboplastin time (APTT) tests another pathway, the intrinsic clotting cascade.
  • Genetic testing of blood DNA to identify gene mutations

Platelet Function Testing

  • Platelet Aggregometry: Platelet-rich plasma is the medium of free, circulating platelets which make it cloudy. When platelets aggregate together, this clumping clears portions of the plasma, allowing more light to pass through it (less cloudiness).
  • Whole Blood Aggregometry: The same as with plasma, but with whole blood.
  • Light Scattering methods: another version of evaluation via light transmission, using the light-scattering effects of clots vs free, circulating platelets.
  • Verify Now Assay: The latest technology in aggregometry.
  • Clot Signature Analyzer: Uses a tube of blood with holes that can reveal platelet clot “plugs” as a measure of platelet function.
  • Thrombotic Status Analyzer: Uses whole blood drawn into a small “capillary” tube to measure platelet activation via capillary tube occlusion.
  • Platelet Function Analyzer: a measure of the drop-in flow rate through a capillary tube as platelets form hemostatic plugs.
  • High Shear Filterometer: controlled pressure used to push blood through a filter and measure the time until the filter is blocked.

Diagnosis of inherited bleeding disorders, such as coagulation deficiencies, mutations, and platelet inhibition can be made from a battery of selected tests individualized for the patient.

Diagnosis of abnormal platelet function begins with an in-depth history and a thorough physical exam. A bleeding history can reveal problems a patient may have had with bleeding after surgery, tooth extractions, and in women, menstrual flow. The patient can be asked about bloody urine, blood in the stool, or persistent bleeding beyond what was expected after minor trauma. A history of transfusions is obtained. Family history of clotting or bleeding abnormalities can identify those at risk for congenital clotting dysfunction.

The physical exam can readily identify suspicious, unprovoked (by history) bruises (“ecchymoses”), petechiae (small hemorrhagic blood spots under the skin), or “splinter hemorrhages” (small bloody streaks under the nails). Large, spreading soft tissue hematomas can be documented.

Management of Platelet Function Assays

The management and treatment of bleeding/clotting disorders due to platelet dysfunction relies initially on ruling out other causes unrelated to platelets. This can be difficult, since platelets play a role in more than one clotting cascade of biochemical reaction. A history of drugs that interfere with platelet function (e.g., aspirin) can result in a cure from simply discontinuing the drug.

Once a distinct intrinsic platelet dysfunction is identified, treatment is implemented to restore normal function by either inhibiting platelet overreaction to clot or improve platelet function when platelets fail to clot.

Treatment of Platelet Dysfunction Leading to Bleeding

This is usually due to an inherited genetic disorder, such as von Willebrand disease, giant platelet dysfunction, micro platelet dysfunction, etc. Dysfunction can also be acquired, as with liver disease, uremia, diabetes, trauma, cardiopulmonary bypass, and malnutrition. Drugs that reverse or improve insufficient platelet function are limited in number:

  • Desmopressin is related to vasopressin, a pituitary hormone that acts as an anti-hemophilic and hemostatic agent.
  • Estrogens can be used to take advantage of their tendency to increase coagulability.
  • Erythropoietin (bone marrow stimulator) has been successful in increasing production of platelets in patients with kidney failure and uremia.
  • Platelet transfusion: used when other methods fail or in cases of overt thrombocytopenia which can occur in malignancies, pregnancy, and HIV/AIDS.
  • Antifibrinolytic agents: just as platelets are the beginning of the clotting process, dissolution of the clot by “fibrinolytic” factors in the blood participates in finalizing the healing process. Drugs that oppose these clot-dissolving factors can maintain what platelet aggregation and clotting does occur. Agents: tranexamic acid, aminocaproic acid.

Treatment of Platelet Dysfunction Leading to Thrombosis

An overreaction of the clotting process with premature, unprovoked, or exaggerated platelet initiation can use medications that interfere with this, i.e., antiplatelet agents:

  • Aspirin: in doses of 50-100 mg/day.
  • Non-aspirin NSAIDs: non-steroidal anti-inflammatory drugs. Complications can include upper gastrointestinal bleeding.
  • Dipyridamole, sometimes used in combination with low-dose aspirin.
  • Platelet receptor site antagonists: interfere with platelet activation.
  • Nitrates: reduce platelet reactivity, adhesion, and aggregation.
  • Calcium channel blockers: reduce platelet aggregation and adhesion.
  • Heparin: reduces platelet adhesion.

Prevention of Platelet Dysfunction

Prevention of platelet dysfunction relies on screening methods, such as blood work and platelet function testing in those at risk, such as patients with a strong history of bleeding diathesis (disorders), venous thrombosis, hemophilia, stroke, and inappropriate blood loss after minor trauma. A family history positive for platelet dysfunction is a major risk that calls for preventative measures. Identification of those as risk is the best strategy for preventing stroke, hemorrhage, gastrointestinal bleeding, surgery-associated blood loss, and spontaneous bleeding.

Prevention of Clotting

  • Those with an increased tendency toward clotting (i.e., previous thrombosis, strong family history, previous stroke, venous stasis, or atherosclerosis): May benefit from antiplatelet therapy, using aspirin, NSAIDs, heparin, warfarin, or other agents.

Prevention of Bleeding

  • Those with an increased tendency toward, or history of, uncontrolled bleeding: Can be treated preventatively with desmopressin, estrogens, or in critical thrombocytopenia where hemorrhagic stroke is likely, platelet transfusion. Stroke prevention is a major incentive for such preventative therapy.
  • Prevention of the causes of platelet dysfunction: Can also prevent the dysfunction, such as prevention of liver disease (alcohol rehabilitation and avoiding high-risk sexual behavior that increases the risk of acquiring hepatitis B and C) and aggressive approaches to kidney disease.
  • Using therapeutic agents is prudent when there is a planned surgery involving cardiopulmonary bypass.
  • Strict glycemic control in diabetics: With a targeted hemoglobin A1c goal of >7%, can reduce the risk of bleeding diathesis in diabetics.
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This information is provided by Vascular Health Clinics and is not intended to replace the medical advice of your doctor or healthcare provider. Please consult your healthcare provider for advice about a specific medical condition.

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