title: Monitoring of coagulation factor therapy in patients with von Willebrand disease type 3 using a microchip flow chamber system.
abstract: Patients with type 3 von Willebrand disease (VWD-3) have no measurable levels of VW factor (VWF) and usually require treatment with VWF-FVIII concentrate to prevent and/or stop bleeding. Even though the patients are treated prophylactically, they may experience bleeding symptoms. The aim of this study was to evaluate the effect of VWF-FVIII concentrate treatment in VWD-3 patients with the Total Thrombus Analysis System (T-TAS®), which measures thrombus formation under flow conditions. Coagulation profiles of 10 VWD-3 patients were analysed using T-TAS before and 30 minutes after VWF-FVIII concentrate (Haemate®) injection. Results were compared to VWF- and FVIII activity in plasma, and results with thromboelastometry and ristocetin-activated platelet impedance aggregometry (Multiplate®) in whole blood. For comparison, 10 healthy controls were also analysed with T-TAS. A median dose of 27 (range 15-35) IU/kg of VWF-FVIII concentrate increased VWF- and FVIII activity as expected. T-TAS thrombus formation was enhanced when a tissue factor/collagen-coated flow chamber was used at low shear, but treatment effects at high shear using a collagen-coated flow chamber were minimal. Whole blood coagulation assessed by thromboelastometry was normal and did not change (p > 0.05) but ristocetin-induced platelet aggregation improved (p < 0.001). In conclusion, T-TAS detects effects of VWF-FVIII concentrate treatment on coagulation-dependent thrombus formation at low shear, but minor effects are observed on platelet-dependent thrombus formation at high shear. The poor prediction of bleeding by conventional laboratory monitoring in VWD-3 patients might be related to insufficient restoration of platelet-dependent thrombus formation.
authors.affiliation: Anna Ågren, MD, PhD, Coagulation Unit, Hematology Center, Karolinska University Hospital, 171 76 Stockholm, Sweden, Tel.: +46 8 517 73373, Fax: +46 8 51775084, E-mail: anna.agren@karolinska.se.
authors.forename: Anna
authors.initials: A
authors.lastname: Ågren
authors.forename: Margareta
authors.initials: M
authors.lastname: Holmström
authors.forename: David E
authors.initials: DE
authors.lastname: Schmidt
authors.forename: Kazuya
authors.initials: K
authors.lastname: Hosokawa
authors.forename: Margareta
authors.initials: M
authors.lastname: Blombäck
authors.forename: Paul
authors.initials: P
authors.lastname: Hjemdahl
mesh_terms: D000328:Adult; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests / Q000295:instrumentation*; D016022:Case-Control Studies; D003029:Coagulants / Q000009:adverse effects / Q000627:therapeutic use*; D004867:Equipment Design; D005169:Factor VIII / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D056656:Lab-On-A-Chip Devices; D008297:Male; D046208:Microchip Analytical Procedures; D008875:Middle Aged; D011237:Predictive Value of Tests; D016896:Treatment Outcome; D056729:von Willebrand Disease, Type 3 / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D014841:von Willebrand Factor / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D003029:Coagulants; D014841:von Willebrand Factor; D005169:Factor VIII
keywords: Coagulation tests; flow chamber system; thromboelastography; von Willebrand disease; von Willebrand factor