From: Elizabeth M. Van Cott, M.D., and Michael Laposata, M.D., Ph.D., "Coagulation." In: Jacobs DS et al, ed. The Laboratory Test Handbook, 5th Edition. Lexi-Comp, Cleveland, 2001; 327-358.
Index of Tests
Platelet Aggregation [CO003900]
Synonyms Aggregometer Test; Platelet Function Studies
Applies to ATP:ADP Ratio; Beta-Thromboglobulin
Test Includes Response to adenosine diphosphate (ADP), epinephrine,
collagen, ristocetin, and arachidonic acid
Abstract Platelet aggregation tests are used to assess platelet
Patient Preparation Patients should not have aspirin (or
any medication containing aspirin) for at least 7 days prior to
testing. Nonsteroidal anti-inflammatory drugs or other platelet-inhibiting
agents should also be avoided.
Specimen Platelet-rich plasma
Container Three blue top or plastic (sodium citrate) tubes
Collection Routine venipuncture. Immediately invert tubes
gently at least 4 times to mix. Deliver tubes immediately to the
laboratory at room temperature (platelets are activated at cold
Storage Instructions Keep specimen at room temperature and
perform test immediately (or within 2 hours, if transportation to
a reference laboratory is required). Do not refrigerate or freeze
Causes for Rejection Specimen received more than 2 hours
after collection, specimen clotted, specimen received on ice.
Turnaround Time Less than 1 day
Special Instructions Usually must be scheduled in advance
with the laboratory.
Reference Interval >60% of platelets aggregate with each
agonist tested. Normally no significant spontaneous aggregation.
Normal newborns can have decreased aggregation compared to adults.1
Use Assess platelet function. When a familial bleeding disorder
is suspected, this test is usually not performed unless routine
tests are normal (PT, PTT, and platelet count) and von Willebrand
tests are normal, because von Willebrand disease is much more common
than hereditary platelet dysfunction.
Methodology Citrated plasma is centrifuged at a gentle speed,
to draw red and white blood cells into a pellet, leaving platelets
suspended in the plasma. Various platelet aggregating agents (agonists)
are added to aliquots of the platelet-rich plasma, and the resulting
platelet aggregation is measured in an aggregometer.2 The aggregometer measures platelet aggregation by monitoring optical
density. As platelets aggregate, more light can pass through the
specimen. The platelet agonists commonly include arachidonate, ADP,
collagen, epinephrine, and ristocetin. One aliquot usually has no
platelet agonist added, to assess for spontaneous platelet aggregation.
A rapid, whole blood point-of-care device has been compared to
platelet aggregation in monitoring platelet function during antiplatelet
therapy.3 Another rapid whole blood platelet function
analyzer has been studied in small numbers of patients with various
platelet function abnormalities.4
Additional Information The most common cause of platelet
dysfunction detected in this assay is medications. With aspirin
and related compounds, arachidonate aggregation is markedly decreased
or absent, and other aggregation tracings may be variably impaired.
A variety of other platelet-inhibiting agents, such as ticlopidine,
clopidogrel, and abciximab, are known to impair platelet aggregation.
A vast number of other medications have been implicated in impaired in vitro platelet aggregation, and the clinical significance,
if any, is usually uncertain. If a patient is found to have impaired
platelet aggregation in this assay, a careful review of prescribed,
as well as over-the-counter medications, is indicated. An on-line
literature search for each medication is often informative. Other
acquired causes of impaired platelet aggregation include uremia
and paraproteinemia (monoclonal gammopathy). Myeloproliferative
disorders can impair platelet aggregation, by epinephrine in particular.
Hyperaggregation has also been reported with myeloproliferative
Hereditary platelet dysfunction is far less common than acquired
dysfunction. A hereditary disorder may be considered in patients
with bleeding histories and no obvious acquired etiology to account
for an abnormal platelet aggregation study. Ideally, the aggregation
study is repeated on a fresh specimen to determine if the abnormality
is reproducible. The presence of the same abnormality in family
members supports the diagnosis of a hereditary defect. Platelet
storage pool disorders may variably decrease responses to epinephrine,
ADP, and occasionally other agonists. Platelet storage pool disorders
are characterized by deficiencies in alpha or dense platelet granules.
Alpha granules normally store platelet factor 4 (PF4), beta-thromboglobulin,
and other substances. Dense granules normally contain ADP, serotonin,
and other compounds. Alpha granule deficiency is a rare disorder
called "gray platelet syndrome", because platelets appear gray with
light microscopy due to a lack of alpha granules. Alpha granules
give normal platelets their purple granular appearance. In gray
platelet syndrome, platelets are large; thrombocytopenia may be
present; and beta-thromboglobulin (a research test) is decreased
in platelets but may be elevated in plasma. A research test for
dense granule deficiency is the platelet ATP:ADP ratio, which is
increased with dense granule deficiency. Uncommonly, patients are
deficient in both alpha and dense granules. Rare genetic disorders
may underlie some cases of storage pool deficiency, including Hermansky-Pudlak
syndrome (dense granule granule deficiency with pulmonary fibrosis
and albinism), Chédiak-Higashi syndrome, Wiskott-Aldrich
syndrome, or thrombocytopenia with absent radius syndrome.
Glanzmann thrombasthenia is a rare inherited condition in which
platelet glycoprotein IIb/IIIa (GPIIb/IIIa) is deficient. GPIIb/IIIa
mediates platelet aggregation using fibrinogen to link platelets
to each other. Therefore, in Glanzmann thrombasthenia, aggregation
is decreased with all agonists (ADP, collagen, epinephrine, arachidonate)
except ristocetin. Ristocetin agglutinates platelets using von Willebrand
factor and platelet glycoprotein Ib (GPIb). Bernard-Soulier disease
is a rare inherited disorder characterized by GPIb deficiency and
therefore decreased ristocetin-induced aggregation. Giant platelets
and often thrombocytopenia are also present. With severe von Willebrand
disease, ristocetin aggregation can be decreased, but most cases
of von Willebrand disease are mild and ristocetin aggregation is
most often normal. For that reason, platelet aggregation is not
used to screen for von Willebrand disease.
Note: The term "agglutination" is often used to describe
ristocetin-induced platelet aggregation, because true platelet aggregation
links platelets through fibrinogen and GPIIb/IIIa, whereas ristocetin
links platelets through von Willebrand factor and GPIb.
1. Michelson AD, "Platelet Function in the Newborn,"Semin Thromb
Hemost, 1998, 24(6):507-12.
2. Brown BA, Hematology: Principles and Procedures, 6th
ed, Philadelphia, PA: Lea & Febiger, 1993, 271-4.
3. Kereiakes DJ, Broderick TM, Roth EM, et al, "Time Course, Magnitude,
and Consistency of Platelet Inhibition by Abciximab, Tirofiban,
or Eptifibatide in Patients With Unstable Angina Pectoris Undergoing
Percutaneous Coronary Intervention,"Am J Cardiol, 1999, 84(4):391-5.
4. Fressinaud E, Veyradier A, Truchaud F, et al, "Screening for
von Willebrand Disease With a New Analyzer Using High Shear Stress:
A Study of 60 Cases,"Blood, 1998, 91(4):1325-31.
Gahl WA, Brantly M, Kaiser-Kupfer MI, et al, "Genetic Defects and
Clinical Characteristics of Patients With a Form of Oculocutaneous
Albinism (Hermansky-Pudlak syndrome),"N Engl J Med, 1998,
Nurden AT, "Inherited Abnormalities of Platelets,"Thromb Haemost,