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Parallel decreases of intraplatelet von Willebrand factor (VWF) and plasminogen activator inhibitor-1 (PAI-1) may determine the bleeding phenotype of type 1 von Willebrand disease (VWD)
Abstract number: PP-WE-654
Matus1 V., Panes1 O., Acuña1 S., Pereira1 J., Mezzano1 D.
11Hematology-Oncology, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile
How-to-cite Matus V, Panes O, Acuña S, Pereira J, Mezzano D. Parallel decreases of intraplatelet von Willebrand factor (VWF) and plasminogen activator inhibitor-1 (PAI-1) may determine the bleeding phenotype of type 1 von Willebrand disease (VWD). Journal of Thrombosis and Haemostasis 2009; Volume 7, Supplement 2: Abstract PP-WE-654
Laboratory diagnosis of type 1 VWD is based on decreased concentration and function of plasma VWF. However, weak correlation exists between bleeding and plasma VWF concentration/function, and healthy subjects may have very low VWD with no bleeding. So, low VWF level has been proposed more as risk factor, than a unique cause of bleeding. Patients with mild bleeding disorders have lower mean plasma levels of PAI-1, and congenital PAI-1 deficiency courses with hemorrhages. Moreover, VWD patients respond well to antifibrinolytic therapy. Our aim was to examine the contribution of plasma, intraplatelet and mRNA PAI-1 expression, as well as platelet VWF-mRNA to the phenotype of nine patients with type 1 VWD. As expected, platelet VWF:Ag and VWF:CBA were significantly lower in patients than in 13 controls (P < 0.006 and < 0.003, respectively). Platelet VWF multimers were enriched in HMW forms and lacked the lowest MW subunit. Intraplatelet PAI-1:Ag was lower in VWD than in controls (110 ± 9 vs. 160 ± 16 ng/109 platelets, P = 0.041) and the same trend was observed in plasma PAI-1 (9.3 ± 4.6 vs. 18 ± 13 ng/mL, P = 0.085). PAI-1 and VWF cDNA were amplified in 12/13 controls, whereas in VWD PAI-1 cDNA was weakly amplified in 2/9 patients and PAI-1 cDNA in 3/9 patients. Densitometric analysis confirmed these differences (both with P < 0.0001). Interestingly, one of the healthy controls had low VWF:Ag (30%) and VWF:CBA (38%), but her platelet PAI-1 was 310 ng/109 platelets, around three times the mean normal value. These results support the notion that combined, not isolated, weak hemostatic defects are necessary to trigger bleeding. This could explain the phenotypic variability observed in the disease. Further exploration inside the platelets, not so much in plasma VWF, should advance our knowledge on the mechanisms of VWF-PAI-1 interaction in bleeding disorders. Similar relationships between VWF with other platelet hemostatic factors are open as a new research field.
Disclosure of interest: none declared.
To cite this abstract use the following format:
Journal of Thrombosis and Haemostasis 2007; Volume 5, Supplement 2: abstract number
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