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Related Experiment Video

Updated: Oct 7, 2025

Dynamic Multiparameter Platelet Function Assessment Using a Capacitive Biosensor
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Multiparameter platelet function analysis of bleeding patients with a prolonged platelet function analyser closure

Floor C J I Heubel-Moenen1, Sanne L N Brouns2, Linda Herfs3,4

  • 1Department of Hematology, Internal Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands.

British Journal of Haematology
|January 10, 2022
PubMed
Summary

Patients with prolonged platelet function analyzer (PFA) tests but no clear bleeding disorder show impaired shear-dependent platelet function. This defect, missed by standard tests, involves reduced platelet adhesion and thrombus formation under flow conditions.

Keywords:
bleeding disordersdiagnostic haematologyflowgenetics of thrombosis and haemostasisplatelet function

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Area of Science:

  • Hematology
  • Biomedical Engineering
  • Translational Medicine

Background:

  • Prolonged platelet function analyzer (PFA) closure time can occur in patients with bleeding symptoms without diagnosed von Willebrand disease or platelet aggregation defects.
  • Standard hemostatic tests may not fully capture all causes of bleeding diathesis.

Purpose of the Study:

  • To investigate a potential shear-dependent platelet function defect in patients with isolated PFA prolongation and bleeding symptoms.
  • To characterize platelet function under flow conditions in this patient cohort.

Main Methods:

  • Microfluidic analysis of shear-dependent, collagen-induced whole-blood thrombus formation.
  • Assessment of platelet adhesion, thrombus formation parameters, integrin activation, and P-selectin expression.
  • Conventional von Willebrand factor (VWF) and platelet function tests, alongside exome sequencing.

Main Results:

  • Patients with PFA-only prolongation exhibited significantly reduced platelet adhesion and thrombus formation under shear compared to healthy controls.
  • Lower integrin activation, phosphatidylserine exposure, and P-selectin expression were observed in these patients.
  • Principal component analysis suggested VWF influences PFA prolongation, while conventional aggregation tests explained reduced shear thrombus parameters.

Conclusions:

  • A shear-dependent platelet function defect, not detected by static assays, is present in patients with isolated PFA prolongation.
  • This defect may result from single or combined effects of low-normal VWF and platelet aggregation.
  • Multiparameter assessment of whole-blood thrombus formation under shear is crucial for diagnosing such complex bleeding disorders.