Laboratory Diagnosis of Platelet Functional Defects

Platelet function defects (PFD) should be considered in patients with symptoms suggestive of a defect in primary hemostasis. A genetic disorder may be present, particularly if symptoms are lifelong or familial; however, most PFD encountered in clinical practice are acquired. An acquired PFD may be the cause of excessive bleeding, but it may also be an incidental finding or a purely in vitro phenomenon. The complex laboratory diagnosis of a specific PFD should be undertaken only when other more readily identifiable causes for the clinical observations have been ruled out using blood cell counts, peripheral smear, coagulation screening tests, von Willebrand disease (VWD) profile, and a careful history.

Normal platelet function involves over 100 gene products, defects in many of which could potentially cause PFD. Disorders of major clinical significance, such as Glanzmann thrombasthenia (GT) and Bernard–Soulier syndrome (BSS), or with striking clinical presentations, such as Hermansky–Pudlak syndrome, have been well characterized but are rare in most populations. Table 141.1 provides a detailed but not exhaustive list of genetic disorders categorized by mechanism. Many disorders listed have been described in only a few individuals. Examples of the platelet aggregation results expected in some genetic disorders are shown in Table 141.2 .

Acquired PFD are most commonly due to drug effects but may result from the effects of an underlying disorder. Hospitalized patients are likely to have at least one drug or intervention affecting platelet function. Outpatients may take prescription or over-the-counter drugs. Herbal remedies have also been implicated in PFD. Sensitive platelet aggregation and release tests will be influenced by common drugs such as aspirin, which causes irreversible effects as long as 2 weeks post ingestion, or foods containing flavonoids. Ideally, abnormal studies should be repeated after 10–14 days with no medications and with flavonoid-rich foods avoided for 24 hours. Marked improvement in platelet function tests should cause the drug to be considered not only as an assay confounder but also as a potential cause of the patient’s symptoms. Abnormal test results have occurred in about 20% of healthy individuals, including those documented to be drug-free. Gender, race, and flavonoid-rich foods have been shown to affect their results, and a high false-positive rate is inherent in some test systems. Table 141.3 gives a list of drugs influencing platelet function. It is not exhaustive, and because the impact of many drugs is unknown, exclusion from published lists does not indicate a lack of effect. PFD may also be secondary to a variety of disorders. Bleeding due to acquired PFD is usually mild to moderate; however, it can be life-threatening in the presence of other hemostatic defects, such as thrombocytopenia and coagulation factor deficiencies.