Abstract

Background: von Willebrand’s disease (VWD) is the most common bleeding disorder, affecting between 1–10% of the general population. There is a need for a simple test to screen patients with bleeding symptoms before more labor-intensive diagnostic steps are taken. The Impact-R [Cone and Plate(let) Analyzer (CPA)] (DiaMed Switzerland), was designed in an attempt to test platelet function under close to physiological conditions. Citrated whole blood is applied on polystyrene surface, under controlled shear conditions using a cone and plate device, followed by a quantitative analysis of platelet deposition to immobilized plasma von Willebrand’s factor (VWF) and fibrinogen. Results of the test are presented for adhesion as % surface coverage (SC) and for aggregation as average size (μm2, AS). In this study we report the use of CPA test in evaluation of children with suspected bleeding disorder.

Methods: Fifty-four consecutive children with bleeding symptoms and normal platelet count and coagulation tests were evaluated between August 1st, 2006 and July 31, 2007. In addition to the CPA test, all children were tested for VWF: antigen plasma level, VWF: ristocetin activity, factor VIII: C plasma level, platelet aggregation test using turbidometric aggregometer (Helena, USA) and blood type. The study was approved by the local Helsinki committee. Statistical analysis was done by SPSS.

Results: Of 54 children, 10 (18.9%) were diagnosed with VWD and 6 (11.1%) children were diagnosed with platelet function defect according to bleeding history, family history, aggregation and factor VIII/VWF tests. To test the validity of the CPA as a screening test for diagnosis of VWD and platelet function defects a ROC curve was formulated for both SC and AS measurements. The best cutting point for a positive test was equal or less then 6.5% for SC measurement (sensitivity 60%, specificity 65%), and equal or lest then 26.5μm2 for AS measurement (sensitivity 67%, specificity 81.6%). The predictive value of a normal CPA test (negative predictive value), i.e. SC > 6.5% and AS > 26.5μm2, was 92%. Of the 26 normal CPA tests, one child was diagnosed with mild type I VWD and one child was diagnosed with mild platelet defect in response to epinephrine (40%). The predictive value of an abnormal CPA test (positive predictive value) was 50%. Of the 28 abnormal CPA test, 9 children were diagnosed with VWD, 4 children with platelet defect in response to epinephrine (<30%) and one child with platelet defect in response to collagen (10%). Significant bleeding symptoms (bleeding score 3 or more) were reported in 4 of 14 children with abnormal CPA test but with normal VWF, normal factor VIII and normal platelet aggregation.

Conclusions: The CPA test was found to be a useful tool for excluding VWD and platelet function defect in children suspected for bleeding disorder. Yet, in case of an abnormal CPA test, further testing are needed. Interestingly, abnormal CPA test was the only finding in some children with a significant bleeding history, suggesting other underlying adhesion defects yet to be described.

Author notes

Disclosure:Ownership Interests: DV is a founder of Matis-Medical, developing the Impact technology.