ABSTRACT
Endothelial cells secrete von Willebrand factor (vWF) multimers that are larger than
those found in the circulating plasma. These very large multimeric forms of vWF, capable
of spontaneously binding to and agglutinating the blood platelets under conditions
of high fluid shear rate, are degraded by a specific metalloprotease cleaving the
peptide bond 842Tyr-843Met of the vWF subunit. The vWF-cleaving protease was found
to be deficient in patients with familial thrombotic thrombocytopenic purpura (TTP).
The acute events in these patients can be successfully treated and prophylactically
prevented by repletion of the missing protease using fresh frozen plasma (FFP). In
another, apparently more common, form of TTP, the protease deficiency is due to inhibiting
circulating antibodies directed against the vWF-cleaving protease. Therapy of these
patients should include immunosuppressive treatment in addition to plasma exchange
and replacement with FFP. Normal activity of vWF-cleaving protease was established
in patients with a clinically similar disorder: hemolytic-uremic syndrome (HUS). The
level of vWF-cleaving protease activity is thus a laboratory parameter that provides
important information for the differential diagnosis and treatment of patients with
TTP/HUS. Several assays of vWF-cleaving protease have been described and are summarized
here.
KEYWORDS
TTP - HUS - von Willebrand factor - vWF-cleaving protease - assay
