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Extensive Experiments in (Un)Diagnosed Bleeding Patients with Prolonged Platelet Function Analyser Closure Times

1Maastricht University Medical Center, Department of Hematology, Internal Medicine, Maastricht, the Netherlands, 2Maastricht University, Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, the Netherlands, 3Flowchamber, Maastricht, the Netherlands, 4University of Cambridge, Cambridge, United Kingdom, 5Maastricht University Medical Center, Central Diagnostic Laboratory, Unit for Hemostasis and Transfusion, Maastricht, the Netherlands, 6University of Cambridge, Department of Haematology, Cambridge, United Kingdom

Abstract Number: PB0533

Meeting: ISTH 2020 Congress

Theme: Diagnostics and OMICs » Laboratory Diagnostics

Background: Patients referred for evaluation of bleeding symptoms occasionally have unexplained prolonged platelet function analyser (PFA) results, without laboratory evidence for von Willebrand disease (VWD) or platelet function defect (PFD). This abnormal PFA might indicate shear stress-dependent abnormalities in VWF or platelet function.

Aims: To perform extensive experiments, including flowchamber and whole genome sequencing (WGS) in bleeding patients with unexplained prolonged PFA results.

Methods: Patients were included if they had unexplained prolonged PFA results. ISTH BAT score was assessed. Performed laboratory tests included PFA, light transmission aggregometry (LTA) with ATP release, VWF:RCo, VWF:ag, VWF multimers, collagen binding assay, flowcytometry, flowchamber analysis and WGS. For flowchamber experiments, collagen I and III surfaces were used at shear rates of 1000s-1 and 1600s-1 at 37°C. Formed thrombi were assessed for platelet surface area coverage; platelet aggregation; thrombus morphological score (MS), thrombus multilayer score (MT), thrombus contraction score (CS) at 3, 5 and 7 minutes and for P-selectin secretion, integrin αIIbβ3 activation and phosphatidylserine (PS) expression.

Results: 13 PFA-only patients were included. Mean ISTH-BAT score was 11 ± 5; mean PFA-ADP was 119 ± 28 s; mean PFA-EPI was 149 ± 43 s; no patient had abnormal VWF levels. LTA indicated a thrombopathy, not otherwise specified (NOS) in 1 patient. In 6/13 patients repeated unexplained prolonged PFA results were found. Flowchamber results of these patients showed decreased thrombus formation scores, PS expression and integrin activation. Furthermore, 4 patients with VWD and/or glanzmann’s disease showed abnormal integrin activation and PS expression in the flowchamber. The patient with thrombopathy NOS, showed severely altered thrombus formation.

Conclusions: Unexplained prolonged PFA closure times, in patients with a bleeding tendency, can be confirmed by flowchamber experiments and cannot be ignored in the final diagnosis of these patients. WGS results are awaiting and might give more insight in the underlying genetic abnormality in these patients.


[Heatmap Flowchamber Thrombus Formation]


[Heatmap Flowchamber labels at 1600s-1]

To cite this abstract in AMA style:

Heubel-Moenen F, Swieringa F, Herfs L, Sims M, Downes K, Greene D, Wetzels R, Verhezen P, Machiels P, Ouwehand W, Heemskerk J, Beckers E, Henskens Y. Extensive Experiments in (Un)Diagnosed Bleeding Patients with Prolonged Platelet Function Analyser Closure Times [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/extensive-experiments-in-undiagnosed-bleeding-patients-with-prolonged-platelet-function-analyser-closure-times/. Accessed October 2, 2023.

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