Differentiation of Patients with Symptomatic Low von Willebrand Factor from Those with Asymptomatic Low von Willebrand Factor

Abstract

Background Accurate diagnosis of symptomatic low von Willebrand factor (VWF) remains a major challenge in von Willebrand disease (VWD). However, present tests do not adequately take into account flow forces that, at very high shear rates, reveal a weakness in the VWF-platelet glycoprotein glycoprotein Ib bond in normal subjects. The degree of this weakness is greater in symptomatic, but not asymptomatic, low VWF. Objective The aim of this study is to distinguish patients with symptomatic low VWF (levels in the 30–50 IU/dL range) from those with asymptomatic low VWF and normal subjects. Methods We measured platelet adhesion (PA)/aggregation in our novel microfluidic flow system that permits real-time assessment of PA (surface coverage) and PA/aggregation (V, aggregate volume) using epifluorescence digital videomicroscopy in flowing noncitrated whole blood at 4,000 second−1. Blood samples from 24 low VWF patients and 15 normal subjects were collected into plastic tubes containing 4 U/mL enoxaparin. MetaMorph software was used to quantify rates of PA and V increase. Results Rates of PA increase showed a bimodal distribution, with values for 16/24 patients (Group I) all below the 2.5th percentile of normal, and values for 8/24 patients (Group II) similar to controls. Bleeding scores (mean ± standard error) were 5.50 ± 0.45 versus 2.75 ± 0.45 (p = 0.00077), and 10 clinically significant bleeding events were observed in seven versus zero (p = 0.0295) Group I and Group II subjects, respectively. Conclusion The present approach may offer a definitive means to distinguish symptomatic low VWF from either asymptomatic low VWF or normal controls.

Point-of-Care Testing in Patients with Hereditary Disorders of Primary Hemostasis: A Narrative Review

“…Therefore, this assay might have a role in predicting bleeding tendency in patients with VWD or low VWF, although its utility as a POCT is limited by the need for incubation prior to testing. 169…”

“…Therefore, this assay might have a role in predicting bleeding tendency in patients with VWD or low VWF, although its utility as a POCT is limited by the need for incubation prior to testing. 169 Another device that optically measures clot formation in flow chambers was called the clotMAT. 170 In this device, micropillars are placed inside the channels.…”

Classic Light Transmission Platelet Aggregometry: Do We Still Need it?

“…Fluorescence microscopy and other sophisticated imaging approaches are available in vivo and in vitro for further differentiation of functional and/or histological time-independent analysis of platelets. [87][88][89][90][91][92][93][94][95][96] Fluorescence microscopy has advanced our understanding of platelet biology by providing real-time visualization of intracellular processes. Fluorescent markers bind to specific platelet components or molecules, emitting light when excited, thus enabling the visualization of these components under a fluorescence microscope.…”