What platelet studies are done for patients with possible Ehlers-Danlos syndrome (EDS)?

Platelet Studies for Ehlers-Danlos Syndrome

For patients with possible Ehlers-Danlos syndrome, perform light transmission aggregometry (LTA) with standard agonists (ADP, collagen, epinephrine, ristocetin) and flow cytometry screening for platelet glycoproteins (GPIIb/IIIa, GPIb, GPIb/IX), along with assessment of platelet granule release (α and δ granules), as platelet function abnormalities are present in 78-90% of EDS patients and correlate directly with bleeding severity. 1, 2

Core Platelet Testing Panel

Light Transmission Aggregometry (LTA)

• LTA with standard agonists (ADP, collagen, epinephrine, ristocetin) is the primary functional test recommended to evaluate platelet aggregation responses in EDS patients 1
• Platelet aggregation abnormalities are found in approximately 26% of EDS patients, though many have uncertain clinical significance 3
• The number of platelet function abnormalities directly correlates with bleeding risk—patients with more than three abnormalities have an odds ratio of 5.19 for bleeding complications 2

Flow Cytometry for Glycoprotein Expression

• Flow cytometry screening should evaluate antibodies against GPIIb/IIIa (CD41), GPIIIa (CD61), GPIb (CD42b), and GPIb/IX (CD42a) to identify specific platelet glycoprotein defects 1
• If initial screening is inconclusive, expanded flow cytometry should assess additional glycoproteins including GPIa/IIa, GPIV, and GPVI 4

Granule Release Assessment

• Evaluation of α and δ granule release is necessary to detect secretion defects, as storage pool disorders (particularly δ-storage pool disease) are among the platelet abnormalities found in EDS 1
• Platelet release defects occur in approximately 8% of EDS patients 3

Additional Platelet-Related Studies

Bleeding Time and Platelet Count

• Complete blood count (CBC) with platelet count should be obtained, though platelet counts are typically normal in EDS 1, 2
• Bleeding time may be prolonged in approximately 8% of patients, often in association with platelet aggregation abnormalities 3
• Borderline thrombocytopenia should not exclude further platelet function testing, as several inherited platelet disorders present with mild thrombocytopenia 4

Advanced Testing When Initial Studies Are Abnormal

• Transmission electron microscopy (TEM) to assess platelet granule content and structural abnormalities if granule defects are suspected 4
• Clot retraction testing and serum thromboxane B2 (TxB2) measurement for suspected signaling pathway defects 4
• Genetic testing may be considered for specific mutations associated with inherited platelet disorders if a clear pattern emerges 4

Clinical Context and Interpretation

Prevalence of Abnormalities

• At least one platelet function abnormality is found in 90% of EDS patients with abnormal bleeding scores and 78% of those with normal bleeding scores 2
• However, 83% of EDS patients with bleeding tendencies have completely normal hemostatic testing, supporting that vascular and connective tissue fragility—not platelet dysfunction—is the primary mechanism 3

Important Caveats

• Haematological studies including platelet function tests are usually normal in most EDS patients, and when abnormalities are found, they may not fully explain the bleeding tendency 5
• The Hess test (Rumple-Leede test) may be abnormal, indicating capillary fragility rather than platelet dysfunction 5
• Blood samples should be processed according to standardized protocols and repeated testing should be separated by at least one month to allow disappearance of acquired interfering factors 4
• Pre-analytical variables including patient stress, recent exercise, and sample processing can affect results 4

Complementary Non-Platelet Studies

While not platelet studies per se, the following should be obtained simultaneously:

• Prothrombin time (PT) and activated partial thromboplastin time (PTT), as mild coagulation factor deficiencies (Factor XI in 6%, Factor XIII in 4%) can coexist 3
• Von Willebrand factor testing (VWF:Ag, VWF:RCo, Factor VIII) to exclude concurrent von Willebrand disease 1, 6

The key principle is that while platelet function abnormalities are common in EDS and correlate with bleeding severity, the majority of bleeding manifestations result from structural defects in blood vessels and perivascular connective tissue rather than primary platelet dysfunction. 2, 3, 5