Microfluidic testing in patients with Bleeding Disorder of Unknown Cause (BDUC)
In 40–70% of patients referred to a hematologist for an increased bleeding tendency, no diagnosis is established despite extensive laboratory testing. These patients are classified as having a bleeding disorder of unknown cause (BDUC), often presenting with a bleeding phenotype similar to known mild bleeding disorders, including platelet function defects. This study aimed to assess whether a microfluidic assay can detect shear-dependent hemostatic defects in BDUC patients.
BDUC patients with elevated ISTH-BAT scores and normal von Willebrand factor levels, platelet aggregation by light transmission aggregometry (LTA), and ATP release were selected from the Predictors of Bleeding Evaluation in Adult Hematologic Patients (ProBe-AHP) cohort. Shear-dependent platelet adhesion, activation, and aggregation were evaluated using microfluidic analysis of collagen- or collagen plus tissue factor-induced whole blood thrombus formation at 37 °C.
Abnormal shear-dependent platelet function was observed in 25 of 47 (53%) BDUC patients, with a mean ISTH-BAT score of 10, compared to 49 healthy controls. Affected patients exhibited reduced platelet adhesion, integrin activation, phosphatidylserine exposure, and/or P-selectin expression. Additionally, thrombus morphology, contraction, and multilayer formation were impaired in 5 patients. Fibrin formation on collagen with tissue factor did not differ significantly from controls.
Microfluidic analysis of whole blood thrombus formation under shear identifies abnormalities in over half of BDUC patients, providing more detailed insights into flow-dependent platelet abnormalities and supporting a flow-related platelet defect diagnosis.