Platelet dysfunction associated with wilms tumor and hyaluronic acid
Article first published online: 11 JUL 2006
Copyright © 1987 Wiley-Liss, Inc., A Wiley Company
American Journal of Hematology
Volume 24, Issue 3, pages 247–257, March 1987
How to Cite
Bracey, A. W., Wu, A. H. B., Aceves, J., Chow, T., Carlile, S. and Hoots, W. K. (1987), Platelet dysfunction associated with wilms tumor and hyaluronic acid. Am. J. Hematol., 24: 247–257. doi: 10.1002/ajh.2830240304
- Issue published online: 11 JUL 2006
- Article first published online: 11 JUL 2006
- Manuscript Accepted: 2 OCT 1986
- Manuscript Received: 5 MAY 1986
- von Willebrand disease
Acquired von Willebrand disease (AVWD) has been described in two cases of nephroblastoma. We studied a patient with nephroblastoma who presented with a coagulopathy suggestive of AVWD. The subject had undetectable levels of F. VIIIR: Ag, diminished F. VIIIR: WF (16.3%), F. VIII: C activity (37%), and lack of platelet aggregation to ADP, epinephrine, collagen, and arachidonic acid. These results were associated with abnormally high serum levels (850 mg/dl) of hyaluronic acid (HA), which made the patient's serum hyperviscous. Examination of the neoplasm revealed HA in the tumor matrix. All abnormalities of coagulation resolved after chemotherapy and extirpation of the neoplasm, which produced normal serum HA levels.
To study the effects of HA on platelet function, we added HA to normal platelet-poor plasma (NPP), which rendered F. VIIIR: Ag undetectable; treatment of HA with hyaluronidase eliminated F. VIIIR: Ag assay interference caused by HA. F. VIII: C activity decreased in vitro when HA was mixed with normal platelet-poor plasma (NPP). HA reduced the initial slope of normal platelet aggregation. Partial correction of platelet aggregation occurred after hyaluronidase treatment of HA-spiked PRP. Experiments in rabbits exposed to HA (serum level 400 mg/dl) demonstrated abnormalities similar to those noted in the patient. Shear rate studies of whole blood containing HA (500 mg/dl) yielded high shear stress, 27-136 dynes/cm2 over shear rates of 10-216 sec-1. We conclude that the coagulopathy demonstrated in this case is secondary to hyperviscosity produced by elevated levels of HA, which interferes with the assay for F. VIIIR: Ag. Thus the acquired coagulopathy associated with other cases of nephroblastoma may present as spurious von Willebrand disease.