Evaluation of a modified thromboelastography assay for the screening of von Willebrand disease

Abstract

Thromboelastography (TEG) has been shown to be a valuable point-of-care device for the rapid diagnosis of various bleeding disorders. However, TEG has thus far not been used for the screening for von Willebrand disease (VWD). We evaluated the performance of a modified TEG assay for the laboratory screening of VWD. Three hundred twenty-eight patients (148 male, 180 female, median age 8.4 years, range 0.1 - 72.7 years) were included in the study. The diagnosis and classification of patients was based on personal and familial case history, von Willebrand factor antigen, ristocetin cofactor levels, collagen binding assay, factor VIII coagulant activity and multimer analysis. The ratio of clot strength after preincubation with ristocetin, and without ristocetin, represents the component of clot strength that is formed by cross-linked fibrin fibres and is dependent on the agglutinated platelet fraction. The decrease of the maximum amplitude is a function of the ristocetin concentration and provides a diagnostic parameter able to differentiate between healthy individuals and patients having VWD. Based on a preliminary cut-off value of 25% for the area under the curve (AUC) ratio, the sensitivity varied from 53% to 100% for the different VWD patient groups. The test is suitable for use as a screening test using whole blood and has the additional benefit of being suitable as a point of care test. It appears also useful for monitoring responses to desmopressin (DDAVP) and infusion therapy.

Biomechanics of haemostasis and thrombosis in health and disease: from the macro‐ to molecular scale

“…For normal persons, addition of ristocetin lowered clot strength because the agglutination of platelets removed platelets from the coagulation cascade. In patients with vWD, the TEG traces were only slightly inhibited because addition of ristocetin did not affect platelets because of the lack of vWF . This technique demonstrates the importance of platelets in maintaining clot mechanical properties and shows how the understanding of clot mechanical properties can be exploited to diagnose blood disorders.…”

“…Type II results from qualitative deficiencies, and is split into Type 2A, 2B, 2M and 2N. Type III is a quantitative deficiency, although vWF is nearly absent in the blood in these patients . Ristocetin is an antibiotic that causes vWF to bind to platelets, resulting in platelet agglutination.…”

“…Normal blood experiences a reduction in clot strength when incubated with ristocetin contrary to vWD patients. [46,48] Surface coverage of platelets on collagen thin films under flow is decreased.…”

A novel use of thromboelastography in type 2B von Willebrand disease

“…The applications of TEG have expanded greatly over the past 5 years with substantial attention given to standardization [13][14][15][16]. A recent report has shown evidence for TEG as a screening tool in VWD [17] and indicated that maximum amplitude (MA) is related to VWF:RCo. However, there have been no reports/data regarding the use of TEG in type 2B VWD.…”

Aktuelle Gerinnungsdiagnostik in der Intensivmedizin

“…In diesem Sinne kann beispielsweise durch eine spezielle Titrationstechnik auch ein Protamineffekt oder ein Hirudineffekt [28] mittels der Rotationsthrombelastometrie abgeschätzt werden. Kürz-lich wurde sogar ein Ansatz zur Erfassung eines Willebrand-Syndroms beschrieben [30]. Bisher haben diese speziell modifizierten thrombelastometrischen Ansätze jedoch keinen Eingang in den klinischen Alltag gefunden.…”